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Sample records for ceruloplasmin

  1. Ceruloplasmin in neurodegenerative diseases.

    Science.gov (United States)

    Vassiliev, Vadim; Harris, Zena Leah; Zatta, Paolo

    2005-11-01

    For decades, abnormalities in ceruloplasmin (Cp) synthesis have been associated with neurodegenerative disease. From the early observation that low circulating serum ceruloplasmin levels served as a marker for Wilson's disease to the recent characterization of a neurodegenerative disorder associated with a complete lack of serum ceruloplasmin, the link between Cp and neuropathology has strengthened. The mechanisms associated with these different central nervous system abnormalities are very distinct. In Wilson's disease, a defect in the P-type ATPase results in abnormal hepatic copper accumulation that eventually leaks into the circulation and is abnormally deposited in the brain. In this case, copper deposition results in the neurodegenerative phenotype observed. Patients with autosomal recessive condition, aceruloplasminemia, lack the ferroxidase activity inherent to the multi-copper oxidase ceruloplasmin and develop abnormal iron accumulation within the central nervous system. In the following review ceruloplasmin gene expression, structure and function will be presented and the role of ceruloplasmin in iron metabolism will be discussed. The molecular events underlying the different forms of neurodegeneration observed will be presented. Understanding the role of ceruloplasmin within the central nervous system is fundamental to further our understanding of the pathology observed. Is the ferroxidase function more essential than the antioxidant role? Does Cp help maintain nitrosothiol stores or does it oxidize critical brain substrates? The answers to these questions hold the promise for the treatment of devastating neurodegenerative conditions such as Alzheimer's and Parkinson's diseases. It is essential to further elucidate the mechanism of the neuronal injury associated with these disorders.

  2. The role of ceruloplasmin in iron metabolism.

    Science.gov (United States)

    Roeser, H P; Lee, G R; Nacht, S; Cartwright, G E

    1970-12-01

    The importance of ceruloplasmin in iron metabolism was studied in swine made hypoceruloplasminemic by copper deprivation. When the plasma ceruloplasmin level fell below 1% of normal, cell-to-plasma iron flow became sufficiently impaired to cause hypoferremia, even though total body iron stores were normal. When ceruloplasmin was administered to such animals, plasma iron increased immediately and continued to rise at a rate proportional to the logarithm of the ceruloplasmin dose. The administration of inorganic copper induced increases in plasma iron only after ceruloplasmin appeared in the circulation. Thus, ceruloplasmin appeared to be essential to the normal movement of iron from cells to plasma. Studies designed to define the mechanism of action of ceruloplasmin were based on the in vitro observation that ceruloplasmin behaves as an enzyme (ferroxidase) that catalyzes oxidation of ferrous iron. Retention of injected ferrous iron in the plasma of ceruloplasmin-deficient swine was significantly less than that of ferric iron, reflecting impaired transferrin iron binding. Rat ceruloplasmin, which has little ferroxidase activity, was much less effective than porcine or human ceruloplasmin in inducing increases in plasma iron. These observations suggest that ceruloplasmin acts by virtue of its ferroxidase activity. Eight patients with Wilson's disease were evaluated in order to investigate iron metabolism in a disorder characterized by reduced ceruloplasmin levels. Evidence of iron deficiency was found in six of these, and in five of the six, plasma ceruloplasmin was less than 5% of normal. In comparison, the two patients without evidence of iron deficiency had ceruloplasmin levels of 11 and 18% of normal. It is suggested that iron deficiency tends to occur in those patients with Wilson's disease who have the severest degrees of hypoceruloplasminemia, possibly because of defective transfer of iron from intestinal mucosal cells to plasma.

  3. Evaluation of ceruloplasmin concentration in prognosis of human cancer.

    Directory of Open Access Journals (Sweden)

    Chakravarty,Prabir Kishore

    1986-04-01

    Full Text Available The serum ceruloplasmin concentration was determined in cancer patients before and after radiotherapy, and after relapse of cancer, The ceruloplasmin concentration in patients who responded to therapy, decreased to the range of normal controls. In patients who did not respond to treatment, the ceruloplasmin concentration was more or less elevated. In patients with relapse of cancer, the ceruloplasmin concentration was higher than before treatment.

  4. Study on the synthesis of ceruloplasmin as a functional radioprotector

    Energy Technology Data Exchange (ETDEWEB)

    Kim, In Gyu; Kim, Kug Chan; Shim, Hae Won; Lee, Chang Woo; Park, Hyo Kook; Park, Seon Young

    1998-12-01

    Ceruloplasmin is a normal, copper-containing plasma protein that has extracellular antioxidant properties in human and mammals. The in vivo physiological function has not yet been clarified, however, it has been proposed that ceruloplasmin may have a role in oxidation of Fe{sup 2+} to Fe{sup 3+} (ferroxidase) and promotion of lipoprotein oxidation under some circumstances. In this investigation, in addition to the many already known functions of ceruloplasmin, we would like to propose that ceruloplasmin has a thio-linked peroxidase function. The results are followings. 1) Human ceruloplasmin exhibited different antioxidant effects according to the electron donors in a metal-catalyzed oxidation system. 2) Purified ceruloplasmin did not plat a significant role in the protection of DNA stand breaks in the ascorbate/Fe{sup 3+}/O{sub 2} system. However, when ascorbate were replaced with a thiol-reducing equivalent such as dithiothreitol, DNA strand breaks were significantly prevented by the same amount of ceruloplasmin. 3) Human ceruloplasmin showed a potent peroxidase ability to destroy H{sub 2}O{sub 2} in the presence reduced glutathione. 4) Structural integrity may be needed for the glutathione-linked peroxidase activity of human ceruloplasmin. Intact human ceruloplasmin has a potent peroxidase properties to decompose H{sub 2}O{sub 2} in the presence of reduced glutathione.

  5. Correlation of serum ceruloplasmin with preeclampsia

    OpenAIRE

    Ghaseminejad A; Khodadai N; Nouri jaliani K; Shariat M; Hoshemian E

    2009-01-01

    "nBackground: Preeclampsia is a disorder of pregnancy with increased maternal and perinatal morbidity and mortality. An imbalance between free radical induced lipid peroxidation and antioxidant system has been suggested as possible pathogenesis of preeclapsia. It has been shown correlation of some serum antioxidant agents (for example ceruloplasmin) with preeclampsia and its severity. The purpose of this study was to evaluate of this correlation. "nMethods: In a analytic case-contro...

  6. Molecular studies of ceruloplasmin deficiency in Wilson's disease.

    OpenAIRE

    Czaja, M J; Weiner, F R; Schwarzenberg, S J; Sternlieb, I.; Scheinberg, I. H.; Van Thiel, D.H.; LaRusso, N F; Giambrone, M. A.; Kirschner, R.; Koschinsky, M L

    1987-01-01

    Deficiency of serum ceruloplasmin is a characteristic biochemical abnormality of Wilson's disease, although the mechanism of this finding is unknown. Ceruloplasmin messenger RNA (mRNA) levels were therefore examined in five patients with Wilson's disease and five controls with other types of hepatic disease. Northern and dot blot hybridizations showed that detectable ceruloplasmin mRNA was present in all of the patients with Wilson's disease, including one patient with no detectable serum cer...

  7. Molecular studies of ceruloplasmin deficiency in Wilson's disease.

    Science.gov (United States)

    Czaja, M J; Weiner, F R; Schwarzenberg, S J; Sternlieb, I; Scheinberg, I H; Van Thiel, D H; LaRusso, N F; Giambrone, M A; Kirschner, R; Koschinsky, M L

    1987-10-01

    Deficiency of serum ceruloplasmin is a characteristic biochemical abnormality of Wilson's disease, although the mechanism of this finding is unknown. Ceruloplasmin messenger RNA (mRNA) levels were therefore examined in five patients with Wilson's disease and five controls with other types of hepatic disease. Northern and dot blot hybridizations showed that detectable ceruloplasmin mRNA was present in all of the patients with Wilson's disease, including one patient with no detectable serum ceruloplasmin. However, the ceruloplasmin mRNA levels in the Wilson's disease patients were only 33% that of controls (P less than 0.001). In contrast, albumin mRNA levels in the Wilson's disease patients averaged 161% that of controls. In an attempt to better delineate the level of gene expression responsible for this decrease in ceruloplasmin mRNA, the nuclear run-on assay was used to analyze transcriptional rates. The amount of ceruloplasmin gene transcription in four Wilson's patients was decreased to 44% that of three controls. These results indicate that the diminished serum ceruloplasmin levels in patients with Wilson's disease are due at least in part to a decrease in ceruloplasmin gene transcription.

  8. Ceruloplasmin and serum MDA levels in hypothyroid patients

    OpenAIRE

    Bhattacharya, Aruna; Saha, Rama; Mondal, Tridbeshwar; Choudhuri, Subhadeep; Gupta, Soma

    2014-01-01

    The present study was designed to investigate the relationship between serum levels of MDA which is a marker of oxidative stress and Ceruloplasmin with thyroid hormone status in hypothyroid females pre &posttreatment.The study group comprised of 46 patients with primary hypothyroidism, The patients were reevaluated after 6 months of L-thyroxine therapy. The patients were compared with equal number of normal healthy controls. Serum MDA and Ceruloplasmin were measured according to an enzyma...

  9. Ceruloplasmin-ferroportin system of iron traffic in vertebrates

    Institute of Scientific and Technical Information of China (English)

    Giovanni; Musci; Fabio; Polticelli; Maria; Carmela; Bonaccorsi; di; Patti

    2014-01-01

    Safe trafficking of iron across the cell membrane is a delicate process that requires specific protein carriers. While many proteins involved in iron uptake by cells are known, only one cellular iron export protein has been identified in mammals: ferroportin(SLC40A1). Ceruloplasmin is a multicopper enzyme endowed with ferroxidase activity that is found as a soluble isoform in plasma or as a membrane-associated isoform in specific cell types. According to the currently accepted view, ferrous iron transported out of the cell by ferroportin would be safely oxidized by ceruloplasmin to facilitate loading on transferrin. Therefore, the ceruloplasminferroportin system represents the main pathway for cellular iron egress and it is responsible for physiological regulation of cellular iron levels. The most recent findings regarding the structural and functional features of ceruloplasmin and ferroportin and their relationship will be described in this review.

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

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    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.

  11. Human ceruloplasmin. Intramolecular electron transfer kinetics and equilibration

    DEFF Research Database (Denmark)

    Farver, O; Bendahl, L; Skov, L K;

    1999-01-01

    Pulse radiolytic reduction of disulfide bridges in ceruloplasmin yielding RSSR(-) radicals induces a cascade of intramolecular electron transfer (ET) processes. Based on the three-dimensional structure of ceruloplasmin identification of individual kinetically active disulfide groups and type 1 (T1...... with a rate constant of 3.9 +/- 0.8. No reoxidation of T1B Cu(I) could be resolved. It appears that the third T1 center (T1C of domain 2) is not participating in intramolecular ET, as it seems to be in a reduced state in the resting enzyme....

  12. CA-125 and Ceruloplasmin Levels in Ovarian Cancer Patients

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    Mangala Hegde

    2015-09-01

    Conclusion: Serum ceruloplasmin as well CA-125 level decline after treatment, and have been associated with efficacy and safety of novel therapeutic strategy to improve diagnosis and treatment for cancer. [Cukurova Med J 2015; 40(3.000: 510-516

  13. Serum Selenium and Ceruloplasmin in Nigerians with Peripartum Cardiomyopathy

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    Kamilu M. Karaye

    2015-04-01

    Full Text Available The study aimed to determine if selenium deficiency, serum ceruloplasmin and traditional birth practices are risk factors for peripartum cardiomyopathy (PPCM, in Kano, Nigeria. This is a case-control study carried out in three hospitals, and PPCM patients were followed up for six months. Critically low serum selenium concentration was defined as <70 µg/L. A total of 39 PPCM patients and 50 controls were consecutively recruited after satisfying the inclusion criteria. Mean serum selenium in patients (61.7 ± 14.9 µg/L was significantly lower than in controls (118.4 ± 45.6 µg/L (p < 0.001. The prevalence of serum selenium <70 µg/L was significantly higher among patients (76.9% than controls (22.0% (p < 0.001. The mean ceruloplasmin and prevalence of socio-economic indices, multiparity, pregnancy-induced hypertension, obesity and twin pregnancy were not different between the groups (p > 0.05. Logistic regression showed that rural residency significantly increased the odds for serum selenium <70 µg/L by 2.773-fold (p = 0.037. Baseline serum levels of selenium and ceruloplasmin were not associated with six-month mortality. This study has shown that selenium deficiency is a risk factor for PPCM in Kano, Nigeria, and is related to rural residency. However, serum ceruloplasmin, customary birth practices and some other characteristics were not associated with PPCM in the study area.

  14. Milk ceruloplasmin and its expression by mammary gland and liver in pigs.

    Science.gov (United States)

    Cerveza, P J; Mehrbod, F; Cotton, S J; Lomeli, N; Linder, M C; Fonda, E G; Wickler, S J

    2000-01-15

    Concentrations of ceruloplasmin and copper in milk and blood plasma, the nature of milk ceruloplasmin, and the effects of lactation and gestation on these parameters, as well as the expression of ceruloplasmin mRNA by the mammary gland, were examined in pigs. As seen previously in humans, ceruloplasmin and copper concentrations in sow milk were much higher a few days after birth than 1 month later, averaging 26.5 and 6.6 mg ceruloplasmin/L (by immunoassay) and 1.67 and 0.34 mg total Cu/L, on days 3 and 33 postpartum, respectively. Values for ceruloplasmin oxidase activity (measured with p-phenylene diamine) were 7.8 and 1.3 nmol/min/L, respectively. Daily milk ceruloplasmin production went from 61 to 22 mg/day and daily copper output from 38 to 12 mg/day. In contrast, there was little or no variation in serum ceruloplasmin concentration during lactation or gestation, although total plasma copper was high at the end of gestation. Milk ceruloplasmin was of the same apparent size as serum ceruloplasmin, as determined by SDS-PAGE and immunoblotting, and ceruloplasmin mRNAs of liver and mammary gland were indistinguishable by Northern analysis and RT-PCR of the various exons. Expression of total RNA and ceruloplasmin mRNA, as detected in biopsies of mammary gland, increased markedly upon onset of lactation and then declined during the next month in conjunction with a drop in milk ceruloplasmin production. The results indicate that milk ceruloplasmin, while being the same protein as in plasma, is not derived from the plasma but is produced by the mammary gland.

  15. Milk ceruloplasmin and its expression by mammary gland and liver in pigs.

    Science.gov (United States)

    Cerveza, P J; Mehrbod, F; Cotton, S J; Lomeli, N; Linder, M C; Fonda, E G; Wickler, S J

    2000-01-15

    Concentrations of ceruloplasmin and copper in milk and blood plasma, the nature of milk ceruloplasmin, and the effects of lactation and gestation on these parameters, as well as the expression of ceruloplasmin mRNA by the mammary gland, were examined in pigs. As seen previously in humans, ceruloplasmin and copper concentrations in sow milk were much higher a few days after birth than 1 month later, averaging 26.5 and 6.6 mg ceruloplasmin/L (by immunoassay) and 1.67 and 0.34 mg total Cu/L, on days 3 and 33 postpartum, respectively. Values for ceruloplasmin oxidase activity (measured with p-phenylene diamine) were 7.8 and 1.3 nmol/min/L, respectively. Daily milk ceruloplasmin production went from 61 to 22 mg/day and daily copper output from 38 to 12 mg/day. In contrast, there was little or no variation in serum ceruloplasmin concentration during lactation or gestation, although total plasma copper was high at the end of gestation. Milk ceruloplasmin was of the same apparent size as serum ceruloplasmin, as determined by SDS-PAGE and immunoblotting, and ceruloplasmin mRNAs of liver and mammary gland were indistinguishable by Northern analysis and RT-PCR of the various exons. Expression of total RNA and ceruloplasmin mRNA, as detected in biopsies of mammary gland, increased markedly upon onset of lactation and then declined during the next month in conjunction with a drop in milk ceruloplasmin production. The results indicate that milk ceruloplasmin, while being the same protein as in plasma, is not derived from the plasma but is produced by the mammary gland. PMID:10620372

  16. Effect of estrogen on plasma ceruloplasmin level in rats exposed to acute stress

    OpenAIRE

    Ganaraja B; Pavithran P; Ghosh S

    2004-01-01

    BACKGROUND: Plasma ceruloplasmin, a copper containing protein, belongs to a class called acute phase proteins. Reduced level of ceruloplasmin was associated with Wilson′s disease and Menke′s kinky hair disease in man, primarily affecting copper metabolism. Stress was known to increase Ceruloplasmin. Several stress associated changes were commonly observed in women at menopause and also those who underwent overiectomy. Present experiment investigated the effect of estrogen on cer...

  17. The Clinical Utility of a Low Serum Ceruloplasmin Measurement in the Diagnosis of Wilson Disease.

    Science.gov (United States)

    Kelly, D; Crotty, G; O'Mullane, J; Stapleton, M; Sweeney, B; O'Sullivan, S S

    2016-01-01

    The first step in screening for potential Wilson disease is serum ceruloplasmin testing, whereby a level of less than 0.2g/L is suggestive of the disease. We aimed to determine what proportion of an Irish population had a low ceruloplasmin level, whether low measurements were appropriately followed-up and what were the clinical outcomes. We conducted a retrospective review of all serum ceruloplasmin measurements between August 2003 and October 2009 in a large tertiary referral centre in Southern Ireland. Clinical data, serum ceruloplasmin, liver function tests, urinary copper and liver biopsy reports were all recorded where available. 1573 patients had a serum ceruloplasmin measurement during the 7-year study period. 96 patients (6.1%) had a ceruloplasmin level Wilson disease. There was only 1 new diagnosis. Only 27 patients (28.1%) had some form of confirmatory testing performed. In our centre's experience, the positive predictive value of a significantly low ceruloplasmin level is 11.1% (95% CI 2.91-30.3%). In practice a low serum ceruloplasmin measurement is often not followed by appropriate confirmatory testing. Measuring serum ceruloplasmin as a singular diagnostic test for Wilson disease or as part of the battery of unselected liver screening tests is inappropriate and low-yield.

  18. Molecular responses of ceruloplasmin to Edwardsiella ictaluri infection and iron overload in channel catfish (Ictalurus punctatus)

    Science.gov (United States)

    Ceruloplasmin is a serum ferroxidase that carries more than 90% of the copper in plasma and has documented roles in iron homeostasis as well as antioxidative functions. In our previous studies, it has been shown that the ceruloplasmin gene is strongly up-regulated in catfish during challenge with Ed...

  19. Ceruloplasmin Oxidation, a Feature of Parkinson's Disease CSF, Inhibits Ferroxidase Activity and Promotes Cellular Iron Retention

    KAUST Repository

    Olivieri, S.

    2011-12-14

    Parkinson\\'s disease is a neurodegenerative disorder characterized by oxidative stress and CNS iron deposition. Ceruloplasmin is an extracellular ferroxidase that regulates cellular iron loading and export, and hence protects tissues from oxidative damage. Using two-dimensional electrophoresis, we investigated ceruloplasmin patterns in the CSF of human Parkinson\\'s disease patients. Parkinson\\'s disease ceruloplasmin profiles proved more acidic than those found in healthy controls and in other human neurological diseases (peripheral neuropathies, amyotrophic lateral sclerosis, and Alzheimer\\'s disease); degrees of acidity correlated with patients\\' pathological grading. Applying an unsupervised pattern recognition procedure to the two-dimensional electrophoresis images, we identified representative pathological clusters. In vitro oxidation of CSF in two-dimensional electrophoresis generated a ceruloplasmin shift resembling that observed in Parkinson\\'s disease and co-occurred with an increase in protein carbonylation. Likewise, increased protein carbonylation was observed in Parkinson\\'s disease CSF, and the same modification was directly identified in these samples on ceruloplasmin. These results indicate that ceruloplasmin oxidation contributes to pattern modification in Parkinson\\'s disease. From the functional point of view, ceruloplasmin oxidation caused a decrease in ferroxidase activity, which in turn promotes intracellular iron retention in neuronal cell lines as well as in primary neurons, which are more sensitive to iron accumulation. Accordingly, the presence of oxidized ceruloplasmin in Parkinson\\'s disease CSF might be used as a marker for oxidative damage and might provide new insights into the underlying pathological mechanisms.

  20. Effect of estrogen on plasma ceruloplasmin level in rats exposed to acute stress

    Directory of Open Access Journals (Sweden)

    Ganaraja B

    2004-04-01

    Full Text Available BACKGROUND: Plasma ceruloplasmin, a copper containing protein, belongs to a class called acute phase proteins. Reduced level of ceruloplasmin was associated with Wilson′s disease and Menke′s kinky hair disease in man, primarily affecting copper metabolism. Stress was known to increase Ceruloplasmin. Several stress associated changes were commonly observed in women at menopause and also those who underwent overiectomy. Present experiment investigated the effect of estrogen on ceruloplasmin level in acute stress. AIMS: To assess the estradiol induced changes in plasma ceruloplasmin concentration on exposure of the rats to acute stress. SETTINGS AND DESIGN: Acute stress was induced by forcing the rats to swim till exhaustion. The rats were overiectomised bilaterally to remove the primary source of sex hormones. And hormone replacement was done later. MATERIAL AND METHODS: Wistar albino female rats were used. Acute stress was induced before overiectomy, following recovery from surgery, and again after Estradiol Valerate injection (for 10 days in same group of rats. The plasma ceruloplasmin was estimated immediately after stress during each stage - that is preoperative control, stressed control, after overiectomy and then following treatment with Estradiol Valerate. STATISTICAL ANALYSIS USED: Paired sample T test was applied to analyze the findings. Results: We found lowest ceruloplasmin level after stress in overiectomised animals, while on substitution of estradiol the trend appeared to be reversed. CONCLUSION: The result suggested a direct effect of estrogen on hepatic ceruloplasmin production/release and this could account for some of the beneficial effects of hormone replacement therapy.

  1. Role of serum copper and ceruloplasmin level in patients with dysfunctional uterine bleeding

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    Ketki P. Khandhadiya

    2014-04-01

    Conclusions: This study has concluded that serum copper and ceruloplasmin could be a sensitive indicator of angiogenesis in endometrium leading to DUB in females. [Int J Reprod Contracept Obstet Gynecol 2014; 3(2.000: 330-334

  2. Ceruloplasmin and other copper binding components of blood plasma and their functions: an update.

    Science.gov (United States)

    Linder, M C

    2016-09-01

    We know that blood plasma contains many proteins and also other components that bind copper. The largest contributor to copper in the plasma is ceruloplasmin, which accounts for 40-70 percent. Apart from ceruloplasmin and albumin, most of these components have not been studied extensively, and even for ceruloplasmin and albumin, much remains to be discovered. New components with new functions, and new functions of known components are emerging, some warranting reconsideration of earlier findings. The author's laboratory has been actively involved in research on this topic. This review summarizes and updates our knowledge of the nature and functions of ceruloplasmin and the other known and emerging copper-containing molecules (principally proteins) in this fluid, to better understand how they contribute to copper homeostasis and consider their potential significance to health and disease. PMID:27426697

  3. Immune mechanisms of the radioprotective effects of ceruloplasmin

    International Nuclear Information System (INIS)

    Immunotropic features of ceruloplasmin (Cp) were examined and its capacity as radioprotector was estimated. Pulse radiolysis method was used to set the mechanism of elementary reactions, which were responsible for antioxidant activity and to demonstrate a particular role of reversible oxycomplexes Cp...O2. Within in vitro test-systems the effects of Cp were examined on the model of interaction between lymphocytes from Shelter staff which constantly contacts with ionizing radiation and autologous erythrocytes in rosset-forming phenomenon. Expression of this Index in the presence of antigens with known polyspecificity was determined (antigens were taken from cortical and pyramid sections of kidney, liver, lungs, myocard, pancreatic gland, grey matter and aorta). Simultaneously the presence of analogous autoantibodies was determined. It has been shown that Cp can reprogram the level of expression of immunovaluable receptors towards to norm. It has been also defined that Cp presence in blood irradiated in vitro (1-15 rem) promotes the masking of active centers of autoantibodies of different tissue specificity

  4. The molecular mechanism for interaction of ceruloplasmin and myeloperoxidase

    Science.gov (United States)

    Bakhautdin, Bakytzhan; Bakhautdin, Esen Göksöy

    2016-04-01

    Ceruloplasmin (Cp) is a copper-containing ferroxidase with potent antioxidant activity. Cp is expressed by hepatocytes and activated macrophages and has been known as physiologic inhibitor of myeloperoxidase (MPO). Enzymatic activity of MPO produces anti-microbial agents and strong prooxidants such as hypochlorous acid and has a potential to damage host tissue at the sites of inflammation and infection. Thus Cp-MPO interaction and inhibition of MPO has previously been suggested as an important control mechanism of excessive MPO activity. Our aim in this study was to identify minimal Cp domain or peptide that interacts with MPO. We first confirmed Cp-MPO interaction by ELISA and surface plasmon resonance (SPR). SPR analysis of the interaction yielded 30 nM affinity between Cp and MPO. We then designed and synthesized 87 overlapping peptides spanning the entire amino acid sequence of Cp. Each of the peptides was tested whether it binds to MPO by direct binding ELISA. Two of the 87 peptides, P18 and P76 strongly interacted with MPO. Amino acid sequence analysis of identified peptides revealed high sequence and structural homology between them. Further structural analysis of Cp's crystal structure by PyMOL software unfolded that both peptides represent surface-exposed sites of Cp and face nearly the same direction. To confirm our finding we raised anti-P18 antisera in rabbit and demonstrated that this antisera disrupts Cp-MPO binding and rescues MPO activity. Collectively, our results confirm Cp-MPO interaction and identify two nearly identical sites on Cp that specifically bind MPO. We propose that inhibition of MPO by Cp requires two nearly identical sites on Cp to bind homodimeric MPO simultaneously and at an angle of at least 120 degrees, which, in turn, exerts tension on MPO and results in conformational change.

  5. Mechanism of Copper Uptake from Blood Plasma Ceruloplasmin by Mammalian Cells.

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    Danny Ramos

    Full Text Available Ceruloplasmin, the main copper binding protein in blood plasma, has been of particular interest for its role in efflux of iron from cells, but has additional functions. Here we tested the hypothesis that it releases its copper for cell uptake by interacting with a cell surface reductase and transporters, producing apoceruloplasmin. Uptake and transepithelial transport of copper from ceruloplasmin was demonstrated with mammary epithelial cell monolayers (PMC42 with tight junctions grown in bicameral chambers, and purified human (64Cu-labeled ceruloplasmin secreted by HepG2 cells. Monolayers took up virtually all the (64Cu over 16h and secreted half into the apical (milk fluid. This was partly inhibited by Ag(I. The (64Cu in ceruloplasmin purified from plasma of (64Cu-injected mice accumulated linearly in mouse embryonic fibroblasts (MEFs over 3-6h. Rates were somewhat higher in Ctr1+/+ versus Ctr1-/- cells, and 3-fold lower at 2 °C. The ceruloplasmin-derived (64Cu could not be removed by extensive washing or trypsin treatment, and most was recovered in the cytosol. Actual cell copper (determined by furnace atomic absorption increased markedly upon 24h exposure to holoceruloplasmin. This was accompanied by a conversion of holo to apoceruloplasmin in the culture medium and did not occur during incubation in the absence of cells. Four different endocytosis inhibitors failed to prevent 64Cu uptake from ceruloplasmin. High concentrations of non-radioactive Cu(II- or Fe(III-NTA (substrates for cell surface reductases, or Cu(I-NTA (to compete for transporter uptake almost eliminated uptake of (64Cu from ceruloplasmin. MEFs had cell surface reductase activity and expressed Steap 2 (but not Steaps 3 and 4 or dCytB. However, six-day siRNA treatment was insufficient to reduce activity or uptake. We conclude that ceruloplasmin is a circulating copper transport protein that may interact with Steap2 on the cell surface, forming apoceruloplasmin, and Cu(I that

  6. Mechanism of Copper Uptake from Blood Plasma Ceruloplasmin by Mammalian Cells.

    Science.gov (United States)

    Ramos, Danny; Mar, David; Ishida, Michael; Vargas, Rebecca; Gaite, Michaella; Montgomery, Aaron; Linder, Maria C

    2016-01-01

    Ceruloplasmin, the main copper binding protein in blood plasma, has been of particular interest for its role in efflux of iron from cells, but has additional functions. Here we tested the hypothesis that it releases its copper for cell uptake by interacting with a cell surface reductase and transporters, producing apoceruloplasmin. Uptake and transepithelial transport of copper from ceruloplasmin was demonstrated with mammary epithelial cell monolayers (PMC42) with tight junctions grown in bicameral chambers, and purified human (64)Cu-labeled ceruloplasmin secreted by HepG2 cells. Monolayers took up virtually all the (64)Cu over 16h and secreted half into the apical (milk) fluid. This was partly inhibited by Ag(I). The (64)Cu in ceruloplasmin purified from plasma of (64)Cu-injected mice accumulated linearly in mouse embryonic fibroblasts (MEFs) over 3-6h. Rates were somewhat higher in Ctr1+/+ versus Ctr1-/- cells, and 3-fold lower at 2 °C. The ceruloplasmin-derived (64)Cu could not be removed by extensive washing or trypsin treatment, and most was recovered in the cytosol. Actual cell copper (determined by furnace atomic absorption) increased markedly upon 24h exposure to holoceruloplasmin. This was accompanied by a conversion of holo to apoceruloplasmin in the culture medium and did not occur during incubation in the absence of cells. Four different endocytosis inhibitors failed to prevent 64Cu uptake from ceruloplasmin. High concentrations of non-radioactive Cu(II)- or Fe(III)-NTA (substrates for cell surface reductases), or Cu(I)-NTA (to compete for transporter uptake) almost eliminated uptake of (64)Cu from ceruloplasmin. MEFs had cell surface reductase activity and expressed Steap 2 (but not Steaps 3 and 4 or dCytB). However, six-day siRNA treatment was insufficient to reduce activity or uptake. We conclude that ceruloplasmin is a circulating copper transport protein that may interact with Steap2 on the cell surface, forming apoceruloplasmin, and Cu(I) that

  7. Plasma Glucose and Serum Ceruloplasmin in Metabolic Syndrome and Diabetes Mellitus Type 2

    Directory of Open Access Journals (Sweden)

    Ashok Kumar Jeppu

    2016-04-01

    Full Text Available Diabetes mellitus type 2 and metabolic syndrome are conditions associated with insulin resistance and hyperglycemia. Metabolic syndrome is a risk factor for diabetes mellitus type 2. Plasma glucose (fasting/postprandial and serum ceruloplasmin levels and their relationship were studied. Study population consisted of 150 individuals—50 individuals with diabetes mellitus type 2, 50 individuals with metabolic syndrome, and 50 age- and sex-matched healthy controls. Plasma levels of fasting and postprandial glucose were measured along with serum ceruloplasmin. Data was analyzed by ANOVA and Pearson correlation. The fasting and postprandial plasma glucose levels in metabolic syndrome and diabetes mellitus type 2 were increased when compared to control. Serum ceruloplasmin level was 327.8 ± 68.9 in control, 227.3 ± 46.8 in metabolic syndrome, and 194.0 ± 49.6 in diabetes mellitus type 2 individuals. There was a statistically significant negative correlation between the fasting, postprandial plasma glucose, and serum ceruloplasmin in type 2 diabetes mellitus.

  8. Role of serum copper and ceruloplasmin level in patients with dysfunctional uterine bleeding

    OpenAIRE

    Ketki P. Khandhadiya; Yousef Rezaei Chianeh; Pragna Rao

    2014-01-01

    Background: Objective of current study was to study serum copper and ceruloplasmin levels in abnormal endometrial angiogenesis observed in dysfunctional uterine bleeding patients. Methods: Design: The present cross sectional study was undertaken in the departments of biochemistry and department of OBG, Kasturba medical college, Manipal University, Manipal, India. Population: This study was done in 40 females age between 18-45 years with history of, bleeding excessively for more than 3 mont...

  9. Copper and ceruloplasmin contents in the blood serum of peripheral and pre-hepatic veins

    Directory of Open Access Journals (Sweden)

    H. M. Canelas

    1976-03-01

    Full Text Available Copper and ceruloplasmin contents were determined in samples of peripheral and pre-hepatic venous blood of 11 patients with Manson's schistosomiasis and one patient with hepatolenticular degeneration, all of çhich submitted either to porto-caval or spleno-renal shunt. Individual difference were not significant in any of the non-Wilsonian patients. The results are discussed in regard to the current knowledge on the pathogenesis of Wilson's disease.

  10. Association of bilirubin and protein thiols in relation to copper and ceruloplasmin in hyperbilirubinemic patients

    Institute of Scientific and Technical Information of China (English)

    Mungli Prakash; Jeevan K Shetty; Roshan D'Souza; Suhasa Upadhya; Vijay Kumar

    2009-01-01

    Objective:Bilirubin is a double edged sword in biological system,acting as a toxic molecule and cytoprotecrant.Unconjugated bilirubin is proved to show antioxidant activity in vitro and in vivo.In the current work we tried to know the relationship between both conjugated and unconjugated bilirubin with copper and protein thiols in patients with hyperbilirnbinemia.Methods:Study was conducted on 56 hyperbilirubinemic cases and 56 healthy controls.Serum copper,ceruloplasmin,protein thiols,total bilirubin,conjugated and unconjugated bilirubin,unconjugated bilimbin/albumin ratio,total protein,albumin,AST,ALT and ALP were estimated.Results:There was significant increase in serum copper,total bilirubin,conjugated and unconjugated bilimbin.uriconjugated bilirubin/albumin ratio,AST,ALT,and ALP,and decrease in serum ceruloplasmin,protein thiols,total protein,and albumin in hyperbilimbinemic cases when compared to healthy controls.Conjugated bilimbin correlated positively with liver enzymes AST and ALP,and negatively with protein thials,total protein and albumin.Unconjugated bilirubin correlated positively with ALT.Protein thiols correlated negatively with copper and positively with ceruloplasmin,and also correlated negativelv with liver enzymes like AST,ALT and ALP,and positively with total protein and albumin.Conclusion:Combination of elevated levels of trace elements like copper and availability of reducing agent like bilimbin may prove deleterious by generating free radicals.

  11. A STUDY ON RELATIONSHIP BETWEEN FASTING PLASMA GLUCOSE, COPPER AND CERULOPLASMIN LEVELS IN TYPE 2 DIABETES MELLITUS

    Directory of Open Access Journals (Sweden)

    Rangaswamy

    2015-08-01

    Full Text Available INTRODUCTION: Diabetes mellitus (DM is an endocrine disease associated with hyperglycemia characterized by both insulin resistance and defective insulin secretion. Copper a transition metal is present in many tissues like liver, muscle etc., It can oxidize proteins and lipids which lead to increased production of free radical compounds. Ceruloplasmin an alpha 2 globulin is an acute phase copper containing plasma protein synthesized mainly by hepatic parenchymal cells, lymphocytes etc., Reactive oxygen species (ROS/ free radicals production due to hyperglycemia in diabetes mellitus can directly or indirectly alter the integrity and physiological function of cells. Present study was undertaken to study the relationship b etween fasting plasma glucose (FPG, copper and ceruloplasmin in type 2 Diabetes mellitus. MATERIALS AND METHODOLOGY: The study group consisted of a total 100 subjects which included non - diabetic healthy control subjects (n = 50 and type 2 diabetic patien ts (n = 50. Fasting blood samples were collected and analysed for estimation of fasting plasma glucose, serum copper and ceruloplasmin. RESULTS : Results shows increase in levels of copper and FPG (P<0.001 and decrease in ceruloplasmin (P<0.001 in type 2 DM patients compared to healthy controls. CONCLUSION: Our study shows an increase in copper and FPG with decreased levels of ceruloplasmin which may be due to generation of ROS which leads to increased consumption of available antioxidants in the body .

  12. Copper and ceruloplasmin levels in relation to total thiols and GST in type 2 diabetes mellitus patients.

    Science.gov (United States)

    Sarkar, A; Dash, S; Barik, B K; Muttigi, Manjunatha S; Kedage, V; Shetty, J K; Prakash, M

    2010-01-01

    Presence of oxidative stress in type 2 diabetes mellitus (DM) is well proved. Current study was undertaken to know the relation between fasting plasma glucose (FPG) and copper along with antioxidants like total thiols and ceruloplasmin, and antioxidant enzyme glutathione S transferase (GST). The study group consisted of a total of 201 subjects which included nondiabetic healthy control subjects (n = 78) and diabetic patients (n = 123). Plasma total thiols, GST, copper and ceruloplasmin levels were measured all the subjects using spectrophotometric methods and FPG levels were determined in clinical chemistry analyzer Hitachi 912. There was significant increase in FPG (P<0.001) and copper (P<0.001) and decrease in ceruloplasmin (P<0.001) and protein thiols (P<0.001) in type 2 DM cases compared to healthy controls. There was no significant change in GST between type 2 DM cases and controls. There was significant negative correlation of FPG with antioxidants like ceruloplasmin (r = -0.420, P<0.001) and total thiols (r = -0.565, P<0.001). Protein thiols correlated positively with ceruloplasmin (r = 0.364, P<0.001). Our study indicates possible increase in copper mediated generation of ROS leading to increased consumption of available antioxidants in the body.

  13. Ceruloplasmin revisited: structural and functional roles of various metal cation-binding sites

    International Nuclear Information System (INIS)

    The three-dimensional molecular structure of human serum ceruloplasmin has been reinvestigated using X-ray synchrotron data collected at 100 K from a crystal frozen to liquid-nitrogen temperature. The three-dimensional molecular structure of human serum ceruloplasmin has been reinvestigated using X-ray synchrotron data collected at 100 K from a crystal frozen to liquid-nitrogen temperature. The resulting model, with an increase in resolution from 3.1 to 2.8 Å, gives an overall improvement of the molecular structure, in particular the side chains. In addition, it enables the clear definition of previously unidentified Ca2+-binding and Na+-binding sites. The Ca2+ cation is located in domain 1 in a configuration very similar to that found in the activated bovine factor Va. The Na+ sites appear to play a structural role in providing rigidity to the three protuberances on the top surface of the molecule. These features probably help to steer substrates towards the mononuclear copper sites prior to their oxidation and to restrict the size of the approaching substrate. The trinuclear copper centre appears to differ from the room-temperature structure in that a dioxygen moiety is bound in a similar way to that found in the endospore coat protein CotA from Bacillus subtilis

  14. Non-ceruloplasmin bound copper and ATP7B gene variants in Alzheimer's disease.

    Science.gov (United States)

    Squitti, R; Siotto, M; Arciello, M; Rossi, L

    2016-09-01

    ATP7B, a protein mainly expressed in the hepatocytes, is a copper chaperone that loads the metal into the serum copper-protein ceruloplasmin during its synthesis and also escorts superfluous copper into the bile, by a sophisticated trafficking mechanism. Impaired function of this ATPase is associated with a well-known inborn error of copper metabolism, Wilson's disease (WD). Several mutations of ATP7B are known, involving different regions of the protein, thus resulting in a plethora of phenotypes in WD patients. It is a consolidated notion that copper dysmetabolism occurs in Alzheimer's disease (AD) as well. Besides the molecular mechanisms relating copper to the protein hallmarks of this disease and neurodegeneration, more recently the observation that a free-copper in the serum, not bound to ceruloplasmin (non-Cp-Cu), characterizes AD patients, prompted our research to identify possible genetic defects of the ATP7B gene in AD patients. Four specific single nucleotide polymorphisms and a WD rare mutation have a statistical association with AD. They contribute to characterize a copper subtype of AD. Additional facets of this AD phenotype, typified by higher levels of non-Cp-Cu, are presented and discussed in the framework of copper failure as an accelerator risk factor of neurological disorders with different aetiology.

  15. Variations in serum copper and ceruloplasmin levels in advanced gastrointestinal cancer treated with polychemotherapy.

    Science.gov (United States)

    Scanni, A; Tomirotti, M; Licciardello, L; Annibali, E; Biraghi, M; Trovato, M; Fittipaldi, M; Adamoli, P; Curtarelli, G

    1979-06-30

    Serum copper and ceruloplasmin levels (SCL, SCeL) in 57 patients with advanced cancer of the stomach (35 cases) or large intestine (22 cases) treated with polychemotherapy were studies. In gastroenteric cancer, SCL, which are already high in untreated patients, have a tendency to increase further in cases of progression of the disease, while they seem to significantly decrease in cases of remission. SCeL during the trial appeared to be correlated to the clinical evolution of the disease only in the case of stomach cancer. In large intestine cancer, SCeL did not show any significant variation in relation to the normal range. These observations, in particular on the behavior of SCL in the neoplasms of the digestive tract, are in accordance with the results of other studies. The authors are inclined to attach a diagnostic and prognostic value to the variation in SCL and SCeL in gastrointestinal cancer.

  16. Copper toxicosis gene MURR1 is not changed in Wilson disease patients with normal blood ceruloplasmin levels

    Institute of Scientific and Technical Information of China (English)

    Karl Heinz Weiss; Uta Merle; Mark Schaefer; Peter Ferenci; Joachim Fullekrug; Wolfgang Stremmel

    2006-01-01

    AIM: To analyze our Wilson disease patient cohort (n = 106) for alterations in the gene coding forMURR1.METHODS: Patients with an established diagnosis of Wilson disease but normal ceruloplasmin blood levels were chosen for our study (n = 14). Patients with two known disease-causing mutations in the ATP7B gene were not included. The three exons of the human MURR1 gene were sequenced after amplification of the genomic DNA by polymerase chain reaction.RESULTS: Our study did not reveal any mutations leading to an amino acid change in the MURR1 sequence of Wilson disease patients. A polymorphism at 472 bp of the coding sequence could be confirmed.CONCLUSION: The MURR1 gene plays no role in the pathogenesis of Wilson disease patients with normal serum ceruloplasmin levels.

  17. Two-stage method for purification of ceruloplasmin based on its interaction with neomycin.

    Science.gov (United States)

    Sokolov, A V; Kostevich, V A; Romanico, D N; Zakharova, E T; Vasilyev, V B

    2012-06-01

    A two-stage chromatography that yields highly purified ceruloplasmin (CP) from human plasma and from rat and rabbit serum is described. The isolation procedure is based on the interaction of CP with neomycin, and it provides a high yield of CP. Constants of inhibition by gentamycin, kanamycin, and neomycin of oxidase activity of CP in its reaction with p-phenylenediamine were assayed. The lowest K(i) for neomycin (11 µM) corresponded to the highest specific adsorption of CP on neomycin-agarose (10 mg CP/ml of resin). Isolation of CP from 1.4 liters of human plasma using ion-exchange chromatography on UNO-Sphere Q and affinity chromatography on neomycin-agarose yields 348 mg of CP with 412-fold purification degree. Human CP preparation obtained with A(610)/A(280) ~ 0.052 contained neither immunoreactive prothrombin nor active thrombin. Upon storage at 37°C under sterile conditions, the preparation remained stable for two months. Efficient preparation of highly purified CP from rat and rabbit sera treated according to a similar protocol suggests the suitability of our method for isolation of CP from plasma and serum of other animals. The yield of CP in three separate purifications was no less than 78%.

  18. Fibrinogen and ceruloplasmin in plasma and milk from dairy cows with subclinical and clinical mastitis.

    Science.gov (United States)

    Tabrizi, A Davasaz; Batavani, R A; Rezaei, S Asri; Ahmadi, M

    2008-02-15

    The potential using of Acute Phase Proteins (APPs) in the assessment of mammary gland health was studied by examining the levels of Fibrinogen (Fb) and Ceruloplasmin (Cp) in plasma and milk from dairy cows with different grades of mastitis. Plasma samples were taken from jugular vein and milk samples were collected from quarters of cows with subclinical and clinical mastitis, as well as healthy controls. California Mastitis Test (CMT) were performed on each udder quarter of cows for detection of CMT2+ and CMT3+ quarters. CMT (0) and culture negative cases were considered healthy cows. Clinical mastitis, was graded as mild (clots in milk) or moderate (clots in milk and visible signs of inflammation in the mammary gland/s). The concentrations of Fb in the plasma of the cows with subclinical and clinical mastitis were higher than in the plasma of the healthy cows (p0.05), but differences between clinical and healthy groups were significant (pmastitis were higher than in the milk of the healthy cows (pmastitis in dairy cows. PMID:18817128

  19. Defective copper binding to apo-ceruloplasmin in a rat model and patients with Wilson's disease.

    Science.gov (United States)

    Kojimahara, N; Nakabayashi, H; Shikata, T; Esumi, M

    1995-06-01

    To examine the mechanism of decrease in serum ceruloplasmin (Cp) in Long-Evans Cinnamon (LEC) rats, a proposed model of Wilson's disease, we analyzed Cp products at the stages of transcription and translation. Northern blot analysis and immunoblot analysis showed that the level and the molecular size of Cp mRNA and protein in LEC rats were similar to those in control Long-Evans-Agouti (LEA) rats. However, the ferroxidase activity of Cp was significantly decreased in LEC rats. We separated serum Cp into two forms by native polyacrylamide gel electrophoresis with pH modification: one was a holo-Cp with copper and ferroxidase activity, and the other was an inactive apo-Cp without copper. Holo-Cp was the predominant form in LEA rats and normal humans, whereas apo-Cp was the major form in LEC rats and patients with Wilson's disease. The cosegregation of apo-Cp predominance with the disease in LEC rats was analyzed using backcross rats. Apo-Cp was dominant in 8 of 11 offspring with disease but in none of 19 normal offspring. These results indicate that a genetic disturbance of copper binding to apo-Cp may be closely associated with the pathogenesis in LEC rats, and probably in Wilson's disease.

  20. Ceruloplasmin and Hypoferremia: Studies in Burn and Non-Burn Trauma Patients

    Directory of Open Access Journals (Sweden)

    Michael A. Dubick

    2015-03-01

    Full Text Available Objective: Normal iron handling appears to be disrupted in critically ill patients leading to hypoferremia that may contribute to systemic inflammation. Ceruloplasmin (Cp, an acute phase reactant protein that can convert ferrous iron to its less reactive ferric form facilitating binding to ferritin, has ferroxidase activity that is important to iron handling. Genetic absence of Cp decreases iron export resulting in iron accumulation in many organs. The objective of this study was to characterize iron metabolism and Cp activity in burn and non-burn trauma patients to determine if changes in Cp activity are a potential contributor to the observed hypoferremia. Material and Methods: Under Brooke Army Medical Center Institutional Review Board approved protocols, serum or plasma was collected from burn and non-burn trauma patients on admission to the ICU and at times up to 14 days and measured for indices of iron status, Cp protein and oxidase activity and cytokines. Results: Burn patients showed evidence of anemia and normal or elevated ferritin levels. Plasma Cp oxidase activity in burn and trauma patients were markedly lower than controls on admission and increased to control levels by day 3, particularly in burn patients. Plasma cytokines were elevated throughout the 14 days study along with evidence of an oxidative stress. No significant differences in soluble transferrin receptor were noted among groups on admission, but levels in burn patients were lower than controls for the first 5 days after injury. Conclusion: This study further established the hypoferremia and inflammation associated with burns and trauma. To our knowledge, this is the first study to show an early decrease in Cp oxidase activity in burn and non-burn trauma patients. The results support the hypothesis that transient loss of Cp activity contributes to hypoferremia and inflammation. Further studies are warranted to determine if decreased Cp activity increases the risk of

  1. Copper balance and ceruloplasmin in chronic hepatitis in a Wilson disease animal model, LEC rats

    Energy Technology Data Exchange (ETDEWEB)

    Komatsu, Yutaka; Ogra, Yasumitsu; Suzuki, Kazuo T. [Graduate School of Pharmaceutical Sciences, Chiba University, Inage, Chiba 263-8522 (Japan)

    2002-09-01

    In an animal model of Wilson disease, Long-Evans rats with cinnamon-colored coat (LEC rats), copper (Cu) accumulates in the liver with age up to the onset of acute hepatitis owing to a hereditary defective transporter for the efflux of Cu, ATP7B. The plasma Cu concentration is low in LEC rats because of the excretion of apo-ceruloplasmin (apo-Cp). However, toward and after the onset of chronic hepatitis, plasma Cu concentration increases in the form of holo-Cp, while the liver Cu concentration is maintained at a constant level without the occurrence of fulminant hepatitis. In the present study, the material balance of Cu was studied in LEC rats with chronic hepatitis in order to elucidate the mechanisms underlying the increase of holo-Cp in plasma and the maintenance of Cu at a constant level in the liver. The relationship between the Cu concentration and ferroxidase activity of Cp was analyzed in the plasma of LEC rats of different ages and of Wistar rats fed a Cu-deficient diet for different durations. Cu was suggested to be delivered to Cp in an all-or-nothing manner, resulting in the excretion of fully Cu-occupied holo-Cp (Cu{sub 6}-Cp) or totally Cu-unoccupied Cu{sub 0}-Cp (apo-Cp), but not partially Cu-occupied Cu{sub n}-Cp (where n=1-5). The increase of holo-Cp in acute and chronic hepatitis in LEC rats was explained by the delivery of Cu, accumulating in the non-metallothionein-bound form, to Cp outside the Golgi apparatus of the liver. The plasma Cu concentration and ferroxidase activity were proposed to be specific indicators of the appearance of non-metallothionein-bound Cu in the liver of LEC rats. (orig.)

  2. Variations in plasma ceruloplasmin and whole body retention of sup 67 Cu in guinea pigs recovering from vitamin C deficiency

    Energy Technology Data Exchange (ETDEWEB)

    Hosestenbach, R.D. Jr.; Harris, E.D. (Texas A and M Univ., College Station (United States))

    1991-03-15

    Parallels may be drawn between the symptoms of scurvy and copper deficiency. This realization led the authors to examine the effects of ascorbic acid supplementation on plasma ceruloplasmin and whole body turnover of copper in scorbutic guinea pigs. Weanling guinea pigs were fed an ascorbate free semi-purified diet for 10-14 days then randomly divided into 3 treatment groups receiving oral supplementation of ascorbic acid at levels: deficient, normal, and excess. In two experiments with different groups of animals, the plasma ceruloplasmin IU, measured by p-phenylenediamine oxidase activity, was significantly higher in the deficient groups, 53.5 {plus minus} 7.7 and 41.2 {plus minus} 9.2, than in the normal and excess groups, 18.3 {plus minus} 7.7, 21.6 {plus minus} 2.6 and 30.2 {plus minus} 9.2, 18.3 {plus minus} 2.6, respectively. {sup 67}Cu was administered intraperitoneally and whole body gamma radiation was measured at 24 h intervals to determine excretion and retention rates of the 3 treatment groups. A higher retention of {sup 67}Cu was observed in the deficient group, t1/2 = 4.8 days compared to 2.6 and 1.6 in the normal and excess groups, respectively. The affect of ascorbic acid on the regulatory mechanism of copper retention, either directly or indirectly, and the increase in plasma ceruloplasmin activity indicates ascorbic acid may perform a functional role in copper utilization in a biological system.

  3. Plasma protein thiols, ceruloplasmin, C-reactive protein and red blood cell acetylcholinesterase in patients undergoing intrauterine insemination

    OpenAIRE

    Krishnananda Prabhu; Pratap Kumar; Satish Kumar Adiga; Anjali Rao; Anupama Lanka; Jaipal Singh

    2009-01-01

    Objective: To estimate acetylcholinesterase (AChE), protein thiols (PT), ceruloplasmin (CP) and C-reactive proteins (CRPs) to assess any change in their levels following intrauterine insemination (IUI). Materials and Methods: Forty-two patients aged 31 ± 4.65 years (mean ± SD) with primary infertility selected for IUI. All of them had induced ovulation with clomiphene citrate 50 mg from day 2 to day 6. After taking the consent, 2 ml of blood was withdrawn before and after 24 h of IUI for bio...

  4. Role of hypoxia-inducible factor-1 in transcriptional activation of ceruloplasmin by iron deficiency

    Science.gov (United States)

    Mukhopadhyay, C. K.; Mazumder, B.; Fox, P. L.

    2000-01-01

    A role of the copper protein ceruloplasmin (Cp) in iron metabolism is suggested by its ferroxidase activity and by the tissue iron overload in hereditary Cp deficiency patients. In addition, plasma Cp increases markedly in several conditions of anemia, e.g. iron deficiency, hemorrhage, renal failure, sickle cell disease, pregnancy, and inflammation. However, little is known about the cellular and molecular mechanism(s) involved. We have reported that iron chelators increase Cp mRNA expression and protein synthesis in human hepatocarcinoma HepG2 cells. Furthermore, we have shown that the increase in Cp mRNA is due to increased rate of transcription. We here report the results of new studies designed to elucidate the molecular mechanism underlying transcriptional activation of Cp by iron deficiency. The 5'-flanking region of the Cp gene was cloned from a human genomic library. A 4774-base pair segment of the Cp promoter/enhancer driving a luciferase reporter was transfected into HepG2 or Hep3B cells. Iron deficiency or hypoxia increased luciferase activity by 5-10-fold compared with untreated cells. Examination of the sequence showed three pairs of consensus hypoxia-responsive elements (HREs). Deletion and mutation analysis showed that a single HRE was necessary and sufficient for gene activation. The involvement of hypoxia-inducible factor-1 (HIF-1) was shown by gel-shift and supershift experiments that showed HIF-1alpha and HIF-1beta binding to a radiolabeled oligonucleotide containing the Cp promoter HRE. Furthermore, iron deficiency (and hypoxia) did not activate Cp gene expression in Hepa c4 hepatoma cells deficient in HIF-1beta, as shown functionally by the inactivity of a transfected Cp promoter-luciferase construct and by the failure of HIF-1 to bind the Cp HRE in nuclear extracts from these cells. These results are consistent with in vivo findings that iron deficiency increases plasma Cp and provides a molecular mechanism that may help to understand these

  5. The acute phase protein ceruloplasmin as a non-invasive marker of pseudopregnancy, pregnancy, and pregnancy loss in the giant panda.

    Directory of Open Access Journals (Sweden)

    Erin L Willis

    Full Text Available After ovulation, non-pregnant female giant pandas experience pseudopregnancy. During pseudopregnancy, non-pregnant females exhibit physiological and behavioral changes similar to pregnancy. Monitoring hormonal patterns that are usually different in pregnant mammals are not effective at determining pregnancy status in many animals that undergo pseudopregnancy, including the giant panda. Therefore, a physiological test to distinguish between pregnancy and pseudopregnancy in pandas has eluded scientists for decades. We examined other potential markers of pregnancy and found that activity of the acute phase protein ceruloplasmin increases in urine of giant pandas in response to pregnancy. Results indicate that in term pregnancies, levels of active urinary ceruloplasmin were elevated the first week of pregnancy and remain elevated until 20-24 days prior to parturition, while no increase was observed during the luteal phase in known pseudopregnancies. Active ceruloplasmin also increased during ultrasound-confirmed lost pregnancies; however, the pattern was different compared to term pregnancies, particularly during the late luteal phase. In four out of the five additional reproductive cycles included in the current study where females were bred but no birth occurred, active ceruloplasmin in urine increased during the luteal phase. Similar to the known lost pregnancies, the temporal pattern of change in urinary ceruloplasmin during the luteal phase deviated from the term pregnancies suggesting that these cycles may have also been lost pregnancies. Among giant pandas in captivity, it has been presumed that there is a high rate of pregnancy loss and our results are the first to provide evidence supporting this notion.

  6. Plasma protein thiols, ceruloplasmin, C-reactive protein and red blood cell acetylcholinesterase in patients undergoing intrauterine insemination

    Directory of Open Access Journals (Sweden)

    Krishnananda Prabhu

    2009-01-01

    Full Text Available Objective: To estimate acetylcholinesterase (AChE, protein thiols (PT, ceruloplasmin (CP and C-reactive proteins (CRPs to assess any change in their levels following intrauterine insemination (IUI. Materials and Methods: Forty-two patients aged 31 ± 4.65 years (mean ± SD with primary infertility selected for IUI. All of them had induced ovulation with clomiphene citrate 50 mg from day 2 to day 6. After taking the consent, 2 ml of blood was withdrawn before and after 24 h of IUI for biochemical estimations. Results: We observed a significant decrease in plasma CP, PT and RBC AChE ( P < 0.001 following IUI compared with the respective pre-procedure levels. Highly sensitive CRP showed a marginal increase after IUI. Conclusion: Fluctuations in levels of the above parameters point to their role in the female reproductive system and in the outcome of the IUI.

  7. Significance of detection of serum ceruloplasmin in diagnosis of MODS patients%MODS患者血清铜蓝蛋白测定的意义

    Institute of Scientific and Technical Information of China (English)

    胡志华; 陈勉; 饶平

    2012-01-01

    Objective To investigate the significance of dynamic changes of serum ceruloplasmin in multiple organ dysfunction syndrome (MODS)for early diagnosis and treatment of the cases. Methods The levels of serum ceruloplasmin (CP),high-sensitivity C-reactive protein (CRCP), α-acid glycoprotein (AAG in 60 MODS patients,MODS group)on the day of admission and 30 cases of non-MODS patients (control group)were determined and analyzed. The APACHE Ⅱ ,MODS score were compared between two groups. Results The APACHE Ⅱ , MODS score, based on the levels of serum ceruloplasmin,high-sensitivity C-reactive protein and α -acid glyeoprotein in MODS group were significantly different compared to the control group (P<0.05). Compared with non-infection group,ceruloplasmin and C-reactive protein were significantly increased,the difference was significant (P<0.05). Conclusion In MODS patients,ceruloplasmin and C-reactive protein test can help early diagnose the syndrome; ceruloplasmin and C-reactive protein monitoring also can help determine the cause of MODS useful for guiding treatment of MODS patients.%目的 探讨血清中铜蓝蛋白动态变化对多器官功能障碍综合症(MODS)患者早期诊断和病因判断的价值.方法 于入院当天分别检测60例MODS患者(MODS组)、30例非MODS患者(对照组)血清铜蓝蛋白(CP)、超敏C反应蛋白(CRCP)、α-酸性糖蛋白(AAG)的含量,并对入选的住院患者进行APACHEⅡ和MODS评分.结果 MODS组与对照组相比其APACHEⅡ、MODS评分、血清铜蓝蛋白(CP)、超敏C反应蛋白(cRCP)、α-酸性糖蛋白(AAG)的比较,差异有统计学意义(P<0.05).非感染组与感染组相比较,铜蓝蛋白与超敏C反应蛋白均明显升高,差异有统计学意义(P<0.05).结论 MODS患者铜蓝蛋白、超敏C反应蛋白、α-酸性糖蛋白的检测有助于MODS早期诊断;铜蓝蛋白及超敏C反应蛋白的监测有助于MODS病因的初步判断.

  8. Glutathione synthesis inhibitor butathione sulfoximine regulates ceruloplasmin by dual but opposite mechanism: Implication in hepatic iron overload.

    Science.gov (United States)

    Tapryal, Nisha; Mukhopadhyay, Chaitali; Mishra, Manoj Kumar; Das, Dola; Biswas, Sudipta; Mukhopadhyay, Chinmay K

    2010-06-01

    Glutathione (GSH) depletion is often detected in chronic pathological conditions like hepatitis C infection, alcohol consumption or xenobiotic assault with simultaneous reactive oxygen species (ROS) generation and hepatic iron overload. However, relation between GSH depletion and regulators of iron homeostasis is not clear so far. To determine that hepatic HepG2 cells were treated with GSH synthesis inhibitor butathione sulfoximine (BSO) and a dual regulation of ceruloplasmin (Cp) that involves in hepatic iron release was detected unlike other iron homeostasis regulators. BSO treatment that caused marginal GSH deficiency increased Cp synthesis due to increased transcription mediated by activator protein (AP)-1-binding site. In higher GSH deficiency (> 40 %) with increased ROS generation, Cp expression was decreased due to promotion of Cp mRNA decay mediated by 3'untranslated region (3'UTR) as found by transfecting chimera of chloramphenicol acetyl transferase (CAT) gene with Cp 3'UTR. RNA gel shift assay showed significant reduction in 3'UTR binding protein complex in similar condition. Decreased CAT expression and RNA-protein complex binding are reversed by pretreatment with antioxidant N-acetyl cysteine suggesting 3'UTR binding protein complex is redox-sensitive. This unique and opposite regulation of Cp provides a mechanism of hepatic iron-deposition during glutathione deficiency detected in chronic pathological conditions.

  9. Automation of o-dianisidine assay for ceruloplasmin activity analyses: usefulness of investigation in Wilson's disease and in hepatic encephalopathy.

    Science.gov (United States)

    Siotto, Mariacristina; Pasqualetti, Patrizio; Marano, Massimo; Squitti, Rosanna

    2014-10-01

    Ceruloplasmin (Cp) is a serum ferroxidase that plays an essential role in iron metabolism. It is routinely tested by immunoturbidimetric assays that quantify the concentration of the protein both in its active and inactive forms. Cp activity is generally analyzed manually; the process is time-consuming, has a limited repeatability, and is not suitable for a clinical setting. To overcome these inconveniences, we have set the automation of the o-dianisidine Cp activity assay on a Cobas Mira Plus apparatus. The automation was rapid and repeatable, and the data were provided in terms of IU/L. The assay was adapted for human sera and showed a good precision [coefficient of variation (CV) 3.7 %] and low limit of detection (LoD 11.58 IU/L). The simultaneous analysis of Cp concentration and activity in the same run allowed us to calculate the Cp-specific activity that provides a better index of the overall Cp status. To test the usefulness of this automation, we tested this assay on 104 healthy volunteers and 36 patients with Wilson's disease, hepatic encephalopathy, and chronic liver disease. Cp activity and specific activity distinguished better patients between groups with respect to Cp concentration alone, and providing support for the clinical investigation of neurological diseases in which liver failure is one of the clinical hallmarks.

  10. Transplanted Neural Stem Cells: Playing a Neuroprotective Role by Ceruloplasmin in the Substantia Nigra of PD Model Rats?

    Science.gov (United States)

    Xiao, Jia-Jia; Yin, Ming; Wang, Ze-Jian; Wang, Xiao-Ping

    2015-01-01

    Although mounting evidence suggests that ceruloplasmin (CP) deficiency and iron deposition are pivotal factors responsible for exacerbating demise of dopaminergic neurons in the substantia nigra (SN) of the Parkinsonism and neural stem cells (NSCs) are believed to be excellent candidates for compensating the lost dopaminergic neurons, there are few researches to explore the change of CP expression and of iron deposition in the pathological microenvironment of SN after NSCs transplantation and the ability of grafted NSCs to differentiate directionally into dopaminergic neurons under the changed homeostasis. With substantia nigral stereotaxic technique and NSCs transplantation, we found that tyrosine hydroxylase and CP expression decreased and iron deposition increased in the lesioned SN after 6-OHDA administration compared with control, while tyrosine hydroxylase and CP expression increased and iron deposition decreased after NSCs transplantation compared to 6-OHDA administration alone. Only a small number of embedding NSCs are able to differentiate into dopaminergic neurons. These results suggest that grafted NSCs have an influence on improving the content of CP expression, which may play a neuroprotective role by decreasing iron deposition and ameliorating damage of dopaminergic neurons and possibly underline the iron-related common mechanism of Parkinson's disease and Wilson's disease.

  11. Response of plasma copper, ceruloplasmin, iron and ions in carp, Cyprinus carpio to waterborne copper ion and nanoparticle exposure.

    Science.gov (United States)

    Hedayati, Aliakbar; Hoseini, Seyyed Morteza; Hoseinifar, Seyed Hossein

    2016-01-01

    In this study, Cyprinus carpio was exposed to 0.25mgL(-1) copper as either copper sulfate (CuSO4) or copper oxide nanoparticles (nano-Cu), and 25mgL(-1) copper as nano-Cu for 14days. CuSO4 and high concentration of nano-Cu led to a significant increase in plasma total copper levels. Plasma free copper levels increased significantly in all copper-exposed treatments. Except for low concentration of nano-Cu after 7 and 14days, copper exposure generally led to a significant decrease in plasma ceruloplasmin levels. Plasma iron levels increased significantly in CuSO4 (all times) and nano-Cu (7th and 14th days) treatments. A significant elevation in plasma total iron binding capacity (TIBC) was observed after 3days in the fish exposed to low concentration nano-Cu, and after 14days in all copper-exposed treatments. Transferrin saturation (TSA) ratio showed significant increase in CuSO4 (3rd and 7th days) and the high concentration nano-Cu (7th day) treatments. Decrease in plasma chloride (7th and 14th days) and sodium (14th days) was observed in CuSO4 treatment. In conclusion, the results suggest that ionic copper is mainly absorbed via fish gill, whereas, nano-copper are more likely absorbed via gut. Also, data suggest that ionic copper has more adverse effects on the examined plasma biochemical characteristics compared to the equivalent nano-copper concentration, which may be due to the lower copper absorption by fish in the nano-copper suspension.

  12. Association of Serum Ceruloplasmin Level with Obesity: Some Components of Metabolic Syndrome and High-Sensitive C-Reactive Protein in Iran

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    Seyyed Morteza Safavi

    2012-01-01

    Full Text Available Background. One of the mechanisms that has been suggested for obesity related metabolic disturbances is obesity-induced inflammation. Pro-inflammatory cytokines generated in adipose tissue can increase hepatic synthesis of inflammation-sensitive plasma proteins (ISPs including ceruloplasmin (Cp. In this study we aimed to investigate the relation between serum Cp level and obesity. Methods. 61 persons with body mass index (BMI ≥ 25 kg/m2 (case group and 61 persons with BMI < 25 kg/m2 (control group were included in this study with a case-control design. Serum Cp levels, triglyceride level, fating blood glucose, total cholesterol, LDL-cholesterol, HDL-cholesterol and hsCRP were measured in both groups. Results. We did not observe any significant association between serum Cp level and BMI in all subjects [OR: 1.02 (CI, 0.967 to 1.07] and in case (β=0.012, P=0.86 and control groups (β=0.49, P=0.07 separately. However, in control group, this positive association was marginally significant. We found a positive correlation between serum Cp level and serum triglyceride level. Conclusion. Serum Cp level was not related to obesity in this group of subjects. None of the baseline variables could predict obesity in this group of subjects, including serum Cp level, FBS, total cholesterol, LDL and HDL- cholesterols and hsCRP.

  13. Ceruloplasmin deficiency reduces levels of iron and BDNF in the cortex and striatum of young mice and increases their vulnerability to stroke.

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    Sarah J Texel

    Full Text Available Ceruloplasmin (Cp is an essential ferroxidase that plays important roles in cellular iron trafficking. Previous findings suggest that the proper regulation and subcellular localization of iron are very important in brain cell function and viability. Brain iron dyshomeostasis is observed during normal aging, as well as in several neurodegenerative disorders such as Alzheimer's, Parkinson's and Huntington's diseases, coincident with areas more susceptible to insults. Because of their high metabolic demand and electrical excitability, neurons are particularly vulnerable to ischemic injury and death. We therefore set out to look for abnormalities in the brain of young adult mice that lack Cp. We found that iron levels in the striatum and cerebral cortex of these young animals are significantly lower than wild-type (WT controls. Also mRNA levels of the neurotrophin brain derived neurotrophic factor (BDNF, known for its role in maintenance of cell viability, were decreased in these brain areas. Chelator-mediated depletion of iron in cultured neural cells resulted in reduced BDNF expression by a posttranscriptional mechanism, suggesting a causal link between low brain iron levels and reduced BDNF expression. When the mice were subjected to middle cerebral artery occlusion, a model of focal ischemic stroke, we found increased brain damage in Cp-deficient mice compared to WT controls. Our data indicate that lack of Cp increases neuronal susceptibility to ischemic injury by a mechanism that may involve reduced levels of iron and BDNF.

  14. Functional link between ferroxidase activity of ceruloplasmin and protective effect of apo-lactoferrin: studying rats kept on a silver chloride diet.

    Science.gov (United States)

    Kostevich, Valeria A; Sokolov, Alexey V; Kozlov, Stanislav O; Vlasenko, Anna Yu; Kolmakov, Nikolay N; Zakharova, Elena T; Vasilyev, Vadim B

    2016-08-01

    Strongly pronounced argyrosis caused by adding AgCl to the feed of laboratory rats efficiently mimics the deficiency of ceruloplasmin (CP) ferroxidase activity. Bringing the concentration of AgCl in the feedstuff of lactating rats to 250 mg % and keeping their progeny (Ag-rats) for 3 months on the same silver-containing feed provided the serum iron content 1.4 times lower than that in the control group. Besides, the ferroxidase activity of CP dropped to zero. In CP purified from sera of Ag-rats two copper ions were substituted with two silver ions. Using rat models of both post-hemorrhagic and hemolytic anemia we showed that the deficiency of CP ferroxidase activity in Ag-rats affects the iron content in serum, though does not prevent the recovery of hemoglobin level accompanied by exhaustion of iron caches in liver and spleen. When apo-lactoferrin (apo-LF) was administered to Ag-rats suffering from either post-hemorrhagic or hemolytic anemia, both hemoglobin and serum iron were restored more rapidly than in the control animals. In independent experiments Ag-rats were compared with those fed on regular diet and the former displayed a prolonged 3-day stabilization of hypoxia-inducible factors 1 and 2 alpha (HIF-1a and HIF-2a) along with an increased serum concentration of erythropoietin. Introduction to Ag-rats of active CP separately or together with apo-LF reduced that effect to 1 day only. It is concluded that saturation of apo-LF with iron, provided by active CP, can strongly affect its protective capacity. PMID:27377930

  15. Delayed translational silencing of ceruloplasmin transcript in gamma interferon-activated U937 monocytic cells: role of the 3' untranslated region

    Science.gov (United States)

    Mazumder, B.; Fox, P. L.

    1999-01-01

    Ceruloplasmin (Cp) is an acute-phase protein with ferroxidase, amine oxidase, and pro- and antioxidant activities. The primary site of Cp synthesis in human adults is the liver, but it is also synthesized by cells of monocytic origin. We have shown that gamma interferon (IFN-gamma) induces the synthesis of Cp mRNA and protein in monocytic cells. We now report that the induced synthesis of Cp is terminated by a mechanism involving transcript-specific translational repression. Cp protein synthesis in U937 cells ceased after 16 h even in the presence of abundant Cp mRNA. RNA isolated from cells treated with IFN-gamma for 24 h exhibited a high in vitro translation rate, suggesting that the transcript was not defective. Ribosomal association of Cp mRNA was examined by sucrose centrifugation. When Cp synthesis was high, i.e., after 8 h of IFN-gamma treatment, Cp mRNA was primarily associated with polyribosomes. However, after 24 h, when Cp synthesis was low, Cp mRNA was primarily in the nonpolyribosomal fraction. Cytosolic extracts from cells treated with IFN-gamma for 24 h, but not for 8 h, contained a factor which blocked in vitro Cp translation. Inhibitor expression was cell type specific and present in extracts of human cells of myeloid origin, but not in several nonmyeloid cells. The inhibitory factor bound to the 3' untranslated region (3'-UTR) of Cp mRNA, as shown by restoration of in vitro translation by synthetic 3'-UTR added as a "decoy" and detection of a binding complex by RNA gel shift analysis. Deletion mapping of the Cp 3'-UTR indicated an internal 100-nucleotide region of the Cp 3'-UTR that was required for complex formation as well as for silencing of translation. Although transcript-specific translational control is common during development and differentiation and global translational control occurs during responses to cytokines and stress, to our knowledge, this is the first report of translational silencing of a specific transcript following cytokine

  16. The levels and significance of ceruloplasmin in hepatitis B with different liver function status%血浆铜蓝蛋白在乙型肝炎不同肝功能状态的水平及意义

    Institute of Scientific and Technical Information of China (English)

    杨波; 吴元凯; 曹红; 陈忠诚; 高志良; 柯伟民

    2012-01-01

    Objective To clarify the difference and significance of ceruloplasmin levels in patients with Wilson's disease and chronic hepatitis B patients with different liver function status. Methods Model for end-stage liver disease (MELD) was used to measure severities of liver function injury. The levels of ceruloplasmin in patients with Wilson' s disease, patients at the fastigium and convalescent period of acute-on-chronic liver failure with hepatitis B and in patients with chronic hepatitis B were measured by nephelometric immunoassay. Results The MELD scores in patients with Wilson' s disease (re =50) , fastigum and convalescent period of acute-on-chronic liver failure with hepatitis B (n = 30) , chronic hepatitis B (re =50) were 11.1 ?. 5 , 20. 4 ?. 2 , 10.9 ?.9 and 9. 6 ?. 8, respectively, and the levels of ceruloplasmin in those patients were (0.065 ?.036)g/L, (0. 176 ?.037)g/L, (0.210 ?.056)g/L and (0. 197 ?. 038 ) g/L, respectively. There were statistically significant differences among the four groups(F=111.4 , P <0.001). The level of ceruloplasmin in Wilson's disease patients was significant lower than that in the other groups (P<0.001). Conclusion Ceruloplasmin level is remarkably decreased in patients with Wilson's disease. Compared with Wilson's disease, ceruloplasmin level is almost normal in patients with chronic hepatitis B without liver failure. Ceruloplasmin level just is decreased slightly at the fastigium of acute-on-chronic liver failure with hepatitis B and returned to normal level along with the recovery of liver failure.%目的 探讨肝豆状核变性、乙型肝炎不同肝功能状态时血浆铜蓝蛋白水平的差异及其临床意义.方法 用终末期肝病模型(model for end-stage liver disease,MELD)评分衡量肝功能损害的严重性,采用散射比浊法检测并比较分析肝豆状核变性、慢加急性肝衰竭极期以及恢复期、慢性乙型肝炎患者的血浆铜蓝蛋白水平.结果 肝豆状核变性(n=50)、慢加

  17. Detection of Oxidasic Activity of Ceruloplasmin in Serum and Analysis of the Results%血清铜蓝蛋白氧化酶活性检测及其结果分析

    Institute of Scientific and Technical Information of China (English)

    陈珺; 冯子敬; 薛启缮; 王得新

    2006-01-01

    目的:分析低血清铜蓝蛋白氧化酶活性在41例Wilson病(Wilson's disease,WD)和52例非Wilson病(nonWilson's disease,NWD)患者之间的差异,协助临床尽早确诊或排除WD.方法:用分光光度计测定血清铜蓝蛋白(ceruloplasmin,CP)催化邻联大茴香胺产生的反应产物的吸光值,计算出酶活力.结果:WD组的CP活性为(11.17±13.80)IU·L-1,NWD组为(39.42±9.77)IU·L-1,两组差异有统计学意义P<0.001.部分NWD患者经治疗后,CP活性可显著升高,而WD组治疗前后未见明显变化.结论:极度降低的CP活性结合临床表现可确诊WD;治疗后CP活性显著升高,可作为排除WD的一个参考依据.

  18. Avaliação dos níveis de hiper-homocisteinemia, vitamina E, selênio, cobre, ceruloplasmina e ferritina em pacientes com diagnóstico de acidente vascular cerebral isquêmico Assesment of homocysteine, vitamin E, selenium, copper, ceruloplasmin and ferritin levels in patients with ischemic stroke diagnosis

    Directory of Open Access Journals (Sweden)

    Lillian Harboe-Gonçalves

    2007-02-01

    Full Text Available OBJETIVO: Avaliar níveis sangüíneos de hiper-homocisteinemia, vitamina E, selênio, cobre, ceruloplasmina e ferritina em pacientes com diagnóstico de acidente vascular cerebral isquêmico (AVCI. CASUÍSTICA, MATERIAIS E MÉTODOS: Estudo transversal analítico de 104 pacientes diagnosticados com AVCI e 98 controles. Dosagem de homocisteína e vitamina E feita por cromatografia líquida de alta performance. O selênio foi dosado por tecnologia de espectrometria de massa por plasma indutivamente acoplado; o cobre o foi por colorimetria; a ceruloplasmina, por nefelometria; e a ferritina, por imunoensaio enzimático conjugado à fluorescência (Elfa. Análise estatística feita com testes t de Student e análise de variância. RESULTADOS: Encontrada hiper-homocisteinemia em 43% dos pacientes e 13% dos controles. Os valores obtidos nas dosagens de vitamina E, cobre, ceruloplasmina e ferritina foram significativamente maiores no grupo paciente do que no grupo controle. Quanto ao selênio, a diferença entre os dois grupos não foi significativa. DISCUSSÃO: Níveis de hiper-homocisteinemia foram maiores que os encontrados na literatura, podendo ser conseqüência da genética ou dos hábitos alimentares da população. Os resultados encontrados para vitamina E, selênio, cobre, ceruloplasmina e ferritina coincidem com os de alguns trabalhos publicados, mas o modelo deste estudo não avalia se os níveis de vitamina E e selênio foram alterados pelo AVCI ou por mudanças nos hábitos dos pacientes. A ferritina e a ceruloplasmina podem ser marcadores de AVCI, e não fator causal da sua patogênese. CONCLUSÃO: A hiper-homocisteinemia é mais prevalente nos pacientes diagnosticados com AVCI. Os níveis de vitamina E, cobre, ceruloplasmina e ferritina mais elevados encontrados nos pacientes não podem ser atribuídos à ocorrência de AVCI.OBJECTIVE: To assess blood levels of hyperhomocysteinaemia, vitamin E, selenium, copper, ceruloplasmin and

  19. On Cloning,Sequence Analysis and Tissue Expression of Ceruloplasmin Gene in Rare Gudgeon%稀有鮈鲫铜蓝蛋白基因 cDNA 克隆及组织表达分析

    Institute of Scientific and Technical Information of China (English)

    景致; 彭作刚; 张耀光

    2014-01-01

    铜蓝蛋白(Ceruloplasmin ,Cp)是一种重要的铜转运蛋白,合成于肝脏并参与生物体铁的代谢,在医学上是各种炎症、感染、中毒及癌症疾病的标志性蛋白.铜蓝蛋白的研究已在多种真骨鱼类中被报道,文中第一次在稀有鮈鲫(Gobiocypris rarus)中报道此基因.采用cDNA末端快速扩增技术(rapid amplification of cDNA ends ,RACE)克隆了稀有鮈鲫铜蓝蛋白基因,使用荧光定量PCR的方法构建了该基因组织表达谱.序列分析表明稀有鮈鲫铜蓝蛋白基因包含3264 bp全长编码序列,该序列编码1087个氨基酸,其核苷酸和氨基酸序列与斑马鱼同源性最高(分别为88.1%和90.3%).理论相对分子质量和等电点分别为124429.1 D和6.41.荧光定量PCR检测表明该基因在肝脏和脾脏中相对表达量最高,在肌肉和鳃中相对表达量最低.使用氨基酸序列进行蛋白结构保守域分析,结果表明铜蓝蛋白基因在脊椎动物中是相对保守的,推测其功能也与其他物种相似.这为进一步研究稀有鮈鲫该基因的功能及其应用奠定了基础.%Ceruloplasmin (Cp) ,which is the major copper-carrying protein synthesized in the liver ,plays a role in iron metabolism .It is a marker protein for inflammation ,infection ,poisoning and cancer .The Cp gene has been reported in several teleosts and here the gene in rare gudgeon (Gobiocy p ris rarus) has been first characterized . In this study , the Cp gene has been cloned by rapid amplification of cDNA ends (RACE) .Real-time PCR has been performed to demonstrate the expression pattern in different tissues . The CDS of Cp gene is 3 264 bp long ,which encodes 1 087 amino acids .BLAST result indicates that the most similar homologue of rare gudgeon Cp is from zebrafish ,with a homology of 88 .1% (DNA ) and 90 .3% (amino acid) .The predicted relative molecular mass of the protein is 124 429.1 D with an estimated PI of 6

  20. 氯碘羟喹对实验性脑出血大鼠铜蓝蛋白表达的影响%Influence of clioquinol on experimental cerebral hemorrhage in rats with ceruloplasmin expression

    Institute of Scientific and Technical Information of China (English)

    陈艳丽; 王改青; 尹永峰; 赵瑞

    2014-01-01

    Objective To study the effect of clioquinol on the expression of ceruloplasmin in experimental cerebral hemorrhage ( ICH) rats.Methods 48 Wistar rats were randomly divided into 2 groups: control group and the intervention group with each group of 24 rats, using stereotactic injection of collagenase preparation ICH model to the caudate nucleus of rats, after molding success the intervention group were given clioquinol 50 mg /kg orally every 12 h;intragastric saline control group.From each of 2 groups, six rats decapitated at different time points after 1, 3,7,14 d, using immunohistochemical stai-ning and real-time PCR detection of Cp .Results ICH model after preparation , two groups with time Cp positive expression was significantly increased in the first seven days of the peak;compared with the control group , the intervention group within the brain tissue of rats in the first Cp day showed no significant difference ( P >0.05), the expression at 3-14 d were higher ( P <0.05).2 groups'Cp mRNA expression levels peaked at 7 days, and the first 3,7,14 d were higher than the first day expression level ( P <0.05).Compared with the control group , the intervention group 3,7,14 day Cp mRNA expression lev-els were higher ( P <0.05).Conclusion CQ adjust cerebral hemorrhage by regulating the expression of ceruloplasmin in brain tissue, brain tissue may accelerate the removal of iron ions and thus play a protective role in the brain .%目的:研究金属螯合剂氯碘羟喹(CQ)干预大鼠脑出血(ICH)后铁超载状态下铜蓝蛋白(Cp)的表达。方法将48只Wistar大鼠随机分为2组:对照组、干预组各24只,均采用立体定向技术向大鼠尾状核区注射胶原酶制备ICH模型,制模成功后干预组给予氯碘羟喹50 mg/kg灌胃,1次/12 h;对照组用等量生理盐水灌胃。2组在术后1、3、7、14 d不同时间点各取6只大鼠断头取脑,采用免疫组化染色和实时荧光定量PCR检测Cp的表达。结

  1. Interaction of [Rh2(O2CCH3)4(H2O)2] and [Rh2(O2CCH(OH)Ph)2(phen)2(H2O)2](O2C-CH(OH)Ph)2 With Sulfhydryl Compounds and Ceruloplasmin

    OpenAIRE

    Jakimowicz, Piotr; Ostropolska, Lucja; Pruchnik, Florian P.

    2000-01-01

    The interaction of binuclear rhodium(II) complexes [Rh2(OOCCH3)4(H2O)2], [Rh2{OOCCH(OH)Ph}2(phen)2(H2O)2] {OOCCH(OH)Ph}2, [Rh2(OOCCH3)2(bpy)2(H2O)2](OOCCH3)2 and [Rh2Cl2(OOCMe)2(bpy)2](3H2O) with ceruloplasmin, cysteine, glutathione and coenzyme A have been investigated using. UV-Vis and CD spectroscopies. The complexes containing phen or bpy at pH = 7.4 and 4.0 are readily reduced with sulfhydryl compounds, while rhodium(II) acetate is relatively stable in these conditions. Complex [Rh2{OOCC...

  2. Ceruloplasmina y su importancia clínica como factor indicador del riesgo cardiovascular en una población de escolares de Granada Ceruloplasmin and its clinical relevance as an indactor of cardiovascular risk factor in a school population of Granada

    Directory of Open Access Journals (Sweden)

    Mª J. Aguilar Cordero

    2011-06-01

    Full Text Available La ceruloplasmina también conocida como ferroxidasa, pertenece a la familia de las proteínas sensibles a la inflamación, siendo su función principal la de transportar el cobre en la sangre. Si bien, además de esta función transportadora, en la actualidad, son numerosos los estudios que han intentado hacer uso de la determinación de sus concentraciones séricas, como un indicador predictivo del riesgo de padecer trastornos cardiovasculares en pacientes que presentan sobrepeso u obesidad. Los resultados obtenidos en este estudio confirman la existencia de una correlación significativa entre los niveles séricos de ceruloplasmina y el estado nutricional de los sujetos, lo que significa que para la población de escolares valorada, las concentraciones séricas de esta proteína suponen un importante factor para predecir el riesgo de padecer trastornos cardiovasculares.Also known as ferroxidase ceruloplasmin, belongs to the family of inflammation-sensitive proteins, and its main function to transport copper in the blood. Although, in addition to this transport function, at present, there are numerous studies that have attempted to use the determination of serum concentrations as a predictive indicator of cardiovascular risk in patients who are overweight or obese. The results of this study confirm the existence of a significant correlation between serum ceruloplasmin and nutritional status of the subjects, which means that for the population of students assessed, serum levels of this protein are an important predictor the risk of cardiovascular disease.

  3. Copper and ceruloplasmin contents in the blood serum of peripheral and pre-hepatic veins Concentrações de cobre e ceruloplasmina no soro sanguíneo de veias periférica e pré-hepática

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    H. M. Canelas

    1976-03-01

    Full Text Available Copper and ceruloplasmin contents were determined in samples of peripheral and pre-hepatic venous blood of 11 patients with Manson's schistosomiasis and one patient with hepatolenticular degeneration, all of çhich submitted either to porto-caval or spleno-renal shunt. Individual difference were not significant in any of the non-Wilsonian patients. The results are discussed in regard to the current knowledge on the pathogenesis of Wilson's disease.Foram determinadas as concentrações de cobre e ceruloplasmina em amostras de sangue venoso periférico e pré-hepático de 11 pacientes esquistossomóticos e de 1 paciente com degeneração hepatolenticular, submetidos a anastomose portocava ou esplenorrenal. Nos 11 pacientes não wilsonianos, as diferenças individuais não se revelaram estatisticamente significantes. Os resultados são comentados em relação aos conhecimentos atuais sobre a patogenia da moléstia de Wilson.

  4. Determinação sérica de haptoglobina, ceruloplasmina e alfa-glicoproteína ácida em cães com gastrenterite hemorrágica Determination of serum haptoglobin, ceruloplasmin and acid alpha-glycoprotein in dogs with haemorrhagic gastroenteritis

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    Márcia Mery Kogika

    2003-06-01

    confidence for the ceruloplasmin (p <0.0478 when compared to the control group. In conclusion, dogs with haemorrhagic gastroenteritis during the leukopenic phase showed high serum levels of haptoglobin, ceruloplasmin and alpha-acid-glycoprotein.

  5. Estudio de los niveles séricos de leptina, ceruloplasmina y lipoproteína (a como indicadores del riesgo cardiovascular en una población de adolescentes de Granada (España Study of the serum levels of leptin, ceruloplasmin and lipoprotein (a as indicators of cardiovascular risk in a population of adolescents in Granada (Spain

    Directory of Open Access Journals (Sweden)

    Mª J. Aguilar Cordero

    2011-10-01

    Full Text Available Han sido numerosos los estudios orientados a establecer una relación entre los valores séricos de biomoléculas como la leptina, ceruloplasmina, lipoproteína (a y el estado nutricional y niveles de presión arterial sistólica y diastólica en sujetos con problemas de sobrepeso u obesidad, no siendo concluyentes en muchos casos los datos alcanzados. Los resultados obtenidos en este estudio confirman la existencia de una asociación estadísticamente significativa entre los niveles séricos de dichas biomoléculas el estado nutricional de los sujetos y los niveles de presión arterial sistólica y diastólica. Resultado de ello y para la población de adolescentes con sobrepeso y obesidad estudiada, la valoración de las concentraciones séricas de estas biomoléculas resultó ser un importante instrumento para identificar aquellos sujetos con un riesgo elevado de padecer trastornos cardiovasculares, fundamentalmente derivados de un estatus hipertensivo.Numerous studies have focused on establishing a relation between the serum values of biomolecules such as leptin, ceruloplasmin, and lipoprotein (a, and the nutritional state and levels of diastolic and systolic blood pressure in subjects with problems of overweight or obesity. However, in many cases, the results obtained have not been conclusive. The results of our study confirm the existence of a statistically significant association between the serum levels of these biomolecules, the nutritional state of the subjects, and levels of diastolic and systolic blood pressure. For the population of overweight and obese adolescents studied, the evaluation of the serum concentrations of these biomolecules was found to be an important instrument that could be used to identify those subjects with an elevated risk of suffering cardiovascular disorders basically derived from a hypertensive status.

  6. Determinação sérica de haptoglobina, ceruloplasmina, α1-glicoproteína ácida, transferrina e α1-antitripsina, em equinos com cólica Determination of serum haptoglobin, ceruloplasmin, α1-acid glycoprotein, transferrin and α1-antitrypsin in colic horses

    Directory of Open Access Journals (Sweden)

    Paula Alessandra Di Filippo

    2011-12-01

    Full Text Available Foram examinados 46 equinos adultos, 6 hígidos (G1 e 40 com cólica, submetidos à laparotomia. Vinte apresentavam lesões no intestino grosso (G2 e 20 no intestino delgado (G3. Avaliaram-se os teores séricos das proteínas de fase aguda: haptoglobina, ceruloplasmina, antitripsina, transferrina e glicoproteína ácida, antes e até sete dias após a laparotomia. Após centrifugação e fracionamento das amostras, as proteínas de fase aguda foram separadas por eletroforese em gel de poliacrilamida contendo SDS-PAGE, e suas concentrações determinadas por densitometria computadorizada. Constatou-se elevação dos valores das proteínas de fase aguda nos animais com cólica, antes e após laparotomia, porém com valores mais elevados, precoces e persistentes nos animais do G3. Os resultados deveram-se ao processo inflamatório intestinal, desencadeado pela lesão entérica e indicam que o proteinograma sérico pode auxiliar na identificação do segmento intestinal obstruído e, consequentemente, na elaboração do prognóstico de equinos com cólica.Forty six equines were examined, 6 were healthy (G1 and 40 with colic, submitted to laparotomy. Twenty were showing lesions on the large intestine (G2 and 20 lesions on the small intestine (G3. The serum concentrations of acute phase proteins: haptoglobin, ceruloplasmin, antitrypsin, transferrin, and - acid glycoprotein before and until 7 days after laparotomy. After centrifugation and fractioning of the samples, the acute phase proteins were individualized by electrophoresis on polyacrylamide gel containing SDS-PAGE, and the concentrations were determined by computerized densitometry. The increase was verified on the levels of acute phase proteins from animals with colic, before and after laparotomy, however with higher levels, premature and persistent on animals from G3. The results were due to the process of intestinal inflammation, caused by enteric injury and indicate that the serum protein

  7. CA-125 and Ceruloplasmin Levels in Ovarian Cancer Patients

    OpenAIRE

    Mangala Hegde; Yousef Rezaei Chianeh; Jeevan Shetty; Donald J. Fernandes; Pragna Rao

    2015-01-01

    Purpose: The initial stage of proliferation of epithelial ovarian carcinoma (EOCa) is usually asymptomatic. Due to the lack of sensitive and reliable markers in majority of patients the disease is widespread at the time of diagnosis. The reliable serum biomarkers currently accepted is CA125 but there is limitation in case of sensitivity of CA125 as it is detectable only in 50% of patients in stage I and 80% of patients with advanced stage. We have investigated a correlation between serum CA12...

  8. Serum Levels of Copper, Ceruloplasmin and Angiotensin Converting Enzyme among Silicotic and Non-Silicotic Workers

    Directory of Open Access Journals (Sweden)

    Safia Beshir

    2015-06-01

    CONCLUSION: Since respirable dust exposure-linked lung fibrosis disease is non-curable, the biochemical parameters (Cu, ACE and Cp can be used as exposure biomarkers to silica dust, providing a better way for early diagnosis of this deadly disease. Down regulating the inflammatory responses could potentially reduce the adverse clinical pulmonary effects of air pollution.

  9. The Effects of Plasma Vitamin C and Ceruloplasmin Levels and Exogen Vitamin C Supplementation on Reproduction in Sheep

    OpenAIRE

    HALİLOĞLU, Seyfullah; SERPEK, Behiç

    2000-01-01

    The effects of vitamin C on progesterone and oestradiol 17b synthesis, and fertility rate were studied in Merino sheep. A total of 60 sheep, aged between 2 and 7 years, of which 30 had low, and the other 30 had high plasma vitamin C levels were used. Each low and high vitamin C group was divided into 2 subgroups. Each subgroup had equal numbers of sheep. Subgroups 2 and 4 served as controls in the low and high vitamin C groups, respectively. 500 mg of vitamin C was injected intramuscularly...

  10. Mutations in SLC33A1 cause a lethal autosomal-recessive disorder with congenital cataracts, hearing loss, and low serum copper and ceruloplasmin

    DEFF Research Database (Denmark)

    Huppke, Peter; Brendel, Cornelia; Kalscheuer, Vera;

    2012-01-01

    , hearing loss, and severe developmental delay. Cerebral MRI showed pronounced cerebellar hypoplasia and hypomyelination. Homozygosity mapping was performed and displayed a region of commonality among three families at chromosome 3q25. Deep sequencing and conventional sequencing disclosed homozygous...

  11. Ceruloplasmin is a novel adipokine which is overexpressed in adipose tissue of obese subjects and in obesity-associated cancer cells

    NARCIS (Netherlands)

    Arner, Erik; Forrest, Alistair R R; Ehrlund, Anna; Mejhert, Niklas; Itoh, Masayoshi; Kawaji, Hideya; Lassmann, Timo; Laurencikiene, Jurga; Rydén, Mikael; Arner, Peter; Clevers, Hans

    2014-01-01

    Obesity confers an increased risk of developing specific cancer forms. Although the mechanisms are unclear, increased fat cell secretion of specific proteins (adipokines) may promote/facilitate development of malignant tumors in obesity via cross-talk between adipose tissue(s) and the tissues prone

  12. The relationship of erythrocyte sedimentation rate,c-reactive protien,ceruloplasmin and haptoglobin in connective tissue inflammatory diseases%结缔组织疾病患儿血沉、C-反应蛋白与铜兰蛋白、触珠蛋白的相关性探讨

    Institute of Scientific and Technical Information of China (English)

    朱小舟; 李宝青; 王哲雄

    2002-01-01

    目的:探讨风湿热和幼年性类风湿性关节炎患儿血沉、C-反应蛋白与铜兰蛋白、触珠蛋白的关系及意义.方法:采用免疫散射比浊法检测C-反应蛋白、铜兰蛋白、触珠蛋白,和血沉分析仪检测血沉,并与对照组25例健康儿对比.结果:结缔组织疾病患儿血沉、C-反应蛋白与铜兰蛋白、触珠蛋白均有不同程度的升高,25例健康儿童的检测结果均在正常范围之内,并且所有实验数据以均值±标准差(x±s)表示,T检验作组间差异显著性检验(P<0.01).用直线回归及其系数的显著性检验作相关分析,铜兰蛋白、触珠蛋白的水平与血沉、C-反应蛋白呈正相关(P<0.01).结论:在结缔组织疾病患儿中铜兰蛋白、触珠蛋白的测定与血沉、C-反应蛋白的作用相仿.

  13. The relationship between serum ceruloplasmin and iron deficiency,inflammation and peroxidation in hemodialysis patients%血液透析患者血清铜兰蛋白与铁缺乏、炎症反应及过氧化反应的关系

    Institute of Scientific and Technical Information of China (English)

    王悦; 阿拉塔; 梁力均; 史钧宝; 张爱华; 朱宁; 范敏华

    2004-01-01

    目的探讨维持性血液透析患者血清铜兰蛋白与铁缺乏、炎症反应及过氧化反应之间的关系.方法检测68名维持性血液透析患者血清铜兰蛋白、血清铁、转铁蛋白、铁蛋白以及白细胞介素-6、肿瘤坏死因子-α、丙二醛,分析铜兰蛋白与上述各指标间的相互关系. 结果与正常人相比,透析患者血清铜兰蛋白显著增高,血清铁和转铁蛋白显著降低,白细胞介素-6、肿瘤坏死因子-α和丙二醛显著增高;血清铁和转铁蛋白与铜兰蛋白水平呈显著负相关,白细胞介素-6、肿瘤坏死因子-α和丙二醛与铜兰蛋白水平呈显著正相关. 结论血清铜兰蛋白水平检测可综合反映透析患者体内铁缺乏、炎症状态和过氧化反应水平.

  14. Wilson's病患者亲体部分肝移植和全肝移植术后血清铜蓝蛋白及尿铜水平的变化%Changes of Serum Ceruloplasmin and Urinary Copper Excretion in Wilson's Disease after Liver-Related Liver Transplantation and Orthotopic Liver Transplantation

    Institute of Scientific and Technical Information of China (English)

    张峰; 成峰; 王学浩; 李相成; 孙连宝; 李君; 李国强; 钱晓峰; 汤琪云; 夏永祥

    2004-01-01

    目的总结Wilson's病患者亲体肝移植和全肝移植术后血清铜蓝蛋白及尿铜水平的恢复情况.方法自2000年9月至2003年11月我院为26例Wilson's病患者施行了肝移植术,均并发终末期肝硬变,其中3例发生急性肝功能衰竭.术前血清铜蓝蛋白和尿铜水平分别为(124.8±22.8) mg/L和(1 524.8±328.6) μg/24h,其中行活体部分肝移植22例,全肝移植4例,亲体肝移植供体术前血清铜蓝蛋白水平为(230.4 ±29.6) mg/L,尿铜水平均<50 μg/24h.结果所有患者手术顺利,全肝移植患者术后1、3、6及12个月血清铜蓝蛋白和尿铜水平分别为(320.2±36.8) mg/L、(380.4±45.6) mg/L、(360.5±37.6) mg/L、(356.2±27.6) mg/L和(240.4±22.8) μg/24h、(86.5±10.6) μg/24h、(54.2±6.8) μg/24h及(46.8±3.4) μg/24h; 亲体肝移植患者术后1、3、6及12个月血清铜蓝蛋白和尿铜水平分别为(216.8 ±20.4) mg/L、(248.5±32.6) mg/L、(285.4±44.3) mg/L、(260.2±36.6) mg/L和(380.8±37.6) μg/24h、(150.6±24.5) μg/24h、(75.5±9.6) μg/24h及(60.3±5.8) μg/24h.结论全肝移植和亲体肝移植是治疗Wilson's病的有效方法,不仅解决肝功能不全的问题,而且术后血清铜蓝蛋白及尿铜水平均可恢复正常.

  15. Wilson's Disease and Hepatic Transplantation

    Institute of Scientific and Technical Information of China (English)

    唐荣华; 薛峥; 叶启发

    2002-01-01

    Summary: To investigate the changes in neurological symptoms and signs, as well as serum copper,serum ceruloplasmin after hepatic transplantation in patients with Wilson's disease, neurological symptoms and signs, serum copper, serum ceruloplasmin before and after hepatic transplantation in18 patients with Wilson's disease were observed, and those changes were followed up in 20 non-oper ative controls treated with penicillamine. Our results showed that the neurological symptoms and signs, serum copper and serum ceruloplasmin were improved in the operative group but deteriorated in the non-operative control group. Our study showed that hepatic transplantation is better than peni cillamine in the treatment of Wilson's disease.

  16. Neonatal erythroderma as a first manifestation of Menkes disease

    DEFF Research Database (Denmark)

    Galve, Javier; Vicente, Asunción; González-Enseñat, María Antonia;

    2012-01-01

    Menkes disease is an X-linked recessive lethal multisystemic disorder of copper metabolism. Progressive neurodegeneration, connective tissue disturbances, and peculiar kinky hair are the main manifestations. The low serum copper and ceruloplasmin suggests the diagnosis, which is confirmed...

  17. Hepatic but not brain iron is rapidly chelated by deferasirox in aceruloplasminemia due to a novel gene mutation

    OpenAIRE

    Finkenstedt, Armin; Wolf, Elisabeth; Höfner, Elmar; Gasser, Bethina Isasi; Bösch, Sylvia; Bakry, Rania; Creus, Marc; Kremser, Christian; Schocke, Michael; Theurl, Milan; Moser, Patrizia; Schranz, Melanie; Bonn, Guenther; Poewe, Werner; Vogel, Wolfgang

    2010-01-01

    Background & Aims Aceruloplasminemia is a rare autosomal recessive neurodegenerative disease associated with brain and liver iron accumulation which typically presents with movement disorders, retinal degeneration, and diabetes mellitus. Ceruloplasmin is a multi-copper ferroxidase that is secreted into plasma and facilitates cellular iron export and iron binding to transferrin. Results A novel homozygous ceruloplasmin gene mutation, c.2554+1G>T, was identified as the cause of aceruloplasminem...

  18. Copper transport.

    Science.gov (United States)

    Linder, M C; Wooten, L; Cerveza, P; Cotton, S; Shulze, R; Lomeli, N

    1998-05-01

    In adult humans, the net absorption of dietary copper is approximately 1 mg/d. Dietary copper joins some 4-5 mg of endogenous copper flowing into the gastrointestinal tract through various digestive juices. Most of this copper returns to the circulation and to the tissues (including liver) that formed them. Much lower amounts of copper flow into and out of other major parts of the body (including heart, skeletal muscle, and brain). Newly absorbed copper is transported to body tissues in two phases, borne primarily by plasma protein carriers (albumin, transcuprein, and ceruloplasmin). In the first phase, copper goes from the intestine to the liver and kidney; in the second phase, copper usually goes from the liver (and perhaps also the kidney) to other organs. Ceruloplasmin plays a role in this second phase. Alternatively, liver copper can also exit via the bile, and in a form that is less easily reabsorbed. Copper is also present in and transported by other body fluids, including those bathing the brain and central nervous system and surrounding the fetus in the amniotic sac. Ceruloplasmin is present in these fluids and may also be involved in copper transport there. The concentrations of copper and ceruloplasmin in milk vary with lactational stage. Parallel changes occur in ceruloplasmin messenger RNA expression in the mammary gland (as determined in pigs). Copper in milk ceruloplasmin appears to be particularly available for absorption, at least in rats.

  19. Copper transport.

    Science.gov (United States)

    Linder, M C; Wooten, L; Cerveza, P; Cotton, S; Shulze, R; Lomeli, N

    1998-05-01

    In adult humans, the net absorption of dietary copper is approximately 1 mg/d. Dietary copper joins some 4-5 mg of endogenous copper flowing into the gastrointestinal tract through various digestive juices. Most of this copper returns to the circulation and to the tissues (including liver) that formed them. Much lower amounts of copper flow into and out of other major parts of the body (including heart, skeletal muscle, and brain). Newly absorbed copper is transported to body tissues in two phases, borne primarily by plasma protein carriers (albumin, transcuprein, and ceruloplasmin). In the first phase, copper goes from the intestine to the liver and kidney; in the second phase, copper usually goes from the liver (and perhaps also the kidney) to other organs. Ceruloplasmin plays a role in this second phase. Alternatively, liver copper can also exit via the bile, and in a form that is less easily reabsorbed. Copper is also present in and transported by other body fluids, including those bathing the brain and central nervous system and surrounding the fetus in the amniotic sac. Ceruloplasmin is present in these fluids and may also be involved in copper transport there. The concentrations of copper and ceruloplasmin in milk vary with lactational stage. Parallel changes occur in ceruloplasmin messenger RNA expression in the mammary gland (as determined in pigs). Copper in milk ceruloplasmin appears to be particularly available for absorption, at least in rats. PMID:9587137

  20. Altered metal metabolism in patients with HCV-related cirrhosis and hepatic encephalopathy.

    Science.gov (United States)

    Marano, Massimo; Vespasiani Gentilucci, Umberto; Altamura, Claudia; Siotto, Mariacristina; Squitti, Rosanna; Bucossi, Serena; Quintiliani, Livia; Migliore, Simone; Greco, Federico; Scarciolla, Laura; Quattrocchi, Carlo Cosimo; Picardi, Antonio; Vernieri, Fabrizio

    2015-12-01

    Dysfunctional metal homeostasis contributes to oxidative stress and neuronal damage. These have been implicated in hepatic encephalopathy pathogenesis. To investigate whether altered metal metabolism is associated with hepatic encephalopathy. Twenty-one controls and 34 HCV-cirrhotic patients (ENC/NEC patients according to presence/absence of previous overt episodes of hepatic encephalopathy) and a control group were studied. Serum iron, copper, ceruloplasmin, ceruloplasmin activity, transferrin, and ceruloplasmin/transferrin ratio were determined. Neuropsychological tests were performed by the repeatable battery of neuropsychological status. Magnetic resonance assessed basal ganglia volumes and metal deposition (pallidal index and T2*). Cirrhotic patients performed worse than controls at cognitive tests, especially ENC patients,. At biochemical analysis copper concentrations, ceruloplasmin activity and transferrin levels were lower in ENC than in NEC patients and controls (p < 0.05 and p < 0.01, respectively). Ceruloplasmin/transferrin ratio was higher in ENC compared to NEC patients (p < 0.05), and controls (p < 0.01). By brain magnetic resonance, ENC patients showed reduced caudate and globus pallidus volumes compared to controls (p < 0.05), and ENC and NEC patients an increased pallidal index compared to controls (p < 0.01). In ENC patients, ceruloplasmin activity correlated with caudate volume and pallidal index (ρ = 0.773 and ρ = -0.683, p < 0.05). Altered metal metabolism likely contributes to cirrhotic hepatic encephalopathy. PMID:26307419

  1. 营养补充对运动性低血色素大鼠血清、组织铜蓝蛋白及血清铁等铁代谢指标变化规律的研究%Effect of nutrition supplement on serum and tissue ceruloplasmin, serum iron and other index related to iron metabolism when sports hypochrosis happens in rats

    Institute of Scientific and Technical Information of China (English)

    曹建民; 田野; 赵杰修; 金丽; 郑弘溶; 李进挺; 赵宁宁

    2005-01-01

    为了探寻营养补充对运动性低血色素大鼠铜蓝蛋白与铁代谢指标变化的规律,以大鼠为实验对象,采用跑台作为运动方式建立运动性低血色素大鼠模型,并对大鼠进行营养干预,对其血清、组织中的铜蓝蛋白以及铁代谢相关指标进行测定.实验结果表明:长时间的运动训练导致运动性低血色素大鼠血清铜蓝蛋白、转铁蛋白明显上升,铁蛋白明显下降,而且与血清铁浓度具有较高的相关性,说明血清铜蓝蛋白、铁蛋白、转铁蛋白可以反映机体铁代谢情况;运动训练导致运动性低血色素大鼠组织铜蓝蛋白含量与血清铜蓝蛋白变化不一致;营养补剂的干预显著降低了运动性低血色素大鼠血清铜蓝蛋白、转铁蛋白含量,提高了血清铁及铁蛋白含量,表明抗贫血铁制剂复合营养补剂对提高大鼠铁贮备和维持大鼠铁代谢稳定具有积极作用.

  2. A family study of the biochemical defects in Wilson's disease.

    Science.gov (United States)

    Soothill, J F; Blainey, J D; Neale, F C; Fischer-Williams, M; Melnick, S C

    1961-05-01

    Estimations of serum copper, serum ceruloplasmin (immunochemical), and urinary amino-acids excretion (quantitative and chromatographic) in 44 healthy relatives of patients with Wilson's disease (39 from one family) are reported. Each technique revealed some abnormal individuals. Good agreement was obtained between the serum copper and serum ceruloplasmin estimations and between the quantitative and chromatographic estimations of amino-acid excretion. Some individuals were abnormal to one or other of the pairs of tests only. These results cast doubt on the hypothesis that the symptoms of Wilson's disease are secondary to a quantitative (or qualitative) abnormality of ceruloplasmin. They also suggest that the mode of inheritance of the biochemical defects may be more complicated than that of a simple recessive mutant gene. Two of the relatives (one pregnant and one immediately post-partum) had a high serum copper level, as is expected in pregnancy, but normal serum ceruloplasmin. This suggests that the mechanism of control of the serum ceruloplasmin concentration may, normally, depend on the serum copper concentration.

  3. Cholestatic liver disease masquerading as Wilson disease.

    Science.gov (United States)

    Sood, Vikrant; Rawat, Dinesh; Khanna, Rajeev; Alam, Seema

    2015-03-01

    Wilson disease and cholestatic liver diseases may present as a diagnostic dilemma if standard guidelines incorporating markers of copper overload are followed. We hereby present a series of four cases of sclerosing cholangitis masquerading as Wilson disease. True Wilson disease cases had significantly lower ceruloplasmin (6 vs. 16 mg/dL) and higher 24-hour urinary copper (322.3 vs. 74.5 μg/day) as compared to mimickers. Initial low serum ceruloplasmin levels normalized in mimickers on follow up, and this may used as a diagnostic indicator. Standard Wilson disease diagnostic criteria thus need further modification especially in developing countries to help avoid mismanagement.

  4. Spontaneous hepatic copper accumulation in Long-Evans Cinnamon rats with hereditary hepatitis. A model of Wilson's disease.

    OpenAIRE

    Li, Y; Togashi, Y; S. Sato; Emoto, T; J. H. Kang; TAKEICHI N.; Kobayashi, H; Y. Kojima; Une, Y.; Uchino, J

    1991-01-01

    Long-Evans Cinnamon (LEC) rats, an inbred strain of a mutant rat isolated from Long-Evans rats, develop hereditary hepatitis. To elucidate the role of copper metabolism in the development of the hepatitis in LEC rats, we examined the copper concentration in the tissues and serum levels of copper and ceruloplasmin. Copper concentration in the liver of LEC rats was over 40 times that of normal Long-Evans Agouti (LEA) rats, while the serum ceruloplasmin and copper concentrations in LEC rats decr...

  5. Wilson disease : from clinical to molecular

    NARCIS (Netherlands)

    Houwen, Roderick Henk Johan

    1991-01-01

    Wilson disease is an autosomal recessive copper storage disease. It is characterized by an inability of the liver to; excrete copper into bile and to incorporate copper into ceruloplasmin. This results in a gradual accumulation of copper in the liver and subsequently in the brain and other organs, I

  6. 低铜蓝蛋白血症相关性运动障碍临床研究论文简介

    Institute of Scientific and Technical Information of China (English)

    金莉蓉; 金建军; 钟春玖

    2010-01-01

    @@ 目前已知与血清铜蓝蛋白(serum ceruloplasmin,sCP)降低或缺乏相关的神经系统疾病有Wilson病(Wilson's disease,WD)、遗传性铜蓝蛋白缺乏症(hereditary aceruloplasminemia,HA)和门客斯病(Menkes disease,MD)等.

  7. Chemical and enzymatic oxidative coupling of 5-hydroxy-N,N-dimethyltryptamine with amines.

    Science.gov (United States)

    Babin, F; Huynh-Dinh, T

    1987-07-01

    As part of a program aiming to obtain a covalent labeling of serotoninergic receptors we have studied the oxidative coupling of serotonin derivatives with amino compounds. The oxidation of bufotenine (2) by MnO2 and human ceruloplasmin followed by the Michael type addition with dansylcadaverine and dansyllysine gave a fluorescent adduct identified as fused oxazole structure 4. PMID:3599029

  8. Copper transport in rats involving a new plasma protein

    International Nuclear Information System (INIS)

    The time course of distribution of high-specific activity 67CuCl2 to tissues and plasma components was followed in adult, female rats. Immediately after intubation or injection, tracer 67Cu associated with two components of the blood plasma separable on columns of Sephadex G-150: albumin and another (larger) component, which was not ceruloplasmin. The latter, tentatively named transcuprein, had an apparent molecular weight of 270,000 and a high affinity for Cu2+, as judged by processing through Chelex-100, dilution, and exchange with albumin copper, in vitro and in vivo. It was capable of donating copper to tumor cells in serum-free medium. Analysis of ''cold'' plasma by furnace atomic absorption confirmed the presence of 10-15% of plasma copper in this peak. Plots of percent dose and 67Cu specific activity against time showed that copper followed a very specific pathway after binding to albumin and transcuprein, entering mainly the liver, then reappearing in the plasma on ceruloplasmin, and then achieving peak distribution in peripheral tissues (muscles, brain, etc.). 67Cu disappeared from liver and kidney with an apparent half-life of 4.5 days, the same exponential rate found for whole body turnover. Apparent turnover of ceruloplasmin copper was more rapid. Even after 7-12 days, tracer copper in plasma was still found exclusively with ceruloplasmin. The results indicate that copper follows a carefully prescribed path, on entering the blood and binding to a new transport protein

  9. [Reparative regeneration of connective tissue structures of mammals under antioxidant therapy conditions].

    Science.gov (United States)

    Belova, S V; Norkin, I A; Puchin'ian, D M

    2015-01-01

    The influence of administration of the antioxidant complexes consisting of nonenzymatic antioxidants (alpha-tocopherol acetate preparation) and enzymatic antioxidants (ceruloplasmin) has been studied in rabbits with experimental arthritis. The introduction of alpha-tocopherol acetate (at a daily dose of 4 mg) improved metabolic processes in the organism (decreased in the rate of erythrocyte precipitation, total leukocytes and their stub and segmental forms; increased in erythrocyte count; reduced the glycosaminoglycan content as determined from uronic acid and hexose level; decreased ceruloplasmin activity and malonic dialdehyde level ion blood serum, all at p < 0.05), thus favoring reduction in the total activity of the inflammatory process as judged from hematological and biochemical data. Intra-articular introduction of ceruloplasmin (1.5 mg/kg, once per week) positively influenced the state of joint structures in damaged knee joints of the animals: decreased the activity of ceruloplasmin (from 5.28 ± 0.06 to 3.94 ± 0.01 AU), and malonic dialdehyde level (0.18 ± 0.02 to 0.08 ± 0.01 μM) in the articular fluid (all at p < 0.05). These effects are probably related to the elimination of inefficiency of the antioxidant system in the synovial medium, thus preventing inflammatory destruction of articular tissues, hindering the development of pannus, and assisting the activation of reparative regeneration of connective tissue structures.

  10. Rapid and Sensitive Detection of Protein Biomarker Using a Portable Fluorescence Biosensor based on Quantum Dots and a Lateral Flow Test Strip

    Energy Technology Data Exchange (ETDEWEB)

    Li, Zhaohui; Wang, Ying; Wang, Jun; Tang, Zhiwen; Pounds, Joel G.; Lin, Yuehe

    2010-08-15

    A portable fluorescence biosensor with rapid and ultrasensitive response for trace protein has been built up with quantum dots and lateral flow test strip. The superior signal brightness and high photostability of quantum dots are combined with the promising advantages of lateral flow test strip and resulted in high sensitivity, selectivity and speedy for protein detection. Nitrated ceruloplasmin, a significant biomarker for cardiovascular disease, lung cancer and stress response to smoking, was used as model protein to demonstrate the good performances of this proposed Qdot-based lateral flow test strip. Quantitative detection of nitrated ceruloplasmin was realized by recording the fluorescence intensity of quantum dots captured on the test line. Under optimal conditions, this portable fluorescence biosensor displays rapid responses for nitrated ceruloplasmin in wide dynamic range with a detection limit of 0.1ng/mL (S/N=3). Furthermore, the biosensor was successfully utilized for spiked human plasma sample detection with the concentration as low as 1ng/mL. The results demonstrate that the quantum dot-based lateral flow test strip is capable for rapid, sensitive, and quantitative detection of nitrated ceruloplasmin and hold a great promise for point-of-care and in field analysis of other protein biomarkers.

  11. Copper transport from mother to fetus, at the end of gestation, in rats

    International Nuclear Information System (INIS)

    The authors have followed the fate of 67Cu in pregnant rats, from 1-4 days before the end of gestation, after its intravenous infusion in the form of in vivo labeled ceruloplasmin (Cp) or 67Cu(II)-treated rat serum. One and 4 hours after administration, radioactivity administered as Cp was still with Cp in the maternal circulation and that of ionic copper was still associated with transcuprein and albumin (Tc and Alb). On the basis of % dose, Cp appeared to be more effective than Tc + Alb as a source of copper for the placenta and fetus. In contrast, maternal liver took up less 67Cu from Cp than from Tc + Alb. Four hours after administration, about 8% of the 67Cu administered as Cp had been taken up by the placenta and fetuses compared with about 2% in the case of 67Cu from Tc + Alb. The amounts of 67Cu in fetuses and fetal liver increased with time. Initial trials indicated that Cu administered as Cp became attached mainly to Tc in the fetal circulation, but was also associated with Alb and with Cp, at least by 4 hours. mRNA for ceruloplasmin was detected in maternal liver, placenta, and fetal liver, where it was present primarily on ER-bound (rather than free) polyribosomes. They conclude that normally ceruloplasmin is probably the main source of copper for the fetus, at least in the rat, although transcuprein and albumin can substitute as sources; and after entering the placenta, copper from ceruloplasmin may be transferred to transcuprein and albumin in the fetal circulation, from whence it enters the liver for storage and incorporation into fetal ceruloplasmin

  12. Non-hepatic tumors change the activity of genes encoding copper trafficking proteins in the liver.

    Science.gov (United States)

    Babich, Polina S; Skvortsov, Alexey N; Rusconi, Paolo; Tsymbalenko, Nadezhda V; Mutanen, Marja; Puchkova, Ludmila V; Broggini, Massimo

    2013-07-01

    To assess the statistical relationship between tumor growth and copper metabolism, we performed a metaanalysis of studies in which patients with neoplasms were characterized according to any of the copper status indexes (atomic copper serum concentration, serum oxidase activity, ceruloplasmin protein content). Our metaanalysis shows that in the majority of cases (more than 3100 patients), tumor growth positively correlates with the copper status indexes. Nude athymic CD-1 nu/nu mice with subcutaneous tumors of human origin, C57Bl/6J mice with murine melanoma and Apc(Min) mice with spontaneously developing adenomas throughout the intestinal tract were studied to experimentally determine the relationship between tumor progression, liver copper metabolism, and copper status indexes. We showed that the copper status indexes increased significantly during tumor growth. In the liver tissue of tumor-bearing mice, ceruloplasmin gene expression, as well as the expression of genes related to ceruloplasmin metallation (CTR1 and ATP7B), increased significantly. Moreover, the presence of an mRNA splice variant encoding a form of ceruloplasmin anchored to the plasma membrane by glycosylphosphatidyl inositol, which is atypical for hepatocytes, was also detected. The ATP7A copper transporter gene, which is normally expressed in the liver only during embryonic copper metabolism, was also activated. Depletion of holo-ceruloplasmin resulted in retardation of human HCT116 colon carcinoma cell growth in nude mice and induced DNA fragmentation in tumor cells. In addition, the concentration of cytochrome c increased significantly in the cytosol, while decreasing in the mitochondria. We discuss a possible trans-effect of developing tumors on copper metabolism in the liver.

  13. 一例Wilson病的影像学表现%Imaging findings of liver in the Wilson's disease:a case report

    Institute of Scientific and Technical Information of China (English)

    孔文韬; 张炜炜; 桑剑锋; 陈骏

    2011-01-01

    @@ Introduction Wilson's disease is a rare inherited disorder of copper metabolism which is characterized by the inability to secrete the copper-ceruloplasmin complex into plasma and free copper into the bile.In the liver,the copper deposits in the periportal regions and incites an inflammatory reaction, resulting in chronic liver disease[1].%IntroductionWilson 's disease is a rare inherited disorder of copper metabolism which is characterized by the inability to secrete the copper ceruloplasmin complex into plasma and free copper into the bile.In the liver,the copper deposits in the peliportal regiorks and incites an inflammatory reaction,resulting in chronic liver disease[ 1].Untreated Wilson 's disease is progressive and fatal,so the early diagnosis is important for working out treatment strategy [2].

  14. On the transfer of serum proteins to the rat intestinal juice

    DEFF Research Database (Denmark)

    Andersen, Vibeke; Hansen, G H; Olsen, J;

    1994-01-01

    The in vivo pattern of serum proteins in the rat small-intestinal juice was characterized by crossed immunoelectrophoresis. Immunoglobulins and albumin, alpha-1-antitrypsin, transferrin, and orosomucoid were present. Larger serum proteins were absent (ceruloplasmin, haptoglobin, alpha-1-macroglob......The in vivo pattern of serum proteins in the rat small-intestinal juice was characterized by crossed immunoelectrophoresis. Immunoglobulins and albumin, alpha-1-antitrypsin, transferrin, and orosomucoid were present. Larger serum proteins were absent (ceruloplasmin, haptoglobin, alpha-1...... was seen to leak out into the intestinal lumen from the opened interstitial spaces. A weak labelling was also found in the lysosomal/endosomal-like structures, especially in the crypt enterocytes, indicating pinocytosis of albumin. We conclude that the main reason for the occurrence of certain serum...... proteins in the intestinal juice is a selective passage through the capillary wall followed by passive intercellular transport via delivery of the serum in the interstitial space during disintegration of the enterocytes....

  15. R778L, H1069Q, and I1102T mutation study in neurologic Wilson disease

    OpenAIRE

    Kalita Jayantee; Somarajan Bindu; Misra Usha; Mittal Balraj

    2010-01-01

    There is paucity of the studies on mutations in neurologic Wilson disease (WD) in India. We studied H1069Q, R778L, I1102T mutations in 26 patients with neurologic WD from 25 families in north India. The basis of diagnosis of neurologic WD was clinical, Kayser-Fleischer (KF) ring, and ceruloplasmin. Data collected included: family history, clinical characteristics, laboratory data, ultrasound findings, magnetic resonance imaging (MRI) findings, and severity of the disease. DNA was isolated fro...

  16. Wilson's Disease Presenting With Pancytopenia

    OpenAIRE

    Acıpayam, Can; Altunay, Ali; Nilüfer İLHAN; Atçı, Nesrin

    2015-01-01

    Wilson’s disease is an autosomal recessive disorder of copper metabolism characterized by excessive amount of copper in liver, brain, eye and other body tissues. Diagnosis is based on the presence of Kayser-Fleischer rings, typical neurological symptoms, and/or a low serum ceruloplasmin concentration. The main clinical symptoms are usually due to hepatic and/or neurologic involvement. Pancytopenia is a rare initial symptom of Wilson Disease. An 11-year-old female presented with pancytopenia. ...

  17. Wilson’s disease in pregnancy: case series and review of literature

    OpenAIRE

    Malik, Ayesha; Khawaja, Ali; Sheikh, Lumaan

    2013-01-01

    Background Wilson’s disease is a rare, autosomal recessive inherited disorder characterized by impaired liver metabolism of copper leading to decreased biliary excretion and incorporation of ceruloplasmin levels mainly in the liver and brain. Untreated Wilson’s disease has been shown to cause subfertility and even in cases where pregnancy occurs, it often results in spontaneous miscarriage. Case presentations We present four cases of successful pregnancy outcomes in three patients diagnosed w...

  18. Effect of dietary restriction on sperm characteristic and oxidative status on testicular tissue in young rats exposed to long-term heat stress.

    Science.gov (United States)

    Aydilek, N; Varisli, O; Kocyigit, A; Taskin, A; Kaya, M S

    2015-11-01

    This study was conducted to evaluate the effects of dietary restriction on oxidative status and sperm parameters in rats exposed to long-term heat stress. Forty healthy Sprague-Dawley rats, aged 2.5 month, were divided into four groups of 10 with respect to feeding and temperature regimen (room temperature (22 °C)-ad libitum, room temperature-dietary restriction (40%), high temperature (38 °C)-ad libitum, high temperature-dietary restriction). At the end of the 9th week, some oxidants (lipid hydroperoxide, total oxidant status, oxidative stress index) and antioxidants (total antioxidant status, sulfhydryl groups, ceruloplasmin, paraoxonase and arylesterase activities) were measured in the testis tissue. The concentration, motility, volume, abnormal sperm count, acrosome and membrane integrity of epididymal spermatozoon and intratesticular testosterone levels were evaluated. High temperature did not change oxidative and antioxidative parameters except for sulfhydryl groups and ceruloplasmin, yet it impaired all sperm values. Neither sperm values nor oxidative status apart from sulfhydryl groups, ceruloplasmin and arylesterase was affected by dietary restriction in the testis tissue. These results suggest that long-term heat stress does not have a significant effect on testicular oxidative status, while the spermatozoa are sensitive to heat stress in young rats. Dietary restriction failed to improve the sperm quality and oxidative status except some individual antioxidant parameters; conversely, it decreased intratesticular testosterone level in the young rats exposed to long-term heat stress. PMID:25418546

  19. [Copper pathology (author's transl)].

    Science.gov (United States)

    Mallet, B; Romette, J; Di Costanzo, J D

    1982-01-30

    Copper is an essential dietary component, being the coenzyme of many enzymes with oxidase activity, e.g. ceruloplasmin, superoxide dismutase, monoamine oxidase, etc. The metabolism of copper is complex and imperfectly known. Active transport of copper through the intestinal epithelial cells involves metallothionein, a protein rich in sulfhydryl groups which also binds the copper in excess and probably prevents absorption in toxic amounts. In hepatocytes a metallothionein facilitates absorption by a similar mechanism and regulates copper distribution in the liver: incorporation in an apoceruloplasmin, storage and synthesis of copper-dependent enzymes. Metallothioneins and ceruloplasmin are essential to adequate copper homeostasis. Apart from genetic disorders, diseases involving copper usually result from hypercupraemia of varied origin. Wilson's disease and Menkes' disease, although clinically and pathogenetically different, are both marked by low ceruloplasmin and copper serum levels. The excessive liver retention of copper in Wilson's disease might be due to increased avidity of hepatic metallothioneins for copper and decreased biliary excretion through lysosomal dysfunction. Menkes' disease might be due to low avidity of intestinal and hepatic metallothioneins for copper. The basic biochemical defect responsible for these two hereditary conditions has not yet been fully elucidated.

  20. Neocortex and allocortex respond differentially to cellular stress in vitro and aging in vivo.

    Directory of Open Access Journals (Sweden)

    Jessica M Posimo

    Full Text Available In Parkinson's and Alzheimer's diseases, the allocortex accumulates aggregated proteins such as synuclein and tau well before neocortex. We present a new high-throughput model of this topographic difference by microdissecting neocortex and allocortex from the postnatal rat and treating them in parallel fashion with toxins. Allocortical cultures were more vulnerable to low concentrations of the proteasome inhibitors MG132 and PSI but not the oxidative poison H2O2. The proteasome appeared to be more impaired in allocortex because MG132 raised ubiquitin-conjugated proteins and lowered proteasome activity in allocortex more than neocortex. Allocortex cultures were more vulnerable to MG132 despite greater MG132-induced rises in heat shock protein 70, heme oxygenase 1, and catalase. Proteasome subunits PA700 and PA28 were also higher in allocortex cultures, suggesting compensatory adaptations to greater proteasome impairment. Glutathione and ceruloplasmin were not robustly MG132-responsive and were basally higher in neocortical cultures. Notably, neocortex cultures became as vulnerable to MG132 as allocortex when glutathione synthesis or autophagic defenses were inhibited. Conversely, the glutathione precursor N-acetyl cysteine rendered allocortex resilient to MG132. Glutathione and ceruloplasmin levels were then examined in vivo as a function of age because aging is a natural model of proteasome inhibition and oxidative stress. Allocortical glutathione levels rose linearly with age but were similar to neocortex in whole tissue lysates. In contrast, ceruloplasmin levels were strikingly higher in neocortex at all ages and rose linearly until middle age. PA28 levels rose with age and were higher in allocortex in vivo, also paralleling in vitro data. These neo- and allocortical differences have implications for the many studies that treat the telencephalic mantle as a single unit. Our observations suggest that the topographic progression of protein

  1. Electroencephalographic Fractal Dimension in Healthy Ageing and Alzheimer's Disease.

    Science.gov (United States)

    Smits, Fenne Margreeth; Porcaro, Camillo; Cottone, Carlo; Cancelli, Andrea; Rossini, Paolo Maria; Tecchio, Franca

    2016-01-01

    Brain activity is complex; a reflection of its structural and functional organization. Among other measures of complexity, the fractal dimension is emerging as being sensitive to neuronal damage secondary to neurological and psychiatric diseases. Here, we calculated Higuchi's fractal dimension (HFD) in resting-state eyes-closed electroencephalography (EEG) recordings from 41 healthy controls (age: 20-89 years) and 67 Alzheimer's Disease (AD) patients (age: 50-88 years), to investigate whether HFD is sensitive to brain activity changes typical in healthy aging and in AD. Additionally, we considered whether AD-accelerating effects of the copper fraction not bound to ceruloplasmin (also called "free" copper) are reflected in HFD fluctuations. The HFD measure showed an inverted U-shaped relationship with age in healthy people (R2 = .575, p < .001). Onset of HFD decline appeared around the age of 60, and was most evident in central-parietal regions. In this region, HFD decreased with aging stronger in the right than in the left hemisphere (p = .006). AD patients demonstrated reduced HFD compared to age- and education-matched healthy controls, especially in temporal-occipital regions. This was associated with decreasing cognitive status as assessed by mini-mental state examination, and with higher levels of non-ceruloplasmin copper. Taken together, our findings show that resting-state EEG complexity increases from youth to maturity and declines in healthy, aging individuals. In AD, brain activity complexity is further reduced in correlation with cognitive impairment. In addition, elevated levels of non-ceruloplasmin copper appear to accelerate the reduction of neural activity complexity. Overall, HDF appears to be a proper indicator for monitoring EEG-derived brain activity complexity in healthy and pathological aging.

  2. Blood plasma proteins and protein fractions in roe deer Capreolus capreolus L.

    Directory of Open Access Journals (Sweden)

    Dorota CYGAN-SZCZEGIELNIAK

    2015-09-01

    Full Text Available The aim of the research was to investigate some selected biochemical blood parameters in roe deer (Capreolus capreolus L.. The experiment covered 15 from 2 to 3-year-old bucks from Kuyavian-Pomeranian Voivodeship. The animals were shot by individual hunters on the shooting grounds during the hunting season of 2008/2009 (in the accordance with the Journal of Laws No 48. The material for the research was blood plasma obtained after centrifuging full, nonhemolyzed blood. The blood was collected from the zygomatic vein directly to the test tubes with EDTA and transported in cooling conditions to the laboratory. After transporting the samples of blood to a certified analytical laboratory, the following elements of the obtained blood plasma were examined: ceruloplasmin . using turbidimetric method; transferrin . using immunoturbimetric method; troponin- using a third generation assay on an Elecsys; total protein, albumin, globulin . using spectrophotometric method and total iron . using colorimetric method. The results were statistically analyzed, i.e. the correlation between the parameters was measured by means of Pearsonfs correlation coefficient. The analysis of the results revealed a number of statistically significant relations between the parameters under the investigation, especially among the compounds directly responsible for metabolism of iron and copper. A statistically important positive correlation was observed between ceruloplasmin and ferritin (r = 0.563; P.0.05 and a negative one between transferrin and troponin (r = -0.609; P.0.05. Moreover, the content of transferrin . an iron-binding protein . was 0.17 g/l, while the concentration of iron was 58 ƒĘmol/l. The content of ceruloplasmin . a protein responsible for metabolism of copper . was very low (0.036 g/l. The level of proteins in the blood plasma of the animals under the research was approximately 72 g/l, with the share of albumins about 46%. The albumin-globulin ratio was 0.86.

  3. Electroencephalographic Fractal Dimension in Healthy Ageing and Alzheimer’s Disease

    Science.gov (United States)

    Cottone, Carlo; Cancelli, Andrea; Rossini, Paolo Maria; Tecchio, Franca

    2016-01-01

    Brain activity is complex; a reflection of its structural and functional organization. Among other measures of complexity, the fractal dimension is emerging as being sensitive to neuronal damage secondary to neurological and psychiatric diseases. Here, we calculated Higuchi’s fractal dimension (HFD) in resting-state eyes-closed electroencephalography (EEG) recordings from 41 healthy controls (age: 20–89 years) and 67 Alzheimer’s Disease (AD) patients (age: 50–88 years), to investigate whether HFD is sensitive to brain activity changes typical in healthy aging and in AD. Additionally, we considered whether AD-accelerating effects of the copper fraction not bound to ceruloplasmin (also called “free” copper) are reflected in HFD fluctuations. The HFD measure showed an inverted U-shaped relationship with age in healthy people (R2 = .575, p < .001). Onset of HFD decline appeared around the age of 60, and was most evident in central-parietal regions. In this region, HFD decreased with aging stronger in the right than in the left hemisphere (p = .006). AD patients demonstrated reduced HFD compared to age- and education-matched healthy controls, especially in temporal-occipital regions. This was associated with decreasing cognitive status as assessed by mini-mental state examination, and with higher levels of non-ceruloplasmin copper. Taken together, our findings show that resting-state EEG complexity increases from youth to maturity and declines in healthy, aging individuals. In AD, brain activity complexity is further reduced in correlation with cognitive impairment. In addition, elevated levels of non-ceruloplasmin copper appear to accelerate the reduction of neural activity complexity. Overall, HDF appears to be a proper indicator for monitoring EEG-derived brain activity complexity in healthy and pathological aging. PMID:26872349

  4. Electroencephalographic Fractal Dimension in Healthy Ageing and Alzheimer's Disease.

    Science.gov (United States)

    Smits, Fenne Margreeth; Porcaro, Camillo; Cottone, Carlo; Cancelli, Andrea; Rossini, Paolo Maria; Tecchio, Franca

    2016-01-01

    Brain activity is complex; a reflection of its structural and functional organization. Among other measures of complexity, the fractal dimension is emerging as being sensitive to neuronal damage secondary to neurological and psychiatric diseases. Here, we calculated Higuchi's fractal dimension (HFD) in resting-state eyes-closed electroencephalography (EEG) recordings from 41 healthy controls (age: 20-89 years) and 67 Alzheimer's Disease (AD) patients (age: 50-88 years), to investigate whether HFD is sensitive to brain activity changes typical in healthy aging and in AD. Additionally, we considered whether AD-accelerating effects of the copper fraction not bound to ceruloplasmin (also called "free" copper) are reflected in HFD fluctuations. The HFD measure showed an inverted U-shaped relationship with age in healthy people (R2 = .575, p < .001). Onset of HFD decline appeared around the age of 60, and was most evident in central-parietal regions. In this region, HFD decreased with aging stronger in the right than in the left hemisphere (p = .006). AD patients demonstrated reduced HFD compared to age- and education-matched healthy controls, especially in temporal-occipital regions. This was associated with decreasing cognitive status as assessed by mini-mental state examination, and with higher levels of non-ceruloplasmin copper. Taken together, our findings show that resting-state EEG complexity increases from youth to maturity and declines in healthy, aging individuals. In AD, brain activity complexity is further reduced in correlation with cognitive impairment. In addition, elevated levels of non-ceruloplasmin copper appear to accelerate the reduction of neural activity complexity. Overall, HDF appears to be a proper indicator for monitoring EEG-derived brain activity complexity in healthy and pathological aging. PMID:26872349

  5. Antioxidant status in children with juvenile rheumatoid arthritis (JRA) living in Cairo, Egypt.

    Science.gov (United States)

    Ashour, M; Salem, S; Hassaneen, H; el-Gadban, H; Elwan, N; Awad, A; Basu, T K

    2000-03-01

    The aim of this study was to examine both enzymatic and non-enzymatic antioxidant status in a select group of children with juvenile rheumatoid arthritis (JRA), living in Cairo, Egypt. The plasma concentrations of albumin, ceruloplasmin, vitamin C, vitamin E as well as erythrocyte superoxide dismutase and whole blood glutathione peroxidase activities were all significantly decreased in the presence of JRA compared to those without JRA. Unlike these antioxidant factors, vitamin A and its carrier (e.g. retinol binding protein), which have very little or no antioxidant property, remained unaffected by JRA. These results suggest that the children with JRA are subject to oxidative stress.

  6. Wilson's disease in an adult asymptomatic patient: a potential role for modifying factors of copper metabolism.

    Science.gov (United States)

    Loudianos, Georgios; Incollu, Simona; Mameli, Eva; Lepori, Maria B

    2016-01-01

    Diagnosis of Wilson's disease (WD) still remains a challenge since no single test has an accuracy of 100%. Molecular testing for ATP7B gene mutations can help reach the diagnosis when routine testing is equivocal. We herein report an asymptomatic WD patient diagnosed accidentally by genetic analysis. Th is case suggests that WD is a challenge even in particular contexts such as family screening. Genetic testing of ATP7B gene should be recommended in the family members of WD patients with minimal alterations of specific tests such as ceruloplasmin, and presence of steatosis or increased body mass index.

  7. Pathogenesis and management of Wilson disease.

    Science.gov (United States)

    Harada, Masaru

    2014-04-01

    Hepatolenticular degeneration, commonly known as Wilson disease, is an autosomal recessive inherited disease of abnormal copper metabolism, characterized by the accumulation of copper in the body due to decreased biliary excretion of copper from hepatocytes. Wilson disease protein, ATP7B, functions in copper excretion into bile and in copper secretion to the bloodstream coupled with ceruloplasmin synthesis. Various kinds of mutations of ATP7B cause Wilson disease. Wilson disease is a rare genetic disease that can be treated pharmacologically. Recognition and prompt diagnosis are very important, because Wilson disease is fatal if left untreated. In this review, I summarize the pathogenesis and management of Wilson disease.

  8. A combination of serum iron, ferritin and transferrin predicts outcome in patients with intracerebral hemorrhage

    OpenAIRE

    Guang Yang; Rong Hu; Chao Zhang; Christopher Qian; Qian-Qian Luo; Wing-Ho Yung; Ya Ke; Hua Feng; Zhong-Ming Qian

    2016-01-01

    Association of a high-serum ferritin with poor outcome showed that iron might play a detrimental role in the brain after intracerebral hemorrhage (ICH). Here, we investigated changes in serum iron, ferritin, transferrin (Tf) and ceruloplasmin (CP) in patients with ICH (n = 100) at day 1 (admission), 3, 7, 14 and 21 and those in control subjects (n = 75). The hematoma and edema volumes were also determined in ICH-patients on admission and at day 3. The Modified Rankin Scale (mRS) of 59 patient...

  9. [The effect of the inhalation of ethanol and acetone on the indices of the antioxidant protection system and on lipid peroxidation in the brain tissue and blood serum of rats].

    Science.gov (United States)

    Burmistrov, S O; Mashek, O N; Stepanova, I I

    1992-01-01

    Ethanol or acetone inhalation resulted in a reduction in motor activity in rats, affecting largely their explorative behavior. The biochemical parameters of free-radical processes (catalyse and SOD activities, LPO levels) remained unchanged in the inhaling animals. Ethanol or acetone inhalation caused a significant decrease in blood catalyse activity and serum LPO levels. The acetone- and ethanol-induced changes in the activity of ceruloplasmin were heterodirectional. It can be concluded that it is useful to study the biochemical parameters of serum free-radical processes and to employ the findings in the therapy of inhalation toxicomanias.

  10. Soft Tissue Regeneration under the Effect of Wound Coating Based on Chitosan (Natural Biopolymer).

    Science.gov (United States)

    Gladkova, E V; Babushkina, I V; Norkin, I A; Mamonova, I A; Puchin'yan, D M; Konyuchenko, E A

    2016-03-01

    We developed wound coating based on natural biopolymer chitosan with additional components (ceruloplasmin, L-asparaginic acid, and glycerol). Experiments on albino male rats demonstrated its regeneratory, antioxidant, and antibacterial effects on wounds involving all layers of the skin. Due to chemical composition and buffer component, the biodegraded wound coating optimizes all phases of the wound process, accelerates by 22-28% the reparative regeneration, and leads to anatomic and functional restoration of injured sites. High absorption capacity recommends its use in the treatment of wounds with profuse exudation.

  11. Early prognosis of survival or death after a recent stroke by blood levels of acute-phase proteins.

    Science.gov (United States)

    Ionescu, D A; Haţegan, D; Jipescu, I; Steinbruch, L; Ghiţescu, M

    1991-01-01

    From 129 patients with a recent stroke 105 survived and 24 died within 3 weeks from stroke-onset. At around 40 hours after the latter, the blood-levels of the acute-phase proteins ceruloplasmin and albumin did not forecast the death of the respective patients, but, in contradistinction, the level of fibrinogen was significantly higher in those who eventually died, than in those who survived. Therefore, a higher level of fibrinogen could be a risk-factor for death after stroke.

  12. Preliminary study of cell metabolism, by use of NBT test, determination the intensity of lipid peroxidation and antioxidant activity

    Directory of Open Access Journals (Sweden)

    Diana BEI

    2009-05-01

    Full Text Available Otto Warburg, in the early part of the 20th century, originated a hypothesis, that the cause of cancer is primarily a defect in energy metabolism.A decrease in the capacity of mitochondria to reduce NAD(P, together with a decline in the NAD(PH/NAD(P redox couple, uncouples oxidative phosphorylation, lead to depletion of ATP and decrease the cell viability.Nitro-bleu tetrazolium have been used to assay cell proliferation and viability. The method to measure cell proliferation is based on enzymatic cleavage of the tetrazolium salts to a water-soluble formazan dye.Succinate-tetrazolium reductase, is an enzymatic sistem, which belongs to the respiratory chain of the mitochondria and it is active only in viable cells. The reagent diffuses into the cells and it is cleaved to formazan. The absorption change is measured and analysed.Free radicals such as superoxide, can cause a damage in cellular components, but several antioxidants inhibiting the lipid peroxidation and limiting the level of free radicals in cells.In the present study we had in view the proliferation and viability of leukemia cells during antineoplastic treatment along with the alteration of the serum level of malondialdehyde (MDA and ceruloplasmin (CP. With serum level of malondialdehyde we monitored the presence of the lipid peroxidation by the reactive oxygen species, and with the oxidized ceruloplasmin level in blood serum we evidenced the activity of antioxidant system in blood.

  13. Increased Copper-Mediated Oxidation of Membrane Phosphatidylethanolamine in Autism

    Directory of Open Access Journals (Sweden)

    Abha Chauhan

    2008-01-01

    Full Text Available We have previously reported that levels of phosphatidylethanolamine (PE in the erythrocyte membrane and of ceruloplasmin, a copper-transport antioxidant protein, in the serum are lower in children with autism than in control subjects. In the present study, we report that (a copper oxidizes and reduces the levels of membrane PE and (b copper-mediated oxidation of PE is higher in lymphoblasts from autistic subjects than from control subjects. The effect of copper was examined on the oxidation of liposomes composed of brain lipids from mice and also on the lymphoblasts from autism and control subjects. Among the various metal cations (copper, iron, calcium, cadmium and zinc, only copper was found to oxidize and decrease the levels of PE. The metal cations did not affect the levels of other phospholipids. The action of copper on PE oxidation was time-dependent and concentration-dependent. No difference was observed between copper-mediated oxidation of diacyl-PE and alkenyl-PE (plasmalogen, suggesting that plasmalogenic and non-plasmalogenic PE are equally oxidized by copper. Together, these studies suggest that ceruloplasmin and copper may contribute to oxidative stress and to reduced levels of membrane PE in autism.

  14. ACUTE PHASE REACTANCTS IN PERICARDIAL FLUID ARE INDICATORS OF CORONARY ARTERY DISEASE

    Directory of Open Access Journals (Sweden)

    Yılmaz Mehmet Ali

    2012-12-01

    Full Text Available Inflammation in formation of atherosclerosis, and acute phase reactants in the site of inflammation have major functions. Thus, do the acute phase reactants constitute the biggest risk factor for coronary artery disease? 55 patients are included in the study. Patients with coronary artery bypass surgery are included in Group I (38 patients and patients with valve operation are included in Group II (17 patients. CABG patients are further divided into two sub-groups as on-pump and off-pump. In both groups, homocystein, high sensitivity C reactive protein, ceruloplasmin, lipoprotein A and serum amyloid A protein levels are analyzed from blood and pericardial fluid. In patients with coronary artery disease, the measured high specific C- reactive protein levels from blood and pericardial fluid are found to be significantly high compared to patients with valve operation.Homocystein levels of pericardial fluids of patients with CABG are found to be higher than patients with valve operation and it is confirmed that the situation is correlated with blood homocystein levels. Although there are lots studies expressing the relation between coronary artery disease and lipoprotein A, ceruloplasmin and serum amyloid A protein levels; no significant difference for those parameters was obtained in our study. We determined that other phase reactants are higher in patients with coronary artery disease, in accordance with the literature. We aimed to state that acute phase reactants not only increase as a result of disease, but their levels are also elevated beforehand, as an indicator of the disease.

  15. Experimental caprine coccidiosis: the pattern of changes in antioxidant micronutrients and vitamins

    Directory of Open Access Journals (Sweden)

    Ehsan Rakhshandehroo

    2014-09-01

    Full Text Available This study aimed at investigating the status of non-enzymatic antioxidant agents during experimental caprine coccidiosis. A total of 20 newborn kids were selected and allocated into 2 (diseased and healthy groups. Ten of the kids were infected with sporulated oocysts of the most pathogenic species of Eimeria and ten served as controls. Blood samples were taken at 0 (before inoculation, 3, 7, 14, 21, 28 and 35 days post infection (dpi and the concentrations of antioxidant trace elements, antioxidant vitamins and ceruloplasmin were measured. Our data showed remarkable reductions in serum concentrations of some antioxidant trace elements (zinc, manganese and selenium and vitamins (vitamin C in the diseased kids, however, significant increases were observed in the serum level of ceruloplasmin in infected animals. These alterations became more prominent at 14 to 21 dpi. These observations suggest that Eimeria parasites can significantly interfere with the levels of some antioxidant trace elements and vitamins during caprine coccidiosis. These changes indicate the overproduction of oxidative radicals during the pathogenesis of Eimeria species that may account for extensive oxidative damage in infected animals.

  16. Wilson disease with hepatic presentation in an eight-month-old boy.

    Science.gov (United States)

    Abuduxikuer, Kuerbanjiang; Li, Li-Ting; Qiu, Yi-Ling; Wang, Neng-Li; Wang, Jian-She

    2015-08-01

    Wilson disease is an autosomal recessive disorder of copper metabolism that can cause fatal neurological and hepatic disease if not diagnosed and treated. The youngest child with normal liver function reported so far is an 8-mo-old Japanese boy with low ceruloplasmin levels, and the youngest child with elevated aminotransferase ever reported so far is a 9-mo-old Korean boy with confirmed by genetic testing. Here we report an 8-mo-old Chinese boy presented with elevated liver enzymes, and low serum ceruloplasmin level. Genetic analysis of ATP7B gene detected two heterozygous disease causing mutations (c.2621C>T/p.A874V and c.3809A>G/p.N1270S), and parental origins were determined. Persistent elevation of serum aminotransferase in this infant was normalized after zinc therapy. To our best knowledge, this is the youngest patient with elevated liver enzymes ever reported worldwide. We hope that this will raise awareness among pediatricians, leading to earlier diagnosis, timely treatment, and better clinical outcome.

  17. A study on the radiation and environment safety -Development of technology for biological dosimetry-

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Kang Suk; Kim, Kook Chan; Kim, In Kyoo; Kim, Jin Kyoo; Chun Kee Jung; Park, Hyo Kook; Kim, Sang Bok; Park Sun Yung [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

    1995-07-01

    Adult rats were treated a single, whole body exposure to a dose of 0.1, 0.5, 1.0, 2.0, 3.0 Gy. The animals were sacrificed 6, 24, 48, 72, 96 hours following exposure. The amount of serum acute phase proteins(haptoglobin, ceruloplasmin, C-reactive protein, alpha-1 antitrypsin, alpha-1 acid glycoprotein, transferrin) were measured by competitive ELISA. In the 0.1 Gy irradiated rats, serum haptoglobin, C-reactive protein and alpha-1 antitrypsin were 400% higher and serum transferrin was 50% lower as compared to controls, 96 hours after irradiation. Ceruloplasmin increased by 400%, 24 hours after irradiation, but 96 hours after irradiation, the concentration of this protein in rat returned to normal level. On the other hand, no changes were observed in the case of alpha-1 acid glycoprotein. In the group of the 3.0 Gy irradiated rats, transferrin increased by 200%, 96 hours after irradiation. These biochemical responses to radiation did not show dose-dependent relation, but the sensitivity of the indicators was high enough to detect absorbed dose of 0.1 Gy. The above results can be applied to the measurements of acute phase reactants in human serum for the assessment of exposure doses in radiation workers and patients under radiation therapy. 39 figs, 72 refs. (Author).

  18. Serum ferritin and stomach cancer risk among A-bomb survivors

    International Nuclear Information System (INIS)

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

  19. Association between maternal micronutrient status, oxidative stress, and common genetic variants in antioxidant enzymes at 15 weeks׳ gestation in nulliparous women who subsequently develop preeclampsia.

    Science.gov (United States)

    Mistry, Hiten D; Gill, Carolyn A; Kurlak, Lesia O; Seed, Paul T; Hesketh, John E; Méplan, Catherine; Schomburg, Lutz; Chappell, Lucy C; Morgan, Linda; Poston, Lucilla

    2015-01-01

    Preeclampsia is a pregnancy-specific condition affecting 2-7% of women and a leading cause of perinatal and maternal morbidity and mortality. Deficiencies of specific micronutrient antioxidant activities associated with copper, selenium, zinc, and manganese have previously been linked to preeclampsia at the time of disease. Our aims were to investigate whether maternal plasma micronutrient concentrations and related antioxidant enzyme activities are altered before preeclampsia onset and to examine the dependence on genetic variations in these antioxidant enzymes. Predisease plasma samples (15±1 weeks׳ gestation) were obtained from women enrolled in the international Screening for Pregnancy Endpoints (SCOPE) study who subsequently developed preeclampsia (n=244) and from age- and BMI-matched normotensive controls (n=472). Micronutrient concentrations were measured by inductively coupled plasma mass spectrometry; associated antioxidant enzyme activities, selenoprotein-P, ceruloplasmin concentration and activity, antioxidant capacity, and markers of oxidative stress were measured by colorimetric assays. Sixty-four tag-single-nucleotide polymorphisms (SNPs) within genes encoding the antioxidant enzymes and selenoprotein-P were genotyped using allele-specific competitive PCR. Plasma copper and ceruloplasmin concentrations were modestly but significantly elevated in women who subsequently developed preeclampsia (both Ppreeclampsia. The modest elevation in copper may contribute to oxidative stress, later in pregnancy, in those women that go on to develop preeclampsia. The lack of evidence to support the hypothesis that functional SNPs influence antioxidant enzyme activity in pregnant women argues against a role for these genes in the etiology of preeclampsia.

  20. Antioxidant status of neonates exposed in utero to tobacco smoke.

    Science.gov (United States)

    Fayol, L; Gulian, J M; Dalmasso, C; Calaf, R; Simeoni, U; Millet, V

    2005-01-01

    To investigate the influence of maternal smoke exposure on neonatal and maternal antioxidant status, 39 mothers who were active smokers, 14 mothers exposed to environmental tobacco smoke (ETS), 17 controls, and their newborns were included in a prospective, controlled study. Plasma total antioxidant capacity, measured as total radical-trapping antioxidant parameter (TRAP) and ferric reducing antioxidant power (FRAP), and concentrations of specific antioxidants were measured in cord and in maternal blood. A similar, significant increase in ceruloplasmin concentration was observed in neonates born to actively smoking mothers and in those born to ETS exposed mothers. Uric acid and TRAP concentrations were significantly increased in ETS-exposed newborns and their mothers, compared to newborns and mothers from the active smoking and no-exposure groups with a trend towards increased uric acid, TRAP and FRAP concentrations being observed in the active smokers group. Neonatal and maternal antioxidant concentrations correlated significantly, except for ceruloplasmin. Cord blood vitamin A, E and C concentrations were unaffected by smoke exposure. These results show that maternal active smoking as well as ETS exposure significantly affect neonatal and maternal antioxidant status. PMID:15539769

  1. Studies of Internal Environment of Psoriasis and Its Therapy

    Institute of Scientific and Technical Information of China (English)

    XU; Han-qing

    2001-01-01

    Psoriasis is a kind of refractory disease, though it is less serious than cancer. The etiology is not clear, the morbidity is high, and it cannot be radically cured. It is an urgent problem that needs to be solved. Since 1980, the authors have studied the pathogenic mechanisms of psoriasis from aspects of pathology, biochemistry, pharmacology, and immunology. It was proved that abnormalities in biochemical components, neural media, immunological state and cell metabolism existed in psoriatic cases. We have published more than ten articles, and formulated two anti-psoriasis drugs, which is reported as follows:    1. The levels of serum zinc, copper, calcium, magnesium, iron, selenium, ceruloplasmin, vitamin A and vitamin E in 138 psoriatic patients were measured by atomic absorption spectrometry. The results showed that serum copper level in the progressive and stable stage was decreased significantly (P<0.01). The levels of serum calcium and vitamin E lowered too. The levels of serum ceruloplasmin, selenium and iron were considerably higher in psoriatic than those in the normal control. This is an evidence that there are biochemical abnormalities in the internal environment of psoriatic patients.……

  2. Studies of Internal Environment of Psoriasis and Its Therapy

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    @@  Psoriasis is a kind of refractory disease, though it is less serious than cancer. The etiology is not clear, the morbidity is high, and it cannot be radically cured. It is an urgent problem that needs to be solved. Since 1980, the authors have studied the pathogenic mechanisms of psoriasis from aspects of pathology, biochemistry, pharmacology, and immunology. It was proved that abnormalities in biochemical components, neural media, immunological state and cell metabolism existed in psoriatic cases. We have published more than ten articles, and formulated two anti-psoriasis drugs, which is reported as follows:   1. The levels of serum zinc, copper, calcium, magnesium, iron, selenium, ceruloplasmin, vitamin A and vitamin E in 138 psoriatic patients were measured by atomic absorption spectrometry. The results showed that serum copper level in the progressive and stable stage was decreased significantly (P<0.01). The levels of serum calcium and vitamin E lowered too. The levels of serum ceruloplasmin, selenium and iron were considerably higher in psoriatic than those in the normal control. This is an evidence that there are biochemical abnormalities in the internal environment of psoriatic patients.

  3. Role of hepcidin and its downstream proteins in early brain injury after experimental subarachnoid hemorrhage in rats.

    Science.gov (United States)

    Tan, Guanping; Liu, Liu; He, Zhaohui; Sun, Jiujun; Xing, Wenli; Sun, Xiaochuan

    2016-07-01

    Early brain injury (EBI) is a major cause of mortality from subarachnoid hemorrhage (SAH). We aimed to study the pathophysiology of EBI and explore the role of hepcidin, a protein involved in iron homeostatic regulation, and its downstream proteins. One hundred and thirty-two male Sprague-Dawley rats were assigned into groups (n = 24/group): sham, SAH, SAH + hepcidin, SAH + hepcidin-targeting small interfering ribonucleic acid (siRNA), and SAH + scramble siRNA. Three hepcidin-targeting siRNAs and one scramble siRNA for hepcidin were injected 24 h before hemorrhage induction, and hepcidin protein was injected 30 min before induction. The rats were neurologically evaluated at 24 h and euthanized at 72 h. Hepcidin, ferroportin-1, and ceruloplasmin protein expression were measured by immunohistochemistry and Western blotting. Brain water content, blood-brain barrier (BBB) leakage, non-heme tissue iron and Garcia scale were evaluated. Hepcidin expression increased in the cerebral cortex and hippocampus after experimental SAH (P Hepcidin injection lowered the expression of ferroportin-1 and ceruloplasmin further but siRNA reduced the levels of hepcidin (P hepcidin, but decreased by siRNA (P hepcidin enhanced iron-dependent oxidative damage and may be the potential mechanism of SAH. PMID:27250827

  4. Spontaneous hepatic copper accumulation in Long-Evans Cinnamon rats with hereditary hepatitis. A model of Wilson's disease.

    Science.gov (United States)

    Li, Y; Togashi, Y; Sato, S; Emoto, T; Kang, J H; Takeichi, N; Kobayashi, H; Kojima, Y; Une, Y; Uchino, J

    1991-05-01

    Long-Evans Cinnamon (LEC) rats, an inbred strain of a mutant rat isolated from Long-Evans rats, develop hereditary hepatitis. To elucidate the role of copper metabolism in the development of the hepatitis in LEC rats, we examined the copper concentration in the tissues and serum levels of copper and ceruloplasmin. Copper concentration in the liver of LEC rats was over 40 times that of normal Long-Evans Agouti (LEA) rats, while the serum ceruloplasmin and copper concentrations in LEC rats decreased significantly. The hepatocytes of LEC rats show steatosis in cytoplasm and pleomorphism of mitochondria, resembling the histologic features of the liver in Wilson's disease. These findings suggest that the hereditary hepatitis in LEC rats is closely associated with copper toxicity, and may be dealing with a rat form of Wilson's disease. Thus the LEC rats will provide a unique and useful animal model for clarifying the mechanism and for developing treatment strategies for Wilson's disease and other abnormal copper metabolism in humans.

  5. Wilson's disease.

    Science.gov (United States)

    Loudianos, G; Gitlin, J D

    2000-01-01

    Wilson's disease is an autosomal recessive disorder of copper metabolism resulting from the absence or dysfunction of a copper transporting P-type ATPase encoded on chromosome 13. This ATPase is expressed in hepatocytes where it is localized to the trans-Golgi network and transports copper into the secretory pathway for incorporation into ceruloplasmin and excretion into the bile. Under physiologic circumstances, biliary excretion represents the sole mechanism for copper excretion, and thus affected individuals have progressive copper accumulation in the liver. When the capacity for hepatic storage is exceeded, cell death ensues with copper release into the plasma, hemolysis, and tissue deposition. Presentation in childhood may include chronic hepatitis, asymptomatic cirrhosis, or acute liver failure. In young adults, neuropsychiatric symptoms predominate and include dystonia, tremor, personality changes, and cognitive impairments secondary to copper accumulation in the central nervous system. The laboratory diagnosis of Wilson's disease is confirmed by decreased serum ceruloplasmin, increased urinary copper content, and elevated hepatic copper concentration. Molecular genetic analysis is complex as more than 100 unique mutations have been identified and most individuals are compound heterozygotes. Copper chelation with penicillamine is an effective therapy in most patients and hepatic transplantation is curative in individuals presenting with irreversible liver failure. Elucidation of the molecular genetic basis of Wilson's disease has permitted new insights into the mechanisms of cellular copper homeostasis.

  6. Protection of DNA strand breakage by radiation exposure

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jeong Ho; Kim, In Gyu; Lee, Kang Suk; Kim, Kug Chan; Shim, Hae Won

    1997-12-01

    Human ceruloplasmin, the plasma copper containing protein, is thought to play an essential role in iron metabolism, but it also has antioxidant properties. Ceruloplasmin directly scavenged hydroxyl radicals (.OH) generated in dithiothreitol/FeCl{sub 3} system besides inhibitory function of hydroxyl radical formation and lipid peroxidation. Polyamines, spermidine and spermine, significantly protected the supercoiled DNA strand breakage by hydroxyl radicals and DNA strand breakage by UV was highly protected by all four polyamines used in this study. In polyamine deficient mutant KL527. It was shown that cell survivability following UV irradiation was slightly increased by exogenous polyamines putrescine and spermidine supplement. However the cell survivability of wild type (MG 1655) was not influenced by polyamine supplement. In {gamma}-irradiated cells, cell survivability of polyamine-deficient mutant strain KL527 was significantly increased by exogenous putrescine supplement and that of wild type strain MG1655 was similar irrespective of polyamine supplement. These results implicate the possibility that polyamines play a potent role in radioprotection of cell and DNA level. (author). 32 refs., 8 figs

  7. In-vitro use of radiominerals to determine mineral imbalances in farm animals. Part of a coordinated programme on the use of isotopes to diagnose moderate mineral imbalances in farm animals

    International Nuclear Information System (INIS)

    This research programme involved the use of in vitro radioisotopic procedures as well as stable element analysis and enzyme determinations to evaluate selenium, copper and zinc deficiency states in sheep in Turkey. Uptake of radioactive selenium by red blood cells was effective in determining the selenium status of sheep. Animals on a selenium deficient diet had red cell selenium uptakes significantly greater than those of sheep fed normal levels of selenium. When sheep on a selenium deficient diet were tested and then supplemented with selenium for several weeks, the red cell uptakes of radioselenium after supplementation were significantly less than before supplementation. A similar technique was used to study the zinc status of sheep. Uptake of radioactive zinc by red cells was greater in deficient sheep than in zinc-supplemented animals. Zinc deficient sheep also had lower serum zinc levels than in supplemented animals, and alkaline phosphatase activity levels. Assays of erythrocyte uptake, using a scintillation counter may be useful in the absence of equipment for total mineral analysis or enzyme assays. In another study the serum copper levels of sheep of different genetic types were compared to serum ceruloplasmin levels and to the incidence of enzootic ataxia in offspring of these animals. A definite correlation was found between haemoglobulin type, serum copper level and ceruloplasmin level. Comparisons of these parameters in sheep with copper and molybdenum levels in forage samples indicated that copper deficiency in sheep in Turkey is apparently a secondary copper deficiency due to high levels of molybdenum in forage

  8. Analysis of clinical and biochemical spectrum of Wilson Disease patients

    Directory of Open Access Journals (Sweden)

    Sumreena Mansoor

    2012-01-01

    Full Text Available Background and Aims: Wilson disease (WD is autosomal recessive disorder of copper metabolism. Wilson disease patients usually suffer from hepatic or neuropsychiatric complications. The symptoms appear between ages five to 35 but it can vary from two years to 72 years. Materials and Methods : Study was carried out from June 2008 to November 2010. This study included nine families with eleven cases of WD to determine clinical presentation, diagnostic findings (including laboratory results and liver histology. It included 11 patients who presented with hepatic manifestations and/or Neuropsychiatric manifestations and/or family history suggesting features of WD. Patients with hepatitis B and C and those with history of taking antipsychotic drugs were excluded from the study. Patient′s data was included in a well designed performa. Liver function test, serum ceruloplasmin, serum copper, 24 hour urinary copper, blood complete picture were analyzed. Quantitative data such as age, hemoglobin etc were expressed as mean with ± SD and quantitative variables such as sex, movement disorders, hepatic involvement etc were expressed as frequency and percentage. Results: There were five male and six female patients with evidence of various manifestations here (i hepatic in which they had only liver dysfunction (ii hepatic and neurological (iii neurological. The mean age of presentation was 8.7±3.92 years (range 4-19 years and 45% were male patients. Decreased serum ceruloplasmin, enhanced 24-h urinary copper excretion and signs of chronic liver damage were confirmed in all patients and Kayser-Fleischer rings (KF rings in 72% of patients. In severe WD patients, serum prothrombin activity was less than 50%, serum ceruloplasmin were low and serum copper levels were high than those in non-severe WD patients. High degree of suspicion leads to early treatment with good outcome. Conclusions: The WD is rare but important cause of chronic liver disease. Clinical and

  9. Copper metabolism after living related liver transplantation for Wilson's disease

    Institute of Scientific and Technical Information of China (English)

    Xue-Hao Wang; Feng Cheng; Feng Zhang; Xiang-Cheng Li; Jian-Ming Qian; Lian-Bao Kong; Hao Zhang; Guo-Qiang Li

    2003-01-01

    AlM: Liver transplantation is indicated for Wilson's disease(WD) patients with the fulminant form and end-stage liverfailure. The aim of this study was to review our experiencewith living-related liver transplantation (LRLT) for WD.METHODS: A retrospective review was made for WDundergoing LRLT at our hospital from January 2001 toFebuary 2003.RESULTS: LRLT was carried out in 15 patients with WD,one of them had fulminant hepatic failure and the others had end-stage hepatic insufficiency. The mean age of the patients was 14.5±2.5 years (range 6 to 20 years). All the recipients had low serum ceruloplasmin levels with a mean value of 126.8±34t.8 mg/L before transplantation. The serum ceruloplasmin levels increased to an average of 238.6±34.4mg/L after LRLT at the latest evaluation, between 2 and 27months after transplantation. A marked reduction in urinary copper excretion was observed in all the recipients after transplantation. Among the eight recipients with preoperative Kayser-Fleischer (K-F) rings, this abnormality resolved completely after LRLT in five patients and partially in three.All the recipients are alive and remain well, and none has developed signs of recurrent WD after a mean follow-up period of 15.4±9.3 months (range 2-27 months) except one who died of severe rejection. The donors were 14t mothers and 1 father. The serum ceruloplasmin levels were within normal limits in all the donors (mean: 220±22.4 mg/L). The mean donor age was 35.0±4.0 years (range, 30 to 45 years).Two donors had biliary leakage and required reoperation.Grafts were harvested as follows: four right lobe grafts without hepatic middle vein and eleven left lobe grafts with hepatic middle vein. The grafts were blood group-compatible in all recibents. Two patients had hepatic artery thrombosis and underwent retransplantation.CONCLUSION: LRLT is a curative procedure in Wilson's disease manifested as fulminant hepatic failure and/or endstage hepatic insufficiency. After liver

  10. [Hepatolenticular degeneration].

    Science.gov (United States)

    Zudenigo, D; Relja, M

    1990-01-01

    Hepatolenticular degeneration (Wilson's disease) is a hereditary disease in which metabolic disorder of copper leads to its accumulation in the liver, brain, cornea and kidneys with consequent pathologic changes in those organs. Hereditary mechanism of the disease is autosomal recessive with prevalence of 30-100 per 1,000,000 inhabitants. Etiology of this disease is not yet explained. There are two hypotheses. The first one is that it is the disorder of ceruloplasmine metabolism caused by insufficient synthesis of normal ceruloplasmine, or synthesis of functionally abnormal ceruloplasmine. The second one is: the block of copper biliar excretion which is the consequence of the liver lysosomes functional defect. Pathogenetic mechanism of disease is firstly long-term accumulation of copper in the liver, and later, when the liver depo is full, its releasing in circulation and accumulation in the brain, cornea, kidneys and bones, which causes adequate pathologic changes. Toxic activity of copper is the consequence of its activity on enzymes, particularly on those with -SH group. There are two basic clinical forms of the disease: liver disease or neurologic disease. Before puberty the liver damage is more frequent, while in adolescents and young adults neurologic form of the disease is usual. The liver disease is nonspecific and characterized by symptoms of cirrhosis and chronic aggressive hepatitis. The only specificity is hemolytic anemia which, in combination with previous symptoms, is important for diagnosis of the disease. Neurologic symptoms are the most frequent consequence of pathologic changes in the basal ganglia. In our patients the most frequent symptoms were tremor (63%); dysarthria, choreoathetosis and rigor (38%); ataxia and mental disorders (31%); dysphagia and dystonia (12%), diplopia, hypersalivation, nystagmus and Babinski's sign (6%). Among pathologic changes in other tissues and organs the most important is the finding of Kayser-Fleischer ring in the

  11. Genetic effects on acute phase protein response to the stresses of weaning and transportation in beef calves.

    Science.gov (United States)

    Qiu, X; Arthington, J D; Riley, D G; Chase, C C; Phillips, W A; Coleman, S W; Olson, T A

    2007-10-01

    The objective herein was to estimate heterosis and breed effects in purebred and crossbred Romosinuano, Brahman, and Angus calves on acute phase protein response to weaning and transportation. Calves (n = 1,032) were weaned in September of 2002, 2003, and 2004 at approximately 7 mo of age. Approximately 28 d after weaning, steer calves (n = 482) were transported 1,800 km (20 h) to Oklahoma. Concentrations of 3 acute phase proteins (ceruloplasmin, fibrinogen, and haptoglobin) were measured in blood samples. Calves (steers and heifers) were sampled at weaning, and 24 and 72 h postweaning. For separate analyses, steers sent to Oklahoma were sampled before shipment, upon arrival, and 24 and 72 h after arrival. Combinations of the following fixed effects were investigated: sire breed, dam breed, sampling time, birth location, calf sex (weaning only), year, cow age, and interactions. Effects of special interest were sire breed x dam breed as an indication of breed group of calf, and the interaction of sire and dam breeds with sampling time. Weaning age and BW were investigated as linear and quadratic covariates. Sire of calf within sire breed was a random term. The correlation structure of repeated measures was determined by comparison of information criterion values for different structures within each analysis. In general, plasma acute phase protein concentrations in weaned calves increased with sampling time. Concentrations in the transported steers increased through sampling at 24 h after arrival, and were lower at 72 h. Significant estimates of heterosis were detected for Brahman-Angus haptoglobin concentrations at weaning (0.38 +/- 0.14 mg/dL x 100; 44%), and for Romosinuano-Angus fibrinogen concentrations at weaning (11.4 +/- 5.5 mg/dL; 10%) and in transported steers (22.5 +/- 8.4 mg/dL; 20%). The direct effect of Romosinuano was to increase (P Angus was to lower ceruloplasmin concentrations in weaned calves (-3.9 +/- 1.2; P = 0.001). Significant maternal effects

  12. Inflammatory markers following acute fuel oil exposure or bacterial lipopolysaccharide in mallard ducks (Anas platyrhynchos).

    Science.gov (United States)

    Lee, Kelly A; Tell, Lisa A; Mohr, F Charles

    2012-12-01

    Adult mallard ducks (Anas platyrhynchos) were orally dosed with bunker C fuel oil for 5 days, and five different inflammatory markers (haptoglobin, mannan-binding lectin, ceruloplasmin, unsaturated iron-binding capacity, and plasma iron) were measured in blood plasma prior to and 8, 24, 48, and 72 hr following exposure. In order to contrast the response to fuel oil with that of a systemic inflammatory response, an additional five ducks were injected intramuscularly with bacterial lipopolysaccharide (LPS). Oil-treated birds had an inflammatory marker profile that was significantly different from control and LPS-treated birds, showing decreases in mannan-binding lectin-dependent hemolysis and unsaturated iron-binding capacity, but no changes in any of the other inflammatory markers. Birds treated with oil also exhibited increased liver weights, decreased body and splenic weights, and decreased packed cell volume.

  13. Clinical perspective on C-reactive protein in prognostication of major adverse cardiac events in the elderly with established coronary heart disease

    Institute of Scientific and Technical Information of China (English)

    Olabode Oladeinde

    2006-01-01

    @@ The systemic response to tissue injury, regardless of cause is characterized by a cytokine-mediated alteration in the hepatic synthesis of a number of different plasma proteins,known collectively as 'acute phase reactants'. These proteins include C-reactive protein, serum amyloid A protein, alphal glycoprotein, ceruloplasmin, alpha macroglobulins, complement components (C1-C4, factor B, C9, C11), alpha1antitrypsin, alpha1 antichymotrypsin, fibrinogen, prothrombin,factor Ⅷ, plasminogen, haptoglobin, ferritin, immunoglobulins and lipoproteins. The initiation of the acute phase response is linked to the production of hormone-like polypeptide mediators now called cytokines, namedly, interleukin 1(IL-1),tumor necrosis factor, interferon gamma, interleukin 6 (IL-6),leukemia inhibitory factor, ciliary neurotropic factor, oncostatin M, and interleukin 11 (IL- 11).

  14. Expression of Iron-Related Proteins at the Neurovascular Unit Supports Reduction and Reoxidation of Iron for Transport Through the Blood-Brain Barrier

    DEFF Research Database (Denmark)

    Burkhart, Annette; Skjørringe, Tina; Johnsen, Kasper Bendix;

    2015-01-01

    The mechanisms for iron transport through the blood-brain barrier (BBB) remain a controversy. We analyzed for expression of mRNA and proteins involved in oxidation and transport of iron in isolated brain capillaries from dietary normal, iron-deficient, and iron-reverted rats. The expression...... cells provide the machinery for receptor-mediated uptake of ferric iron-containing transferrin. Ferric iron can then undergo reduction to ferrous iron by ferrireductases inside endosomes followed by DMT1-mediated pumping into the cytosol and subsequently cellular export by ferroportin. The expression...... of soluble ceruloplasmin by brain endothelial cells, pericytes, and astrocytes that together form the neurovascular unit (NVU) provides the ferroxidase activity necessary to reoxidize ferrous iron once released inside the brain....

  15. The Challenges of Diagnosing and Following Wilson Disease in the Presence of Proteinuria

    Science.gov (United States)

    Khan, Soofia; Schilsky, Michael; Silber, Gary; Morgenstern, Bruce

    2016-01-01

    The coexistence of Wilson disease with Alport syndrome has not previously been reported. The diagnosis of Wilson disease and its ongoing monitoring is challenging when associated with an underlying renal disease such as Alport syndrome. Proteinuria can lead to low ceruloplasmin since it is among serum proteins inappropriately filtered by the damaged glomerulus, and can also lead to increased urinary loss of heavy metals such as zinc and copper. Elevated transaminases may be attributed to dyslipidemia or drug induced hepatotoxicity. The accurate diagnosis of Wilson disease is essential for targeted therapy and improved prognosis. We describe a patient with a diagnosis of Alport syndrome who has had chronic elevation of transaminases eventually diagnosed with Wilson disease based on liver histology and genetics. PMID:27437191

  16. Laboratory and histological similarities between Wilson's disease and rats with copper toxicity.

    Directory of Open Access Journals (Sweden)

    Narasaki,Mikio

    1980-04-01

    Full Text Available Rats were injected intraperitoneally with copper-lactate daily for over 160 days (total dose of 30 mg copper in each animal. At 120 to 160 days of copper administration, animals developed symptoms similar to those of Wilson's disease, i.e., kidney functional disturbances, proteinuria, aminoaciduria, decreased blood ceruloplasmin oxidase activity and increased urinary copper excretion. Cirrhosis was found in some animals. Tubular necrosis of the kidneys, liver fibrosis and tigrolysis of thalamic nerve cells were also found. Copper depositions were observed in liver parenchymal cells, renal tubular epithels, thalamus glia cells and on the Descemet's membrane of the cornea. The similarities between induced copper- intoxication in rats and Wilson's disease are discussed.

  17. Screening for Wilson disease in acute liver failure: a comparison of currently available diagnostic tests

    DEFF Research Database (Denmark)

    Korman, J.D.; Volenberg, I.; Balko, J.;

    2008-01-01

    yielded a sensitivity of 94%, specificity of 96%, and a likelihood ratio of 23 for diagnosing fulminant WD. In addition, an AST:ALT ratio >2.2 yielded a sensitivity of 94%, a specificity of 86%, and a likelihood ratio of 7 for diagnosing fulminant WD. Combining the tests provided a diagnostic sensitivity...... a diagnostic sensitivity of 21% and specificity of 84% while, by nephelometry, a sensitivity of 56% and specificity of 63%. Serum copper levels exceeded 200 microg/dL in all ALF-WD patients measured (13/16), but were also elevated in non-WD ALF. An alkaline phosphatase (AP) to total bilirubin (TB) ratio ... and specificity of 100%. CONCLUSION: Conventional WD testing utilizing serum ceruloplasmin and/or serum copper levels are less sensitive and specific in identifying patients with ALF-WD than other available tests. More readily available laboratory tests including alkaline phosphatase, bilirubin and serum...

  18. The Challenges of Diagnosing and Following Wilson Disease in the Presence of Proteinuria.

    Science.gov (United States)

    Khan, Soofia; Schilsky, Michael; Silber, Gary; Morgenstern, Bruce; Miloh, Tamir

    2016-06-01

    The coexistence of Wilson disease with Alport syndrome has not previously been reported. The diagnosis of Wilson disease and its ongoing monitoring is challenging when associated with an underlying renal disease such as Alport syndrome. Proteinuria can lead to low ceruloplasmin since it is among serum proteins inappropriately filtered by the damaged glomerulus, and can also lead to increased urinary loss of heavy metals such as zinc and copper. Elevated transaminases may be attributed to dyslipidemia or drug induced hepatotoxicity. The accurate diagnosis of Wilson disease is essential for targeted therapy and improved prognosis. We describe a patient with a diagnosis of Alport syndrome who has had chronic elevation of transaminases eventually diagnosed with Wilson disease based on liver histology and genetics.

  19. Application of Glow Discharge Aes for Investigation of Metal Ions and Water in Biology and Medicine

    CERN Document Server

    Bregadze, Vasil G; Tsakadze, Ketevan J

    2007-01-01

    AES VHF inductively coupled plasmatron may be applied to wide range of studies. It enables rapid microanalysis of various solutions including biological objects and peripheral blood serum. In addition, it may be used for investigation of water desorption from solid bodies and for determination of energetic metal-macromolecule complexes. Study of hydration energy and hydration number by kinetic curves of water glow discharge atomic spectral analysis of hydrogen (GD EAS analysis of hydrogen) desorption from Na-DNA humidified fibers allowed to reveal that structural and conformational changes in activation energy of hydrated water molecules increases by 0.65kcal/Mole of water. The developed method of analysis of elements in solutions containing high concentrations of organic materials allows systematic study of practically healthy persons and reveals risk factors for several diseases. Microelemental content of blood serum fractions showed that amount of not bounded with ceruloplasmin copper was three times more ...

  20. [The imbalance of metal-containing proteins and free metal ions in the amniotic fluid during fetal growth].

    Science.gov (United States)

    Pogorelova, T N; Linde, V A; Gunko, V O; Selyutina, S N

    2016-01-01

    The levels of zinc, copper, iron, and magnesium ions, and some of their binding proteins have been investigated in an amniotic fluid under the fetal growth retardation (FGR). FGR, developed under conditions of placental insufficiency, is characterized by a decrease in the content of zinc, iron, and magnesium ions and by an increase in the copper content in the amniotic fluid in the II and III trimesters of pregnancy. During these trimesters the levels of ceruloplasmin, ferritin, and Ca2+,Mg2+-ATPase were lower in FGR, while the level of zinc-a-2-glycoprotein was higher than during the same periods of normal pregnancy. Changes in the parameters studied in the amniotic fluid were associated with developmental disorders of the newborns. These changes obviously have a pathogenetic importance in the development of FGR, and the levels of metal ions and their ratio in the amniotic fluid can be used as markers of the pre- and postnatal pathology.

  1. Aceruloplasminaemia: a rare but important cause of iron overload.

    Science.gov (United States)

    Doyle, Adam; Rusli, Ferry; Bhathal, Prithi

    2015-01-01

    We present a case of a 20-year-old man referred to our service with iron overload and mildly deranged liver biochemistry. Although liver histopathology was consistent with haemochromatosis, iron studies were not consistent with this diagnosis. Serum ceruloplasmin levels were undetectable, leading to a diagnosis of aceruloplasminaemia. Unlike other iron overload disorders, neurological complications are a unique feature of this illness, and often irreversible, once established. The patient was treated with iron chelation prior to the onset of neurological injury, and experienced progressive normalisation of his ferritin and liver biochemistry. This is one of the youngest diagnosed cases in the published literature and, crucially, was a rare case of diagnosis and treatment prior to the onset of neurological sequelae. This is presented alongside a review of previously published cases of aceruloplasminaemia, including responses to iron chelation therapy. PMID:25976187

  2. Different dietary lifestyles and serum zinc and copper in women of reproductive age

    Energy Technology Data Exchange (ETDEWEB)

    Breskin, M.W.; Worthington-Roberts, B.S.; Monsen, E.R.

    1986-03-01

    Nutrient intakes and biochemical measures of zinc and copper were compared in non-pregnant young women representing different dietary lifestyles, viz, those who habitually ate red meat (RM), fish or poultry (FP), or lacto-ovo-vegetarian (LV) sources of protein. All were in good health and concerned about their diets; none was using supplements or oral contraceptives. Three-day food records were analyzed for nutrient content. Serum and drinking water samples were assayed for zinc and copper (AAS), and serum, for ceruloplasmin (RID). Sign. diff. in dietary Zn or Cu content were not reflected by serum(Zn) or (Cu), but the incidence of serum(Zn) < the 95% CI for RM eaters was sign. higher in FP and LV groups (X/sup 2/ = 20.65, p < 0.001). Thus, use of diets limited in animal protein sources may be associated with an increase risk of low serum (Zn).

  3. Increased DNA damage and oxidative stress among silver jewelry workers.

    Science.gov (United States)

    Aktepe, Necmettin; Kocyigit, Abdurrahim; Yukselten, Yunus; Taskin, Abdullah; Keskin, Cumali; Celik, Hakim

    2015-04-01

    Silver has long been valued as a precious metal, and it is used to make ornaments, jewelry, high-value tableware, utensils, and currency coins. Human exposures to silver and silver compounds can occur oral, dermal, or by inhalation. In this study, we investigated genotoxic and oxidative effects of silver exposure among silver jewelry workers. DNA damage in peripheral mononuclear leukocytes was measured by using the comet assay. Serum total antioxidative status (TAS), total oxidative status (TOS), total thiol contents, and ceruloplasmin levels were measured by using colorimetric methods among silver jewelry workers. Moreover, oxidative stress index (OSI) was calculated. Results were compared with non-exposed healthy subjects. The mean values of mononuclear leukocyte DNA damage were significantly higher than control subjects (p jewelry workers caused oxidative stress and accumulation of severe DNA damage.

  4. Menkes Disease: Report of Two Cases

    Directory of Open Access Journals (Sweden)

    Mohammad Barzegar

    2007-09-01

    Full Text Available Introduction: Menkes disease is a rare X-linked recessive disorder of copper metabolism. It is characterized by progressive cerebral degeneration with psychomotor deterioration, hypothermia, seizures and characteristic facial appearance with hair abnormalities.Case Presentation: We report on two cases of classical Menkes disease with typical history, (progressive psychomotor deterioration and seizures}, clinical manifestations (cherubic appearance, with brittle, scattered and hypopigmented scalp hairs, and progression. Light microscopic examination of the hair demonstrated the pili torti pattern. The low serum copper content and ceruloplasmin confirmed the diagnosis.Conclusion: Menkes disease is an under-diagnosed entity, being familiar with its manifestation and maintaining high index of suspicion are necessary for early diagnosis.

  5. Identification and quantification of serum proteins secreted into the normal human jejunum

    DEFF Research Database (Denmark)

    Andersen, Vibeke; Hegnhøj, J H

    1990-01-01

    The in vivo transfer of serum proteins to the human intestinal lumen was characterized by crossed immunoelectrophoretic analyses of intestinal perfusates from four healthy volunteers. Serum proteins with molecular masses below 100 kDa and the immunoglobulins were found in human jejunal perfusates....... Larger serum proteins were either absent (alpha and beta lipoproteins) or present in small amounts (alpha 2-macroglobulin, haptoglobulin and ceruloplasmin). These results demonstrate the existence of a selective transfer of serum proteins to the intestinal lumen under physiological conditions....... The intestinal clearance rate was 0.1 ml serum per hour per 10 cm jejunum for albumin, prealbumin, alpha 1-antitrypsin, orosomucoid, transferrin and haemopexin. The rate of secretion of total protein to the jejunal lumen was 100 mg protein per hour per 10 cm jejunum. About 45% was due to immunoglobulins...

  6. On the transfer of serum proteins to the rat intestinal juice

    DEFF Research Database (Denmark)

    Andersen, Vibeke; Norén, Ove; Poulsen, Mona D;

    1994-01-01

    The in vivo pattern of serum proteins in the rat small-intestinal juice was characterized by crossed immunoelectrophoresis. Immunoglobulins and albumin, alpha-1-antitrypsin, transferrin, and orosomucoid were present. Larger serum proteins were absent (ceruloplasmin, haptoglobin, alpha-1......-macroglobulin, alpha and beta lipoproteins). Thus, apart from immunoglobulins, only serum proteins with a molecular mass less than approximately 100 kDa were demonstrated. The origin and epithelial transfer were further characterized, using albumin as a model. No sign of local synthesis of albumin...... proteins in the intestinal juice is a selective passage through the capillary wall followed by passive intercellular transport via delivery of the serum in the interstitial space during disintegration of the enterocytes....

  7. Meningiomas and Proteomics: Focus on New Potential Biomarkers and Molecular Pathways.

    Science.gov (United States)

    Abbritti, Rosaria Viola; Polito, Francesca; Cucinotta, Maria; Lo Giudice, Claudio; Caffo, Maria; Tomasello, Chiara; Germanò, Antonino; Aguennouz, Mohammed

    Meningiomas are one of the most common tumors affecting the central nervous system, exhibiting a great heterogeneity in grading, treatment and molecular background. This article provides an overview of the current literature regarding the molecular aspect of meningiomas. Analysis of potential biomarkers in serum, cerebrospinal fluid (CSF) and pathological tissues was reported. Applying bioinformatic methods and matching the common proteic profile, arising from different biological samples, we highlighted the role of nine proteins, particularly related to tumorigenesis and grading of meningiomas: serpin peptidase inhibitor alpha 1, ceruloplasmin, hemopexin, albumin, C3, apolipoprotein, haptoglobin, amyloid-P-component serum and alpha-1-beta-glycoprotein. These proteins and their associated pathways, including complement and coagulation cascades, plasma lipoprotein particle remodeling and lipid metabolism could be considered possible diagnostic, prognostic biomarkers, and eventually therapeutic targets. Further investigations are needed to better characterize the role of these proteins and pathways in meningiomas. The role of new therapeutic strategies are also discussed. PMID:27566655

  8. Deregulation of proteins involved in iron metabolism in hepcidin-deficient mice.

    Science.gov (United States)

    Viatte, Lydie; Lesbordes-Brion, Jeanne-Claire; Lou, Dan-Qing; Bennoun, Myriam; Nicolas, Gaël; Kahn, Axel; Canonne-Hergaux, François; Vaulont, Sophie

    2005-06-15

    Evidence is accumulating that hepcidin, a liver regulatory peptide, could be the common pathogenetic denominator of all forms of iron overload syndromes including HFE-related hemochromatosis, the most prevalent genetic disorder characterized by inappropriate iron absorption. To understand the mechanisms whereby hepcidin controls iron homeostasis in vivo, we have analyzed the level of iron-related proteins by Western blot and immunohistochemistry in hepcidin-deficient mice, a mouse model of severe hemochromatosis. These mice showed important increased levels of duodenal cytochrome b (Dcytb), divalent metal transporter 1 (DMT1), and ferroportin compared with control mice. Interestingly, the level of ferroportin was coordinately up-regulated in the duodenum, the spleen, and the liver (predominantly in the Kupffer cells). Finally, we also evidenced a decrease of ceruloplasmin in the liver of hepcidin-deficient mice. We hypothesized that the deregulation of these proteins might be central in the pathogenesis of iron overload, providing key therapeutic targets for iron disorders. PMID:15713792

  9. Alcoholic Stem Extract of Coscinium fenestratum Regulates Carbohydrate Metabolism and Improves Antioxidant Status in Streptozotocin–Nicotinamide Induced Diabetic Rats

    Directory of Open Access Journals (Sweden)

    I. R. Punitha

    2005-01-01

    Full Text Available Alcoholic extract of the stems of Coscinium fenestratum, a medicinal plant indigenous to India and Sri Lanka used in ayurveda and siddha medicine for treating diabetes, was studied for its carbohydrate metabolism effect and antioxidant status in streptozotocin–nicotinamide induced type 2 diabetic rats. Oral administration of C. fenestratum stem extract in graded doses caused a significant increase in enzymatic antioxidants such as catalase, superoxide dismutase, glutathione synthetase, peroxidase, and glutathione peroxidase and in the nonenzymatic antioxidants ascorbic acid, ceruloplasmin and tocopherol. Effects of alcoholic extract on glycolytic enzymes such as glucose-6-phosphate dehydrogenase, lactate dehydrogenase and hexokinase showed a significant increase in their levels, whereas a significant decrease was observed in the levels of gluconeogenic enzyme, glucose-6-phosphatase and alanine aminotransferase in treated diabetic rats. Serum creatinine and urea levels also declined significantly. This investigation demonstrates significant antidiabetic activity of C. fenestratum.

  10. [The bioregulatory therapy of patients with chronic pyelonephritis].

    Science.gov (United States)

    al-Shukri, S Kh; Gorbachev, A G; Kuz'min, I V

    1997-01-01

    Prostatilen (5 mg/day i.m. for 5 days) was given to 46 patients with chronic pyelonephritis in the latent inflammation phase. The treatment resulted in relief of clinical symptoms, positive trend in laboratory indices characterizing activity of renal inflammation, albumin-globulin ratio. There was a decrease in leukocyturia, bacteriuria, ESR, blood fibrinogen and ceruloplasmin levels. Prostatilen reduced hypercoagulation and enhanced fibrinolytic activity of blood. The immunograms showed prostatilen-induced correction of immunity: T-lymphocyte count and functional activity increased, proportion of T-cell subpopulations returned to normal, metabolic activity of phagocyte oxygen-dependent substances became more intensive. The ability of prostatilen to initiate normalization of hemocoagulation and immunity is thought to be an essential factor of its therapeutic efficacy in chronic pyelonephritis.

  11. [Effect of prostatilen AC suppositories on course of experimental prostatitis].

    Science.gov (United States)

    Savateeva-Liubimova, T N; Sivak, K V; Malinin, V V

    2012-01-01

    The article presents the results of evaluation of efficacy of new drug prostatilen AC (rectal suppositories), containing regulatory peptides of the bovine prostate and zinc arginate-glycinate complex, in the treatment of prostatitis. The experiment was conducted on 40 Sprague-Dawley rats weighing 180-200 g. Chronic prostatitis was modeled by injection of 10% Dimexidum in combination with water, mixed with turpentine, a volumetric ratio of 4:1. It is shown that prostatilen AC has pronounced organotropic antiinflammatory effect, which manifests in reducing the weight of the prostate, reducing the protein level in the urine, activity of acid phosphatase, and levels of ceruloplasmin and C-reactive protein. In addition, this drug normalizes the act of urination and increases the diurnal diuresis, has antioxidant properties and increases the blood level of the male sex hormone testosterone.

  12. A review on laboratory liver function tests

    Directory of Open Access Journals (Sweden)

    Shruthi Kulkarni

    2009-11-01

    Full Text Available Laboratory liver tests are broadly defined as tests useful in the evaluation and treatment of patients with hepatic dysfunction. The liver carries out metabolism of carbohydrate, protein and fats. Some of the enzymes and the end products of the metabolic pathway which are very sensitive for the abnormality occurred may be considered as biochemical marker of liver dysfunction. Some of the biochemical markers such as serum bilirubin, alanine amino transferase, aspartate amino transferase, ratio of aminotransferases, alkaline phosphatase, gamma glutamyl transferase, 5´ nucleotidase, ceruloplasmin, alpha-fetoprotein are considered in this article. An isolated or conjugated alteration of biochemical markers of liver damage in patients can challenge the clinicians during the diagnosis of disease related to liver directly or with some other organs. The term “liver chemistry tests” is a frequently used but poorly defined phrase that encompasses the numerous serum chemistries that can be assayed to assess hepatic function and/or injury.

  13. [A case of Wilson's disease in an elderly patient initially diagnosed with NASH].

    Science.gov (United States)

    Seishima, Jun; Sakai, Yoshio; Kitahara, Noriaki; Kitamura, Kazuya; Arai, Kuniaki; Kagaya, Takashi; Yamashita, Tatsuya; Mizukoshi, Eishiro; Honda, Masao; Kaneko, Shuichi

    2015-02-01

    A 62-year-old female was admitted to our hospital for examination of icterus and thrombocytopenia. She had a history of diabetes mellitus (under treatment), and liver cirrhosis was evident on abdominal CT. Because she was clinically obese and had no past history of alcohol consumption, the initial diagnosis was NASH. However, subsequent MRI findings and normal serum transaminase levels were not consistent with this diagnosis. We then performed additional examinations, including liver biopsy, measurements of serum Cu and ceruloplasmin concentrations, and measurement of urinary Cu secretion, which resulted in a diagnosis of Wilson's disease. It is necessary to include Wilson's disease in the differential diagnosis of NASH in cases of unidentified liver disease even among elderly patients.

  14. Early stage transplantation of bone marrow cells markedly ameliorates copper metabolism and restores liver function in a mouse model of Wilson disease

    Directory of Open Access Journals (Sweden)

    Wang Chuhuai

    2011-06-01

    Full Text Available Abstract Background Recent studies have demonstrated that normal bone marrow (BM cells transplantation can correct liver injury in a mouse model of Wilson disease (WD. However, it still remains unknown when BM cells transplantation should be administered. The aim of this study was to investigate the potential impact of normal BM cells transplantation at different stages of WD to correct liver injury in toxic milk (tx mice. Methods Recipient tx mice were sublethally irradiated (5 Gy prior to transplantation. The congenic wild-type (DL BM cells labeled with CM-DiI were transplanted via caudal vein injection into tx mice at the early (2 months of age or late stage (5 months of age of WD. The same volume of saline or tx BM cells were injected as controls. The DL donor cell population, copper concentration, serum ceruloplasmin oxidase activity and aspartate aminotransferase (AST levels in the various groups were evaluated at 1, 4, 8 and 12 weeks post-transplant, respectively. Results The DL BM cells population was observed from 1 to 12 weeks and peaked by the 4th week in the recipient liver after transplantation. DL BM cells transplantation during the early stage significantly corrected copper accumulation, AST across the observed time points and serum ceruloplasmin oxidase activity through 8 to 12 weeks in tx mice compared with those treated with saline or tx BM cells (all P P P > 0.05. Conclusions Early stage transplantation of normal BM cells is better than late stage transplantation in correcting liver function and copper metabolism in a mouse model of WD.

  15. Intracellular trafficking of the human Wilson protein: the role of the six N-terminal metal-binding sites.

    Science.gov (United States)

    Cater, Michael A; Forbes, John; La Fontaine, Sharon; Cox, Diane; Mercer, Julian F B

    2004-01-01

    The Wilson protein (ATP7B) is a copper-transporting CPx-type ATPase defective in the copper toxicity disorder Wilson disease. In hepatocytes, ATP7B delivers copper to apo-ceruloplasmin and mediates the excretion of excess copper into bile. These distinct functions require the protein to localize at two different subcellular compartments. At the trans-Golgi network, ATP7B transports copper for incorporation into apo-ceruloplasmin. When intracellular copper levels are increased, ATP7B traffics to post-Golgi vesicles in close proximity to the canalicular membrane to facilitate biliary copper excretion. In the present study, we investigated the role of the six N-terminal MBSs (metal-binding sites) in the trafficking process. Using site-directed mutagenesis, we mutated or deleted various combinations of the MBSs and assessed the effect of these changes on the localization and trafficking of ATP7B. Results show that the MBSs required for trafficking are the same as those previously found essential for the copper transport function. Either MBS 5 or MBS 6 alone was sufficient to support the redistribution of ATP7B to vesicular compartments. The first three N-terminal motifs were not required for copper-dependent intracellular trafficking and could not functionally replace sites 4-6 when placed in the same sequence position. Furthermore, the N-terminal region encompassing MBSs 1-5 (amino acids 64-540) was not essential for trafficking, with only one MBS close to the membrane channel, necessary and sufficient to support trafficking. Our findings were similar to those obtained for the closely related ATP7A protein, suggesting similar mechanisms for trafficking between copper-transporting CPx-type ATPases. PMID:14998371

  16. Effect of pomegranate juice supplementation on matrix metalloproteinases 2 and 9 following exhaustive exercise in young healthy males

    International Nuclear Information System (INIS)

    Objectives: To evaluate the efficacy of pomegranate juice supplementation on matrix metalloproteinases 2 and 9 serum levels and improving antioxidant function in young healthy males during exhaustive exercise. Methods: The study was conducted at Ardabil University of Medical Sciences, Iran, in 2010-11 and comprised 28 healthy subjects in 18-24 age bracket. They were randomly divided into control and supplemented groups. One cup of pomegranate juice and one cup of tap water were given to supplemented and control groups daily for two weeks respectively. Fasting blood samples were taken at baseline and at the end of two weeks of intervention. The subjects were given one exhaustive exercise and then fasting blood samples were taken for testing blood glutathione peroxidase and superoxide dismutase and serum levels of high sensitivity C-reactive protein, zinc, ceruloplasmin, matrix metalloproteinases 2 and 9, malondialdehyde and total antioxidant capacity. Data was analysed using descriptive statistical tests, paired and independent sample t-test. Results: The blood levels of glutathione peroxidase and superoxide dismutase and serum levels of total antioxidant capacity after exhaustive exercise in the supplemented group were significantly increased (p<0.05), while the content of matrix metalloproteinases 2 and 9, ceruloplasmin and malondialdehyde showed a significant decrease in comparison to the control group (p<0.05). Besides, there were no significant changes in other biochemical factors. Conclusion: Regular intake of pomegranate juice significantly modulates matrix metalloproteinases 2 and 9 serum levels of some inflammatory factors and thus protects against exhaustive exercise-induced oxidative injury in young healthy males. (author)

  17. Isotopic analysis of Cu in blood serum by multi-collector ICP-mass spectrometry: a new approach for the diagnosis and prognosis of liver cirrhosis?

    Science.gov (United States)

    Costas-Rodríguez, Marta; Anoshkina, Yulia; Lauwens, Sara; Van Vlierberghe, Hans; Delanghe, Joris; Vanhaecke, Frank

    2015-03-01

    The isotopic composition of blood serum Cu has been investigated as a potential parameter for the diagnosis and prognosis of liver cirrhosis. Serum samples from supposedly healthy women (reference population) and from a group of female patients suffering from liver cirrhosis of different etiologies were analysed. The procedure for isolation of serum Cu and the measurement protocol for its isotopic analysis by multi-collector inductively coupled plasma-mass spectrometry (MC-ICP-MS) were evaluated. Significant differences in the isotopic composition of Cu were observed between the reference population and the patients. A wide spread in δ(65)Cu was observed within the cirrhosis population and δ(65)Cu seems to be linked to the severity of the disease. Patients with end-stage liver disease showed a significantly lighter serum Cu isotopic composition. Many clinical parameters used for the diagnosis and monitoring of liver diseases, i.e. the levels of aspartate aminotransferase, De Ritis ratio, prothrombin and international normalized ratio, albumin, bilirubin, Na and C-reactive protein, correlate well with the δ(65)Cu values, as did the ceruloplasmin level and the ceruloplasmin/Cu concentration ratio. The isotopic composition of serum Cu appears to reveal the synthetic and hepatocellular function of the liver synergistically with inflammation and fluid retention in the cohort studied. A relevant relationship was also observed between δ(65)Cu and scores of mortality risk, such as the Model for End-stage Liver Disease (MELD) and MELD-Na. Thus, the isotopic composition of serum Cu shows potential as a new approach for the prognosis of liver disease, and although further investigation is required, for evaluation of the mortality risk in end-stage liver disease and prioritization of liver transplants.

  18. Pre-conditioning induces the precocious differentiation of neonatal astrocytes to enhance their neuroprotective properties

    Directory of Open Access Journals (Sweden)

    Sandra J Hewett

    2011-07-01

    Full Text Available Hypoxic preconditioning reprogrammes the brain's response to subsequent H/I (hypoxia–ischaemia injury by enhancing neuroprotective mechanisms. Given that astrocytes normally support neuronal survival and function, the purpose of the present study was to test the hypothesis that a hypoxic preconditioning stimulus would activate an adaptive astrocytic response. We analysed several functional parameters 24 h after exposing rat pups to 3 h of systemic hypoxia (8% O2. Hypoxia increased neocortical astrocyte maturation as evidenced by the loss of GFAP (glial fibrillary acidic protein-positive cells with radial morphologies and the acquisition of multipolar GFAP-positive cells. Interestingly, many of these astrocytes had nuclear S100B. Accompanying their differentiation, there was increased expression of GFAP, GS (glutamine synthetase, EAAT-1 (excitatory amino acid transporter-1; also known as GLAST, MCT-1 (monocarboxylate transporter-1 and ceruloplasmin. A subsequent H/I insult did not result in any further astrocyte activation. Some responses were cell autonomous, as levels of GS and MCT-1 increased subsequent to hypoxia in cultured forebrain astrocytes. In contrast, the expression of GFAP, GLAST and ceruloplasmin remained unaltered. Additional experiments utilized astrocytes exposed to exogenous dbcAMP (dibutyryl-cAMP, which mimicked several aspects of the preconditioning response, to determine whether activated astrocytes could protect neurons from subsequent excitotoxic injury. dbcAMP treatment increased GS and glutamate transporter expression and function, and as hypothesized, protected neurons from glutamate excitotoxicity. Taken altogether, these results indicate that a preconditioning stimulus causes the precocious differentiation of astrocytes and increases the acquisition of multiple astrocytic functions that will contribute to the neuroprotection conferred by a sublethal preconditioning stress.

  19. Diminution of toxic copper accumulation in toxic milk mice modeling Wilson disease by embryonic hepatocyte intrasplenic transplantation

    Institute of Scientific and Technical Information of China (English)

    Zhu Shi; Xiu-Ling Liang; Bing-Xun Lu; Su-Yue Pan; Xi Chen; Qi-Qiang Tang; Ying Wang; Fan Huang

    2005-01-01

    AIM: To observe the therapeutic effect of intrasplenic transplantation with embryonic hepatocytes on amelioration of hereditary copper accumulation in toxic milk (TX) mouse modeling Wilson disease. METHODS: Donor hepatocytes were harvested from 14-d fetal liver of a pregnant homogeneous DL mouse. These cells were successively cultured, labeled with fluorescein dye Hoechst 33342 for 24 h, and sequentially infused into the spleen parenchyma of the recipient TX mice. No host immunosuppression measures were taken. Two and four weeks after transplantation, the recipients were killed for routine histologic investigation and immunohistochemistry study up to 4 wk after transplantation. The serum copper and ceruloplasmin concentrations of the recipient mice were determined by graphite furnace atomic absorption spectroscopy.RESULTS: In the following 2nd and 4th wk after transplantation, the donor hepatocytes could be visualized in the livers of 47.3% recipients. The serum ceruloplasmin and copper concentrations increased by 1.6-fold after 2 wk and 2.0-fold times after 4 wk respectively, which ultimately rose from about 30% of the normal level to nearly 60%(P<0.01). The hepatic copper concentration decreased 7.2%, 4 wk after transplantation. Pathologic examination showed that there were many actively proliferative hepatocyte precursor cells with specific embryonic hepatocyte marker AFP migrated into hepatic sinusoidsof the recipients. A large number of cells carrying hepatocytes marker and albumin were observed in the recipient spleen tissues.CONCLUSION: Embryonic hepatocytes are capable of differentiating into mature hepatocytes in vivo. After transplantation, the hereditary abnormalities of copper metabolism in TX mice could be corrected partially by intrasplenic transplantation of homogeneous embryonic hepatocytes.

  20. Western United States field trials and radioisotopic investigations on the molybdenum-copper interactions in livestock

    International Nuclear Information System (INIS)

    A review of western United States field trials on the molybdenum-copper interaction in cattle is presented. Historically, investigations in the western United States of America have focused on techniques to improve livestock production by copper supplementation. Initially, to evaluate copper-responsive situations, the molybdenum content of plant tissues was explored, and techniques were developed to reduce molybdenum levels in forage. Later, molybdenum levels were evaluated in combination with dietary copper and sulphate levels, and their relation to the occurrence of molybdenosis in livestock. Efforts are now directed at determining efficient methods of direct copper supplementation of livestock. Present techniques used in the western United States for copper supplementation include addition of copper sulphate to the diet or injection of copper glycinate. Current concepts of the Mo-Cu-SO4 interactions are discussed. Based on a review of radioisotopic investigations in ruminants, a mechanism for molybdenum-antagonized copper utilization by the liver includes the hypothesis that molybdenum does not interfere with copper transport to the liver, but interferes with the synthesis of the plasma enzyme, ceruloplasmin (Cp). The resultant apoceruloplasmin-like substances, with fewer copper atoms per molecule and less enzyme activity, are catabolized more rapidly than holoceruloplasmin. Such compounds have been reported in the literature. The higher levels of 64Cu in both the plasma and faeces of Mo-treated animals are possibly the result of a greater utilization of 64Cu in the synthesis of ceruloplasmin molecules with some apoproteins, which are more rapidly catabolized and subsequently excreted via bile to faeces. In this case, faecal loss of absorbed copper would be a major route of copper loss in molybdenum-induced copper deficiencies. (author)

  1. Studies of cholecystokinin-stimulated biliary secretions reveal a high molecular weight copper-binding substance in normal subjects that is absent in patients with Wilson's disease.

    Science.gov (United States)

    Iyengar, V; Brewer, G J; Dick, R D; Chung, O Y

    1988-03-01

    Copper is unique among cations in that its balance is regulated by the liver. The liver regulates copper balance by excretion of copper (we call it regulatory copper) in the bile destined for loss in the stool. However, most copper secreted into the gastrointestinal tract, for example, that in saliva and gastric juice, is reabsorbed. The biochemical mechanism by which the normal liver "packages" regulatory copper to prevent its reabsorption is not understood. Whatever the mechanism, it appears to have failed in Wilson's disease, because patients with Wilson's disease do not excrete adequate amounts of regulatory copper in their bile to prevent copper accumulation. In the present work, we have studied cholecystokinin-stimulated biliary secretions obtained by intestinal intubation of five normal subjects and five patients with Wilson's disease. Studies of these secretions reveal: (1) that normal but not Wilson's disease biliary samples had a copper-containing peak in the void volume from Sephadex G-75 columns; (2) that the amount of copper in this peak extrapolated to 24 hours of secretion was appropriate to maintain normal copper balance; (3) that the amount of copper in this peak increased with dietary copper supplementation of normal subjects; (4) that normal but not Wilson's disease biliary samples cross-reacted with each of two ceruloplasmin antibodies; and (5) that the high molecular weight Sephadex G-75 fraction from normal but not from Wilson's disease biliary samples cross-reacted with ceruloplasmin antibody. We postulate that the high molecular weight copper-containing substance observed with Sephadex chromatography in normal biliary samples but absent in Wilson's disease samples is the copper-packaging mechanism for copper balance regulation.(ABSTRACT TRUNCATED AT 250 WORDS)

  2. A synthetic peptide with the putative iron binding motif of amyloid precursor protein (APP does not catalytically oxidize iron.

    Directory of Open Access Journals (Sweden)

    Kourosh Honarmand Ebrahimi

    Full Text Available The β-amyloid precursor protein (APP, which is a key player in Alzheimer's disease, was recently reported to possess an Fe(II binding site within its E2 domain which exhibits ferroxidase activity [Duce et al. 2010, Cell 142: 857]. The putative ligands of this site were compared to those in the ferroxidase site of ferritin. The activity was indirectly measured using transferrin, which scavenges the Fe(III product of the reaction. A 22-residue synthetic peptide, named FD1, with the putative ferroxidase site of APP, and the E2 domain of APP were each reported to exhibit 40% of the ferroxidase activity of APP and of ceruloplasmin. It was also claimed that the ferroxidase activity of APP is inhibited by Zn(II just as in ferritin. We measured the ferroxidase activity indirectly (i by the incorporation of the Fe(III product of the ferroxidase reaction into transferrin and directly (ii by monitoring consumption of the substrate molecular oxygen. The results with the FD1 peptide were compared to the established ferroxidase activities of human H-chain ferritin and of ceruloplasmin. For FD1 we observed no activity above the background of non-enzymatic Fe(II oxidation by molecular oxygen. Zn(II binds to transferrin and diminishes its Fe(III incorporation capacity and rate but it does not specifically bind to a putative ferroxidase site of FD1. Based on these results, and on comparison of the putative ligands of the ferroxidase site of APP with those of ferritin, we conclude that the previously reported results for ferroxidase activity of FD1 and - by implication - of APP should be re-evaluated.

  3. Effects of balneotherapy on the reactants of acute inflammation phase in Ankylosing spondylitis

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    Stamenković Bojana

    2009-01-01

    Full Text Available Introduction. Ankylosing spondylitis (AS is a chronic inflammatory disease that affects sacroiliac joints, spinal column and peripheral joints. Beside medication therapy, physical and balneotherapy play an important role in its complex treatment. Objective. The aim of the research was to establish serum concentrations of C-reactive protein (CRP, α 1-acid glycoprotein (α 1-AGP, ceruloplasmine (CP and erythrocyte sedimentation rate (SE before and after the balneotherapy in ankylosing spondylitis. Methods. The research included 50 AS patients according to the revised New York criteria, of mean age 43 years, who were treated for 14 days on the average at the Clinic for Rheumatology of the Institute 'Niška Banja'. All the patients received medications and balneotherapy (radioactive oligomineral baths, peloid, massage, kinesitherapy; the serum concentrations of CRP, α1-AGP, CP and SE were measured before and after balneotherapy. Serum proteins were determined using original Nor Partigen plates Boehringer. Erythrocyte sedimentation rate was measured by Westergreen method. Balneotherapy was applied individually, intensively or mildly, depending on the AS stage and activity phase. Results. After dosed balneotherapy, a significant decrease in the concentrations of CP (p<0.05, α1-AGP (p<0.01 and CRP (p<0.05 was registered in the serums of AS patients. ESR was not significantly reduced. Conclusion. The research proved that α 1-acid glycoprotein, ceruloplasmine and C-reactive protein represent more sensitive inflammation markers as compared to erythrocyte sedimentation rate. The identification of acute phase reactants is important in the evaluation of dosed balneotherapy efficiency in the treatment of ankylosing spondylitis.

  4. Presentación clínica, diagnóstico y evolución a largo plazo en 29 pacientes con enfermedad de Wilson Clinical presentation, diagnosis, and long-term outcome of 29 patients with Wilson's disease

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    J. L. Rodrigo Agudo

    2008-08-01

    Full Text Available Objetivo: analizar las características clínicas, el tratamiento y evolución de los pacientes diagnosticados de enfermedad de Wilson (EW en la región de Murcia. Pacientes y método: se realizó un análisis retrospectivo de las historias clínicas de los 29 pacientes (edad media ± DE, 20,3 ± 13,4 años con EW diagnosticados en los últimos 16 años. Resultados: el motivo de consulta más frecuente fue el descubrimiento de transaminasas elevadas, en casi la mitad de los pacientes, seguido de temblor o distonía en el 17% respectivamente. El anillo de Kayser-Fleischer se objetivó en 17 de los 29 (58,6% pacientes (100% de los pacientes con afectación neurológica pura y en el 35,3% de los pacientes con clínica hepática pura; p Objective: to analyze the clinical characteristics, treatment, and follow-up of a cohort of 29 patients with Wilson's disease (WD within the region of Murcia. Patients and method: we reviewed the medical records of 29 cases of WD (mean age, 20.3 ± 13.4 years diagnosed during the last 16 years. Results: the most frequent reason for consultation was upon discovering a high transaminase level in almost half the patients, followed by tremors or dystonia in 17% of patients, respectively. A Kayser-Fleischer ring was observed in 17/29 (58.6% of patients (100% of patients with pure neurological involvement and 35% of patients with pure clinical hepatic disease; p < 0.001. Blood copper levels not associated with ceruloplasmin as well as cupruria were notably superior in patients with neurological symptoms and in those with liver cirrhosis at the time of diagnosis. Patient clinical symptoms remained stable with D-penicillamine or trientine, or improved during the observation period, for 18 out of 29 patients (62%, while 11 out of 29 patients (38% got worse. Conclusions: in our region patients with WD are diagnosed at a younger age, and in most cases for hepatic disease. Patients with neurological disease o liver cirrhosis had

  5. Transplantation of ATP7B-transduced bone marrow mesenchymal stem cells decreases copper overload in rats.

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    Shenglin Chen

    Full Text Available BACKGROUND: Recent studies have demonstrated that transplantation of ATP7B-transduced hepatocytes ameliorates disease progression in LEC (Long-Evans Cinnamon rats, a model of Wilson's disease (WD. However, the inability of transplanted cells to proliferate in a normal liver hampers long-term treatment. In the current study, we investigated whether transplantation of ATP7B-transduced bone marrow mesenchymal stem cells (BM-MSCs could decrease copper overload in LEC rats. MATERIALS AND METHODS: The livers of LEC rats were preconditioned with radiation (RT and/or ischemia-reperfusion (IRP before portal vein infusion of ATP7B-transduced MSCs (MSCsATP7B. The volumes of MSCsATP7B or saline injected as controls were identical. The expression of ATP7B was analyzed by real-time quantitative polymerase chain reaction (RT-PCR at 4, 12 and 24 weeks post-transplantation. MSCATP7B repopulation, liver copper concentrations, serum ceruloplasmin levels, and alanine transaminase (ALT and aspartate transaminase (AST levels were also analyzed at each time-point post-transplantation. RESULTS: IRP-plus-RT preconditioning was the most effective strategy for enhancing the engraftment and repopulation of transplanted MSCsATP7B. This strategy resulted in higher ATP7B expression and serum ceruloplasmin, and lower copper concentration in this doubly preconditioned group compared with the saline control group, the IRP group, and the RT group at all three time-points post-transplantation (p<0.05 for all. Moreover, 24 weeks post-transplantation, the levels of ALT and AST in the IRP group, the RT group, and the IRP-plus-RT group were all significantly decreased compared to those of the saline group (p<0.05 compared with the IRP group and RT group, p<0.01 compared with IRP-plus-RT group; ALT and AST levels were significantly lower in the IRP-plus-RT group compared to either the IRP group or the RT group (p<0.01 and p<0.05. respectively. CONCLUSIONS: These results demonstrate

  6. Effects of grain, fructose, and histidine feeding on endotoxin and oxidative stress measures in dairy heifers.

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    Golder, H M; Lean, I J; Rabiee, A R; King, R; Celi, P

    2013-01-01

    Ruminal endotoxin and plasma oxidative stress biomarker concentrations were studied in dairy heifers challenged with grain, fructose, and histidine in a partial factorial study. Holstein-Friesian heifers [n=30; average body weight (BW) of 359.3±47.3 kg] were randomly allocated to 5 treatment groups: (1) control (no grain); (2) grain [crushed triticale at 1.2% of BW dry matter intake (DMI)]; (3) grain (0.8% of BW DMI) + fructose (0.4% of BW DMI); (4) grain (1.2% of BW DMI) + histidine (6g/head); and (5) grain (0.8% of BW DMI) + fructose (0.4% of BW DMI) + histidine (6 g/head). Rumen samples were collected by stomach tube 5, 65, 115, 165, and 215 min after diet consumption and blood samples at 5 and 215 min after consumption. Rumen fluid was analyzed for endotoxin concentrations. Plasma was analyzed for concentrations of the following oxidative stress biomarkers: reactive oxygen metabolites (dROM), biological antioxidant potential (BAP), advanced oxidation protein products, and ceruloplasmin, and activity of glutathione peroxidase. Dietary treatment had no effect on concentrations of endotoxin or oxidative stress biomarkers. We observed no interactions of treatment by time. Ruminal concentrations of endotoxin decreased during the sampling period from 1.12×10(5) ± 0.06 to 0.92×10(5) endotoxin units/mL ± 0.05 (5 and 215 min after diet consumption, respectively). Concentrations of dROM and the oxidative stress index (dROM/BAP × 100) increased over the sampling period, from 108.7 to 123.5 Carratelli units (Carr U), and from 4.1 to 4.8, respectively. Ceruloplasmin concentrations markedly declined 5 min after the consumption of diets, from 190 to 90 mg/L over the 215-min sampling period. Overall, a single feeding challenge for dairy cattle with grain, fructose, and histidine, and combinations thereof, may not be sufficient to induce marked changes in endotoxin or oxidative stress biomarker concentrations.

  7. Leucograma e teores plasmáticos de proteínas de fase aguda de eqüinos portadores de abdômen agudo e submetidos à laparotomia Leukogram and plasma acute phase protein concentrations in horses with acute abdomen submitted to treatment by laparotomy

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    J.J. Fagliari

    2008-04-01

    Full Text Available Foram examinados 20 eqüinos adultos portadores de abdômen agudo e submetidos à laparotomia. Dez recuperaram-se sem intercorrência pós-operatória (G1 e 10 foram a óbito sete a 10 dias após a cirurgia, com sinais de choque séptico (G2. Avaliaram-se temperatura retal, freqüências cardíaca e respiratória, tempo de preenchimento capilar e teores plasmáticos das proteínas de fase aguda - fibrinogênio, ceruloplasmina, proteína C-reativa, antitripsina, haptoglobina e glicoproteína ácida -, antes e até sete dias após a laparotomia. As leucometrias às 72h e no sétimo dia pós-operatório dos eqüinos que foram a óbito foram, respectivamente, 34,6% e 57,1%, mais altas que a dos animais curados. Os maiores valores de proteína de fase aguda ocorreram no sétimo dia após a cirurgia; os percentuais de elevação de fibrinogênio, antitripsina, glicoproteina ácida, proteína C-reativa, ceruloplasmina e haptoglobina de eqüinos do G2 em relação ao G1 foram 46,8%, 67,9%, 91,9%, 112,2%, 126,9% e 186,2%, respectivamente.Twenty adult horses with acute abdomen were examined and submitted to treatment by laparotomy; ten had no postoperative complication (group 1, and ten showed septic shock symptom and died from seven to ten days after surgery (group 2. Body temperature, heart and respiratory rates, filling capillary time, and plasma acute phase protein concentrations - fibrinogen, ceruloplasmin, C-reactive protein, antitrypsin, haptoglobin, and acid glycoprotein - were evaluated before laparotomy and until seven days after surgery. White blood cell counts at 72h and seven days after surgery in group 2 animals were, respectively, 34.6% and 57.1%, and were higher than those measured in group 1 horses. The highest values of acute phase proteins occurred on the seventh day after surgery. The increase percentages of fibrinogen, antitrypsin, acid glycoprotein, C-reactive protein, ceruloplasmin, and haptoglobin plasma concentrations in group 2

  8. Effects of grain, fructose, and histidine feeding on endotoxin and oxidative stress measures in dairy heifers.

    Science.gov (United States)

    Golder, H M; Lean, I J; Rabiee, A R; King, R; Celi, P

    2013-01-01

    Ruminal endotoxin and plasma oxidative stress biomarker concentrations were studied in dairy heifers challenged with grain, fructose, and histidine in a partial factorial study. Holstein-Friesian heifers [n=30; average body weight (BW) of 359.3±47.3 kg] were randomly allocated to 5 treatment groups: (1) control (no grain); (2) grain [crushed triticale at 1.2% of BW dry matter intake (DMI)]; (3) grain (0.8% of BW DMI) + fructose (0.4% of BW DMI); (4) grain (1.2% of BW DMI) + histidine (6g/head); and (5) grain (0.8% of BW DMI) + fructose (0.4% of BW DMI) + histidine (6 g/head). Rumen samples were collected by stomach tube 5, 65, 115, 165, and 215 min after diet consumption and blood samples at 5 and 215 min after consumption. Rumen fluid was analyzed for endotoxin concentrations. Plasma was analyzed for concentrations of the following oxidative stress biomarkers: reactive oxygen metabolites (dROM), biological antioxidant potential (BAP), advanced oxidation protein products, and ceruloplasmin, and activity of glutathione peroxidase. Dietary treatment had no effect on concentrations of endotoxin or oxidative stress biomarkers. We observed no interactions of treatment by time. Ruminal concentrations of endotoxin decreased during the sampling period from 1.12×10(5) ± 0.06 to 0.92×10(5) endotoxin units/mL ± 0.05 (5 and 215 min after diet consumption, respectively). Concentrations of dROM and the oxidative stress index (dROM/BAP × 100) increased over the sampling period, from 108.7 to 123.5 Carratelli units (Carr U), and from 4.1 to 4.8, respectively. Ceruloplasmin concentrations markedly declined 5 min after the consumption of diets, from 190 to 90 mg/L over the 215-min sampling period. Overall, a single feeding challenge for dairy cattle with grain, fructose, and histidine, and combinations thereof, may not be sufficient to induce marked changes in endotoxin or oxidative stress biomarker concentrations. PMID:24119801

  9. Systemic inflammatory response indicators in rabbits (Oryctolagus cuniculus experimentally infected with sporulated oocysts of Eimeria stiedai (Apicomplexa: Eimeriidae Indicadores da resposta inflamatória sistêmica em coelhos (Oryctolagus cuniculus infectados experimentalmente com oocistos esporulados de Eimeria stiedai (Apicomplexa: Eimeriidae

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    Fagner Luiz da Costa Freitas

    2011-06-01

    Full Text Available Hemograms and acute-phase proteins in adult male New Zealand White rabbits that had been experimentally infected orally with sporulated oocysts of Eimeria stiedai were evaluated over a 28-day period. Fifty animals were used, divided into two groups: group A infected with 1 × 10(4 sporulated oocysts of E. stiedai and group B inoculated with distilled water. On the seventh day after infection, the infected animals presented anemia and leukocytosis with neutrophilia and monocytosis. Protein fractionation by means of electrophoresis identified 19 acute-phase proteins with molecular weights ranging from 24 to 238 kD. Ceruloplasmin, transferrin and haptoglobin showed high levels on the seventh day after infection, with gradual increases in their concentrations until the end of the experimental period. Thus, from the data of the present study, E. stiedai is considered to be a pyogenic etiological agent for which the infection level can be monitored through the leukocyte count and serum concentrations of ceruloplasmin, transferrin and haptoglobin, and these can be recommended as complementary tests.O hemograma e proteínas de fase aguda foram avaliados durante 28 dias em coelhos adultos, machos, raça branco Nova Zelândia, infectados experimentalmente, via oral, com oocistos esporulados de Eimeria stiedai. Foram usados 50 animais distribuídos em dois grupos: grupo A infectado com 1 × 10(4 oocistos esporulados de E. stiedai e grupo B inoculado com água destilada. No 7º dia após a infecção (dpi, os animais infectados tiveram anemia, leucocitose com neutrofilia e monocitose. O método de fracionamento de proteínas por eletroforese identificou 19 proteínas de fase aguda com pesos moleculares que variaram entre 24 e 238 kD. A ceruloplasmina, transferrina e haptoglobina tiveram níveis elevados no 7° dpi com aumento progressivo de suas concentrações até o término do período experimental. Desta forma, considerando-se os dados encontrados no

  10. Wilson's disease in children: clinical and diagnostic features

    International Nuclear Information System (INIS)

    Objective: To study the clinical and diagnostic laboratory features of Wilsons disease in children and adolescents. Design: A prospective cohort study. Place and Duration of study: The study included patients diagnosed as Wilson s disease at the Department of Pediatrics Allied Hospital, Punjab medical College, Faisalabad from May 1997 to June 2001. Patients and methods: Patients presenting with liver or suggestive neurological disease were investigated. Others were diagnosed as a result of family screening. Diagnosis of neurologic disease was made if two of the following were present: Typical neurological findings, Kayser Fleischer corneal rings and low serum ceruloplasmin (100 mu gm) free serum copper (>10 mu gm/dl). In other forms and for family screening, 24 hours. Urinary copper (> 100 mu gm), free serum copper (>10 mu gm/dl), and wherever possible liver biopsy for histopathology and cytochemical staining by rubeanic acid was also done. Results: Twenty-seven patients with a mean age of 10.2 years were diagnosed as suffering from Wilson disease. Mean age for hepatic and neurological disease was 9 years and 11.5 years respectively. Youngest patient (neurologic) was 6 years old. 48% cases presented with neurological, 41% with hepatic and 4% with skeletal manifestations while 7 % were asymptomatic. Mean duration of symptoms before diagnosis was 6.1 months. Dysarthria (84.6%), tremors (69.2%), rigidity and poor school performance and hand writing (61.5%), dysphagia (46.1%) and dystonia (38.5%), were the most common neurologic findings. Chronic liver disease was seen in 73 % while acute forms were seen in 27 % cases. Two cases presented with fulminant hepatic failure. Consanguineous marriage of the parents was found in 70 % and family history of disease was present in 65 % cases. K-F (Kayser Fleischer) rings and low serum ceruloplasmin(<20 mg/dl) was found in 85% of all patients. In non neurologic types other tests of copper metabolism were done. Elevated urinary

  11. Wilson's disease (hepatolenticular degeneration).

    Science.gov (United States)

    Herron, B E

    1976-01-01

    Wilson's disease, or hepatolenticular degeneration, is a rare inherited disorder of copper metabolism which usually affects young people. Excess copper accumulates in the tissues, primarily in the liver, brain, and cornea. This copper deposition results in a wide range of hepatic and neurological symptoms, and may produce psychiatric illness. Hepatic involvement often occurs in childhood, while neurological deficits generally are detected at a later age. The disease is inherited in an autosomal recessive fashion. Ocular findings are of particular importance because the corneal copper deposition, forming the Kayser-Fleischer ring,is the only pathognomonic sign of the disease. The structure of the ring and the presence of copper have been well established. An anterior capsular deposition of copper in the lens results in a characteristic sunflower cataract in some of these patients. Other ocular abnormalities have been described but are much less common. The pathogenesis of the disease and the basic genetic defect remain obscure. It is clear that there is excess copper in the tissues, but the mechanism of its deposition is unknown. It is in some way associated with a failure to synthesize the serum copper protein ceruloplasmin normally. Another theory suggests that an abnormal protein with a high affinity for copper may bind the metal in the tissues. The diagnosis may be suggested by the clinical manifestations and confirmed by the presence of a Kayser-Fleischer ring. In the absence of these findings biochemical determinations are necessary. The most important of these are the serum ceruloplasmin, the urinary copper, and the hepatic copper concentration on biopsy. Treatment consists in the administration of the copper chelating agent, penicillamine, and the avoidance of a high copper intake. This usually results in marked clinical improvement if irreversible tissue damage has not occurred. Maintenance therapy for life is necessary in order to continue the negative

  12. Responses of weanling pigs to dietary supplementation with vitamin C or carbadox.

    Science.gov (United States)

    Yen, J T; Pond, W G

    1984-01-01

    A 2 X 2 factorial arrangement with two levels (0, 660 ppm) of vitamin C and two levels (0, 55 ppm) of carbadox supplementation was used in two experiments with 112 crossbred pigs weaned between 4 and 5 wk of age. An 18% protein corn-soybean meal-oats-dried whey starter diet was used as the basal diet. Each diet was fed ad libitum for a 4-wk period to three replicates of four pigs in Exp. 1 and to four replicates of four pigs in Exp. 2. Vitamin C supplementation produced a significantly higher plasma vitamin C concentration in weanling pigs, but, contrary to results of our previous study, failed to improve average daily gain of the pigs. Daily gain was, however, improved significantly by carbadox supplementation. Carbadox also produced a significantly higher plasma vitamin C concentration in pigs after a 7-d lag period. Plasma Fe concentration of pigs was not affected by supplemental vitamin C, but was significantly higher in those fed carbadox-supplemented diets. Plasma ceruloplasmin concentration increased significantly in all treatment groups from the initial sampling period (d 0) to subsequent periods. No interactions between supplemental vitamin C and carbadox were observed in daily gain, feed efficiency and the measured plasma constituents. PMID:6698894

  13. Analysis behaviour of free radicals produced by ionizing radiations in human blood by EPR for biological dosimetry in patients; Analisis del comportamiento de los radicales libre en la radiolisis de la sangre por EPR para dosimetria biologia en pacientes

    Energy Technology Data Exchange (ETDEWEB)

    Mendoza, O. O.; Almanza, A.; Plazas, M. M. C.

    2006-07-01

    In this work is analyzed the biological dosimetry of the free radicals produced by ionizing radiations in human blood obtained by EPR and the biological behaviour of samples In-Vitro, with Rh: O+, in tubes with EDTA (Acid Etilen Diamino Tetracetic) the samples was extracted of the main investigator, these samples were radiated with gammas of ''60Co of a Theratron 780 between plates of PMMA to a depth of Z{sub m}ax of 0.5 cm and between doses 1 to 25 Gy. In these results the behaviors of signal the free radicals presented a increasing a their intensity depending on applied dose, of equal way are results of the biologic dosimetry displayed in sanguineous populations like. White Globules, Red. Platelets etc, to being compared with Resonance Paramagnetic Electronic (EPR). The results show changes in sanguineous populations in high doses (D>10 Gy) in the case of lymphocytes, granulocitos, macusanita, plaquetas, hemoglobina, haematocrit with change similarly in medium and low doses (D>10Gy) in linfocites, platelets, granulocytes, monocytes and the haematocrit. A sanguineous sample without radiating analyzes by EPR giving the presence of signals with values of g=2.13 2,41 in blood. For the first certain value of g authors have associated it to free radicals like: globin (Fe(IV)=0) or Cu''+ incorporated to the ceruloplasmin molecule. (Author)

  14. Development of technology for biological dosimetry

    International Nuclear Information System (INIS)

    Adult male rats were treated a single, whole body exposure to a dose of 0.1, 0.5, 1, 2, 3, 5, 7 and 9 Gy. The animal were sacrificed 6, 24, 48, 72, 96 and 212 hours following exposure. Enzyme activity changes such as alkaline phosphatase, GOT, creating kinase, MDH and LDH in rat serum as biochemical indicators useful for evaluating radiation exposure were measured. An competitive enzyme linked immunosorbent assay (ELISA) has been developed to measure acute phase reactants (APRs) in rat serum after gamma-irradiation. Rat alpha-2 macroglobulin, alpha-1 acid glycoprotein, haptoglobin, ceruloplasmin, C-reactive protein and alpha-1 antitrypsin were purified from the plasma of turpentine treated rats. In vitro somatic mutation induced by gamma-irradiation and pentachlorophenol (PCP) which is representative of chemical pollutant was measured at the hypoxanthine-guanine phosphorybosyl transferase (HPRT) locus in human T-lymphocytes by a cell cloning assay. Mutant cells were selected by their ability to form a clone in the presence of purine analogue 6-thioguanine. Reverse transcriptase/polymerase chain reaction technique was needed for the mutation spectrum to discriminate combined exposure to radiation and chemicals. (author). 98 refs., 7 tabs., 47 figs

  15. Serum protein concentrations in calves with experimentally induced pneumonic pasteurellosis

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    Fagliari J.J.

    2003-01-01

    Full Text Available Ten healthy 2 to 4-week-old Holstein calves were randomly allotted into control and infected groups. Control calves (n=5 were inoculated intrabronchially with 5ml of Dulbecco's phosphate-buffered saline solution (DPBSS. Infected calves (n=5 were inoculated intrabronchially with 5x10(9 log-phase Mannheimia haemolytica organisms suspended in 5ml of DPBSS. Blood samples were obtained 15 minutes before and one, two, four and six hours after inoculation. Serum protein concentrations were determined by means of sodium dodecyl sulphate-polyacrylamide gel electrophoresis. Serum concentrations of proteins with molecular weights of 125,000 D (ceruloplasmin, 60,000 D (a 1-antitrypsin, 45,000 D (haptoglobin, and 40,000 D (acid glycoprotein were significantly increased in calves with pneumonic pasteurellosis, compared with concentrations in control calves. Results indicate that acute phase proteins increase more rapidly after the onset of inflammation than previously thought. Measurement of serum protein concentrations may be useful in monitoring the progression of the induced pneumonic pasteurellosis in calves.

  16. Urinary Biomarkers in the Assessment of Early Diabetic Nephropathy

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    Gluhovschi, Gheorghe; Petrica, Ligia; Timar, Romulus; Velciov, Silvia; Ionita, Ioana; Kaycsa, Adriana; Timar, Bogdan

    2016-01-01

    Diabetic nephropathy (DN) is a frequent and severe complication of diabetes mellitus (DM). Its diagnosis in incipient stages may allow prompt interventions and an improved prognosis. Towards this aim, biomarkers for detecting early DN can be used. Microalbuminuria has been proven a remarkably useful biomarker, being used for diagnosis of DN, for assessing its associated condition—mainly cardiovascular ones—and for monitoring its progression. New researches are pointing that some of these biomarkers (i.e., glomerular, tubular, inflammation markers, and biomarkers of oxidative stress) precede albuminuria in some patients. However, their usefulness is widely debated in the literature and has not yet led to the validation of a new “gold standard” biomarker for the early diagnosis of DN. Currently, microalbuminuria is an important biomarker for both glomerular and tubular injury. Other glomerular biomarkers (transferrin and ceruloplasmin) are under evaluation. Tubular biomarkers in DN seem to be of a paramount importance in the early diagnosis of DN since tubular lesions occur early. Additionally, biomarkers of inflammation, oxidative stress, podocyte biomarkers, and vascular biomarkers have been employed for assessing early DN. The purpose of this review is to provide an overview of the current biomarkers used for the diagnosis of early DN.

  17. Antioxidant defense markers modulated by glutathione S-transferase genetic polymorphism: results of lung cancer case-control study.

    Science.gov (United States)

    Reszka, Edyta; Wasowicz, Wojciech; Gromadzinska, Jolanta

    2007-12-01

    Oxidative stress and xenobiotic metabolizing enzymes are suspected to be related to carcinogenesis by different cellular mechanisms. Hence, our study aimed at identifying potential relationships between antioxidant defense parameters measured in blood and glutathione S-transferase (GST) genetic polymorphisms of four GST izoenzymes in lung cancer patients and reference individuals. The case-control study included 404 lung cancer patients and 410 non-cancer subjects as controls, matched by age, gender and place of living (central Poland). In control subjects with GSTM3*A/*A, GSTT1 null, GSTM1 null + GSTT1 null, GSTM3*A/*A + GSTT1 null genotype, glutathione peroxidase activity was significantly higher (P < 0.05) than in controls possessing respective potential protective GST genotypes. Controls with GSTM3*A/*A + GSTP1*B genotype presented significantly higher ceruloplasmin activity (P < 0.05) than GSTM3*B + GSTP1*A/*A carriers. Zinc level was significantly higher (P < 0.05) in controls and cases with GSTP1*B + GSTT1 null genotype and in cases with GSTM1 null + GSTP1*B genotype, when compared with respective potential protective GST genotypes. This case-control study indicates that particular defective GST genotypes may enhance the defense against oxidative stress. The potential relationship between the investigated antioxidative enzymes and microelements, and common functional genetic polymorphism of GST was observed mostly in control subjects. PMID:18850183

  18. The effect of dietary Cu and diabetes on indices of Cu nutriture in the rat

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    Rucker, R.B.; Uriu-Hare, J.Y.; Tinker, D.; Keen, C.L. (Univ. of California, Davis (United States))

    1991-03-11

    The uptake-retention of 67Cu is affected by dietary Cu and diabetes. Consequently, the functional activities of select enzymes and tissue Cu status were assessed. STZ-diabetic and control rats were fed Cu suppl. or def. diets. Rats were gavaged with 28 {mu}Ci 67Cu, and killed 8, 16, 24, 32, 64, or 128 h later. Diabetic rats were hyperphagic, hyperglycemic and hypoinsulinemic; with no effect of diet. Plasma ceruloplasmin activity (Cp) was lower in Cu def. rats; diabetic rats tended to have higher Cp than controls. Cu def. rats had low Cu levels in liver, kidney and plasma. Cu suppl. diabetic rats had higher liver and kidney Cu compared to Cu def. diabetic rats. Gel chromatography of liver showed that with time, there was a transfer of 67Cu from low to higher MW ligands. In nondiabetic rats, more 67Cu was associated with the higher MW ligands. The converse was observed for diabetic rats. There was no effect of diabetes on liver 67Cu localization. Diabetic rats had higher metallothionein (MT) concentrations in liver and kidney compared to controls Cu deficiency lowered MT values in both diabetic and control rats. CuZn SOD Cu activity was lowered with Cu def. and diabetes, while Mn SOD activity was similar among groups. Plasma lipid peroxide levels were lower in diabetic rats than controls. The results show that Cu metabolism is affected in diabetes, and the changes are functionally significant.

  19. Wilson’s disease masquerading as nonalcoholic steatohepatitis

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    Sabina Mahmood

    2009-07-01

    Full Text Available Background: Wilson’s disease is one of the most common hereditary causes of unclear hepatopathy. Patient & Method: A 34-year old male patient with a history of hyperlipidemia was admitted with symptoms of abdominal pain and slight hematuria. Abnormal liver function tests, ultrasound reports and liver biopsy were suggestive of nonalcoholic steatohepatitis (NASH. The patient received preliminary treatment for NASH. However, on subsequent follow-up, NASH remained unresolved and liver histology showed fibrosis progression from fibrosis stage 1 to stage 3. Results: Biochemical tests revealed that the levels of serum ceruloplasmin were decreased (7mg/dl while the urinary excretion of copper was found to be increased (174.2 μg/day. Wilson’s disease was confirmed by diagnostic mutation analysis involving Direct Sequencing. Heterogeneity in the patients ATP7B gene confirmed Wilson’s disease. Administration of D-penicilamine resulted in a decrease in fat deposition in the liver and no further progression in fibrosis after 10 months. Conclusion: Adult patient presenting NASH as first symptoms need to be examined for Wilson’s disease and other metabolic conditions affecting the liver, prior to initiation of treatment.

  20. Alagille Syndrome and Wilson Disease in Siblings: A Diagnostic Conundrum

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    Meghan Amson

    2012-01-01

    Full Text Available The authors describe two siblings, each with a different, rare genetic condition that affects liver function. The index case, the 18-year-old asymptomatic brother of a young man recently diagnosed with Wilson disease, presented for Wilson disease screening and was also found to have abnormal liver function suggestive of cholestasis. However, ceruloplasmin level, 24 h urine copper concentration and liver synthetic function were normal. Further hepatic investigations and genetic mutation analysis were performed, ultimately leading to a diagnosis of Alagille syndrome. He was treated with ursodiol, which resulted in normalization of his liver function tests. Subsequently, he was found to be a carrier for a mutation in the Wilson disease gene, ATP7B. In the present report, the potential implications of being a heterozygote for Wilson disease in the context of Alagille syndrome are discussed. Also stressed is that care must be exercised by the clinician when diagnosing family members who may present with two different disorders closely mimicking one another.

  1. Wilson′s disease masquerading as nonalcoholic steatohepatitis

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    Sabina Mahmood

    2009-01-01

    Full Text Available Background : Wilson′s disease is one of the most common hereditary causes of unclear hepatopathy. Patient & Method: A 34-year old male patient with a history of hyperlipidemia was admitted with symptoms of abdominal pain and slight hematuria. Abnormal liver function tests, ultrasound reports and liver biopsy were suggestive of nonalcoholic steatohepatitis (NASH. The patient received preliminary treatment for NASH. However, on subsequent follow-up, NASH remained unresolved and liver histology showed fibrosis progression from fibrosis stage 1 to stage 3. Results: Biochemical tests revealed that the levels of serum ceruloplasmin were decreased (7mg/dl while the urinary excretion of copper was found to be increased (174.2 μg/day. Wilson′s disease was confirmed by diagnostic mutation analysis involving Direct Sequencing. Heterogeneity in the patient′s ATP7B gene confirmed Wilson′s disease. Administration of D-penicillamine resulted in a decrease in fat deposition in the liver and no further progression in fibrosis after 10 months. Conclusion: Adult patient presenting NASH as first symptoms need to be examined for Wilson′s disease and other metabolic conditions affecting the liver, prior to initiation of treatment. ( Mahmood S, Inada N, Izumi A, Kawanaka M, Kobashi H, Yamada G. Wilson′s disease masquerading as nonalcoholic steatohepatitis.

  2. Oral Zinc Supplementation Decreases the Serum Iron Concentration in Healthy Schoolchildren: A Pilot Study

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    Naira Josele Neves de Brito

    2014-09-01

    Full Text Available The recognized antagonistic actions between zinc and iron prompted us to study this subject in children. A convenience sample was used. Thirty healthy children between 8 and 9 years of age were studied with the aim of establishing the effect of a 3-mo oral zinc supplementation on iron status. Fifteen individuals were given a placebo (control group, and 15 were given 10 mg Zn/day (experimental group. Blood samples were collected at 0, 60, 120, 180 and 210 min after a 12-h overnight fast, before and after placebo or zinc supplementation. This supplementation was associated with significant improvements in energy, protein, fat, carbohydrate, fiber, calcium, iron, and zinc intake in accordance with the recommendations for age and sex. The basal serum zinc concentration significantly increased after oral zinc supplementation (p < 0.001. However, basal serum iron concentrations and area under the iron curves significantly decreased in the experimental group (p < 0.0001 and remained at the same level throughout the 210-min study. The values obtained for hemoglobin, mean corpuscular volume, ferritin, transferrin, transferrin saturation, ceruloplasmin and total protein were within normal reference ranges. In conclusion, the decrease in serum iron was likely due to the effects of chronic zinc administration, and the decrease in serum iron was not sufficient to cause anemia.

  3. Effect of bacoside A on brain antioxidant status in cigarette smoke exposed rats.

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    Anbarasi, K; Vani, G; Balakrishna, K; Devi, C S Shyamala

    2006-02-16

    Free radicals mediated oxidative stress has been implicated in the pathogenesis of smoking-related diseases and antioxidant nutrients are reported to prevent the oxidative damage induced by smoking. Therefore, the present study was conducted to evaluate the antioxidant role of bacoside A (triterpenoid saponin isolated from Bacopa monniera) against chronic cigarette smoking induced oxidative damage in rat brain. Adult male albino rats were exposed to cigarette smoke for a period of 12 weeks and simultaneously administered with bacoside A (10 mg/kg b.w./day, p.o.). Antioxidant status of the brain was assessed from the levels of reduced glutathione, vitamin C, vitamin E, and vitamin A and the activities of superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase. The levels of copper, iron, zinc and selenium in brain and serum ceruloplasmin activity were also measured. Oxidative stress was evident from the diminished levels of both enzymatic and non-enzymatic antioxidants. Alterations in the levels of trace elements with accumulation of copper and iron, and depletion of zinc and selenium were also observed. Bacoside A administration improved the antioxidant status and maintained the levels of trace elements. These results suggest that chronic cigarette smoke exposure enhances oxidative stress, thereby disturbing the tissue defense system and bacoside A protects the brain from the oxidative damage through its antioxidant potential.

  4. Psychosis in an adolescent with Wilson's disease: A case report and review of the literature.

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    Grover, Sandeep; Sarkar, Siddharth; Jhanda, Soumya; Chawla, Yogesh

    2014-10-01

    Neuropsychiatric manifestations are common in Wilson's disease and mainly include extrapyramidal and cerebellar symptoms. Presentations with psychotic symptoms have been described less frequently. In this report we present the case of a young boy with Wilson's disease who developed psychotic symptoms. A 12-year-old boy was diagnosed with Wilson's disease on the basis of the physical examination findings and low ceruloplasmin levels (8.1 mg/dl). After 2 weeks of being diagnosed with Wilson's disease, he developed an acute onset illness, characterized by delusion of persecution, fearfulness, hypervigilence and decreased sleep. These symptoms were not associated with any confusion, clouding of consciousness, hallucinations and affective symptoms. There was no past or family history of psychosis. One week after the onset of the symptoms he was prescribed tab penicillamine, initially 250 mg/day, which was increased to 500 mg/day after 3 days. After increase in the dose of penicillamine, his psychiatric symptoms worsened and led to hospitalization. A diagnosis of organic delusional disorder (F06.2) due to Wilson's disease was considered. Tab risperidone 1 mg/day was started, and the dose of penicillamine was reduced with which symptoms resolved. Whenever a young adolescent develops psychosis, especially of delusional type, the possibility of Wilson's disease must be considered.

  5. Doença de Wilson: diagnóstico clínico e sinais das "faces do panda" à ressonância magnética. Relato de caso Wilson's disease: clinical diagnosis and "faces of panda" signs in magnetic resonance imaging. Case report

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    José Correia de Farias Brito

    2005-03-01

    Full Text Available Homem de 25 anos de idade foi internado com sintomatologia polimorfa típica das afecções dos gânglios da base, associada a manifestações psiquiátricas. Fez uso de periciazina; no entanto, a suspensão do medicamento não melhorou a sintomatologia. Foi estabelecido o diagnóstico de doença de Wilson pela visualização do anel de Kayser-Fleischer através de exame com lâmpada de fenda e pelos exames laboratoriais que mostraram diminuição da ceruloplasmina plasmática e aumento de excreção de cobre urinário. A ressonância magnética, ponderada em T2, em cortes axiais do mesencéfalo e ponte, evidenciou imagens das "faces do panda".A 25 year-old man was admitted with polimorph symptomatology resembling basal ganglia disease associated with psychiatric manifestations. The patient had been treated with pericyazine. The drug was stopped but the symptomatology did not improve. The diagnosis of Wilson's disease was established through ophthalmologic examination with slit-lamp that revealed the Kayser-Fleischer ring and laboratory abnomalities showing a low serum ceruloplasmin level and increased urinary copper excretion. T2-weighted axial magnetic resonance imaging demonstrated the " face of panda signs" in the midbrain and pons.

  6. Atypical case of Wilson's disease with psychotic onset, low 24 hour urine copper and the absence of Kayser-Fleischer rings

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    Krstić Dragan

    2014-01-01

    Full Text Available Introduction. Wilson's disease is typically manifested in two clinical forms, neurological and hepatic and in rare cases it starts with psychiatric symptoms exclusively. We presented a rare atypical case of Wilson's disease with psychotic onset. Case report. A 22-year-old male patient was initially presented with predominant signs and symptoms of psychiatric disorder and then later with the development of neurological signs and symptoms. Neuroimaging, detected metal deposits in central nervous system (CNS but not in peripheral organs, while serum analysis excluded pantothenate-kinase associated neurodegeneration (PKAN and aceruloplasminemia. In favor of the diagnosis of Wilson's disease there were reduced concentrations of copper and ceruloplasmin concentrations and metal deposits in CNS, but other pathognomonic signs and symptoms were absent: in-creased copper in urine, Kayser-Fleischer rings in Descemet’s corneal membrane and deposits of copper in liver. Introduction of penicillamine treatment resulted in improvement in mental and general health of the patient. Molecular genetic analysis definitely confirmed the diagnosis of Wilson's disease. Conclusion. Wilson's disease can remain undetected for a long period of time if masked with dominant or exclusive psychiatric symptoms. If clear clinical symptoms and signs, and unambiguous laboratory findings are not present, it is necessary to perform molecular genetic analysis to confirm the definitive diagnosis.

  7. Population screening for Wilson's disease.

    Science.gov (United States)

    Hahn, Si Houn

    2014-05-01

    Wilson's disease is an autosomal recessive disorder of copper transport caused by mutations in the gene encoding an ATPase, ATP7B. Early detection of Wilson's disease is critical because effective medical treatments such as chelating agents and zinc salts are available, which can prevent lifelong neurological disabilities and/or cirrhosis. It is unfortunate that most patients are brought to our attention after they have developed serious complications such as brain damage or cirrhosis, despite the availability of effective treatments. The diagnosis is usually made through copper measurement in the liver tissue, followed by confirmation with genetic testing of the ATP7B gene. Currently, there are no effective biomarkers or methods suitable for newborn screening for Wilson's disease. Ceruloplasmin has been tested for pediatric and newborn screening with limited outcome. Recently, liquid chromatography-multiple reaction monitoring-mass spectrometry (LC-MRM-MS) has emerged as a robust technology that may enable multiplex quantification of signature proteotypic peptides with low abundance. The application of this technology may help facilitate the research on Wilson's disease for protein expression, biomarker study, diagnosis, and, hopefully, screening.

  8. Fracture in a Young Male Patient Leading to the Diagnosis of Wilson's Disease: A Case Report.

    Science.gov (United States)

    Shin, John Junghun; Lee, Jun-Pyo; Rah, Jung-Ho

    2015-02-01

    Wilson's disease is a rare genetic disorder that has abnormal copper metabolism. Although the disease's main problems are found in liver and brain, some studies revealed manifestation of various musculoskeletal problems in the patients. In this report, we encountered a young patient who had fracture in the forearm bone. Initially, exception to a previous history of fracture from a motorcycle accident, the patient did not have any medical or drug use history, and laboratory work-ups were insignificant. However, with suspicion on his bone's integrity, bone densitometry was recommended and revealed osteopenic change. To disclose a cause for the change, questions were made to recall any particular history or event, and his complaint of recent vision loss led to ophthalmologic consultation where under slit-lamp test found Kayser-Fleischer ring. Further laboratory work-up found low levels of serum copper and ceruloplasmin and high copper level in 24-hr urine sample that led to the diagnosis of Wilson's disease. Although Wilson's disease has been frequently noticed with considerable musculoskeletal manifestation, it rarity makes the diagnosis illusive to a physician. Hence, despite of its rarity, it is imperative to remember the disease's bony manifestation, and it should be suspected in young patients with demineralized bone when the reason for brittle bone cannot be answered with other better known conditions.

  9. Creutzfeldt-Jakob disease masked by head trauma and features of Wilson's disease.

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    Scontrini, Alessandra; Di Bonaventura, Carlo; Fiorelli, Marco; Tiple, Dorina; Colaizzo, Elisa; Ladogana, Anna; Parchi, Piero; Pocchiari, Maurizio

    2015-04-01

    Creutzfeldt-Jakob disease (CJD) is a fatal neurodegenerative disorder typically characterized by progressive dementia associated with myoclonus, cerebellar and other focal neurological signs. Electroencephalogram, brain MRI and cerebrospinal fluid (CSF) analyses are helpful diagnostic tools, but diagnosis in patients with atypical presenting neurological signs is often difficult to make. A 55-year-old woman developed disorientation, drowsiness and focal motor signs after a traumatic brain injury due to an accidental fall. In two weeks, her symptoms worsened in spite of a brain MRI showed an improvement of traumatic lesions, but the presence of bilateral hyperintensity in the basal nuclei was suggestive of a metabolic or prion encephalopathy. The high 24-h urinary copper level and reduction of ceruloplasmin initially supported the diagnosis of Wilson's disease, but the absence of Kayser-Fleischer rings, and the positivity of 14-3-3 protein test and elevated tau concentrations in the CSF oriented toward a diagnosis of CJD. She died 5 months after the onset, and the postmortem examination of the brain revealed immunochemical features of CJD. This case exemplifies the difficulty of a timely diagnosis when rapid progressive dementia is masked by concomitant factors (i.e., head trauma) and neurological signs are associated with unclear laboratory findings.

  10. [The clinical analysis of fulminant Wilson's disease in patients with hepatitis B virus infection: a report of 13 cases].

    Science.gov (United States)

    Deng, H H; Xu, M

    2016-08-01

    To analyze the clinical features and prognosis of fulminant Wilson's disease (FWD) in patients with hepatitis B virus (HBV) infection. Twenty-seven patients were enrolled in Guangzhou Eighth People's Hospital from 2005 to 2015, including 13 FWD patients with HBV infection and 14 FWD patients without HBV infection. Clinical efficacy and survival rate were evaluated. Baseline biochemical data in two groups were comparable(P>0.05), including total bilirubin, prothrombin activity, serum albumin, alpha fetal protein, alanine transaminase, ceruloplasmin and 24 hours urine copper .Treatment in FWD group with HBV infection was ineffective, including 9(9/13) deaths and 4(4/13) patients receiveing liver transplants. However, 7(7/14)cases in the other group did not response to the treatment, including 6(6/14)deaths and 1(1/14)patient receiving liver transplant. The prognosis in the two groups is significantly different(P=0.006), which is much worse in FWD patients with HBV infection.

  11. Wilson's disease and other neurological copper disorders.

    Science.gov (United States)

    Bandmann, Oliver; Weiss, Karl Heinz; Kaler, Stephen G

    2015-01-01

    The copper metabolism disorder Wilson's disease was first defined in 1912. Wilson's disease can present with hepatic and neurological deficits, including dystonia and parkinsonism. Early-onset presentations in infancy and late-onset manifestations in adults older than 70 years of age are now well recognised. Direct genetic testing for ATP7B mutations are increasingly available to confirm the clinical diagnosis of Wilson's disease, and results from biochemical and genetic prevalence studies suggest that Wilson's disease might be much more common than previously estimated. Early diagnosis of Wilson's disease is crucial to ensure that patients can be started on adequate treatment, but uncertainty remains about the best possible choice of medication. Furthermore, Wilson's disease needs to be differentiated from other conditions that also present clinically with hepatolenticular degeneration or share biochemical abnormalities with Wilson's disease, such as reduced serum ceruloplasmin concentrations. Disordered copper metabolism is also associated with other neurological conditions, including a subtype of axonal neuropathy due to ATP7A mutations and the late-onset neurodegenerative disorders Alzheimer's disease and Parkinson's disease.

  12. Plasma oxidative stress biomarkers and progesterone profiles in a dairy cow diagnosed with an ovarian follicular cyst.

    Science.gov (United States)

    Talukder, S; Ingenhoff, L; Kerrisk, K L; Celi, P

    2014-01-01

    This study was conducted to examine the oxidative stress biomarkers in a cow diagnosed with a follicular cyst in her left ovary. Progesterone (P4) and plasma oxidative stress status was measured in 13 Holstein cows after synchronization of oestrus with controlled internal drug release (CIDR) and prostaglandinF2α (PGF2α) protocol. The presence and size of ovarian structures were monitored by transrectal ultrasound at 4 hourly intervals. Of the 13 cows, 12 were monitored until ovulation was detected and recorded, whereas one cow failed to ovulate and developed a follicular cyst. Oxidative stress biomarkers; reactive oxygen metabolites (ROMs), biological antioxidant potential (BAP), oxidative stress index (OSI), glutathione (GSH), ceruloplasmin and advanced oxidation protein products (AOPP) were measured in the cystic cow and compared to those of the 12 ovulated cows and are referred to as higher or lower if they are outside the mean ± standard error of mean of those of ovulated cows. The cystic cow had lower ROMs and OSI between 36 and 84 h after PGF2α injection and at 9 h, from 36 to 60 h after PGF2α injection respectively. On the other hand, antioxidant (BAP and GSH) was higher in the cystic cow compared to her ovulated herd mates. The observed imbalance between oxidant and antioxidant might have disrupted the physiological events for ovulation to occur, leading to cystic ovarian disease.

  13. Acute phase proteins in serum and cerebrospinal fluid in the course of bacterial meningitis.

    Science.gov (United States)

    Paradowski, M; Lobos, M; Kuydowicz, J; Krakowiak, M; Kubasiewicz-Ujma, B

    1995-08-01

    We carried out estimations of the following acute phase proteins: C-reactive protein (CRP), alpha-1-antitrypsin (AAT), alpha-1-acid glycoprotein (AAG), alpha-2-ceruloplasmin (CER), and alpha-2-haptoglobin (HPT) in serum and in cerebrospinal fluid (CSF) in patients with bacterial meningitis (BM, n = 30) and viral meningitis (VM, n = 30). We have shown that determinations of concentrations of AAG and CRP in serum and CER in CSF are useful in differentiation between BM and VM. The diagnostic power of these three tests (the areas under their ROC curves equal 0.942, 0.929, and 0.931, respectively) is bigger, though statistically not significantly, than that of traditional parameters of BM in CSF, i.e., total protein concentration and white blood cell count. Determination of AAG, CRP, and AAT in serum is a valuable monitoring marker in the course of BM treatment. Convenience of serum sampling constitutes an advantage over traditional BM parameters in CSF. PMID:8521602

  14. Menkes disease: importance of diagnosis with molecular analysis in the neonatal period

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    Larissa Sampaio de Athayde Costa

    2015-10-01

    Full Text Available Summary Menkes disease is a congenital disorder caused by changes in copper metabolism derived from mutations in the ATP7A gene. It is characterized by physical and neurological alterations. In the neonatal period, these alterations can be nonspecific, which makes early diagnosis a challenge. Diagnosis can be suspected when there are low levels of ceruloplasmin and serum copper. Molecular analysis confirms the diagnosis. Treatment is parenteral administration of copper histidine. We report a familial case with molecular confirmation. The proband had clinical and biochemical suspicious. Treatment with copper histidine was indicated, but initiated at the age of 2 months and 27 days only. He did not present improvements and died at 6 months. The mother became pregnant again, a male fetus was identified and copper histidine was manufactured during pregnancy. He was born healthy, biochemical markers were reduced and treatment was indicated. Molecular analysis was performed confirming mutation in both the mother and the proband, while the other son did not have mutation, so treatment was discontinued. We support the clinical relevance of molecular confirmation for the correct diagnosis and genetic counseling, once clinical findings in the neonatal period are nonspecific and early treatment with parenteral copper histidine must be indicated.

  15. Antihyperglycaemic effect of 'Ilogen-Excel', an ayurvedic herbal formulation in streptozotocin-induced diabetes mellitus.

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    Umamaheswari, Selvaraj; Mainzen Prince, Ponnaian Stanely

    2007-01-01

    'Ilogen-Excel', an Ayurvedic herbal formulation is composed of eight medicinal plants (Curcuma longa, Strychnos potatorum, Salacia oblonga, Tinospora cordifolia, Vetivelia zizanioides, Coscinium fenestratum, Andrographis paniculata and Mimosa pudica). The present study evaluates the antihyperglycemic effect of 'Ilogen-Excel' in streptozotocin induced diabetic rats. Rats were rendered diabetic by streptozotocin (STZ) (45 mg/kg body weight). Oral administration of 'Ilogen-Excel' (50 mg/kg and 100 mg/kg) for 60 days resulted in significantly lowered levels of blood glucose and significantly increased levels of plasma insulin, hepatic glycogen and total hemoglobin. 'Ilogen-Excel' administration also decreased the levels of glycosylated hemoglobin, plasma thiobarbituric acid reactive substances, hydroperoxides, ceruloplasmin and vitamin E in diabetic rats. Plasma reduced glutathione and vitamin C were significantly elevated by oral administration of 'Ilogen-Excel'. Administration of insulin normalized all the biochemical parameters studied in diabetic rats. The effect at a dose of 100 mg/kg was more pronounced than 50 mg/kg and brought back all the parameters to near normal levels. Thus, our study shows the antihyperglycemic effects of 'Ilogen-Excel' in STZ-induced diabetic rats. Our study also shows that combined therapy is better than individual therapy.

  16. Nutrititional Status Assessment of International Space Station Crew Members

    Science.gov (United States)

    Smith, S. M.; Zwart, S. R.; Block, G.; Rice, B. I.; Davis-Street, J. F.

    2005-01-01

    Defining optimal nutrient requirements is imperative to ensure crew health on long-duration space exploration missions. To date, nutrient requirement data have been extremely limited because of small sample sizes and difficulties associated with collecting biological samples. In this study, we examined changes in body composition, bone metabolism, hematology, general blood chemistry, and blood levels of selected vitamins and minerals after long-duration (128-195 d) space flight aboard the International Space Station. Crew members consumed an average of 80% of the recommended energy intakes, and on landing day their body weight had decreased (P=0.051). After flight, hematocrit was less, and serum femtin was greater than before flight (PSerum iron, ferritin saturation, and transferrin had decreased after flight. The finding that other acute-phase proteins, including ceruloplasmin, retinol binding protein, transthyretin, and albumin were not changed after flight suggests that the changes in iron metabolism may not be strictly due to an inflammatory response. Urinary 8- hydroxy-2'-deoxyguanosine concentration was greater and superoxide dismutase was less after flight, indicating that oxidative damage had increased (Pserum 25-hydroxyvitamin D was significantly decreased after flight (Pserum concentration of bone-specific alkaline phosphatase, was elevated only in crew members who landed in Russia, probably because of the longer time lapse between landing and sample collection. These data provide evidence that bone loss, compromised vitamin D status, and oxidative damage remain critical concerns for long-duration space flight.

  17. [Metabolic therapy and pulmonary disfunction in patients with obstetric sepsis].

    Science.gov (United States)

    Iakovlev, A Iu; Zaĭtsev, P M; Zubeev, P S; Mokrov, K B; Balandina, A V; Gushchina, N N; Kucherenko, V E

    2011-01-01

    The role of reamberin, a succinate-containing infusion preparation in correlation of pulmonary metabolic and respiratory disturbances in patients with obstetric puerperal sepsis was estimated. The prospective randomized study enrolled 43 patients with puerperal obstetric sepsis complicated by polyorganic deficiency (SOFA 8-10). Nineteen patients of the 1st group and 24 patients of the 2nd group were additionally treated with reamberin in a dose of 800 ml/day for 8 days. The venous and arterial difference by glucose, lactate, pyruvate, diene conjugates, malondialdehyde and ceruloplasmin was investigated. The blood gases were determined with the Ciba Corning 45 apparatus. Lower metabolic activity of the lungs with prevalence of the glucose anaerobic metabolism and lower activity of the intrapulmonary antioxidant protection were observed in the patients with obstetric sepsis. The use of reamberin in the complex therapy of obstetric sepsis promoted maintenance of the initial balance and anaeroibic and aerobic pulmonary metabolism, thus providing shorter terms of the decompensation and recovery of the lungs respiratory function. PMID:21913408

  18. Quantification of horse plasma proteins altered by xylazine using the fluorogenic derivatization-liquid chromatography-tandem mass spectrometry

    Science.gov (United States)

    MORI, Miwako; ICHIBANGASE, Tomoko; YAMASHITA, Shozo; KIJIMA-SUDA, Isao; KAWAHARA, Masahiro; IMAI, Kazuhiro

    2016-01-01

    ABSTRACT In the doping tests currently used in horse racing, prohibited substances or their metabolites are usually directly detected in urine or blood samples. However, despite their lasting pharmaceutical effects, some prohibited substances are rapidly eliminated from horse urine and blood, making them difficult to detect. Therefore, new indirect biomarkers for doping, such as plasma proteins that are increased by the prohibited substances, have recently attracted much attention. Here, a fluorogenic derivatization-liquid chromatography-tandem mass spectrometry (FD-LC-MS/MS) method was adopted for horse plasma proteomics analysis, in order to identify plasma proteins whose concentrations were altered in response to xylazine in Thoroughbred horses. Xylazine, which is rapidly absorbed and eliminated and has possibility of the change in the levels of plasma proteins, was selected as a model drug. Of the ten plasma proteins identified, four proteins, including three acute phase proteins (haptoglobin, ceruloplasmin, and α-2-macroglobulin-like), were significantly increased after xylazine administration. Therefore, our present approach might be useful in identifying indirect biomarkers of drug administration. PMID:26858580

  19. Effects of Pregnancy and Lactation on Iron Metabolism in Rats

    Directory of Open Access Journals (Sweden)

    Guofen Gao

    2015-01-01

    Full Text Available In female, inadequate iron supply is a highly prevalent problem that often leads to iron-deficiency anemia. This study aimed to understand the effects of pregnancy and lactation on iron metabolism. Rats with different days of gestation and lactation were used to determine the variations in iron stores and serum iron level and the changes in expression of iron metabolism-related proteins, including ferritin, ferroportin 1 (FPN1, ceruloplasmin (Cp, divalent metal transporter 1 (DMT1, transferrin receptor 1 (TfR1, and the major iron-regulatory molecule—hepcidin. We found that iron stores decline dramatically at late-pregnancy period, and the low iron store status persists throughout the lactation period. The significantly increased FPN1 level in small intestine facilitates digestive iron absorption, which maintains the serum iron concentration at a near-normal level to meet the increase of iron requirements. Moreover, a significant decrease of hepcidin expression is observed during late-pregnancy and early-lactation stages, suggesting the important regulatory role that hepcidin plays in iron metabolism during pregnancy and lactation. These results are fundamental to the understanding of iron homeostasis during pregnancy and lactation and may provide experimental bases for future studies to identify key molecules expressed during these special periods that regulate the expression of hepcidin, to eventually improve the iron-deficiency status.

  20. Development of technology for biological dosimetry

    Energy Technology Data Exchange (ETDEWEB)

    Kim, In Gyu; Kim, Kug Chan; Lee, Kang Sik; Kim, Jin Kyu; Chun, Ki Jung; Shim, Hye Won; Park, Seon Young

    1997-07-01

    Adult male rats were treated a single, whole body exposure to a dose of 0.1, 0.5, 1, 2, 3, 5, 7 and 9 Gy. The animal were sacrificed 6, 24, 48, 72, 96 and 212 hours following exposure. Enzyme activity changes such as alkaline phosphatase, GOT, creating kinase, MDH and LDH in rat serum as biochemical indicators useful for evaluating radiation exposure were measured. An competitive enzyme linked immunosorbent assay (ELISA) has been developed to measure acute phase reactants (APRs) in rat serum after gamma-irradiation. Rat alpha-2 macroglobulin, alpha-1 acid glycoprotein, haptoglobin, ceruloplasmin, C-reactive protein and alpha-1 antitrypsin were purified from the plasma of turpentine treated rats. In vitro somatic mutation induced by gamma-irradiation and pentachlorophenol (PCP) which is representative of chemical pollutant was measured at the hypoxanthine-guanine phosphorybosyl transferase (HPRT) locus in human T-lymphocytes by a cell cloning assay. Mutant cells were selected by their ability to form a clone in the presence of purine analogue 6-thioguanine. Reverse transcriptase/polymerase chain reaction technique was needed for the mutation spectrum to discriminate combined exposure to radiation and chemicals. (author). 98 refs., 7 tabs., 47 figs.

  1. Wilson disease with thrombocytopenia (case report).

    Science.gov (United States)

    Zhvania, M; Gogberashvili, K; Gagoshidze, M; Uberi, E

    2014-12-01

    We present an adolescent patient with WD accompanied with secondary amenorrhea, and thrombocytopenia. NK, a 14 year-old girl, had amenorrhea for 5 months despite having had regular menses for 2 years. An abdominal ultrasound scan revealed ascitis and some ovarian cysts. On physical examination: slight jaundice, edema of lower extremities, skin purpuric rash, enlarged abdomen, dry skin. She had no hepatomegaly and no splenomegaly. Breast and pubic hair development was concomitant with Tanner stage 4. There was performed laboratory and instrumental investigations. The patient was diagnosed as WD owing to the low level of ceruloplasmin, with increased level of copper in 24-hour urine excretion and in dry liver tissue. The needle biopsy of liver showed severe hepatocellular necrosis, inflammatory changes and fibrosis. The platelet count was found to be low with lack of increased number of megakaryocytes in the bone marrow aspiration suggesting the thrombocytopenia was not exclusively owing to hypersplenism. The absence of antithrombocyte and other autoimmune and viral antibodies excluded respectively the diagnosis of autoimmune thrombocytopenia, other autoimmune diseases and viral infections. Thus, we support the recommendation that adolescents with amenorrhea or children with thrombocytopenia without any obvious cause should be evaluated for WD, because the early detection and treatment of WD is capable of reversing described changes and restoring a normal liver function. PMID:25617103

  2. Urine proteomic profiling of uranium nephrotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Malard, V.; Gaillard, J.C.; Sage, N. [CEA, DSV, IBEB, SBTN, Laboratoire de Biochimie des Systemes Perturbes (LBSP), Bagnols-sur-Ceze, F-30207 (France); Berenguer, F. [CEA, DSV, IBEB, SBTN, Laboratoire d' Etude des Proteines Cibles (LEPC), Bagnols-sur-Ceze, F-30207 (France); Quemeneur, E. [CEA, DSV, IBEB, SBTN, Bagnols-sur-Ceze, F-30207 (France)

    2009-07-01

    Uranium is used in many chemical forms in civilian and military industries and is a known nephro-toxicant. A key issue in monitoring occupational exposure is to be able to evaluate the potential damage to the body, particularly the kidney. In this study we used innovative proteomic techniques to analyse urinary protein modulation associated with acute uranium exposure in rats. Given that the rat urinary proteome has rarely been studied, we first identified 102 different proteins in normal urine, expanding the current proteome data set for this central animal in toxicology. Rats were exposed intravenously to uranyl nitrate at 2.5 and 5 mg/kg and samples were collected 24 h later. Using two complementary proteomic methods, a classic 2-DE approach and semi-quantitative SDS-PAGE-LC-MS/MS, 14 modulated proteins (7 with increased levels and 7 with decreased levels) were identified in urine after uranium exposure. Modulation of three of them was confirmed by western blot. Some of the modulated proteins corresponded to proteins already described in case of nephrotoxicity, and indicated a loss of glomerular permeability (albumin, alpha-1-anti-proteinase, sero-transferrin). Others revealed tubular damage, such as EGF and vitamin D-binding protein. A third category included proteins never described in urine as being associated with metal stress, such as ceruloplasmin. Urinary proteomics is thus a valuable tool to profile uranium toxicity non-invasively and could be very useful in follow-up in case of accidental exposure to uranium. (authors)

  3. Oxidant stress, antioxidants and nitric oxide in traffic police of Hyderabad, India.

    Science.gov (United States)

    Suresh, Y; Sailaja Devi, M M; Manjari, V; Das, U N

    2000-08-01

    Exposure to environmental pollutants is known to be harmful to health, in general, and to lungs in particular. In this respect, traffic police are at particular risk due to the nature of their job, since they are exposed to emissions from the vehicles. Here, we show that in the traffic police of Hyderabad city, India, the plasma levels of lipid peroxides are high, whereas the concentrations of the nitric oxide are low. In addition, the levels of various antioxidants in the RBC lysate such as catalase, superoxide dismutase and glutathione peroxidase were found to be low with no significant alteration in plasma ceruloplasmin levels. These results suggest that exposure to air pollutants, a major portion of which is due to emissions from the vehicles, can increase oxidant stress, decrease the levels of antioxidants and nitric oxide. This imbalance in the oxidant/antioxidant system may lead to lung damage and is likely to cause respiratory problems in individuals exposed to air pollution. PMID:15092903

  4. Biological research for the radiation protection

    International Nuclear Information System (INIS)

    The work scope of 'Biological Research for the Radiation Protection' had contained the research about polyamine effect on cell death triggered ionizing radiation, H2O2 and toxic agents. In this paper, to elucidate the role of polyamines as mediator in lysosomal damage and stress(H2O2)- induced apoptosis, we utilized α-DiFluoroMethylOrnithine (DFMO), which inhibited ornithine decarboxylase and depleted intracellular putrescine, and investigated the effects of polyamine on the apoptosis caused by H2O2, ionizing radiation and paraquat. We also showed that MGBG, inhibitor of polyamine biosynthesis, treatment affected intracellular redox steady states, intracellular ROS levels and protein oxidation. Thereafter we also investigated whether MGBG may enhance the cytotoxic efficacy of tumor cells caused by ionizing radiation or H2O2 because such compounds are able to potentiate the cell-killing effects. In addition, ceruloplasmin and thioredoxin, possible antioxidant proteins, were shown to have protective effect on radiation- or H2O2(or chemicals)-induced macromolecular damage or cell death

  5. Proteomic analysis of urinary exosomes from patients of early IgA nephropathy and thin basement membrane nephropathy.

    Science.gov (United States)

    Moon, Pyong-Gon; Lee, Jeong-Eun; You, Sungyong; Kim, Taek-Kyun; Cho, Ji-Hoon; Kim, In-San; Kwon, Tae-Hwan; Kim, Chan-Duck; Park, Sun-Hee; Hwang, Daehee; Kim, Yong-Lim; Baek, Moon-Chang

    2011-06-01

    To identify biomarker candidates associated with early IgA nephropathy (IgAN) and thin basement membrane nephropathy (TBMN), the most common causes presenting isolated hematuria in childhood, a proteomic approach of urinary exosomes from early IgAN and TBMN patients was introduced. The proteomic results from the patients were compared with a normal group to understand the pathophysiological processes associated with these diseases at the protein level. The urinary exosomes, which reflect pathophysiological processes, collected from three groups of young adults (early IgAN, TBMN, and normal) were trypsin-digested using a gel-assisted protocol, and quantified by label-free LC-MS/MS, using an MS(E) mode. A total of 1877 urinary exosome proteins, including cytoplasmic, membrane, and vesicle trafficking proteins, were identified. Among the differentially expressed proteins, four proteins (aminopeptidase N, vasorin precursor, α-1-antitrypsin, and ceruloplasmin) were selected as biomarker candidates to differentiate early IgAN from TBMN. We confirmed the protein levels of the four biomarker candidates by semi-quantitative immunoblot analysis in urinary exosomes independently prepared from other patients, including older adult groups. Further clinical studies are needed to investigate the diagnostic and prognostic value of these urinary markers for early IgAN and TBMN. Taken together, this study showed the possibility of identifying biomarker candidates for human urinary diseases using urinary exosomes and might help to understand the pathophysiology of early IgAN and TBMN at the protein level.

  6. Evaluation of possible health risk associated with occupational exposure to formaldehyde

    Science.gov (United States)

    Vargova, Maria; Janota, Stanislav; Karelova, Jarmila; Barancokova, Maria; Sulcova, Margita

    1993-03-01

    Widespread us of formaldehyde in a variety of applications is known to result in appreciable exposure of workers and large segments of the general population. Because of possible genotoxic and immunotoxic effects, we investigated the health condition of people occupationally exposed to formaldehyde in a plant in which woodsplinter materials are manufactured. The concentration of formaldehyde in the workplace was greater than the average and peak concentrations of formaldehyde in Czechoslovakia (0.5 mg/m3 and 1 mg/m3 respectively). Selected parameters of genotoxicity (cytogenetic analysis, nucleolus test) and immunotoxocity (serum immunoglobulin G, A, M; complement C3, C4; alpha-1-anti-trypsine, alpha-2 macroglobulin, ceruloplasmin, transferrin, prealbumin, orosomucoid levels) were determined. The results of the evaluation of mitotic indices and the blastogen transformation point to an effect of the exposure to formaldehyde on r-RNA synthesis inhibition and lymphocyte maturation decrease. The frequency of aberrant cells in the peripheral blood lymphocytes was increased in both, exposed and control group and was above 1.2 - 2% of aberrant cells observed in the normal population in Czechoslovakia. There was no significant differences in the values of natural immunity and specific humoral immunity. Significant differences were observed in the values of mitogen-induced proliferation of lymphocytes between the exposed and the matching and background control groups. These changes are considered to be sensitive indicators of the potential effects on the integrity of a more important immunologic function.

  7. Anti-inflammatory activity of copper-protein complexes with reference to rheumatoid arthritis

    International Nuclear Information System (INIS)

    Work was carried out on the serum of 100 healthy subjects and hundred Rheumatoid Arthritus patients by electrophoresis and atomic absorption model Hitachi-180-80. The different proteins fractions separated by electrophoresis were subjected for estimation of Cu-Concentration. It was found that only 5% copper is present in albumin which remains constant in normal and Rheumatoid Arthritus patients. The other important group of proteins were a2-globulins, in which Cu concentration was found high in Rheumatoid Arthritus patients as compared to normal subject. There was no copper detected in beta and gamma globulins. The study can be used for diagnostic purposes. Copper complexes of alpha 2-Globulins were found anti inflammatory in nature and this quality of self defense can bring revolution in the history of all infectious diseases including Rheumatoid Arthritus simply by separating the copper complexes of alpha 2-globulins (most probably ceruloplasmin) from the blood of donors and injecting into the body of patients. It is possible by this method that the disease-Rheumatoid Arthritus may be eradicated completely. These complexes have also shown antibiotic activity in gynae patients. (author)

  8. [The effect of dietotherapy on the clinico-immunological indices of rheumatoid arthritis patients].

    Science.gov (United States)

    Sharafetdinov, Kh Kh; Denisov, L N; Samsonov, G R; Pokrovskaia, G R; Voĭtko, N E

    1990-01-01

    The main requirements for the dietotherapy of rheumatoid arthritis (RA) patients have been formulated, and for the first time a pathogenetically balanced diet has been developed that produces antiinflammatory and immunocorrective effects. The effectiveness of the dietotherapy included into the combined treatment was studied in 41 patients with classic and proved RA. The authors have studied the influence of the dietotherapy on the clinical signs characterizing the activity of inflammation in the joints, and laboratory immunological parameters (IgG, IgM, IgA, IgD, the complement components: C1-inhibitor, C3, C4, C5, C9; haptoglobin, orrhozomucoid, transferrin, ceruloplasmin, alpha 1-antitrypsin, alpha 2-macroglobulin, prealbumin). The results of the study have shown that the dietotherapy is not only conducive to the improvement of the clinical picture of the disease, that permits diminishing the amount of nonsteroid antiinflammatory drugs used, but also produces a favourable effect on the RA patients' immunological state. It has been concluded that inclusion of the dietotherapy into the combined treatment of RA patients is advisable. PMID:2346005

  9. Transient changes of enzyme activities and expression of stress proteins in the small intestine of piglets after weaning.

    Science.gov (United States)

    Tao, Xin; Xu, Ziwei; Men, Xiaoming

    2015-01-01

    To determine the transient effects of weaning on the small intestine, 16 piglets were slaughtered at days 0, 1, 4 and 7 after weaning. Jejunal samples were collected to examine different enzyme activities and mRNA expressions of two stress protein families, namely, heat-shock proteins (HSP) and trefoil factors (TFF). Results showed that the activities of ceruloplasmin, alkaline phosphatase and lactate dehydrogenase, were significantly changed at Day 1 and/or Day 4. The mRNA expressions of HSP10, HSP60 and HSP90 showed a pattern of increased expression with time after weaning. Expression significantly differed between Day 0 and Day 7 after weaning. The mRNA expression of HSP70 was significantly increased on Day 1 only. Similarly, the mRNA expressions of TFF1 and TFF2 were significantly increased on Day 7 compared with those on Day 0. Expression of TFF3 was not affected by time after weaning. In conclusion, the present study indicated that weaning induced transient injury to small intestinal morphology and function. Particularly it changed enzyme activities and gene expression of stress proteins in the small intestine of piglets. At first time, a change in the gene expression of HSP10 and a gene overexpression of TFF1 in the small intestine of piglets after weaning was found.

  10. Methanolic extract of Ruta graveolens L. inhibits inflammation and oxidative stress in adjuvant induced model of arthritis in rats.

    Science.gov (United States)

    Ratheesh, M; Shyni, G L; Helen, A

    2009-04-01

    Ruta graveolens L. (Rutaceae) are traditionally used for the treatment of rheumatism, arthritis and other inflammatory conditions in the traditional medicine of India. The purpose of this study was to investigate anti-inflammatory and anti-oxidant effects of methanolic extract of Ruta graveolens L. in adjuvant induced arthritis in rats. Methanolic extract of Ruta graveolens (MER) exhibited maximum percentage of oedema inhibition at a dose of 20 mg/kg on 21st day of adjuvant arthritis. The effect was higher than that of standard drug indomethacin. The activities of cycloxygenase-2 and myeloperoxidase and concentration of thiobarbituric acid reactive substance (TBARS) were decreased and the activities of antioxidant enzymes, vitamins C & E and reduced glutathione level were increased on treatment with MER. The increment in ESR and total WBC, reduction in RBC count and haemoglobin and aberrant changes to the C-reactive protein (CRP) and ceruloplasmin levels observed in the arthritic animals were also found to be significantly restored in MER treated rats. Histopathology of paw tissue showed decreased oedema formation and cellular infiltration on supplementation with MER. Thus the results demonstrated the potential beneficiary effect of methanolic extract of Ruta graveolens on adjuvant induced arthritis in rats.

  11. Protective effects of isolated polyphenolic and alkaloid fractions of Ruta graveolens L. on acute and chronic models of inflammation.

    Science.gov (United States)

    Ratheesh, M; Shyni, G L; Sindhu, G; Helen, A

    2010-02-01

    Ruta graveolens L. (Rutaceae) are traditionally used for the treatment of rheumatism, arthritis and other inflammatory conditions in the traditional medicine of India, were evaluated for their protective effect in acute and chronic models of inflammation. Carrageenan induced rat paw edema and adjuvant induced arthritis were employed as the experimental models of acute and chronic inflammation respectively. Isolated polyphenolic and alkaloid fraction (AFR) from Ruta graveolens and evaluated its anti inflammatory activity in carrageenan induced acute model. AFR with a dose 10 mg/kg showed higher anti inflammatory effect than polyphenols and standard drug diclofenec. AFR significantly decreased the paw edema in arthritic rats. TBARS, COX-2, 5-LOX and MPO level were decreased and the levels of antioxidant enzymes and GSH level were increased on treatment with AFR. The increment in CRP level and ceruloplasmin level observed in arthritic animals were also found to be significantly restored in AFR treated rats. The results demonstrated the potential beneficiary effect of isolated polyphenolic and alkaloid fraction of Ruta graveolens L. on acute and chronic models of inflammation in rats.

  12. Assessment of the possible role of iron and copper in cisplatin-induced nephrotoxicity in the rat.

    Science.gov (United States)

    Goudie, J; Chandra, M; Lawrence, G D; Williams, P

    1994-01-01

    Nephrotoxic lesions induced by cisplatin in rats are characterized by acute tubular necrosis in the outer stripe of the medulla. The purpose of this study was to examine the potential role of changes in metal binding proteins, and iron and copper content in urine and renal tissue in cisplatin-induced nephrotoxicity. Cisplatin was administered intravenously to groups of 20 rats at single doses of 0, 1, 2.5, and 5 mg/kg and rats were sacrificed at 1, 2, 3 and 6 days after treatment. Increased serum BUN and creatinine were observed at a dose of 5 mg/kg cisplatin on day 2 through day 6. Increased urinary copper excretion coincided with necrosis and increased BUN and creatinine on day 3 in the high-dose group. Evidence of renal injury was apparent histologically as karyomegaly at all dose levels as early as 48 hours after injection of cisplatin, prior to increases in urinary copper levels. No change in the distribution of metal binding proteins (transferrin, ferritin, ceruloplasmin, and metallothionein) evaluated by immunohistochemical staining, was seen. Based upon these results, it is unlikely that changes in metal excretion play a primary role in cisplatin-induced nephrotoxicity however, changes in nuclear function indicated by karyomegaly may be involved in early renal injury.

  13. [Treatable dementia syndromes].

    Science.gov (United States)

    Biedert, S; Schreiter, U; Alm, B

    1987-03-01

    Dementia--a syndrome of acquired intellectual deterioration--is an etiologically non-specific condition which is permanent, progressive, or reversible. In the evaluation of demented patients, a careful exposure history will determine the possible role of drugs, metals, or toxins. The physical examination may reveal focal deficits in cases of intracranial mass lesions and spasticity or ataxia of the lower limbs if hydrocephalus is present. Coexistance of dementia and peripheral neuropathy usually indicates a toxic or metabolic disorder. Asterixis, myoclonus, and postural tremor are common in toxic-metabolic dementias, while resting tremor, choreoathetosis, and rigidity occur in progressive extrapyramidal disorders. EEG is focally abnormal in cases of cerebral mass lesions and exhibits generalized slowing in toxic-metabolic encephalopathies. CT will aid in the identification of hydrocephalus, subdural hematomas, and intracranial mass lesions. A thorough laboratory evaluation including complete blood count, erythrocyte sedimentation rate, electrolytes, blood urea nitrogen and blood sugar, liver and thyroid tests, calcium and phosphorus levels, B12 and folate levels, serum copper and ceruloplasmin, VDRL, chest X-ray, electrocardiogram, and lumbar puncture may demonstrate treatable disorders that are adversely affecting intellectual function. Elderly individuals are particularly susceptible to the effects of toxic or metabolic disorders, and a mild dementia might be exaggerated by relatively minor fluctuations in metabolic status. Treatable causes of dementia should be considered in all demented patients.

  14. Effect of pumpkin-seed oil on the level of free radical scavengers induced during adjuvant-arthritis in rats.

    Science.gov (United States)

    Fahim, A T; Abd-el Fattah, A A; Agha, A M; Gad, M Z

    1995-01-01

    Pumpkin-seed oil (PSO), a natural supplement rich with antioxidant ingredients, was given to rats in which arthritis was induced using Freund's complete adjuvant. Its effect was compared with that of indomethacin, as a classical anti-inflammatory agent. Two experimental patterns were studied, an acute phase that was applied only with PSO and a chronic phase applied for both PSO and indomethacin. Compared to normal untreated rats, it was shown that the induction of arthritis caused a decrease in serum sulphhydryl groups, with an increase in serum ceruloplasmin in both phases. Blood glutathione was first elevated in the acute phase, then its level was reduced in the chronic phase. Serum N-acetyl-beta-D-glucosaminidase activity was elevated only at the acute phase, while plasma total proteins and albumin were reduced at the chronic phase. Liver glucose-6-phosphate dehydrogenase activity was markedly increased, while no changes were observed in the levels of liver lipid peroxides and glutathione. These changes in the studied parameters were attributed to the superoxides and free radicals during arthritic inflammation. Administration of PSO succeeded in modulating most of the altered parameters affected during arthritis, especially at the chronic phase. Also, a remarkable inhibition of paw oedema was observed. A similar pattern was obtained upon treatment with indomethacin except that indomethacin markedly elevated liver lipid peroxides levels. Concurrent administration of PSO with indomethacin caused no changes in the parameters studied compared to that induced by treatment with indomethacin alone. PMID:7784309

  15. Tetrathiomolybdate therapy protects against bleomycin-induced pulmonary fibrosis in mice.

    Science.gov (United States)

    Brewer, George J; Ullenbruch, Matthew R; Dick, Robert; Olivarez, Leovigildo; Phan, Sem H

    2003-03-01

    Tetrathiomolybdate (TM), a drug developed for the treatment of Wilson's disease, produces an antiangiogenic effect by reducing systemic copper levels. Several angiogenic cytokines appear to depend on normal levels of copper for activity. In both animal tumor models and in cancer patients, TM therapy has proved effective in inhibiting the growth of tumors. We have hypothesized that the activities of fibrotic and inflammatory cytokines are also subject to modulation by the availability of copper in a manner similar to angiogenic cytokines. As a first step in evaluating whether TM plays a therapeutic role in diseases of inflammation and fibrosis, we studied the effects of TM on a murine model of bleomycin-induced pulmonary fibrosis. Oral TM therapy resulted in dose-dependent reduction in serum ceruloplasmin, a surrogate marker of systemic copper levels. Significant decreases in systemic copper levels were associated with marked reduction in lung fibrosis as determined on the basis of histopathologic findings and a biochemical measure of fibrosis. The protection afforded by TM was also reflected in significantly reduced bleomycin-induced body-weight loss. In the next phase of this work, we will seek to determine the mechanisms by which TM brings about this therapeutic benefit.

  16. Aceruloplasminemia With Psychomotor Excitement and Neurological Sign Was Improved by Minocycline (Case Report).

    Science.gov (United States)

    Hayashida, Maiko; Hashioka, Sadayuki; Miki, Hiroyuki; Nagahama, Michiharu; Wake, Rei; Miyaoka, Tsuyoshi; Horiguchi, Jun

    2016-05-01

    Aceruloplasminemia is an autosomal recessive disorder of iron metabolism caused by mutations in the ceruloplasmin gene. Its prevalence is 1 in 2,000,000 people in Japan. This is a disorder of neurodegeneration with iron accumulation in the brain revealed by MRI. The iron overload induces oxidative stress and generation of reactive oxygen species, which triggers a cascade of pathological events that lead to neuronal death. Intravenous administration of an iron chelator, deferoxamine has been proposed as a method of inhibiting the accumulation of iron.The patient was a 46-year-old Japanese woman. She was diagnosed at the age of 33 years. Deferoxamine was administrated for 6 months but was discontinued due to adverse effects. On admission at the age of 46, psychomotor excitement was acute in onset. The extrapyramidal symptoms reflected iron deposition in the basal ganglia and substantia nigra in the midbrain. Ataxia and a wide-based gate reflected iron deposition in the dentate nuclei of the cerebellum. An antibiotic, minocycline at 150 mg/day successfully ameliorated the clinical symptoms.Minocycline, a second generation tetracycline, has a direct radical scavenging property due to its chemical structure. It has been reported that minocycline is similar to deferoxamine in its ability to chelate iron. Minocycline is also involved in preventing the upregulation of proinflammatory cytokines. The iron-chelating, antioxidant, and anti-inflammatory effects of minocycline were involved in this case. PMID:27175663

  17. Minocycline Attenuates Iron-Induced Brain Injury.

    Science.gov (United States)

    Zhao, Fan; Xi, Guohua; Liu, Wenqaun; Keep, Richard F; Hua, Ya

    2016-01-01

    Iron plays an important role in brain injury after intracerebral hemorrhage (ICH). Our previous study found minocycline reduces iron overload after ICH. The present study examined the effects of minocycline on the subacute brain injury induced by iron. Rats had an intracaudate injection of 50 μl of saline, iron, or iron + minocycline. All the animals were euthanized at day 3. Rat brains were used for immunohistochemistry (n = 5-6 per each group) and Western blotting assay (n = 4). Brain swelling, blood-brain barrier (BBB) disruption, and iron-handling proteins were measured. We found that intracerebral injection of iron resulted in brain swelling, BBB disruption, and brain iron-handling protein upregulation (p < 0.05). The co-injection of minocycline with iron significantly reduced iron-induced brain swelling (n = 5, p < 0.01). Albumin, a marker of BBB disruption, was measured by Western blot analysis. Minocycline significantly decreased albumin protein levels in the ipsilateral basal ganglia (p < 0.01). Iron-handling protein levels in the brain, including ceruloplasmin and transferrin, were reduced in the minocycline co-injected animals. In conclusion, the present study suggests that minocycline attenuates brain swelling and BBB disruption via an iron-chelation mechanism. PMID:26463975

  18. P wave dispersion is prolonged in patients with Wilson's disease

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    AIM: To investigate the P wave dispersion as a noninvasive marker of intra-atrial conduction disturbances in patients with Wilson's disease. METHODS: We compared Wilson's disease patients (n=18) with age matched healthy subjects (n=15) as controls. The diagnosis was based on clinical symptoms, laboratory tests (ceruloplasmin, urinary and hepatic copper concentrations). P wave dispersion, a measurement of the heterogeneity of atrial depolarization, was measured as the difference between the duration of the longest and the shortest P-waves in 12 lead electrocardiography. RESULTS: All the patients were asymptomatic on cardiological examination and have sinusal rhythm in electrocardiography. Left ventricular and left atrial diameters, left ventricular ejection fraction and left ventricular mass index were similar in both groups. The Wilson's disease patients had a significantly higher P wave dispersion compared with the controls (44.7+5.8vs 25.7±2.5,P<0.01=. CONCLUSION: There was an increase in P wave dispersion in cardiologically asymptomatic Wilson's disease patients which probably represents an early stage of cardiac involvement.

  19. Postmortem Menkes diagnosis from carrier testing of female relatives.

    Science.gov (United States)

    Tønnesen, T; Silengo, M; Gerdes, A M; Hansen, J C; Reske-Nielsen, E; Franceschini, P; Horn, N

    1987-12-01

    A boy who died at 6 months of age was noted to have sparse, stubby and light hair, pili torti were observed microscopically, and his skin was dry and redundant. As a suspicion of Menkes disease was first raised after his death, serum copper and ceruloplasmin in serum were not measured. Unfortunately, no fibroblasts were available - only fixed and paraffin-embedded samples of brain, spleen and liver. The copper contents of the brain and the liver were lower than in an age-matched control. Fibroblast cultures from the mother, the maternal grandmother, and a maternal aunt of the index patient were analysed for 64Cu-uptake. All these females showed the uptake values expected for Menkes carriers, thus supporting the clinical suspicion of Menkes disease in the index patient. From the above-mentioned results it was highly likely that the index patient had suffered from Menkes disease. Adequate genetic counseling could thus be offered to the family, and in the next pregnancy a first trimester prenatal diagnosis was performed. PMID:3436089

  20. Liver transplantation for hepatic and neurological Wilson's disease.

    Science.gov (United States)

    Geissler, I; Heinemann, K; Rohm, S; Hauss, J; Lamesch, P

    2003-06-01

    Wilson's disease (WD) is an autosomal-recessive inherited disorder of copper metabolism characterized by excessive deposition of copper throughout the body. If medical treatment fails in cases of fulminant hepatic failure and progressive hepatic dysfunction due to advanced cirrhosis, liver transplantation (OLTx) has been demonstrated to be a valuable treatment option. Between December 1993 and December 2002, 225 OLTxs in 198 patients were performed in our institution. In this consecutive series six patients (three females and three males) were liver grafted for WD. The follow-up ranged from 3 to 7 years. All patients are alive with well-functioning grafts at present. The ceruloplasmin levels increased after transplantation and remained normal. The Kayser-Fleischer ring disappeared in all patients, and urinary copper excretion normalized. The neurological manifestations in the two patients with severe neurological symptoms showed after 2 to 5 years a downward tendency; in one the ataxic movements disappeared completely. The psychiatric disorder in one patient disappeared as well the mild neurological symptoms in the patient with CHILD A cirrhosis. These two patients are fully recovered and returned to work. OLTx should be considered as a treatment option in patients with severe progressive neurological deficits even in cases with stable liver function since liver grafting definitely cures the underlying biochemical defect. In such cases an early decision for liver transplantation is justified because neurological deficits may become irreversible.

  1. Quercetin Affects Erythropoiesis and Heart Mitochondrial Function in Mice

    Directory of Open Access Journals (Sweden)

    Lina M. Ruiz

    2015-01-01

    Full Text Available Quercetin, a dietary flavonoid used as a food supplement, showed powerful antioxidant effects in different cellular models. However, recent in vitro and in vivo studies in mammals have suggested a prooxidant effect of quercetin and described an interaction with mitochondria causing an increase in O2∙- production, a decrease in ATP levels, and impairment of respiratory chain in liver tissue. Therefore, because of its dual actions, we studied the effect of quercetin in vivo to analyze heart mitochondrial function and erythropoiesis. Mice were injected with 50 mg/kg of quercetin for 15 days. Treatment with quercetin decreased body weight, serum insulin, and ceruloplasmin levels as compared with untreated mice. Along with an impaired antioxidant capacity in plasma, quercetin-treated mice showed a significant delay on erythropoiesis progression. Heart mitochondrial function was also impaired displaying more protein oxidation and less activity for IV, respectively, than no-treated mice. In addition, a significant reduction in the protein expression levels of Mitofusin 2 and Voltage-Dependent Anion Carrier was observed. All these results suggest that quercetin affects erythropoiesis and mitochondrial function and then its potential use as a dietary supplement should be reexamined.

  2. Enzimas no testículo de ratos em algumas condições experimentais

    Directory of Open Access Journals (Sweden)

    Helion Póvoa Junior

    1980-01-01

    Full Text Available Dosou-se a atividade da GOT, GPT e ceruloplasmina no testículo de ratos normais (a atividade testicular destas enzimas é relativamente baixa e injetados com cloreto de cádmio ( que lesa o testículo, assim como em animais com este órgão lesado e que se administrou testosterona, estradiol, progesterona e gonadotrofina coriônica. Pudemos observar alterações significativas das enzimas por ação destes diferentes hormônios. Infelizmente, como pouco se sabe sobre a função destas enzimas neste órgão, torna-se difícil interpretar os nossos achados.GOT, GPT and ceruloplasmin activities have been determined in testicle of normal rats. Low activities were found for every enzyme. In animals injected with cadmium chloride, there were significant alterations in enzyme activities. Accentuated alterations in enzyme activities were also found in animals with destroyed testicles after injection of several hormones (testosterone, estradiol, progesterone and chorionic gonadotrophin.

  3. Antioxidative defense

    Directory of Open Access Journals (Sweden)

    Stevanović Jelka

    2011-01-01

    Full Text Available Free radicals occur constantly during metabolism and take part in numerous physiological processes, such as: intra-cellular and inter-cellular signalization, gene expression, removal of damaged or senescent cells, and control of the tone of blood vessels. However, there is an increased quantity of free radicals in situations of so-called oxidative stress, when they cause serious damage to cellular membranes (peroxidation of their lipids, damage of membrane proteins, and similar, to interior cellular protein molecules, as well as DNA molecules and carbohydrates. This is precisely why the organism has developed numerous mechanisms for removing free radicals and/or preventing their production. Some of these are enzyme-related and include superoxide-dismutase, catalase, glutathione-peroxidase, and others. Other, non-enzyme mechanisms, imply antioxidative activities of vitamins E and C, provitamin A, coenzyme Q, reduced glutation, and others. Since free radicals can leave the cell that has produced them and become dispersed throughout the body, in addition to antioxidative defense that functions within cellular structures, antioxidant extra-cellular defense has also been developed. This is comprised by: transferrin, lactoferrin, haptoglobin, hemopexin, ceruloplasmin, albumins, extra-cellular isoform SOD, extracellular glutathione-peroxidase, glucose, bilirubin, urates, and many other molecules.

  4. Environmental temperature and stocking density effects on acute phase proteins, heat shock protein 70, circulating corticosterone and performance in broiler chickens

    Science.gov (United States)

    Najafi, Pardis; Zulkifli, Idrus; Amat Jajuli, Nurfarahin; Farjam, Abdoreza Soleimani; Ramiah, Suriya Kumari; Amir, Anna Aryani; O'Reily, Emily; Eckersall, David

    2015-11-01

    An experiment was conducted to determine the effect of different stocking densities on serum corticosterone (CORT), ovotransferrin (OVT), α1-acid glycoprotein (AGP) and ceruloplasmin (CP) concentrations, brain heat shock protein (HSP) 70 expression and performance in broiler chickens exposed to unheated and heated conditions. Day-old chicks were stocked at 0.100 m2/bird (low density (LD)) or 0.063 m2/bird (high density (HD)), in battery cages and housed in environmentally controlled rooms. From 21 to 35 days of age, birds from each stocking density group were exposed to either 24 or 32 °C. Growth performance was recorded during the heat treatment period, and blood and brain samples were collected to determine CORT, OVT, AGP, CP and HSP 70 levels on day 35. Heat treatment but not stocking density was detrimental to growth performance. There were significant temperature × density interactions for CORT, CP and OVT on day 35. Although HD elevated CORT, CP and OVT when compared to LD, the effects of the former were more obvious under heated condition. Both temperature and density had significant effect on AGP and HSP 70. In conclusion, irrespective of temperature, high stocking density was physiologically stressful to broiler chickens, as indicated by CORT, AGP, CP, OVT and HSP 70, but not detrimental to growth performance and survivability. As it was shown in the present study, AGP, CP and OVT could be useful biomarkers to determine the effect of overcrowding and high temperature on the welfare of broiler chickens.

  5. Retinol-binding protein, acute phase reactants and Helicobacter pylori infection in patients with gastric adenocarcinoma

    Institute of Scientific and Technical Information of China (English)

    Nicolas Tsavaris; Christos Koufos; Athanasios Archimandritis; Christos Kosmas; Petros Kopterides; Dimitrios Tsikalakis; Hlias Skopelitis; Fotini Sakelaridi; Nikitas Papadoniou; Michalis Tzivras; Vasilios Balatsos

    2005-01-01

    AIM: To determine the serum levels of c-reactive protein (CRP), transferrin (TRF), a2-macroglobulin (A2M),ceruloplasmin (CER), a1-acid glycoprotein (AAG), prealbumin (P-ALB) and retinol-binding protein (RBP) in gastric carcinoma patients and to explore their possible correlation with underlying Helicobacter pylori (H pylon)infection.METHODS: We measured the serum levels of CRP, TRF,A2M, CER, AAG, P-ALB, and RBP in 153 preoperative patients (93 males; mean age: 63.1±11.3 years) with non-cardia gastric adenocarcinoma and 19 healthy subjects.RESULTS: The levels of CRP, CER, RBP, andAAG in cancer patients were significantly higher than those in healthy controls (P<0.0001), while no difference was found regarding the TRF, P-ALB, and A2M levels. Cancer patients with H pylori infection had significantly lower RBP values compared to non-infected ones (P<0.0001)and also higher values of CRP and AAG (P = 0.09 and P = 0.08, respectively).CONCLUSION: High serum levels of CRP, CER and AAG in cancer patients do not seem to be related to H pylori infection. Retinol-binding protein seems to discriminate between infected and non-infected patients with gastric carcinoma. Further studies are needed to explore if it is directly involved in the pathogenesis of the disease or is merely an epiphenomenon.

  6. Copper and Copper Proteins in Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Sergio Montes

    2014-01-01

    Full Text Available Copper is a transition metal that has been linked to pathological and beneficial effects in neurodegenerative diseases. In Parkinson’s disease, free copper is related to increased oxidative stress, alpha-synuclein oligomerization, and Lewy body formation. Decreased copper along with increased iron has been found in substantia nigra and caudate nucleus of Parkinson’s disease patients. Copper influences iron content in the brain through ferroxidase ceruloplasmin activity; therefore decreased protein-bound copper in brain may enhance iron accumulation and the associated oxidative stress. The function of other copper-binding proteins such as Cu/Zn-SOD and metallothioneins is also beneficial to prevent neurodegeneration. Copper may regulate neurotransmission since it is released after neuronal stimulus and the metal is able to modulate the function of NMDA and GABA A receptors. Some of the proteins involved in copper transport are the transporters CTR1, ATP7A, and ATP7B and the chaperone ATOX1. There is limited information about the role of those biomolecules in the pathophysiology of Parkinson’s disease; for instance, it is known that CTR1 is decreased in substantia nigra pars compacta in Parkinson’s disease and that a mutation in ATP7B could be associated with Parkinson’s disease. Regarding copper-related therapies, copper supplementation can represent a plausible alternative, while copper chelation may even aggravate the pathology.

  7. Effect of copper deficiency on plasma and adrenal catecholamines

    Energy Technology Data Exchange (ETDEWEB)

    Kennedy, B.W.; Bhathena, S.J.; Fields, M.; Voyles, N.R.; Timmers, K.I.; Recant, L.

    1986-03-01

    Copper (Cu) ion is an essential component of enzymes involved in catecholamine (CAT) metabolism. Copper deficiency (CuD) has been shown to affect the CAT content of brain (decreased norepinephrine (NE) and dopamine (DA)) and heart (increased DA and decreased NE). It is thus possible that plasma and adrenal CAT could be altered by CuD. The authors, then, investigated the effect of CuD on plasma and adrenal CAT in rats fed copper-deficient (0.6 ..mu..g Cu/g) or copper-supplemented (6.0 ..mu..g Cu/g) diets with either 62% starch (S) or fructose (F) as the carbohydrate source for 7 weeks after weaning. CuD was ascertained by decreased plasma Cu and ceruloplasmin activity. CuD increased the levels of all three CAT (NE, P < 0.001, epinephrine (E), P < 0.0001 and DA, P < 0.01) in plasma, but had no effect on adrenal CAT content. Dietary F had no significant effect on plasma CAT compared to S but did increase E in adrenal tissue (P < 0.001). They have previously demonstrated that CuD is accompanied by increased plasma glucose, triglyceride and cholesterol and decreased insulin. Thus, increased plasma CAT along with decreased plasma insulin may explain, in part, the glucose intolerance and abnormal lipid metabolism observed in CuD.

  8. Effects of Copper and/or Cholesterol Overload on Mitochondrial Function in a Rat Model of Incipient Neurodegeneration

    Directory of Open Access Journals (Sweden)

    Nathalie Arnal

    2013-01-01

    Full Text Available Copper (Cu and cholesterol (Cho are both associated with neurodegenerative illnesses in humans and animals models. We studied the effect in Wistar rats of oral supplementation with trace amounts of Cu (3 ppm and/or Cho (2% in drinking water for 2 months. Increased amounts of nonceruloplasmin-bound Cu were observed in plasma and brain hippocampus together with a higher concentration of ceruloplasmin in plasma, cortex, and hippocampus. Cu, Cho, and the combined treatment Cu + Cho were able to induce a higher Cho/phospholipid ratio in mitochondrial membranes with a simultaneous decrease in glutathione content. The concentration of cardiolipin decreased and that of peroxidation products, conjugated dienes and lipoperoxides, increased. Treatments including Cho produced rigidization in both the outer and inner mitochondrial membranes with a simultaneous increase in permeability. No significant increase in Cyt C leakage to the cytosol was observed except in the case of cortex from rats treated with Cu and Cho nor were there any significant changes in caspase-3 activity and the Bax/Bcl2 ratio. However, the Aβ(1–42/(1–40 ratio was higher in cortex and hippocampus. These findings suggest an incipient neurodegenerative process induced by Cu or Cho that might be potentiated by the association of the two supplements.

  9. Metrology for metalloproteins--where are we now, where are we heading?

    Science.gov (United States)

    Swart, Claudia

    2013-07-01

    The use of the amount of certain proteins in biological samples as markers for distinguishing between a healthy and a diseased state has become increasingly important in clinical diagnosis. As about 30% of all proteins contain metals in one form or another, either as a cofactor or covalently bound as part of the protein, some of these proteins are regularly analyzed in clinical laboratories. With the increasing number of measurements of those proteins performed all over the world, the necessity of obtaining reliable and comparable results is becoming a focal point for scientists and politicians. Directives such as the EC directive covering in vitro diagnostic medical devices (Directive 98/79/EC) and standards such as EN ISO 17511:2003 demand the traceability of the results obtained for analytes in samples of human origin. However, no reference measurement procedures with results traceable to the SI exist for many metalloproteins. In this article, the situation for a few important metalloproteins, such as hemoglobin, transferrin, superoxide dismutase, ceruloplasmin, and C-reactive protein, for which specific efforts have been made in recent years to achieve comparable and traceable results worldwide, is discussed. These proteins also serve as examples of the difficulties scientists face when they wish to quantify proteins and the pitfalls they should avoid to achieve reliable results.

  10. A boy with developmental delay, malformations, and evidence of a connective tissue disorder: possibly a new type of cutis laxa.

    Science.gov (United States)

    Armstrong, Linlea; Jimenez, Carmencita; Hunter, Alasdair G W

    2003-05-15

    We report a 7.5-year-old boy with loose translucent skin, aortic dilatation, hyperextensible veins, recurrent respiratory problems, pectus excavatum, arthralgias, lax joints, mild epiphyseal dysplasia, and umbilical and inguinal hernias. He also has developmental delay, progressive bilateral sensorineural hearing loss, an unusual facial appearance, terminal digit hypoplasia with unusual radiographic changes in some of the phalanges, glandular hypospadias, shawl scrotum, and undescended testes. Biochemical investigations, including electrophoresis of Types 1 and 3 procollagens and collagens, and quantification of serum copper and ceruloplasmin, are normal. Relative to age-matched control patients the electron micrographs of the boy's dermis show elastin fibers to be decreased in number, and abnormal in appearance, with a low matrix to microfibril ratio. The organ distribution of abnormalities and the nature of the findings suggest a connective tissue disorder. We contrast and compare this boy's phenotype to those of the classic connective tissue disorders. We conclude that he has cutis laxa with features that distinguish him from previously described types of cutis laxa.

  11. Plasma antioxidant capacity is reduced in Asperger syndrome.

    Science.gov (United States)

    Parellada, Mara; Moreno, Carmen; Mac-Dowell, Karina; Leza, Juan Carlos; Giraldez, Marisa; Bailón, Concepción; Castro, Carmen; Miranda-Azpiazu, Patricia; Fraguas, David; Arango, Celso

    2012-03-01

    Recent evidence suggests that children with autism have impaired detoxification capacity and may suffer from chronic oxidative stress. To our knowledge, there has been no study focusing on oxidative metabolism specifically in Asperger syndrome (a milder form of autism) or comparing this metabolism with other psychiatric disorders. In this study, total antioxidant status (TAOS), non-enzymatic (glutathione and homocysteine) and enzymatic (catalase, superoxide dismutase, and glutathione peroxidase) antioxidants, and lipid peroxidation were measured in plasma or erythrocyte lysates in a group of adolescent patients with Asperger syndrome, a group of adolescents with a first episode of psychosis, and a group of healthy controls at baseline and at 8-12 weeks. TAOS was also analyzed at 1 year. TAOS was reduced in Asperger individuals compared with healthy controls and psychosis patients, after covarying by age and antipsychotic treatment. This reduced antioxidant capacity did not depend on any of the individual antioxidant variables measured. Psychosis patients had increased homocysteine levels in plasma and decreased copper and ceruloplasmin at baseline. In conclusion, Asperger patients seem to have chronic low detoxifying capacity. No impaired detoxifying capacity was found in the first-episode psychosis group in the first year of illness.

  12. Copper and zinc metabolism in aminonucleoside-induced nephrotic syndrome.

    Science.gov (United States)

    Pedraza-Chaverrí, J; Torres-Rodríguez, G A; Cruz, C; Mainero, A; Tapia, E; Ibarra-Rubio, M E; Silencio, J L

    1994-01-01

    Copper (Cu) and zinc (Zn) were measured in urine, serum and tissues from rats with nephrotic syndrome (NS) induced with a single subcutaneous dose of puromycin aminonucleoside (PAN; 15 mg/100 g BW). Control animals were pair-fed. Urine was collected daily, and the rats were sacrificed on day 10. PAN-nephrotic rats had proteinuria (days 3-10), high urinary Cu (days 1, 2, 4-10) and Zn (days 3-10) excretion. On day 10, nephrotic rats had: (a) albuminuria, hypoalbuminemia, hypoproteinemia, high urine and low serum levels of ceruloplasmin; (b) low Cu and Zn serum levels; (c) high clearance and fractional excretion of Cu and Zn, and (d) low kidney and liver Cu content and essentially normal tissue Zn levels. The alterations in Cu metabolism were more intense than those in Zn metabolism. Urine Cu and Zn showed a positive correlation with urine total protein on days 3-10 which suggests that high urinary excretion of Cu and Zn may be due to the excretion of its carrier proteins. In conclusion, these rats did not show a typical Zn deficiency but a clear decrease in Cu in the liver and kidney.

  13. Associação da concentração plasmática de cobre com metaloproteínas cobre-dependentes em atletas de elite Association between copper plasma concentration and copper-dependent metaloproteins in elite athletes

    Directory of Open Access Journals (Sweden)

    Josely Correa Koury

    2007-08-01

    Full Text Available O cobre é um elemento-traço essencial para a manutenção de vários processos biológicos, tais como metabolismo energético, homeostase de ferro e mecanismos de proteção antioxidante através da atividade da cobre-zinco superóxido dismutase (Cu-Zn SOD, da ceruloplasmina e da metalotioneína. No entanto, o cobre também participa de reações oxidativas que promovem a liberação de radicais livres, podendo prejudicar a integridade e a funcionalidade celular. A atividade física afeta a homeostase do cobre e promove maior utilização de oxigênio, favorecendo a instalação do estresse oxidativo quando mecanismos naturais de proteção antioxidante, incluindo os dependentes de cobre, não atuam adequadamente. Não há relatos na literatura sobre a associação de diferentes níveis de concentração plasmática de cobre com indicadores antioxidantes cobre-dependentes em atletas de elite. O presente estudo objetivou verificar a associação entre diferentes níveis plasmáticos de cobre e metaloproteínas cobre-dependentes, com atividade antioxidante, em atletas de elite. Os indicadores bioquímicos (metalotioneína e Cu-Zn SOD eritrocitárias, ceruloplasmina e cobre plasmáticos foram avaliados em 50 atletas, homens e adultos, utilizando metodologias já consolidadas. Os resultados mostraram que 32% dos atletas apresentaram níveis de cobre plasmático inferiores a 11µmol/L, 38% entre 11-13µmol/L e 30% > 13µmol/L. As associações encontradas entre cobre plasmático e ceruloplasmina (r = 0,31; p = 0,04 e Cu-Zn SOD (r = 0,32, p = 0,02; metalotioneína eritrocitária e ceruloplasmina (r = 0,40, p = 0,006 e Cu-Zn SOD (0,73, p = 0,001 e entre Cu-Zn SOD e ceruloplasmina (r = 0,37, p Copper is a trace element essential in several biological processes, some of them important for physical activity, such as energy metabolism, iron homeostasis and antioxidant protection through the plasma ceruloplasmin, erythrocyte Cu-Zn superoxide dismutase (Cu

  14. [A young boy with elevated aminotransferases in physical examination--Two novel missense mutations associated with Wilson's disease were found].

    Science.gov (United States)

    Zhu, Yu; Deng, Si-Yan; Wan, Chao-Min

    2015-07-01

    A 3-year-old boy had abnormal liver function, which was found in physical examination, for 5 months before admission. He had no symptoms such as anorexia, poor appetite, and jaundice, had normal growth and development, and showed no hepatosplenomegaly. Laboratory examination revealed significantly reduced ceruloplasmin (35 mg/L), as well as negative hepatotropic virus, cytomegalovirus, and Epstein-Barr virus. There were normal muscle enzymes, blood glucose, and blood ammonia and negative liver-specific autoantibodies. The boy had negative K-F ring and normal 24-hour urine copper (0.56 μmol/L). The ATP7B gene testing for the boy, his sister, and their parents detected two novel missense mutations in the boy and his sister, i.e., compound heterozygous mutations in exon 7 (c.2075T>C, p.L692P) and exon 13 (c.3044T>C, p.L1015P), which were inherited from their father and mother, respectively. Wilson's disease was confirmed by genetic diagnosis in the boy and his sister. The boy and his sister were given a low-copper diet. The boy was administered with penicillamine for decoppering and zinc supplement against copper uptake. His sister received zinc supplement alone because no clinical symptoms were observed. The boy showed normal liver function in the reexamination after 3 months of treatment.

  15. Early gestational gene transfer with targeted ATP7B expression in the liver improves phenotype in a murine model of Wilson's disease.

    Science.gov (United States)

    Roybal, J L; Endo, M; Radu, A; Gray, L; Todorow, C A; Zoltick, P W; Lutsenko, S; Flake, A W

    2012-11-01

    The ideal gene therapy for metabolical liver disorders would target hepatocytes before the onset of disease and be durable, non-toxic and non-immunogenic. Early gestational gene transfer can achieve such goals. Here, we demonstrate that prenatal gene transfer of human Atp7b reduces liver pathology and improves biochemical markers in Atp7b(-/-) mice, a murine model of Wilson's disease (WD). Following prenatal injection of lentivirus vector containing the human Atp7b gene under the transcriptional control of a liver-specific promoter, the full-length ATP7B was detectable in mouse livers for the entire duration of experiments (20 weeks after birth). In contrast to a marked pathology in non-injected animals, livers from age-matched treated mice consistently demonstrated normal gross and histological morphology. Hepatic copper content was decreased in the majority of treated mice, although remaining copper levels varied. Improvement of hepatic copper metabolism was further apparent from the presence of copper-bound ceruloplasmin in the sera and normalization of the mRNA levels for HMG CoA-reductase. With this approach, the complete loss of copper transport function can be ameliorated, as evident from phenotypical improvement in treated Atp7b(-/-) mice. This study provides proof of principle for in utero gene therapy in WD and other liver-based enzyme deficiencies.

  16. Can antioxidants predispose to cancer recurrence?

    Institute of Scientific and Technical Information of China (English)

    Krishnananda Prabhu; Gummadi Maheshwar Reddy; Anjali Rao

    2010-01-01

    Objective:To measure and compare pre-and post-treatment levels of serum total glutathione-S-transferase (GST) in stage IV cervical cancer patients and erythrocytic glutathione (GSH) and malondialdehyde (MDA) and plasma ceruloplasmin (CP) and total GST in stage IV oral cancer patients and to correlate with the response to treatment during a two year follow-up period in respective cancer groups. Methods:Thirty-four biopsy-proven stage IV oral cancer and cervical cancer patients (n=17 in each group) who underwent same mode of treatment were chosen for this study. Erythrocytic MDA and GSH, CP and serum total GST were measured in all patients before the onset of treatment, and the GST level was only measured in cervical cancer patients after radiotherapy. The levels were compared with their respective prognosis in 2 years. Results:Oral cancer patients with higher pretreatment levels of GSH, CP and GST came with cancer recurrence within 2 years after the onset of treatment. Cervical cancer patients with higher post radiotherapy levels of serum total GST had higher recurrence tate. Conclusions:This study indicates there may be a role for these antioxidant parameters namely GST, GSH, CP in assessment of long term survival and prognosis of cancer patients.

  17. [Wilson's disease associated with olfactory paranoid syndrome and idiopathic thrombocytopenic purpura].

    Science.gov (United States)

    Sagawa, Morihiko; Takao, Masaki; Nogawa, Shigeru; Mizuno, Masafumi; Murata, Mitsuru; Amano, Takahiro; Koto, Atsuo

    2003-10-01

    In this study we report an individual of Wilson's disease associated with olfactory paranoid syndrome and idiopathic thrombocytopenic purpura. The initial symptom of this female patient was olfactory paranoia at age 17. Although that psychiatric symptom was well controlled under pharmacological treatment for two years, she developed olfactory paranoia as well as sialorrhea, dysarthria and finger tremor at age 20. A year later rigidity was also present in the extremities. At age 23, idiopathic thrombocytopenic purpura was found based on hematological examinations. Because her extrapyramidal symptoms were progressive, she was referred to our department to evaluate her neurologic condition. She was diagnosed as having Wilson's disease based on (1) the presence of Kayser-Fleischer rings, (2) extrapyramidal signs, and (3) a decreased level of serum copper and ceruloplasmin. T2 and FLAIR images of brain MRI showed hyperintense lesions in the putamen, thalamus and pontine tegmentum. Diffusion-weighted images also showed hyperintense lesions in the thalamus and pontine tegmentum. The biopsy specimen of the liver revealed chronic hepatitis with copper accumulation. Since D-penicillamine treatment was initiated, she has shown no olfactory paranoia and exacerbation of ITP. Her gait disturbance has also improved. Olfactory paranoia and ITP are rare clinical complications of Wilson's disease. Further analysis may warrant consideration of the pathophysiological mechanism of the psychiatric, hematological and neuroradiological condition seen in Wilson's disease.

  18. Interactions of trace elements: clinical significance.

    Science.gov (United States)

    Brewer, G J; Hill, G M; Dick, R D; Prasad, A S; Cossack, Z T

    1985-01-01

    We examined interaction of the trace element zinc with copper and lead. In sickle cell anemia, the usual situation is one of mild to moderate zinc deficiency owing to renal loss of zinc. Zinc deficiency seems to produce a mild overburden of copper and an increased ceruloplasmin level, probably by enhancing copper absorption. With zinc therapy, this process is reversed. Pharmacological doses of zinc, when administered in a way to ensure effectiveness (without food) will usually lead to copper deficiency. We have taken advantage of the copper-depleting effect of zinc to design a new therapy for Wilson's disease. Zinc, by inducing intestinal metallothionein, inhibits absorption of copper from food, and inhibits reabsorption of endogenously secreted copper, thereby producing a negative copper balance in Wilson's disease. Once we are certain that zinc blocks accumulation of copper in the liver of Wilson's disease patients, zinc therapy will be available as one approach for treating this fatal disease. The animal literature indicates that zinc protects against lead toxicity when both elements are given orally, no doubt through the intestinal metallothionein mechanism. In preliminary experiments in rats, we have not been able to show that toxicity from lead that arrives into the body through a nonoral route is affected by oral zinc supplements.

  19. Serial CT scans and Menkes' kinky hair disease

    Energy Technology Data Exchange (ETDEWEB)

    Nakada, Eizo; Kameyama, Junji; Yoshimitsu, Hajime; Mori, Mikio; Tanaka, Mutsuo; Yoshimitsu, Kazunori.

    1988-02-01

    Menkes' kinky hair disease is a sex-linked recessive disorder of copper metabolism, characterized by progressive psychomotor deterioration, seizures, and peculiar hair structure. We examined serial CT scans of patients with this disease. A 2,210-g male infant was delivered after an uneventful gestation of 36 weeks. His one-minute Apgar score was 9. His uncle had died at 1 year of age. His first cousin was also diagnosed as having Menkes' kinky hair disease when our patient was 2 years old. Shortly after birth he had mild respiratory distress. At 5 days of age, he developed setting-sun signs. The first CT scan, at 10 days of age, revealed mild posterior fossa hemorrhages. At 3 months of age, myoclonic seizures began, and the CT scan revealed subdural effusion and mild brain atrophy. The seizures were controllable by using phenobarbital, valproic acid, and nitrazepam. He did not follow light or a fixate, but the fundi were normal. He was diffusely hypotonic. At 9 months of age, the seizures became uncontrollable. The CT scans at 15 and 31 months of age showed subdural hemorrhage and/or brain atrophy. At 15 months of age, the serum copper level was 42 ..mu.. g/dl, while the serum ceruloplasmin level was 3.2 mg/dl. He exhibited severe developmental failure. At 4 years of age, he died.

  20. Serum lipids and proteins during treatment with a new oral contraceptive combination containing desogestrel.

    Science.gov (United States)

    Penttilä, I M; Bergink, E W; Holma, P; Hulkko, S; Makkonen, M; Pyörälä, T; Castrén, O

    1983-12-01

    The present study was carried out to measure lipid and protein levels in serum of healthy women during treatment with a new oral contraceptive combination containing 0.075 mg desogestrel (Org 2969, 17 alpha-ethinyl-18-methyl-11-methylene-4-estren-17-ol) plus 0.050 mg ethinyloestradiol per tablet. All 30 volunteers took 1 tablet daily for 21 consecutive days, followed by a tablet-free period of 7 days. Treatment lasted 3 months. At the end of treatment serum total cholesterol had increased by 0.26 mmol/l (5.0%), high-density lipoprotein-cholesterol by 0.22 mmol/l (15.2%) and triglycerides by 0.43 mmol/l (50%); the calculated low-density lipoprotein cholesterol had decreased by 0.16 mmol/l (4.9%). All lipid concentrations had returned to initial levels 2 months after treatment stopped. After 3 months treatment serum ceruloplasmin, cortisol-binding globulin capacity, sex-hormone-binding globulin capacity and thyroxine-binding globulin had significantly increased by 85.2, 133, 206 and 101%, respectively. All protein levels returned to normal 2 months after treatment stopped. The relationship between serum lipids and hormone-binding proteins has been discussed, as well as the significance of the high-density lipoprotein level with regard to contraceptive treatment. PMID:6232161

  1. BIOCHEMICAL MECHANISMS OF MIXED EFFECT OF ELECTROMAGNETIC RADIATION AND LOW POSITIVE TEMPERATURE ON ANIMALS’ ORGANISM

    Directory of Open Access Journals (Sweden)

    Litovchenko O.L.

    2015-05-01

    Full Text Available At present, biochemical mechanisms of mixed effects of electromagnetic radiation (EMR and cold on the body are not adequately studied, so this problem is urgent for modern medicine. Purpose of study. Establishing pathognomonic criteria and biochemical mechanisms of adverse effect of EMR on the organism of laboratory animals in conditions of cold stress. Materials and methods. The laboratory subacute experiment was carried out on mature white male rats of WAG line, weighing 190-220 g for 1 month. The animals were divided into 4 groups of 10 animals in each group. The first group was subjected to the isolated action of electromagnetic radiation (frequency 70 kHz, tension 600 V/m at a comfortable air temperature of 25 ± 2 ° C. The second group was subjected to the mixed action of EMR and low temperature 4 ± 2°C. The third group served as a control with regard to the first group, and the fourth group - with regard to the second, at air temperature of 25 ± 2°C. Expositions were carried out 5 times a week (for 4:00 every day. To identify changes in biochemical parameters studied during the experiments, blood sampling was performed at the stages of 5, 15, 30 days and urine sampling – at the stages of 15, 30 days in dynamics. Blood serum was used as biomaterial. It was determined the content of malondialdehyde (MDA, conjugated diene, content of SH-groups, superoxide dismutase, ceruloplasmin, cholesterol, high density lipoprotein, low density lipoprotein, very low density lipoprotein (VLDL, triglycerides, atherogenic index was determined, the level of urea, alkaline phosphatase, acid phosphatase, content of chlorides, calcium, magnesium, phosphorus, total protein, glucose, and catalase activity. Renal function was studied by the content of creatinine, cholinesterase, urea, uric acid, chlorides, potassium, sodium, calcium, phosphorus and glucose in urine. Results and discussion. The findings showed that the isolated action of EMR only led to a

  2. 以肝病症状为首发表现的肝豆状核变性93例%Wilson's disease with hepatic manifestations as the first presentation: An analysis of 93 cases

    Institute of Scientific and Technical Information of China (English)

    林连捷; 王东旭; 郑长青; 曹男; 丁楠楠

    2013-01-01

    AIM: To analyze the clinical data for patients with Wilson's disease with hepatic manifestations as the first presentation to provide a reference for the diagnosis of this disease. METHODS: The clinical data for 93 patients with Wilson's disease with hepatic manifestations as the first presentation, who were treated at our hospital from January 1993 to April 2010, were reviewed retrospectively. RESULTS: The age of onset ranged from 4 to 49 years. The average course before achieving a definite diagnosis was 17.48 mo. Main first symptoms were jaundice (47.31%), fatigue (39.78%), and nausea and vomiting (37.63%). Main clinical presentation was cirrhosis. The positive rate of corneal K-F ring was 91.67%. The rate of abnormal urinary copper was 84.48%, and serum ceruloplasmin was abnormal in 81.40% of cases. Varying degrees of abnormality of liver function and blood coagulation were also observed. The percentage of patients showing abnormal liver and spleen ultrasound manifestations was 97.37%. The misdiagnosis rate was 61.29%. CONCLUSION: Patients who are suspected to have Wilson's disease with hepatic manifestations as the first presentation should undergo timely determination of K-F ring, 24-h urinary copper, serum ceruloplasmin, and abdominal ultrasound to improve early diagnosis, treatment, prognosis, and reduce misdiagnosis.%目的:分析以肝病症状为首发表现肝豆状核变性患者的临床资料,指导本病的诊断.方法:回顾性分析1993-01/2010-04于我院首诊的93例以肝病为首发表现肝豆状核变性患者的临床资料.结果:发病年龄4-49岁 ;确诊前平均病程17.48mo;首发症状依次为黄疸(47.3 1%),乏力(39.78%),恶心呕吐(37.63%);临床主要表现为肝硬化;角膜K-F环阳性率91.67%,尿铜异常率84.48%,血清铜蓝蛋白异常率81.40%,肝功及凝血指标有不同程度的异常,肝胆脾超声异常率97.37%;首诊误诊率达61.29%.结论:对可疑肝豆状核变性的肝病患者应

  3. Metabolizable protein supply modulated the acute-phase response following vaccination of beef steers.

    Science.gov (United States)

    Moriel, P; Arthington, J D

    2013-12-01

    Our objective was to evaluate the effects of MP supply, through RUP supplementation, on the acute-phase response of beef steers following vaccination. On d 0, Brangus-crossbred steers (n = 24; 173 ± 31 kg; 175 ± 16 d of age) were randomly assigned to receive 1 of 3 isocaloric diets formulated to provide 85, 100, and 115% of the daily MP requirements of a beef steer gaining 0.66 kg of BW daily. Diets were limit-fed at 1.8% of BW (DM basis) and individually provided to steers once daily (0800 h) from d 0 to 29. Steers were weighed on d 0 and 29, following a 12-h period of feed and water withdrawal. On d 7, steers were vaccinated against Mannheimia haemolytica (OneShot, Pfizer), and blood samples were collected on d 0, 7, 8, 10, 14, 21, and 30. Plasma metabolites were analyzed as repeated measures using the MIXED procedure of SAS. Final BW and ADG were similar (P ≥ 0.50) among treatments (mean = 184 ± 9 kg and 0.5 ± 0.08 kg/d, respectively). Effects of time were detected (P < 0.01) for plasma concentrations of all acute-phase proteins, which peaked between d 7 to 14, returning to baseline concentrations by d 29. Treatment effects were not detected (P ≥ 0.19) for plasma concentrations of acid-soluble protein, albumin, fibrinogen, IGF-1 and serum amyloid-A. Plasma concentrations of total protein (TP) and plasma urea nitrogen (PUN) increased (P ≤ 0.05) with increasing supply of MP (87.1, 89.6, and 90.1 ± 1.09 mg TP/mL and 6.1, 8.3, and 10.3 ± 0.41 mg PUN/dL for 85, 100, and 115% MP steers, respectively). From d 10 to 29, steers provided 115% MP had less (P < 0.001) plasma concentrations of ceruloplasmin than steers fed 85 and 100% MP, which had similar plasma ceruloplasmin concentrations. On d 14, plasma concentrations of haptoglobin were greatest (P ≤ 0.06) for steers fed 115% MP, intermediate for 100% MP, and least for 85% MP (0.98, 0.71 and 0.44 ± 0.099 mg/mL, respectively). On d 10, plasma concentrations of creatinine were greater (P = 0.01) for steers

  4. Plasma protein profiling of mild cognitive impairment and Alzheimer's disease across two independent cohorts.

    Science.gov (United States)

    Muenchhoff, Julia; Poljak, Anne; Song, Fei; Raftery, Mark; Brodaty, Henry; Duncan, Mark; McEvoy, Mark; Attia, John; Schofield, Peter W; Sachdev, Perminder S

    2015-01-01

    To unlock the full potential of disease modifying treatments, it is essential to develop early biomarkers for Alzheimer's disease (AD). For practical reasons, blood-based markers that could provide a signal at the stage of mild cognitive impairment (MCI) or even earlier would be ideal. Using the proteomic approach of isobaric tagging for relative and absolute quantitation (iTRAQ), we compared the plasma protein profiles of MCI, AD, and cognitively normal control subjects from two independent cohorts: the Sydney Memory and Ageing Study (261 MCI subjects, 24 AD subjects, 411 controls) and the Hunter Community Study (180 MCI subjects, 153 controls). The objective was to identify any proteins that are differentially abundant in MCI and AD plasma in both cohorts, since they might be of interest as potential biomarkers, or could help direct future mechanistic studies. Proteins representative of biological processes relevant to AD pathology, such as the complement system, the coagulation cascade, lipid metabolism, and metal and vitamin D and E transport, were found to differ in abundance in MCI. In particular, levels of complement regulators C1 inhibitor and factor H, fibronectin, ceruloplasmin, and vitamin D-binding protein were significantly decreased in MCI participants from both cohorts. Several apolipoproteins, including apolipoprotein AIV, B-100, and H were also significantly decreased in MCI. Most of these proteins have previously been reported as potential biomarkers for AD; however, we show for the first time that a significant decrease in plasma levels of two potential biomarkers (fibronectin and C1 inhibitor) is evident at the MCI stage. PMID:25159666

  5. Genotype phenotype correlation in Wilson's disease within families-a report on four south Indian families

    Institute of Scientific and Technical Information of China (English)

    S Santhosh; GM Chandy; RV Shaji; CE Eapen; V Jayanthi; S Malathi; P Finny; N Thomas; M Chandy; G Kurian

    2008-01-01

    AIM: To study the genotype phenotype correlation inWilson's disease (WD) patients with in families.METHODS: We report four unrelated families from South India with nine members affected withWD. Phenotype was classified as per international consensus phenotypic classification of WD. DNA was extracted from peripheral blood and 21 exons of ATP7B gene and flanking introns were amplified by polymerase chain reaction (PCR). The PCR products were screened for mutations and the aberrant products noted on screening were sequenced.RESULTS: Four separate ATP7B mutations were found in the four families. ATP7B mutations were identical amongst affected members within each family.Three families had homozygous mutations of ATP7B gene while one family had compound heterozygous mutation, of which only one mutation was identified.We noted concordance between ATP7B gene mutation and Wilson's disease phenotype amongst members within each family. The age of onset of symptoms orof detection of asymptomatic disease, baseline serum ceruloplasmin and baseline urinary copper levelswere also similar in affected members of each family.Minor differences in phenotype and baseline serumceruloplasmin level were noted in one family.CONCLUSION: We report concordance between ATP7B mutation and WD phenotype within each familywith > 1 member affected with WD. Homozygous ATP7B mutation was present in 3 of the 4 families studied. Our report supports allelic dominance as adeterminant of WD phenotype. However, in one familywith compound heterozygous mutation, there was a similar WD phenotype which suggests that there may be other factors determining the phenotype.

  6. Nutrititional Status Assessment of International Space Station Crew Members

    Science.gov (United States)

    Smith, S. M.; Zwart, S. R.; Block, G.; Rice, B. I.; Davis-Street, J. F.

    2005-01-01

    Defining optimal nutrient requirements is imperative to ensure crew health on long-duration space exploration missions. To date, nutrient requirement data have been extremely limited because of small sample sizes and difficulties associated with collecting biological samples. In this study, we examined changes in body composition, bone metabolism, hematology, general blood chemistry, and blood levels of selected vitamins and minerals after long-duration (128-195 d) space flight aboard the International Space Station. Crew members consumed an average of 80% of the recommended energy intakes, and on landing day their body weight had decreased (P=0.051). After flight, hematocrit was less, and serum femtin was greater than before flight (Pacute-phase proteins, including ceruloplasmin, retinol binding protein, transthyretin, and albumin were not changed after flight suggests that the changes in iron metabolism may not be strictly due to an inflammatory response. Urinary 8- hydroxy-2'-deoxyguanosine concentration was greater and superoxide dismutase was less after flight, indicating that oxidative damage had increased (P<0.05). Despite the reported use of vitamin D supplements during flight, serum 25-hydroxyvitamin D was significantly decreased after flight (P<0.01). Bone resorption was increased after flight, as indicated by several urinary markers of bone resorption. Bone formation, assessed by serum concentration of bone-specific alkaline phosphatase, was elevated only in crew members who landed in Russia, probably because of the longer time lapse between landing and sample collection. These data provide evidence that bone loss, compromised vitamin D status, and oxidative damage remain critical concerns for long-duration space flight.

  7. Immunometabolic Status during the Peripartum Period Is Enhanced with Supplemental Zn, Mn, and Cu from Amino Acid Complexes and Co from Co Glucoheptonate.

    Science.gov (United States)

    Batistel, Fernanda; Osorio, Johan S; Ferrari, Annarita; Trevisi, Erminio; Socha, Michael T; Loor, Juan J

    2016-01-01

    The peripartum (or transition) period is the most-critical phase in the productive life of lactating dairy cows and optimal supply of trace minerals through more bioavailable forms could minimize the negative effects associated with this phase. Twenty Holstein cows received a common prepartal diet and postpartal diet. Both diets were partially supplemented with an inorganic (INO) mix of Zn, Mn, and Cu to supply 35, 45, and 6 ppm, respectively, of the diet dry matter (DM). Cows were assigned to treatments in a randomized completed block design, receiving an daily oral bolus with INO or organic trace minerals (AAC) Zn, Mn, Cu, and Co to achieve 75, 65, 11, and 1 ppm supplemental, respectively, in the diet DM. Liver tissue and blood samples were collected throughout the experiment. The lower glutamic-oxaloacetic transaminase concentration after 15 days in milk in AAC cows indicate lower hepatic cell damage. The concentration of cholesterol and albumin increased, while IL-6 decreased over time in AAC cows compared with INO indicating a lower degree of inflammation and better liver function. Although the acute-phase protein ceruloplasmin tended to be lower in AAC cows and corresponded with the reduction in the inflammatory status, the tendency for greater serum amyloid A concentration in AAC indicated an inconsistent response on acute-phase proteins. Oxygen radical absorbance capacity increased over time in AAC cows. Furthermore, the concentrations of nitric oxide, nitrite, nitrate, and the ferric reducing ability of plasma decreased with AAC indicating a lower oxidative stress status. The expression of IL10 and ALB in liver tissue was greater overall in AAC cows reinforcing the anti-inflammatory response detected in plasma. The greater overall expression of PCK1 in AAC cows indicated a greater gluconeogenic capacity, and partly explained the greater milk production response over time. Overall, feeding organic trace minerals as complexed with amino acids during the

  8. Experimental Investigation of the Ferrum (III Hydroxide Polymaltosate Preparation Influence Peculiarities on the Lipid Peroxidation Values

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    Lovtsova L.V.

    2010-09-01

    Full Text Available Aim of investigation is a study of the ferrum (III hydroxide polymaltosate preparation influence peculiarities on the lipid peroxidation and antioxidant protection values in blood of experimental animals at the background of a ferrodeficient anemia. Materials and Methods. The experiment is made on 120 nonlinear male-rats. The values of induced biochemiluminescence, a content of malone dialdehyde, an activity of superoxidedismutase and catalase, a concentration of ceruloplasmin in blood of experimental animals at infusion of a preparation, containing a trivalent ferrum, — a ferrum (III hydroxide polymaltosate (maltofer — in equitherapeutic dose of 17.14 mg/kg a day (calculating the elementary ferrum have been detected during investigation for 30 days. Results. A trivalent ferrum (III hydroxide polymaltosate preparation (maltofer stipulates at the early stages an insignificant, and at the later stages — expressed influence on the pointed process, which is confirmed by an increase of a free-radical oxidation process abatement rate in blood plasma of experimental animals, and also a decrease of a superoxidedismutase activity (in a day of its infusion, a decrease of a malone dialdehyde concentration (in 5 days, a decrease of the antioxidant and superoxidedismutase activity (in 10 days, an increase of a plasma free-radical activity and a free-radical oxidation process abatement rate (in 20 days, a decrease of a malone dialdehyde content (in 30 days. Conclusion. The investigating trivalent ferrum preparation activates a process of lipid peroxidation. Its distinctive feature is a more expressed influence on the pointed process at the late stages of its infusion.

  9. Phenotypic and Genetic Characterization of a Cohort of Pediatric Wilson Disease Patients

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    Elnaghy Suzan

    2011-06-01

    Full Text Available Abstract Background In Egypt, Wilson disease seems to be under diagnosed and clinical data on large cohorts are limited. The aim of this study is to highlight the clinical, laboratory and genetic characteristics of this disease in our pediatric population as well as to report our experience with both treatment options and outcome. Methods The study included 77 patients from 50 unrelated families (62 were followed up for a mean period of 58.9 ± 6.4 months and 27 were asymptomatic siblings. Data were collected retrospectively by record analysis and patient interviews. Diagnosis was confirmed by sequencing of the ATP7B gene in 64 patients Results Our patients had unique characteristics compared to other populations. They had a younger age of onset (median: 10 years, higher prevalence of Kayser-Fleischer rings (97.6% in the symptomatic patients, low ceruloplasmin (93.5%, high rate of parental consanguinity (78.9% as well as a more severe course. 71.42% of those on long term D-penicillamine improved or were stable during the follow up with severe side effects occurring in only 11.5%. Preemptive treatment with zinc monotherapy was an effective non-toxic alternative to D-penicillamine. Homozygous mutations were found in 85.7%, yet limited by the large number of mutations detected, it was difficult to find genotype-phenotype correlations. Missense mutations were the most common while protein-truncating mutations resulted in a more severe course with higher incidence of acute liver failure and neurological symptoms. Conclusions Egyptian children with Wilson disease present with early Kayser-Fleischer rings and early onset of liver and neurological disease. The mutational spectrum identified differs from that observed in other countries. The high rate of homozygous mutations (reflecting the high rate of consanguinity may potentially offer further insights on genotype-phenotype correlation

  10. Atomic Absorption Spectrometry in Wilson’s Disease and Its Comparison with Other Laboratory Tests and Paraclinical Findings

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    Rana Fereiduni

    2012-03-01

    Full Text Available Objective: Wilson's disease (WD is an autosomal recessive disease with genetic abnormality on chromosome 13 causing defect in copper metabolism and increased copper concentration in liver, central nervous system and other organs, which causes different clinical manifestations. The aim of this study was to determine the sensitivity of different clinical and paraclinical tests for diagnosis of Wilson’s disease.Methods: Paraffin blocks of liver biopsy from 41 children suspicious of WD were collected. Hepatic copper concentrations were examined with atomic absorption spectrophotometry (Australian GBC, model: PAL 3000. Fifteen specimens had hepatic copper concentration (dry weight more than 250μg/g. Clinical and laboratory data and histologic slides of liver biopsies of these 15 children were reviewed retrospectively. Liver tissue was examined for staging and grading of hepatic involvement and also stained with rubeonic acid method for copper.Findings: Patients were 5-15 years old (mean age=9.3 years, standard deviation=2.6 with slight male predominance (9/15=60%. Five (33% patients were 10 years old. Three (20% of them were referred for icterus, 8 (54% because of positive family history, 2 (13% due to abdominal pain and 2 (13% because of hepatosplenomegaly and ascites. Serum AST and ALT levels were elevated at the time of presentation in all patients. In liver biopsy, histological grade and stage was 0-8 and 0-6 respectively, 2 (13% had cirrhosis, 1 (7% had normal biopsy and 12 (80% showed chronic hepatitis. Hepatic copper concentrations were between 250 and 1595 μg/g dry weight. The sensitivity of various tests were 85% for serum copper, 83% for serum ceruloplasmin, 53% for urinary copper excretion, 44% for presence of KF ring and 40% for rubeonic acid staining on liver biopsies.

  11. Evolution of exchangeable copper and relative exchangeable copper through the course of Wilson's disease in the Long Evans Cinnamon rat.

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    Françoise Schmitt

    Full Text Available BACKGROUND: Wilson's disease (WD is an inherited disorder of copper metabolism leading to liver failure and/or neurological impairment. Its diagnosis often remains difficult even with genetic testing. Relative exchangeable copper (REC has recently been described as a reliable serum diagnostic marker for WD. METHODOLOGY/PRINCIPAL FINDINGS: The aim of this study was to validate the use of REC in the Long Evans Cinnamon (LEC rat, an animal model for WD, and to study its relevance under different conditions in comparison with conventional markers. Two groups of LEC rats and one group of Long-Evans (LE rats were clinically and biologically monitored from 6 to 28 weeks of age. One group of LEC rats was given copper-free food. The other groups had normal food. Blood samples were collected each month and different serum markers for WD (namely ceruloplasmin oxidase activity, exchangeable copper (CuEXC, total serum copper and REC and acute liver failure (serum transaminases and bilirubinemia were tested. Every LEC rat under normal food developed acute liver failure (ALF, with 40% global mortality. Serum transaminases and bilirubinemia along with total serum copper and exchangeable copper levels increased with the onset of acute liver failure. A correlation was observed between CuEXC values and the severity of ALF. Cut-off values were different between young and adult rats and evolved because of age and/or liver failure. Only REC, with values >19%, was able to discriminate LEC groups from the LE control group at every time point in the study. REC sensitivity and specificity reached 100% in adults rats. CONCLUSIONS/SIGNIFICANCE: REC appears to be independent of demographic or clinical data in LEC rats. It is a very simple and reliable blood test for the diagnosis of copper toxicosis owing to a lack of ATP7B function. CuEXC can be used as an accurate biomarker of copper overload.

  12. Oxidative Stress and Cell Apoptosis in Caprine Liver Induced by Molybdenum and Cadmium in Combination.

    Science.gov (United States)

    Yang, Fan; Zhang, Caiying; Zhuang, Yu; Gu, Xiaolong; Xiao, Qingyang; Guo, Xiaoquan; Hu, Guoliang; Cao, Huabin

    2016-09-01

    To investigate the effects of co-exposure to molybdenum (Mo) and cadmium (Cd) on oxidative stress and cell apoptosis in caprine livers, 36 Boer goats were randomly divided into four groups with nine goats in each group. Three groups were randomly assigned with one of three oral treatments of CdCl2 (0.5 mg Cd kg(-1)·BW) and [(NH4)6Mo7O24·4H2O] (15 mg Mo kg(-1)·BW, 30 mg Mo kg(-1)·BW, 45 mg Mo kg(-1)·BW), while the control group received deionized water. Liver tissues on days 0, 25, and 50 were subjected to determine antioxidant activity indexes and the messenger RNA (mRNA) expression levels of ceruloplasmin (CP), cysteinyl aspartate-specific proteinase-3 (caspase-3), second mitochondria-derived activator of caspases (Smac), and cytochrome-C (Cyt-C) genes. The results showed that significant reductions were observed in total antioxidant capacity (T-AOC) and total superoxide dismutase (T-SOD) activities (P < 0.05), while activities or contents of malondialdehyde (MDA), nitric oxide (NO), and nitric oxide synthase (NOS) were increased (P < 0.05). The mRNA expression levels of CP, caspase-3, Smac, and Cyt-C genes were upregulated (P < 0.05). In addition, histopathological lesions showed different degrees of vacuolar degeneration and edematous and mitochondrial swelling. The results suggest that co-exposure to Mo and Cd could induce oxidative stress and cell apoptosis possibly associated with mitochondrial intrinsic pathway in goat liver and show possible synergistic effects between the two elements. PMID:26883837

  13. Searching for early breast cancer biomarkers by serum protein profiling of pre-diagnostic serum; a nested case-control study

    International Nuclear Information System (INIS)

    Serum protein profiles have been investigated frequently to discover early biomarkers for breast cancer. So far, these studies used biological samples collected at or after diagnosis. This may limit these studies' value in the search for cancer biomarkers because of the often advanced tumor stage, and consequently risk of reverse causality. We present for the first time pre-diagnostic serum protein profiles in relation to breast cancer, using the Prospect-EPIC (European Prospective Investigation into Cancer and nutrition) cohort. In a nested case-control design we compared 68 women diagnosed with breast cancer within three years after enrollment, with 68 matched controls for differences in serum protein profiles. All samples were analyzed with SELDI-TOF MS (surface enhanced laser desorption/ionization time-of-flight mass spectrometry). In a subset of 20 case-control pairs, the serum proteome was identified and relatively quantified using isobaric Tags for Relative and Absolute Quantification (iTRAQ) and online two-dimensional nano-liquid chromatography coupled with tandem MS (2D-nanoLC-MS/MS). Two SELDI-TOF MS peaks with m/z 3323 and 8939, which probably represent doubly charged apolipoprotein C-I and C3a des-arginine anaphylatoxin (C3adesArg), were higher in pre-diagnostic breast cancer serum (p = 0.02 and p = 0.06, respectively). With 2D-nanoLC-MS/MS, afamin, apolipoprotein E and isoform 1 of inter-alpha trypsin inhibitor heavy chain H4 (ITIH4) were found to be higher in pre-diagnostic breast cancer (p < 0.05), while alpha-2-macroglobulin and ceruloplasmin were lower (p < 0.05). C3adesArg and ITIH4 have previously been related to the presence of symptomatic and/or mammographically detectable breast cancer. We show that serum protein profiles are already altered up to three years before breast cancer detection

  14. Clinical analysis of forty-six patients with Wilson's disease%Wilson病46例临床分析

    Institute of Scientific and Technical Information of China (English)

    张美英; 田成林

    2011-01-01

    Objective To investigate the clinical features, diagnosis and treatment in wilson 's disease.Methods 46 cases with wilson's disease were analysed by clinical presentation, investigative studies and treatment.Results Among the 46 cases, 41.3% of cases were initially presented syndromes of digestion system; 34.8% of cases were diagnosed errorly; all cases that initially errorly diagnosed were presented syndromes of non-nervous system.The levels of serum ceruloplasmin were low in all cases.Kayser-Fleischer rings were found accounted for 89.13%.the main abnormal in intracranial lied in double basal ganglia.5 cases were treated with liver transplation; and others with usual treatment.Conclusion Due to complex appearance, and many systems were involved, Wilson's disease were easyly errorly diagnosed.D-penicillamine, Zinc and Liver transplantation are effective ways to treat WD.%目的 探讨Wilson病的临床表现特点和诊治.方法 分析我院46例Wilson病患者的临床表现、辅助检查及治疗方案.结果 本文46例患者,41.3%以消化道症状首发;34.8%早期误诊,均为神经系统以外症状起病者.所有患者化验血清铜兰蛋白均降低,89.13%K-F环阳性,颅内以双基底节对称性病变多见.5例行肝移植治疗,余41例予常规治疗.结论 Wilson病临床表现复杂,涉及多系统,易误诊.D-青霉胺、锌剂、肝移植是目前治疗Wilson 病的有效方法.

  15. Most frequent mutation c.3402delC (p.Ala1135GlnfsX13) among Wilson disease patients in Venezuela has a wide distribution and two old origins.

    Science.gov (United States)

    Paradisi, Irene; De Freitas, Laura; Arias, Sergio

    2015-02-01

    Wilson disease is an infrequent autosomal recessive disorder caused by mutations in the ATP7B gene (13q14.3) producing pathologic phenotypes due to copper accumulation in critical tissues. The aim of the research was to probe Wilson disease genetic epidemiology in Venezuela, through the identification in diagnosed index cases, of ATP7B locus mutations, their geographic distribution, frequency, in-phase haplotypes and probable ethnic ancestry. During the last three decades 33 independent Wilson disease families from the country at large were ascertained and diagnosed through severely reduced ceruloplasmin activity, higher urinary copper excretion, and specific clinical signs. Molecular studies of the ATP7B gene were accomplished in 26 of the families. Disease prevalence was estimated as 1:94,000 families between 1985 and 2013, showing geographic aggregation in the state of Zulia with 1:27,000 families in it. DNA analysis in 26 families revealed 13 different mutations. The c.3402delC was the most frequent one (26.9%), presenting two independent in-phase haplotypes, both of likely European descent; which is followed by the not previously reported p.G691V (9.6%) and by the frequent European H1069Q (7.7%). Known mutations c.51 + 4A > T, c.1285 + 5G > T, M645R, T788I, V845SfsX28, T977M, L1088X, T1220M, R1319X and a novel P767L showed frequencies between 5.8 and 1.9%. Despite the ample mutation heterogeneity for Wilson disease in the country, the findings provide a diagnostic algorithm to ease mutation assessment in new patients; the predominant c.3402delC displayed wide geographic distribution and two genetic origins.

  16. Nutritional Assessment During a 14-d Saturation Dive: the NASA Extreme Environment Mission Operation V Project

    Science.gov (United States)

    Smith, S. M.; Davis-Street, J. E.; Fesperman, J. V.; Smith, M. D.; Rice, B. L.; Zwart, S. R.

    2006-01-01

    Ground-based analogs of spaceflight are an important means of studying physiological and nutritional changes associated with space travel, particularly since exploration missions are anticipated, and flight research opportunities are limited. A clinical nutritional assessment of the NASA Extreme Environment Mission Operation V (NEEMO) crew (4 M, 2 F) was conducted before, during, and after the 14-d saturation dive. Blood and urine samples were collected before (D-12 and D-1), during (MD 7 and MD 12), and after (R + 0 and R + 7) the dive. The foods were typical of the spaceflight food system. A number of physiological changes were reported both during the dive and post dive that are also commonly observed during spaceflight. Serum hemoglobin and hematocrit were decreased (P less than 0.05) post dive. Serum ferritin and ceruloplasmin significantly increased during the dive, while transferring receptors tended to go down during the dive and were significantly decreased by the last day (R + 0). Along with significant hematological changes, there was also evidence for increased oxidative damage and stress during the dive. 8-hydroxydeoxyguanosine was elevated (P less than 0.05) during the dive, while glutathione peroxidase and superoxide disrnutase activities were decreased (P less than 0.05) during the dive. Serum C-reactive protein (CRP) concentration also tended to increase during the dive, suggesting the presence of a stress-induced inflammatory response, Decreased leptin during the dive (P less than 0.05) may also be related to the increased stress. Similar to what is observed during spaceflight, subjects had decreased energy intake and weight loss during the dive. Together, these similarities to spaceflight provide a model to further define the physiological effects of spaceflight and investigate potential countermeasures.

  17. Fe and Cu isotope mass balances in the human body

    Science.gov (United States)

    Balter, V.; Albarede, F.; Jaouen, K.

    2011-12-01

    The ranges of the Fe and Cu isotope compositions in the human body are large, i.e. ~3% and ~2%, respectively. Both isotopic fractionations appear to be mainly controlled by redox conditions. The Fe and Cu isotope compositions of the tissues analyzed so far plot on a mixing hyperbolae between a reduced and an oxidized metals pools. The reduced metals pool is composed by erythrocytes, where Fe is bounded to hemoglobin as Fe(II) and Cu to superoxide-dismutase as Cu(I). The oxidized metals pool is composed by hepatocytes, where Fe and Cu are stored as Fe(III) ferritin and as Cu(II) ceruloplasmine, respectively. The position of each biological component in the δ56Fe-δ65Cu diagram therefore reflects the oxidation state of Fe and Cu of the predominant metal carrier protein and allows to quantify Fe and Cu fluxes between organs using mass balance calculations. For instance, serum and clot Fe and Cu isotope compositions show that current biological models of erythropoiesis violates mass conservation requirements, and suggest hidden Fe and Cu pathways during red blood cells synthesis. The results also show that a coupled Fe-Cu strong gender isotopic effect is observed in various organs. The isotopic difference between men and women is unlikely to be due to differential dietary uptake or endometrium loss, but rather reflects the effect of menstrual losses and a correlative solicitation of hepatic stores. We speculate that thorough studies of the metabolism of stable isotopes in normal conditions is a prerequisite for the understanding of the pathological dysregulations.

  18. INFLUENCE OF ACUTE EXERCISE ON OXIDATIVE STRESS IN CHRONIC SMOKERS

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    Zehra Serdar

    2003-09-01

    Full Text Available The relative oxidative insult caused by exercise and smoking on biological systems are well documented, however, their cumulative influence needs to be clarified. In order to examine the collective effects of exercise and smoking on oxidant and antioxidant parameters, young male smokers (n=10 and non-smokers (n=10 made to perform a negative slope (10% cycling exercise for 30 minutes at individual load equivalent to 60% maximal oxygen consumption (VO2max. Pre- and post-exercise (post-ex haematocrit, haemoglobin, white blood cells, plasma malondialdehyde (MDA levels, protein carbonyl formation and non-HDL oxidation, erythrocyte superoxide dismutase (SOD and glutathione peroxidase (GPX activities, serum ceruloplasmin (CER and urinary cotinine concentrations were evaluated. Pre-ex CER and urinary cotinine concentrations of smokers were significantly higher (p<0.05 and p<0.01, respectively compared to that of non-smokers and pre-ex CER concentrations were significantly correlated with cotinine levels in all subjects (p<0.05. Significant (p<0.01 increases were observed in non-HDL oxidation following the exercise in both groups and the elevations were more pronounced in smokers. Pre-ex SOD and GPX activities were not different between the two groups, however post-ex enzyme activities were significantly reduced in smokers (p<0.05. MDA and protein carbonyl concentrations were not different between the two groups and there were not any significant changes due to exercise.In conclusion, according to the results of the present study, we suggest that erythrocyte antioxidants SOD and GPX and plasma non-HDL are more prone to the possible oxidant damage of acute physical exercise in chronic smokers.

  19. Oxidative stress

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    Stevanović Jelka

    2012-01-01

    Full Text Available The unceasing need for oxygen is in contradiction to the fact that it is in fact toxic to mammals. Namely, its monovalent reduction can have as a consequence the production of short-living, chemically very active free radicals and certain non-radical agents (nitrogen-oxide, superoxide-anion-radicals, hydroxyl radicals, peroxyl radicals, singlet oxygen, peroxynitrite, hydrogen peroxide, hypochlorous acid, and others. There is no doubt that they have numerous positive roles, but when their production is stepped up to such an extent that the organism cannot eliminate them with its antioxidants (superoxide-dismutase, glutathione-peroxidase, catalase, transferrin, ceruloplasmin, reduced glutathion, and others, a series of disorders is developed that are jointly called „oxidative stress.“ The reactive oxygen species which characterize oxidative stress are capable of attacking all main classes of biological macromolecules, actually proteins, DNA and RNA molecules, and in particular lipids. The free radicals influence lipid peroxidation in cellular membranes, oxidative damage to DNA and RNA molecules, the development of genetic mutations, fragmentation, and the altered function of various protein molecules. All of this results in the following consequences: disrupted permeability of cellular membranes, disrupted cellular signalization and ion homeostasis, reduced or loss of function of damaged proteins, and similar. That is why the free radicals that are released during oxidative stress are considered pathogenic agents of numerous diseases and ageing. The type of damage that will occur, and when it will take place, depends on the nature of the free radicals, their site of action and their source. [Projekat Ministarstva nauke Republike Srbije, br. 173034, br. 175061 i br. 31085

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

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    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.

  1. Serum parameters predict the severity of ultrasonographicifndingsinnon-alcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    Mohsen Razavizade; Raika Jamali; Abbas Arj; Hamidreza Talari

    2012-01-01

    BACKGROUND: Controversy exists about the correlation between liver ultrasonography and serum parameters for evaluating the severity of liver involvement in non-alcoholic fatty liver disease (NAFLD). This study was designed to determine the association between liver ultrasonography staging in NAFLD and serum parameters correlated with disease severity in previous studies; and set optimal cut-off points for those serum parameters correlated with NAFLD staging at ultrasonography, in order to differentiate ultrasonographic groups (USGs). METHODS: This cross-sectional study evaluated outpatients with evidence of NAFLD in ultrasonography referred to a general hospital. Those with positive viral markers, abnormal serum ceruloplasmin or gamma-globulin concentrations were excluded. A radiologist performed the ultrasonography staging and stratiifed the patients into mild, moderate, and severe groups. Fasting serum alanine aminotransferase (ALT), aspartate aminotransferase, alkaline phosphatase, triglyceride (TG), high and low density lipoprotein (HDL, LDL), and cholesterol were checked. RESULTS:Two hundred and forty-ifve patients with a mean age (±standard deviation) of 41.63(±11.46) years were included. There were no signiifcant differences when mean laboratory concentrations were compared between moderate and severe USGs. Therefore, these groups were combined to create revised USGs ("mild"versus"moderate or severe"). There were associations between the revised USGs, and ALT, TG, HDL levels, and diabetes mellitus [odds ratios=2.81 (95%conifdence interval (CI):1.37-5.76), 2.48 (95%CI:1.29-4.78), 0.36 (95%CI:0.18-0.74), and 5.65 (95%CI:2.86-11.16) respectively;all P values CONCLUSIONS: Serum ALT, TG, and HDL concentrations seem to be associated with the staging by liver ultrasonography in NAFLD. They might be used to predict the staging of liver ultrasonography in these patients.

  2. Dopa-sensitive progressive dystonia of childhood with diurnal fluctuations of symptoms: a case report

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    José Luiz Dias Gherpelli

    1995-06-01

    Full Text Available Progressive dystonia with diurnal fluctuations sensitive to levodopa, also known as Segawa's disease, is a rare form of autosomal dominant extrapyramidal disease in the pediatric age group. The dystonic and Parkinson-like symptoms are the main clinical features of the disease and, characteristically but not in all cases, show a diurnal variation. They are absent or present to a lesser extent in the morning, worsening during the day. Treatment with small doses of levodopa results in remission or marked improvement of the symptomatology. We present the case of a 11 years old female patient that developed a dystonic posture in her feet that led her to a tip-toe walking pattern, since the age of 2. Diurnal fluctuations of the symptomatology were noticed by her mother. At 7 years of age she developed a left deviation of the head and an abnormal flexor posture of the left arm. In the next years the symptoms progressed and the fluctuations became less evident. At the age of 10, they were present soon after she woke up in the morning. The neurological examination disclosed a dystonic posturing of the head and left arm, a generalized rigidity of the extremities and a palpebral tremor. Laboratory examinations, including copper and ceruloplasmin, and neuro-imaging studies were negative. She was started on levodopa 150 mg/day with prompt disappearance of the symptomatology. After one-year follow-up she is symptom-free with only 100 mg/day of levodopa. No adverse effect was observed so far.

  3. Whole-body cryostimulation--potential beneficial treatment for improving antioxidant capacity in healthy men--significance of the number of sessions.

    Directory of Open Access Journals (Sweden)

    Anna Lubkowska

    Full Text Available It is claimed that WBC (whole-body cryotherapy enhances the resistance of the human body, also thanks to the beneficial effect on the antioxidant system. Accordingly, this research aimed to evaluate the effect of a series of whole-body cryostimulations on the level of non-enzymatic antioxidants and the activity of antioxidant enzymes in healthy men. The study was carried out on 30 young and healthy men aged 27.8±6.1 years with average body mass index and peak oxygen consumption (46.34±6.15 ml kg(-1 •min(-1. The participants were daily exposed for 3 minutes to cryogenic temperatures (-130°C. Blood samples were obtained in the morning before cryostimulation, again 30 min after exposure and the following day in the morning, during the 1(st, 10(th and 20(th session. Analysis concerned changes in plasma concentrations of total protein, albumin, glucose, uric acid and ceruloplasmin, and the most important components of the antioxidant system in red blood cells: superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, reduced and oxidized glutathione. To assess the oxidative stress level the 8-isoprostane concentration in plasma was measured. The obtained results indicate that cryogenic temperatures in repeated daily treatments result in changes in the peroxidant and antioxidant status. These changes seem to depend on the number of cryostimulations. After 20 daily treatments there was an increase in SOD, SOD:CAT ratio, a decrease in the concentration of reduced and oxidized glutathione and in the activity of GPx. It could be possible that differences in the activity of GSSG-R after 20 treatments depended on the body mass index of participants.

  4. A new approach to studying ochratoxin A (OTA)-induced nephrotoxicity: expression profiling in vivo and in vitro employing cDNA microarrays.

    Science.gov (United States)

    Luhe, Anke; Hildebrand, Heinz; Bach, Ute; Dingermann, Theodor; Ahr, Hans-Jurgen

    2003-06-01

    Ochratoxin A (OTA) is a mycotoxin often found in cereals as a contaminant, and it is known to cause severe nephrotoxicity in animals and humans. There have been several investigations studying the mode of action of this toxicant, suggesting inhibition of protein synthesis, formation of DNA adducts, and provocation of DNA single-strand breaks as a result of oxidative stress, but little is known about the transcriptional alterations underlying OTA-derived nephrotoxicity so far. We carried out DNA microarray analyses to assess OTA-specific expression profiles in vivo and in vitro. Cultures of primary rat proximal tubular cells and male Wistar rats were treated with a low dose (5 microM and 1 mg/kg, respectively) or a high dose (12.5 microM and 10 mg/kg, respectively) of OTA for 24 or 72 h. Microarray experiments were carried out after dual fluorescent labeling of sample cDNA, and data analysis was performed utilizing different statistical methods. Validity of selected microarray data was confirmed by quantitative real-time PCR. We were able to demonstrate that microarray data derived from our proximal tubule cell (PTC) culture model were highly comparable to the in vivo situation. Marked treatment-specific transcriptional changes were detected for genes involved in DNA damage response and apoptosis (upregulation of GADD 153, GADD 45, annexin V), response to oxidative stress (differential expression of hypoxia-inducible factor 1 and catalase), and inflammatory reactions (upregulation of alpha 2 macroglobulin, ceruloplasmin, and cathepsin S). We conclude that our results provide a molecular basis for interpretation of OTA-induced nephrotoxicity. PMID:12700408

  5. Immunometabolic Status during the Peripartum Period Is Enhanced with Supplemental Zn, Mn, and Cu from Amino Acid Complexes and Co from Co Glucoheptonate.

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    Fernanda Batistel

    Full Text Available The peripartum (or transition period is the most-critical phase in the productive life of lactating dairy cows and optimal supply of trace minerals through more bioavailable forms could minimize the negative effects associated with this phase. Twenty Holstein cows received a common prepartal diet and postpartal diet. Both diets were partially supplemented with an inorganic (INO mix of Zn, Mn, and Cu to supply 35, 45, and 6 ppm, respectively, of the diet dry matter (DM. Cows were assigned to treatments in a randomized completed block design, receiving an daily oral bolus with INO or organic trace minerals (AAC Zn, Mn, Cu, and Co to achieve 75, 65, 11, and 1 ppm supplemental, respectively, in the diet DM. Liver tissue and blood samples were collected throughout the experiment. The lower glutamic-oxaloacetic transaminase concentration after 15 days in milk in AAC cows indicate lower hepatic cell damage. The concentration of cholesterol and albumin increased, while IL-6 decreased over time in AAC cows compared with INO indicating a lower degree of inflammation and better liver function. Although the acute-phase protein ceruloplasmin tended to be lower in AAC cows and corresponded with the reduction in the inflammatory status, the tendency for greater serum amyloid A concentration in AAC indicated an inconsistent response on acute-phase proteins. Oxygen radical absorbance capacity increased over time in AAC cows. Furthermore, the concentrations of nitric oxide, nitrite, nitrate, and the ferric reducing ability of plasma decreased with AAC indicating a lower oxidative stress status. The expression of IL10 and ALB in liver tissue was greater overall in AAC cows reinforcing the anti-inflammatory response detected in plasma. The greater overall expression of PCK1 in AAC cows indicated a greater gluconeogenic capacity, and partly explained the greater milk production response over time. Overall, feeding organic trace minerals as complexed with amino acids

  6. Effect of D-penicillamine on rat lung elastin cross-linking during the perinatal period.

    Science.gov (United States)

    Koçtürk, Semra; Oktay, Gülgün; Güner, Gül; Pekçetin, Cetin; Güre, Ataman

    2006-01-01

    This study was designed to clarify the effects of D-penicillamine (DPA), a drug used for treatment of various pathological events, on lung elastin formation and maturation of the newborn in the perinatal period. The investigation was conducted on 20 newborn rats bred from 40 female and six male rats. DPA doses 400 mg kg(-1) day(-1) and physiological saline were given intraperitoneally (i.p) to experimental and control groups. To assess newborn maturation, their body and lung weights were determined. Serum Cu levels were measured by atomic absorption spectroscopy and ceruloplasmin (Cp) activities were measured spectrophotometrically. Newborn lung tissue elastin, desmosine (DES) and isodesmosine (IDES) levels were measured by HPLC. The results showed that DPA treatment caused loss of skin elasticity and reduction in body and lung weight in newborns of the experimental group. The serum Cu levels and Cp activity were found to be significantly lower in both maternal and newborn of the experimental groups compared with the control group. The lung DES, IDES and elastin values of newborns in the experimental group were decreased compared with the control group. In conclusion, our results indicate that 400 mg kg(-1) day(-1) DPA, a dose that is used in the treatment of Wilson's disease, rheumatoid arthritis and cystinuria, caused the retardation of newborn maturation, a decrease in DES-IDES cross-links and levels of lung elastin of offspring in the perinatal period. Another conclusion to be drawn from this study is that even low levels of Cu depletion due to DPA administration induces a change in cross-linking in lung elastin during the perinatal period.

  7. Alteration of gene expression by alcohol exposure at early neurulation

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    McClintick Jeanette N

    2011-02-01

    Full Text Available Abstract Background We have previously demonstrated that alcohol exposure at early neurulation induces growth retardation, neural tube abnormalities, and alteration of DNA methylation. To explore the global gene expression changes which may underline these developmental defects, microarray analyses were performed in a whole embryo mouse culture model that allows control over alcohol and embryonic variables. Result Alcohol caused teratogenesis in brain, heart, forelimb, and optic vesicle; a subset of the embryos also showed cranial neural tube defects. In microarray analysis (accession number GSM9545, adopting hypothesis-driven Gene Set Enrichment Analysis (GSEA informatics and intersection analysis of two independent experiments, we found that there was a collective reduction in expression of neural specification genes (neurogenin, Sox5, Bhlhe22, neural growth factor genes [Igf1, Efemp1, Klf10 (Tieg, and Edil3], and alteration of genes involved in cell growth, apoptosis, histone variants, eye and heart development. There was also a reduction of retinol binding protein 1 (Rbp1, and de novo expression of aldehyde dehydrogenase 1B1 (Aldh1B1. Remarkably, four key hematopoiesis genes (glycophorin A, adducin 2, beta-2 microglobulin, and ceruloplasmin were absent after alcohol treatment, and histone variant genes were reduced. The down-regulation of the neurospecification and the neurotrophic genes were further confirmed by quantitative RT-PCR. Furthermore, the gene expression profile demonstrated distinct subgroups which corresponded with two distinct alcohol-related neural tube phenotypes: an open (ALC-NTO and a closed neural tube (ALC-NTC. Further, the epidermal growth factor signaling pathway and histone variants were specifically altered in ALC-NTO, and a greater number of neurotrophic/growth factor genes were down-regulated in the ALC-NTO than in the ALC-NTC embryos. Conclusion This study revealed a set of genes vulnerable to alcohol exposure and

  8. Menkes disease – An important cause of early onset refractory seizures

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    Puneet Jain

    2014-01-01

    Full Text Available Context: Menkes disease is an X-linked multisystem disorder characterized by early onset of cerebral and cerebellar neurodegeneration, fair skin, hypopigmented sparse hair and connective tissue abnormalities. Aims: We aimed to evaluate the clinical, electrophysiological and radiological features of children with Menkes disease seen at our institute. Setting/Design: The medical records of children diagnosed with Menkes disease admitted in the pediatric neurology ward or attending the special pediatric neurology clinic at a tertiary care and a referral hospital in North India, from January 2010 to December 2012, were retrospectively reviewed. The clinical data of each case was subsequently summarized and reported. Statistical analysis used: Descriptive statistics were used. Results: During the study period, 1174 children were seen. Out of these, 6 cases were diagnosed as Menkes disease on the basis of clinical phenotype, low serum copper and ceruloplasmin and supportive neuroimaging. All the children were males and had disease onset within 3 months of age, with 4 children presenting in the neonatal period. Global developmental delay and refractory seizures were the predominant clinical symptoms. Two children had symptomatic West syndrome. Other seizure semiologies included tonic-clonic (4, myoclonic (2 and tonic seizures (1. The electroencephalographic abnormalities included hypsarrythmia (2 and multifocal epileptiform discharges (3. The salient radiological features included white matter changes, temporal lobe abnormalities, global atrophy, subdural hygromas and tortuous cerebral blood vessels. Conclusions: Menkes disease should be suspected in a case of refractory early onset seizures especially in the presence of subtle clinical clues. The neuroimaging findings may further support the diagnosis.

  9. Menkes disease: what a multidisciplinary approach can do

    Directory of Open Access Journals (Sweden)

    Ojha R

    2016-08-01

    Full Text Available Rahul Ojha,1 Asuri N Prasad1–4 1Department of Pediatrics, 2Section of Pediatric Neurology, 3Division of Clinical Neurological Sciences, 4Child Health Research Institute, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada Abstract: Disorders of copper homeostasis are currently recognized across the life span. Their recognition and links to human disease have spanned several decades, beginning with the recognition of a degenerative disorder in the offspring of sheep grazing in copper-deficient pastures, through to the description of infants suffering from a progressive neurodegenerative disorder characterized by epileptic seizures, developmental regression, failure to thrive, and an unusual hair quality (giving the condition its distinctive label of “kinky hair disease”. In this review, we trace the historical background and describe the biochemistry and physiology of copper metabolism and transport, inheritance patterns, molecular genetics, and genotype–phenotype correlations based on current understanding of the disorder. It is clear from the clinical presentations and variants that disorders of copper homeostasis include phenotypes ranging from mild occipital horn syndrome to intermediate and severe forms of classical Menkes disease. The symptoms involve multiple organ systems such as brain, lung, gastrointestinal tract, urinary tract, connective tissue, and skin. A multisystem disorder needs a multidisciplinary approach to care, as treatment interventions permit longer survival for some individuals. Animal models have been developed to help screen treatment options and provide a better understanding of these disorders in the laboratory. Finally, we propose a multidisciplinary approach to promote continued research (both basic and clinical to improve survival, quality of life, and care for these conditions. Keywords: Menkes disease, kinky hair, ceruloplasmin, neurodegenerative, copper

  10. Treatment of Wilson's disease with zinc. XIII: Therapy with zinc in presymptomatic patients from the time of diagnosis.

    Science.gov (United States)

    Brewer, G J; Dick, R D; Yuzbasiyan-Gurkan, V; Johnson, V; Wang, Y

    1994-06-01

    The siblings of patients with newly diagnosed Wilson's disease are each at 25% risk of also having this autosomal recessive disease. Screening these siblings allows their detection and institution of prophylactic therapy before they become clinically ill. Herein we report the successful treatment of 13 presymptomatic patients with zinc acetate. These patients who received zinc have been followed for 3 to 9 years. In well-complying patients, 24-hour urine copper and non-ceruloplasmin plasma copper levels have decreased over years of follow-up, consistent with the elimination of the excess easily mobilized copper (the potentially toxic copper) of the body. Effect of therapy and compliance are easily monitored by following 24-hour urine zinc and copper levels. The urine copper level is a good reflection of the body's excess load of easily mobilizable copper. It will increase if control is not adequate. A decrease in urine zinc is an early signal that the patient's compliance is not optimal. The levels of hepatic copper in response to several years of zinc therapy may remain the same, go down, or go up temporarily. This is a reflection of zinc induction of hepatic metallothionein, which sequesters copper in a non-toxic pool. Hepatic copper levels should not be used to manage therapy. Liver function is well preserved by zinc therapy, and no zinc toxicity occurred in these 13 patients. No patient developed symptoms related to Wilson's disease. We conclude that zinc acetate is a fully effective and non-toxic therapy for the prophylactic treatment of the presymptomatic Wilson's disease patient.

  11. Refractory rickets due to Fanconi′s Syndrome secondary to Wilson′s disease

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    Chitra Selvan

    2012-01-01

    Full Text Available Renal tubular disorders are an important cause of refractory rickets. Wilson′s disease, an inherited disorder of copper metabolism has varied presentations. We present a case of refractory rickets due to Fanconi′s syndrome attributable to Wilson′s disease. An adolescent girl presented with pain in the hip and knee joints and a knock-knee deformity since six years. She had received multiple doses of cholecalciferol with little improvement. There was no history of seizures, polyuria, jaundice, intake of drugs, or similar complaints in the family. Examination revealed a severely short stature with widening of the wrist joint and genu valgum. Examination of the central nervous system (CNS was normal. Skeletal radiographs showed features suggestive of rickets at the hip and knee joints. Routine biochemistry was normal, 25-hydroxyvitamin D [25(OHD] was adequate (57.1 ng/dL, with normal corrected calcium (9.24 mg/dL, low phosphate (2.76 mg/dL, elevated bone-specific alkaline phosphatase, and normal renal functions. Twenty-four-hour urine revealed phosphaturia, kaliuresis, and glucosuria with normal blood sugars and aminoaciduria. Blood gas analysis revealed normal anion gap metabolic acidosis with a urine pH of 7. Ammonium chloride (NH 4 CL challenge test revealed proximal tubular acidosis. A search for causes revealed Kayser-Fleischer rings. The diagnosis of Wilson′s disease was confirmed by low serum ceruloplasmin levels (6.5 mg/dL; normal: 18-35 mg/dL with high 24-hour urine copper levels (433 mcg; normal: 20-50 mcg. She was started on a replacement of alkali, phosphate, calcium, and vitamin D, with zinc acetate for Wilson′s disease. Rickets as a presenting feature of Wilson′s disease has been reported rarely. Recognition of this entity is important, as treatment of the primary condition may improve tubular function as well.

  12. Concurrent overexpression of serum p53 mutation related with Helicobacter pylori infection

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    Lorenzo-Peñuelas Antonio

    2010-06-01

    Full Text Available Abstract Background & Aims In the province of Cadiz (Spain, the adjusted mortality rate for gastric cancer in the coastal town of Barbate is 10/100.000 inhabitants, whereas in the inland town of Ubrique, the rate is twice as high. The rate of Helicobacter pylori (H. pylori infection (H. pylori antibodies in the normal population was 54% in Ubrique, but only 32% in Barbate. In the two decades since its original discovery, p53 has found a singularly prominent place in our understanding of human gastric cancer and H. pylori cause accumulation of reactive oxygen species in the mucosa compartment. This study was designed to compare serum levels of p53 in a population characterized by high mortality due to stomach cancer and a high prevalence of H. pylori infection and another population in which mortality from this cause and the prevalence of H. pylori infection are low. Materials and methods 319 subjects from the low mortality population and 308 from the high mortality population were studied, as were 71 patients with stomach cancer. We measured serum immunoglobulin G antibody to H. pylori and serum mutant p53 protein and ceruloplasmin. Results The difference between the two populations in the prevalence of H. pylori infection was significant (p Conclusions There is a significant association between infection with H. pylori, elevated titers of H. pylori antibodies, and positivity for serum mutant p53 protein. Such information can significantly increase our basic knowledge in molecular pathology of gastric cancer and protection against H. pylori infection.

  13. ANAESTHETIC MANAGEMENT OF A PATIENT WITH WILSON’S DISEASE POSTED FOR EMERGENCY LSCS: A CASE REPORT

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    Kousalya

    2015-06-01

    Full Text Available Wilson’s disease (WD, or hepatolenticular degeneration, is a rare autosomal recessive disorder with a prevalence of 1:50,000 - 1:100,000 live births . 1 The genetic disorder causes a reduction in the synthesis of the copper transporting protein ceruloplasmin. Clinical presentation may vary from asymptomatic patients to those presenting with fulminant liver disease or neurological symptoms or psychiatric illness. The course of events in a pregnant patient depends upon the preconception status of the disease spectrum. The neuro - psychiatric illness and hepatorenal involvement in antenatal period may get worsene d. The risk of ascitis, Gatrointestinal bleeding and Varicial rupture is increased in pregnant women with pre - existing cirrhosis. Elevated serum copper levels are associated with post - partum depression (PPD. Copper accumulation may lead to erythrocyte hemolysis resulting in Coombs negative haemolytic anaemia (10 – 15%. There is also an increased risk of Hypertensive disorders in Pregnancy, HELLP syndrome and placental abruption. The disease status at the time of presentation for surgery should determine the mode of Anaesthesia, intraoperative management and post - operative care. Hepatic dysfunction can cause delayed recovery with General anaesthesia. Pre - existing neuro psychological problems may get aggravated by the hypnotic and sedative drugs. Excessive copper may interfere with neuromuscular transmission. Pre - existing neurological deficiency must be documented before attempting an Epidural or a subarachnoid block. We report a case of a primigravida with previously diagnosed Wilson’s disease initially presented with neurological symptoms and muscular weakness in the lower limbs. Though treated for 3yrs with trientene and zinc, she was on irregular treatment when posted for Emergency Caesarean section. After a proper Preanesthetic evaluation of the patient, LSCS was conducted under subarachnoid block. A good intra operative

  14. Evaluation of antiinflammatory activity ofTephrosia purpurea in rats

    Institute of Scientific and Technical Information of China (English)

    Shenoy Smita; Shwetha K; Prabhu K; Maradi R; Bairy KL; Shanbhag T

    2010-01-01

    Objective:To evaluate the antiinflammatory activity of orally administered ethanolic extract of Tephrosia purpurea in acute and subacute inflammation in rats.Methods: An ethanolic extract of Tephrosia purpurea was prepared. Carrageenan induced paw edema and cotton pellet granuloma were the models for acute and subacute inflammation respectively. Four groups of rats in each model were treated orally with 2% gum acacia, 100 mg /kg of aspirin, 500 mg/kg and 1 000 mg/kg of ethanolic extract ofTephrosia purpurea respectively. In carrageenan induced paw edema model, subplantar injection of 1% carrageenan was made into the hind paw of the rats sixty minutes after the administration of the respective drugs. The paw volume was measured immediately after injection of carrageenan, at 3 hours and at 6 hours. Then percentage inhibition of edema was calculated. In the cotton pellet granuloma model, animals were administered drugs for six days after placing cotton pellets in the axilla on each side. On the 7th day, dry weight of granuloma was calculated.Results:The rats treated withTephrosia purpurea did not exhibit any significant decrease in paw volume and serum ceruloplasmin levels as compared to the control and aspirin treated groups in the acute inflammation model; while, there was a significant (P < 0.01) decrease in the weight of granuloma inTephrosia purpurea and aspirin treated groups as compared to control in subacute inflammation.Conclusions:The ethanolic extract of orally administered Tephrosia purpurea shows significant antiinflammatory effect in subacute inflammation but not in acute inflammation in rats.

  15. High-Iron Consumption Impairs Growth and Causes Copper-Deficiency Anemia in Weanling Sprague-Dawley Rats.

    Science.gov (United States)

    Ha, Jung-Heun; Doguer, Caglar; Wang, Xiaoyu; Flores, Shireen R; Collins, James F

    2016-01-01

    Iron-copper interactions were described decades ago; however, molecular mechanisms linking the two essential minerals remain largely undefined. Investigations in humans and other mammals noted that copper levels increase in the intestinal mucosa, liver and blood during iron deficiency, tissues all important for iron homeostasis. The current study was undertaken to test the hypothesis that dietary copper influences iron homeostasis during iron deficiency and iron overload. We thus fed weanling, male Sprague-Dawley rats (n = 6-11/group) AIN-93G-based diets containing high (~8800 ppm), adequate (~80) or low (~11) iron in combination with high (~183), adequate (~8) or low (~0.9) copper for 5 weeks. Subsequently, the iron- and copper-related phenotype of the rats was assessed. Rats fed the low-iron diets grew slower than controls, with changes in dietary copper not further influencing growth. Unexpectedly, however, high-iron (HFe) feeding also impaired growth. Furthermore, consumption of the HFe diet caused cardiac hypertrophy, anemia, low serum and tissue copper levels and decreased circulating ceruloplasmin activity. Intriguingly, these physiologic perturbations were prevented by adding extra copper to the HFe diet. Furthermore, higher copper levels in the HFe diet increased serum nonheme iron concentration and transferrin saturation, exacerbated hepatic nonheme iron loading and attenuated splenic nonheme iron accumulation. Moreover, serum erythropoietin levels, and splenic erythroferrone and hepatic hepcidin mRNA levels were altered by the dietary treatments in unanticipated ways, providing insight into how iron and copper influence expression of these hormones. We conclude that high-iron feeding of weanling rats causes systemic copper deficiency, and further, that copper influences the iron-overload phenotype. PMID:27537180

  16. Identification of genomic biomarkers for concurrent diagnosis of drug-induced renal tubular injury using a large-scale toxicogenomics database

    International Nuclear Information System (INIS)

    Drug-induced renal tubular injury is one of the major concerns in preclinical safety evaluations. Toxicogenomics is becoming a generally accepted approach for identifying chemicals with potential safety problems. In the present study, we analyzed 33 nephrotoxicants and 8 non-nephrotoxic hepatotoxicants to elucidate time- and dose-dependent global gene expression changes associated with proximal tubular toxicity. The compounds were administered orally or intravenously once daily to male Sprague-Dawley rats. The animals were exposed to four different doses of the compounds, and kidney tissues were collected on days 4, 8, 15, and 29. Gene expression profiles were generated from kidney RNA by using Affymetrix GeneChips and analyzed in conjunction with the histopathological changes. We used the filter-type gene selection algorithm based on t-statistics conjugated with the SVM classifier, and achieved a sensitivity of 90% with a selectivity of 90%. Then, 92 genes were extracted as the genomic biomarker candidates that were used to construct the classifier. The gene list contains well-known biomarkers, such as Kidney injury molecule 1, Ceruloplasmin, Clusterin, Tissue inhibitor of metallopeptidase 1, and also novel biomarker candidates. Most of the genes involved in tissue remodeling, the immune/inflammatory response, cell adhesion/proliferation/migration, and metabolism were predominantly up-regulated. Down-regulated genes participated in cell adhesion/proliferation/migration, membrane transport, and signal transduction. Our classifier has better prediction accuracy than any of the well-known biomarkers. Therefore, the toxicogenomics approach would be useful for concurrent diagnosis of renal tubular injury.

  17. Metallothionein and antioxidant enzymes in Long-Evans Cinnamon rats treated with zinc

    Energy Technology Data Exchange (ETDEWEB)

    Medici, Valentina; Sturniolo, Giacomo Carlo; D' Inca, Renata [Department of Surgical and Gastroenterological Sciences, University of Padua, Padua (Italy); Santon, Alessandro; Giannetto, Sabrina; Albergoni, Vincenzo; Irato, Paola [Department of Biology, University of Padua, via U. Bassi 58/B, 35131 Padua (Italy)

    2002-09-01

    The Long-Evans Cinnamon (LEC) rat is a mutant animal model for Wilson's disease. It is known that an abnormal accumulation of Cu and Fe in the liver and low concentrations of both ceruloplasmin and Cu in the serum occur in these rats. The accumulation of Cu is explained by the defective expression of the Cu-transporting P-type ATPase gene, homologous to the gene for Wilson's disease (ATP7B). The aim of this work was to clarify the action mechanism of Zn, and to verify the role that this metal plays in LEC rats in short-term treatment experiments (1 and 2 weeks) on concentrations of Cu, Zn, Fe, metallothionein (MT), 8-hydroxy-2'-deoxyguanosine (oh{sup 8}dG) and on the activity of antioxidant enzymes. It is well known that Zn induces MT and has the ability to prevent redox-active metals, Cu and Fe, binding to and causing oxidative damage at active sites of Zn metalloenzymes and nonspecific binding sites on proteins. Zn administration reduces Cu and Fe transport from mucosal to serosal intestinal sides through competitive mechanisms. Our findings show that treatment with zinc acetate increases tissue Zn and MT contents and decreases Cu and Fe concentrations in the liver and kidneys, even if hepatic Zn and MT concentrations decrease with treatment period. Induction of MT synthesis by Zn contributes to the reduction in free radicals produced by Cu and Fe. We also observed that the superoxide dismutase (SOD)activity in liver decreases with treatment duration in association with the Cu and Fe liver decrease. However, the SOD activity in kidney increases in untreated rats at 2 weeks relative to those untreated for 1 week. (orig.)

  18. Gene Expression Patterns Associated With Histopathology in Toxic Liver Fibrosis.

    Science.gov (United States)

    Ippolito, Danielle L; AbdulHameed, Mohamed Diwan M; Tawa, Gregory J; Baer, Christine E; Permenter, Matthew G; McDyre, Bonna C; Dennis, William E; Boyle, Molly H; Hobbs, Cheryl A; Streicker, Michael A; Snowden, Bobbi S; Lewis, John A; Wallqvist, Anders; Stallings, Jonathan D

    2016-01-01

    Toxic industrial chemicals induce liver injury, which is difficult to diagnose without invasive procedures. Identifying indicators of end organ injury can complement exposure-based assays and improve predictive power. A multiplexed approach was used to experimentally evaluate a panel of 67 genes predicted to be associated with the fibrosis pathology by computationally mining DrugMatrix, a publicly available repository of gene microarray data. Five-day oral gavage studies in male Sprague Dawley rats dosed with varying concentrations of 3 fibrogenic compounds (allyl alcohol, carbon tetrachloride, and 4,4'-methylenedianiline) and 2 nonfibrogenic compounds (bromobenzene and dexamethasone) were conducted. Fibrosis was definitively diagnosed by histopathology. The 67-plex gene panel accurately diagnosed fibrosis in both microarray and multiplexed-gene expression assays. Necrosis and inflammatory infiltration were comorbid with fibrosis. ANOVA with contrasts identified that 51 of the 67 predicted genes were significantly associated with the fibrosis phenotype, with 24 of these specific to fibrosis alone. The protein product of the gene most strongly correlated with the fibrosis phenotype PCOLCE (Procollagen C-Endopeptidase Enhancer) was dose-dependently elevated in plasma from animals administered fibrogenic chemicals (P < .05). Semiquantitative global mass spectrometry analysis of the plasma identified an additional 5 protein products of the gene panel which increased after fibrogenic toxicant administration: fibronectin, ceruloplasmin, vitronectin, insulin-like growth factor binding protein, and α2-macroglobulin. These results support the data mining approach for identifying gene and/or protein panels for assessing liver injury and may suggest bridging biomarkers for molecular mediators linked to histopathology.

  19. The nutritive effect and toxicity of copper and zinc in mice

    Institute of Scientific and Technical Information of China (English)

    WangXZ; YangZQ

    2002-01-01

    The objective of this study was to determine whether the marginal deficient and excessive copper(Cu) and zinc(Zn) would affect the biological indices and cellular structure.Two hundreds mice were divided randomly into 5 groups.Mice were fed with normal diet in control;and supplemented with Cu at 15.9,31.9,63.7 or 127mg·kg-1 in group Ⅱ,at 2.36mg·kg-1 in group Ⅳ;Zn at 126,252,505 and 1010mg·kg-1 in group Ⅲ,at 9.32mg·kg-1 in group Ⅴ.Ten mice were sampled from each group and sacrificed on day 30,60,80 and 95,and the activities of alkaline phosphatase(AKP),superoxidation dismutase (SOD) and ceruloplasmin(CPL) in plasma were determined,the histopathology of organs were observed.The results showed that marginal excessive Cu and Zn in diet had an evidently nutritive effect on growth (P>0.05),increased the Cu and Zn accumulation in liver(P0.05).With the increase of Zn or Cu in diet,the activities of enzymes came to a lower-level(P<0.05).Mouse growth was suppressed.Also,the low-level Cu or Zn in diet reduced the mouse growth,decreased the activities of plasma AKP,CPL and SOD.The marginal deficient or excessive Cu and Zn had serious damages in histology of organs,such as cloudy swelling,necrosis,cytoplasm crack,pyknosis or karyolysis,coagulation necrosis.

  20. Acute mammary and liver transcriptome responses after an intramammary Escherichia coli lipopolysaccharide challenge in postpartal dairy cows.

    Science.gov (United States)

    Minuti, Andrea; Zhou, Zheng; Graugnard, Daniel E; Rodriguez-Zas, Sandra L; Palladino, Alejandro R; Cardoso, Felipe C; Trevisi, Erminio; Loor, Juan J

    2015-04-01

    The study investigated the effect of an intramammary lipopolysaccharide (LPS) challenge on the bovine mammary and liver transcriptome and its consequences on metabolic biomarkers and liver tissue composition. At 7 days of lactation, 7 cows served as controls (CTR) and 7 cows (LPS) received an intramammary Escherichia coli LPS challenge. The mammary and liver tissues for transcriptomic profiling were biopsied at 2.5 h from challenge. Liver composition was evaluated at 2.5 h and 7 days after challenge, and blood biomarkers were analyzed at 2, 3, 7 and 14 days from challenge. In mammary tissue, the LPS challenge resulted in 189 differentially expressed genes (DEG), with 20 down-regulated and 169 up-regulated. In liver tissue, there were 107 DEG in LPS compared with CTR with 42 down-regulated and 65 up-regulated. In mammary, bioinformatics analysis highlighted that LPS led to activation of NOD-like receptor signaling, Toll-like receptor signaling, RIG-I-like receptor signaling and apoptosis pathways. In liver, LPS resulted in an overall inhibition of fatty acid elongation in mitochondria and activation of the p53 signaling pathway. The LPS challenge induced changes in liver lipid composition, a systemic inflammation (rise of blood ceruloplasmin and bilirubin), and an increase in body fat mobilization. The data suggest that cells within the inflamed mammary gland respond by activating mechanisms of pathogen recognition. However, in the liver the response likely depends on mediators originating from the udder that affect liver functionality and specifically fatty acid metabolism (β-oxidation, ketogenesis, and lipoprotein synthesis).

  1. Immunometabolic Status during the Peripartum Period Is Enhanced with Supplemental Zn, Mn, and Cu from Amino Acid Complexes and Co from Co Glucoheptonate

    Science.gov (United States)

    Batistel, Fernanda; Osorio, Johan S.; Ferrari, Annarita; Trevisi, Erminio; Socha, Michael T.; Loor, Juan J.

    2016-01-01

    The peripartum (or transition) period is the most-critical phase in the productive life of lactating dairy cows and optimal supply of trace minerals through more bioavailable forms could minimize the negative effects associated with this phase. Twenty Holstein cows received a common prepartal diet and postpartal diet. Both diets were partially supplemented with an inorganic (INO) mix of Zn, Mn, and Cu to supply 35, 45, and 6 ppm, respectively, of the diet dry matter (DM). Cows were assigned to treatments in a randomized completed block design, receiving an daily oral bolus with INO or organic trace minerals (AAC) Zn, Mn, Cu, and Co to achieve 75, 65, 11, and 1 ppm supplemental, respectively, in the diet DM. Liver tissue and blood samples were collected throughout the experiment. The lower glutamic-oxaloacetic transaminase concentration after 15 days in milk in AAC cows indicate lower hepatic cell damage. The concentration of cholesterol and albumin increased, while IL-6 decreased over time in AAC cows compared with INO indicating a lower degree of inflammation and better liver function. Although the acute-phase protein ceruloplasmin tended to be lower in AAC cows and corresponded with the reduction in the inflammatory status, the tendency for greater serum amyloid A concentration in AAC indicated an inconsistent response on acute-phase proteins. Oxygen radical absorbance capacity increased over time in AAC cows. Furthermore, the concentrations of nitric oxide, nitrite, nitrate, and the ferric reducing ability of plasma decreased with AAC indicating a lower oxidative stress status. The expression of IL10 and ALB in liver tissue was greater overall in AAC cows reinforcing the anti-inflammatory response detected in plasma. The greater overall expression of PCK1 in AAC cows indicated a greater gluconeogenic capacity, and partly explained the greater milk production response over time. Overall, feeding organic trace minerals as complexed with amino acids during the

  2. Influence of dietary copper concentrations on growth performance, serum lipid profiles, antioxidant defenses, and fur quality in growing-furring male blue foxes (Vulpes lagopus).

    Science.gov (United States)

    Liu, Z; Wu, X; Zhang, T; Cui, H; Guo, J; Guo, Q; Gao, X; Yang, F

    2016-03-01

    A 75-d experiment was conducted to evaluate the influence of dietary Cu concentrations on growth performance, serum lipid profiles, antioxidant defenses, and fur quality in growing-furring male blue foxes. Seventy-five male blue foxes (5.78 ± 0.09 kg BW) were selected and randomly allocated to 1 of the following 5 dietary treatments: 1) control (basal diet without supplemental Cu; 7.78 mg Cu/kg), 2) 12.22 mg/kg supplemental Cu (Cu20), 3) 32.22 mg/kg supplemental Cu, 4) 72.22 mg/kg supplemental Cu (Cu80), and 5) 152.22 mg/kg supplemental Cu (Cu160). A dry feed that consisted of animal meals, soybean meal, extruded corn, and soybean oil was used as the basal diet and Cu was supplemented as reagent grade CuSO∙5HO. The results showed that Cu supplementation increased the ADG ( 0.10). Additionally, Cu supplementation linearly increased the concentration of fecal Cu, liver Cu, serum total protein, and albumin ( < 0.01). Foxes in the Cu160 group had higher serum Cu concentration than those in the control and Cu20 groups ( < 0.05). The concentration of serum cholesterol decreased with dietary Cu supplementation ( < 0.05). Serum high-density lipoprotein, on the contrary, tended to increase with Cu supplementation ( = 0.09). Copper supplementation increased the activity of glutathione peroxidase ( < 0.05) and tended to increase the activity of serum ceruloplasmin ( = 0.07). For fur quality, skin length in the Cu80 group was greater than that in the control and Cu20 groups. In addition, hair color tended to deepen with the increasing of dietary Cu concentrations ( = 0.08). In conclusion, this study demonstrates that Cu supplementation can promote growth and increase fat digestibility and fur length. Additionally, dietary Cu supplementation can enhance antioxidant capacity and reduce serum cholesterol in growing-furring blue foxes. PMID:27065271

  3. Alterations in oxidant/antioxidant balance, high-mobility group box 1 protein and acute phase response in cross-bred suckling piglets suffering from rotaviral enteritis.

    Science.gov (United States)

    Kumar De, Ujjwal; Mukherjee, Reena; Nandi, Sukdeb; Patel, Bhimnere Hanumatnagouda Manjunatha; Dimri, Umesh; Ravishankar, Chintu; Verma, Ashok Kumar

    2014-10-01

    Rotaviral enteritis has emerged as a major cause of morbidity and mortality in piglets during their post-natal life. The present study was carried out to examine high-mobility group box 1 (HMGB1) protein, acute phase response and oxidative stress indices in the serum of suckling piglets suffering from enteritis with or without association of porcine group A rotavirus infection. The present investigation utilized 23 clinical cases with signs of acute enteritis and 12 more healthy piglets of a similar age group as control animals. Out of 23 enteritis cases, 12 cases were found to be positive for porcine group A rotavirus infection as confirmed by reverse transcription-polymerase chain reaction (RT-PCR) using specific primers for group A rotavirus, and the rest were found negative. The acute enteritis cases in piglets were associated with an elevated level of HMGB1 protein and serum haptoglobin and ceruloplasmin suggestive of an acute phase response. Among the oxidative stress indices, the concentrations of malondialdehyde (MDA) and nitric oxide (NO) in serum were significantly increased. A pronounced drop of total antioxidant capacity and the activity of antioxidant enzymes such as catalase and superoxide dismutase in the serum of piglets suffering from acute enteritis compared to healthy ones were also noticed. The alterations in HMGB1 protein, acute phase response and oxidative stress indices were more pronounced in cases with the involvement of porcine rotavirus as compared to rotavirus-negative cases. It is concluded that HMGB1 protein, markers of oxidative stress and acute phase proteins might play an important role in the aetiopathogenesis of porcine diarrhoea caused by rotavirus and might be true markers in diagnosing the conditions leading to the extension of the prompt and effective therapeutic care.

  4. CT findings of Wilson's disease

    International Nuclear Information System (INIS)

    Thirteen cases of Wilson's disease were examined by computerized tomography. Two of them were latent cases. The other 11 were typical cases with a Kayser-Fleisher ring and neurological signs, and in which the ceruloplasmin level in serum was low. The caudate heads were measured by Barr's method using two ratios, FH/CC and CC/OT. The CT findings were as follows: (1) caudate head atrophy (10 cases), (2) cerebral atrophy and/or ventricular dilatation (7 cases), (3) symmetrical low density of thalamus (3 cases), (4) symmetrical low density of pallidum (2 cases), (5) low density of midbrain (2 cases), (6) symmetrical low density of putamen (1 case), (7) pons atrophy (1 case), (8) cerebellar atrophy (1 case), (9) low density of r-temporal area (1 case). All of them except for the two latent cases showed some abnormal findings on CT. Only one symptomatic case showed no caudate atrophy one year after the onset, though two other cases already showed marked atrophy after only 10 months. It was stressed that the low-density lesions in the thalamic area were found with a high frequency. There was no correlation between the duration of illness and the degree of caudate atrophy among the patients with Wilson's disease as compared with those with Huntington's chorea. As in a previous study of pneumoencephalography, we failed also to distinguish the two diseases by measuring the ratios on CT films. It may be valuable to study the progression of the CNS lesions of Wilson's disease by using CT repeatedly. (author)

  5. Creutzfeldt-Jakob disease, Heidenhain variant: case report with MRI (DWI) findings; Doenca de Creutzfeldt-Jakob forma Heidenhain: relato de caso com achados de ressonancia magnetica e DWI

    Energy Technology Data Exchange (ETDEWEB)

    Arruda, Walter Oleschko; Bordignon, Kelly C.; Milano, Jeronimo B.; Ramina, Ricardo [Instituto de Neurologia de Curitiba, PR (Brazil)]. E-mail: warruda@speednet.com.br

    2004-06-01

    Creutzfeldt-Jakob disease (CJD) is a pre senile dementia characterized by rapidly progressive mental deterioration, myoclonic jerking, and other less common neurological signs. Few accentuates cases have been described in Brazil. A 54-year-old white woman, was admitted in our service with a month history of progressive, bilateral cortical blindness. After admission, she developed right partial motor seizures (right facial, upper and lower limbs), she became progressively aphasic (mixed aphasia). Seizures were controlled with phenytoine, but she developed choreoathetotic movements on her right dimidium, with partial control after introduction of chlorpromazine 25 mg q/d. She could no longer stand up or walk due to severe ataxia. The first EEG (October, 2001) showed left hemisphere severe seizure activity (status epilepticus partial is). She was delivered home with enteral nutrition, phenytoine, chlorpromazine and mepacrine 100 mg q d. The following laboratory tests were negative or normal: blood series, platelets, ESR, kidney and liver function, copper, ceruloplasmin, Vedril, HIV, HTLV-1, lactate, and cerebral Dsa (performed in other service). A spinal tap with normal opening pressure was perform and CSFR examination was normal. CSFR 14-3-3 protein was positive, CSF specific neuronal enolase 7.5 ng/ml(normal). Genetic study of PRNP gene did not disclosed any known mutation. A MRI (October, 2001) showed areas of hyperintense signal (T 2 and FLAIR) without Gd-enhancement on T1, in the left temporal lobe and in both occipital lobes; basal ganglia have a normal appearance. DWI imaging showed bright areas at the same sites. An EEG (March, 2002) disclosed a periodical sharp triphasic waves pattern, suggestive of CJD. A second MRI (April, 2002) showed mild generalized atrophy, no ventricular dilatation, and the hyperintense sites disappeared. She remained clinically stable and under use of chlorpromazine and mepacrine until she died due to pulmonary complications on April

  6. Macronutrients, aluminium from drinking water and foods, and other metals in cognitive decline and dementia.

    Science.gov (United States)

    Solfrizzi, Vincenzo; Colacicco, Anna Maria; D'Introno, Alessia; Capurso, Cristiano; Parigi, Angelo Del; Capurso, Sabrina A; Torres, Francesco; Capurso, Antonio; Panza, Francesco

    2006-11-01

    A possible role of the macronutrients and the basic elements of carbohydrates (glucose administration or depletion), proteins (amino acids such as tryptophan and tyrosine), and fat (unsaturated fatty acids) was recently proposed for age-related changes of cognitive function, and the cognitive decline of degenerative (AD) or vascular origin. The availability and utilization of glucose has been implicated in cognitive function not only as a result of nutritional and systemic metabolic conditions, but also, although speculatively, as a crucial phase of the mechanism of action of molecules used as cognitive-enhancers. Furthermore, many lines of evidence have focused on the importance of oxidative stress mechanisms and free radical damage in AD pathogenesis. In addition, epidemiological studies have recently reported an association between alcohol and the incidence of AD and predementia syndromes. Foods with large amounts of aluminium-containing additives or aluminium from drinking water may affect the risk of developing AD, aluminium more likely acting as a cofactor somewhere in the cascade of events leading to the demented brain. A role for other metals in dementia have been speculated, given the encouraging results reported from studies on peripheral zinc concentrations, zinc supplementation, serum copper, either bound with ceruloplasmin or not, and iron metabolism in AD. Nonetheless, more data are needed to support a possible role of these metals in dementing diseases. Healthy diets, antioxidant supplements, and the prevention of nutritional deficiencies or exposure to foods and water with high content of metals could be considered the first line of defence against the development and progression of cognitive decline.

  7. Interaction of phytic acid and zinc affecting copper bioavailability in rats

    International Nuclear Information System (INIS)

    The objectives of this investigation were to develop a protocol to measure Cu bioavailability using four different indices of Cu status, and to evaluate the effect of phytic acid on Cu bioavailability using these indices in the rat. Ninety-six Sprague-Dawley male weanling rats were fed a Cu-deficient diet for four weeks. The Cu-depleted rats were divided into twelve groups and fed test diets containing 1, 2, 3, and 10 ug Cu and 0, 0.4 and 0.8% phytic acid at each Cu level. After 3 days of Cu repletion, liver copper (LCu), liver superoxide dismutase (LSOD) activity, serum copper (SCu), and serum ceruloplasmin (CP) were measured. There was a significant decrease in SCu and LCu in rats fed 30 ug Zn/g or 230 ug Zn/g compared to animals fed 12 ug Zn/g. Phytic acid increased the level of Cu in the sera and livers of rats fed the diet with 30 ug Zn/g, but those of rats fed 12 or 230 ug Zn/g did not. Dietary phytic acid appeared to reduce the synthesis of two intestinal proteins: a high molecular weight protein and metallothionein. The incorporation of 35S-cysteine into both proteins increased with increasing levels of dietary Zn. The results of these studied indicated: (1) LCu and SCu are reliable indices of Cu for absorption and utilization in the rat, and (2) phytic acid increases Cu bioavailability by binding dietary Zn and reduces the level of Zn-induced mucosal proteins which allows Cu to be more efficiently absorbed

  8. Computational modeling and analysis of iron release from macrophages.

    Directory of Open Access Journals (Sweden)

    Alka A Potdar

    2014-07-01

    Full Text Available A major process of iron homeostasis in whole-body iron metabolism is the release of iron from the macrophages of the reticuloendothelial system. Macrophages recognize and phagocytose senescent or damaged erythrocytes. Then, they process the heme iron, which is returned to the circulation for reutilization by red blood cell precursors during erythropoiesis. The amount of iron released, compared to the amount shunted for storage as ferritin, is greater during iron deficiency. A currently accepted model of iron release assumes a passive-gradient with free diffusion of intracellular labile iron (Fe2+ through ferroportin (FPN, the transporter on the plasma membrane. Outside the cell, a multi-copper ferroxidase, ceruloplasmin (Cp, oxidizes ferrous to ferric ion. Apo-transferrin (Tf, the primary carrier of soluble iron in the plasma, binds ferric ion to form mono-ferric and di-ferric transferrin. According to the passive-gradient model, the removal of ferrous ion from the site of release sustains the gradient that maintains the iron release. Subcellular localization of FPN, however, indicates that the role of FPN may be more complex. By experiments and mathematical modeling, we have investigated the detailed mechanism of iron release from macrophages focusing on the roles of the Cp, FPN and apo-Tf. The passive-gradient model is quantitatively analyzed using a mathematical model for the first time. A comparison of experimental data with model simulations shows that the passive-gradient model cannot explain macrophage iron release. However, a facilitated-transport model associated with FPN can explain the iron release mechanism. According to the facilitated-transport model, intracellular FPN carries labile iron to the macrophage membrane. Extracellular Cp accelerates the oxidation of ferrous ion bound to FPN. Apo-Tf in the extracellular environment binds to the oxidized ferrous ion, completing the release process. Facilitated-transport model can

  9. The influence of intermittent hypobaric hypoxia on the brain iron metabolism in adult Sprague dawley rats

    Institute of Scientific and Technical Information of China (English)

    Wu Qiong; Li Yaru; Chang Yanzhong

    2015-01-01

    Objective:Iron is an essential element in all living organisms and is required as a cofactor for oxygen-binding proteins. Iron metabolism, oxygen homeostasis and erythropoiesis are consequently strongly inter-connected. In mammalian cells, exposure to a low-oxygen environment triggers a hypoxic response pathway cen-tered on the regulated expression of the hypoxia-inducible transcription factor ( HIF) . Hypoxia has been shown to increase the expression of a variety of proteins involved in iron homeostasis. However, little is known about brain iron metabolism after intermittent hypobaric hypoxia ( IHH) treatment. In this study, adult Sprague dawley ( SD) rats were treated with IHH for 28 days, 8h per day and then we detected iron homeostasis in different brain areas of SD rats. Results:The protein level of hippocampus transferrin receptor 1 ( TfR1 ) , divalent metal transporter 1 (DMT1) with IRE, DMT1 (-IRE), ferritin-H, iron regulatory protein (IRP) 2 and ceruloplasmin (CP) is ele-vated significantly while ferritin-L decreased. We have also found the down regulation of IRP1. We observe the same results in the cerebral cortex in the brain. Conclusions:We first discover that IHH has an influence on the brain iron homeostasis and the decreased ferritin-L corresponds to the down regulation of IRP1 indicating hypoxia can affect the expression of ferritin-L through IRE/IRP system. Although there is a marked increase in TfR1 ex-pression that would lead to the raised level of LIP in cells. It can finally result in the higher ROS which can damage the cells. The concerned mechanisms involved in it remain to be deliberated.

  10. Varying Dietary Levels of Molybdenum Inducing Cell Apoptosis of Spleen Under Cadmium Stress in Caprine.

    Science.gov (United States)

    Xiao, Qingyang; Zhang, Caiying; Gu, Xiaolong; Zhuang, Yu; Luo, Junrong; Liu, Ping; Guo, Xiaoquan; Hu, Guoliang; Cao, Huabin

    2016-07-01

    The present experiment aims at evaluating chronic toxic effects of the combination of cadmium (Cd) and molybdenum (Mo) according to residual element contents, apoptosis gene expression, and ultrastructure and histopathology changes of caprine spleen. In total, 36 Boer goats were randomly divided into four groups with the equal number in each group. The control group was orally administered with deionized water while the experimental groups I, II, and III were administered with the equal quantity of CdCl2 (1 mg kg(-1) BW) and (NH4)6·Mo7O24·4H2O including 15, 30, and 45 mg·Mo kg(-1) BW, respectively. Three individuals from each group were treated with euthanasia on days 0, 25, and 50. The data showed that the content of splenic residual Mo and Cd increased (P < 0.05) in the experimental groups on days 25 and 50, while no significant difference was observed in the content of Cu. The apoptosis-related gene expression levels including Bcl-2, Bax, Caspase-3, Smac, and ceruloplasmin (CP) were also determined. Results showed that significant reductions were observed in Bcl-2 and CP expressions (P < 0.01), while Caspase-3 gene was up-regulated (P < 0.05). However, no significant difference was observed in Smac and Bax expressions. Furthermore, on day 50, spleen tissues were presented to observe ultrastructural changes in lesions by means of transmission electron microscopy, with fragmentized nucleus, vesiculation of cytoplasm, mitochondria hyperplasia, and increasing lysosomes included. In addition, histopathology results corroborated the toxicity by showing cell hemorrhage, thickening central arteries, and enhanced capsule thickness. To sum up, our study revealed that the combination of Cd and Mo could induce remarkable damage to the spleen of goats by promoting cell apoptosis in the mitochondrial pathway and affecting the deposition of Mo and Cd. PMID:26585322

  11. Urinary proteomic shotgun approach for identification of potential acute rejection biomarkers in renal transplant recipients

    Directory of Open Access Journals (Sweden)

    Loftheim Håvard

    2012-08-01

    Full Text Available Abstract Background Acute rejection (AR episodes in renal transplant recipients are suspected when plasma creatinine is elevated and other potential causes out ruled. Graft biopsies are however needed for definite diagnosis. Non-invasive AR-biomarkers is an unmet clinical need. The urinary proteome is an interesting source in the search for such a biomarker in this population. Methods In this proof of principle study, serial urine samples in the early post transplant phase from 6 patients with biopsy verified acute rejections and 6 age-matched controls without clinical signs of rejection were analyzed by shotgun proteomics. Results Eleven proteins fulfilled predefined criteria for regulation in association with AR. They presented detectable regulation already several days before clinical suspicion of AR (increased plasma creatinine. The regulated proteins could be grouped by their biological function; proteins related to growth and proteins related to immune response. Growth-related proteins (IGFBP7, Vasorin, EGF and Galectin-3-binding protein were significantly up-regulated in association with AR (P = 0.03 while proteins related to immune response (MASP2, C3, CD59, Ceruloplasmin, PiGR and CD74 tended to be up-regulated ( P = 0.13. Conclusion The use of shotgun proteomics provides a robust and sensitive method for identification of potentially predictive urinary biomarkers of AR. Further validation of the current findings is needed to establish their potential clinical role with regards to clinical AR diagnosis. Trial registration ClinicalTrials.gov number NCT00139009

  12. Neurodegeneration with brain iron accumulation: update on pathogenic mechanisms.

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    Sonia eLevi

    2014-05-01

    Full Text Available Perturbation of iron distribution is observed in many neurodegenerative disorders, including Alzheimer’s and Parkinson’s disease, but the comprehension of the metal role in the development and progression of such disorders is still very limited. The combination of more powerful brain imaging techniques and faster genomic DNA sequencing procedures has allowed the description of a set of genetic disorders characterized by a constant and often early accumulation of iron in specific brain regions and the identification of the associated genes; these disorders are now collectively included in the category of Neurodegeneration with Brain Iron Accumulation (NBIA. So far 10 different genetic forms have been described but this number is likely to increase in short time. Two forms are linked to mutations in genes directly involved in iron metabolism: Neuroferritinopathy, associated to mutations in the FTL gene and Aceruloplasminaemia, where the ceruloplasmin gene product is defective. In the other forms the connection with iron metabolism is not evident at all and the genetic data let infer the involvement of other pathways: Pank2, COASY,Pla2G6, C19orf12, and FA2H genes seem to be related to lipid metabolism and to mitochondria functioning, WDR45 and ATP13A2 genes are implicated in lysosomal and autophagosome activity, while the C2orf37 gene encodes a nucleolar protein of unknown function. There is much hope in the scientific community that the study of the NBIA forms may provide important insight as to the link between brain iron metabolism and neurodegenerative mechanisms and eventually pave the way for new therapeutic avenues also for the more common neurodegenerative disorders. In this work we will review the most recent findings in the molecular mechanisms underlining the most common forms of NBIA and analyze their possible link with brain iron metabolism.

  13. Proteomic Analysis of Serum from Patients with Major Depressive Disorder to Compare Their Depressive and Remission Statuses

    Science.gov (United States)

    Lee, Jiyeong; Joo, Eun-Jeong; Lim, Hee-Joung; Park, Jong-Moon; Lee, Kyu Young; Park, Arum; Seok, AeEun

    2015-01-01

    Objective Currently, there are a few biological markers to aid in the diagnosis and treatment of depression. However, it is not sufficient for diagnosis. We attempted to identify differentially expressed proteins during depressive moods as putative diagnostic biomarkers by using quantitative proteomic analysis of serum. Methods Blood samples were collected twice from five patients with major depressive disorder (MDD) at depressive status before treatment and at remission status during treatment. Samples were individually analyzed by liquid chromatography-tandem mass spectrometry for protein profiling. Differentially expressed proteins were analyzed by label-free quantification. Enzyme-linked immunosorbent assay (ELISA) results and receiver-operating characteristic (ROC) curves were used to validate the differentially expressed proteins. For validation, 8 patients with MDD including 3 additional patients and 8 matched normal controls were analyzed. Results The quantitative proteomic studies identified 10 proteins that were consistently upregulated or downregulated in 5 MDD patients. ELISA yielded results consistent with the proteomic analysis for 3 proteins. Expression levels were significantly different between normal controls and MDD patients. The 3 proteins were ceruloplasmin, inter-alpha-trypsin inhibitor heavy chain H4 and complement component 1qC, which were upregulated during the depressive status. The depressive status could be distinguished from the euthymic status from the ROC curves for these proteins, and this discrimination was enhanced when all 3 proteins were analyzed together. Conclusion This is the first proteomic study in MDD patients to compare intra-individual differences dependent on mood. This technique could be a useful approach to identify MDD biomarkers, but requires additional proteomic studies for validation. PMID:25866527

  14. Comparative salivary proteome of hepatitis B- and C-infected patients.

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    Lorena Da Rós Gonçalves

    Full Text Available Hepatitis B and C virus (HBV and HCV infections are an important cause of cirrhosis and hepatocellular carcinoma. The natural history has a prominent latent phase, and infected patients may remain undiagnosed; this situation may lead to the continuing spread of these infections in the community. Compelling reasons exist for using saliva as a diagnostic fluid because it meets the demands of being an inexpensive, noninvasive and easy-to-use diagnostic method. Indeed, comparative analysis of the salivary proteome using mass spectrometry is a promising new strategy for identifying biomarkers. Our goal is to apply an Orbitrap-based quantitative approach to explore the salivary proteome profile in HBV- and HCV-infected patients. In the present study, whole saliva was obtained from 20 healthy, (control 20 HBV-infected and 20 HCV-infected subjects. Two distinct pools containing saliva from 10 subjects of each group were obtained. The samples were ultracentrifuged and fractionated, and all fractions were hydrolyzed (trypsin and injected into an LTQ-VELOS ORBITRAP. The identification and analyses of peptides were performed using Proteome Discoverer1.3 and ScaffoldQ + v.3.3.1. From a total of 362 distinct proteins identified, 344 proteins were identified in the HBV, 326 in the HCV and 303 in the control groups. Some blood proteins, such as flavin reductase (which converts biliverdin to bilirubin, were detected only in the HCV group. The data showed a reduced presence of complement C3, ceruloplasmin, alpha(1-acid glycoprotein and alpha(2-acid glycoprotein in the hepatitis-infected patients. Peptides of serotransferrin and haptoglobin were less detected in the HCV group. This study provides an integrated perspective of the salivary proteome, which should be further explored in future studies targeting specific disease markers for HBV and HCV infection.

  15. Zyklopen: a Newly Discovered Multicopper Ferroxidase%胎盘铁转运蛋白Zyklopen研究进展

    Institute of Scientific and Technical Information of China (English)

    关鹏; 王娜; 段相林; 常彦忠

    2011-01-01

    Zyklopen (ZP) is a recently identified ceruloplasmin homologue. ZP is predicted to be tethered to the plasma membrane by its primary sequence. In addition to the placenta, ZP is also present in brain, kidney, retina, mammary gland and testes, but its role in these tissues remains unknown. The protein possessed ferroxidase activity, and protein levels decreased in cellular copper deficiency. In the placenta, ZP is hypothesized to facilitate iron transport from syncytiotrophoblastic cells into the fetal circulation by oxidizing ferrous iron to the ferric form, which is subsequently carried by transferrin.%Zyklopen(ZP)作为铜蓝蛋白的同系物,是近年来发现的铁转运蛋白.ZP具有一个位于羧基末端的跨膜结构域,在胎盘大量表达,也分布于脑、肾、视网膜、乳腺、睾丸等组织,但目前还不清楚ZP在这些组织中的功能.ZP具有亚铁氧化酶的活性,细胞内缺铜会引起ZP蛋白表达减少.在胎盘中,ZP可能通过将二价铁离子氧化为三价铁离子,帮助三价铁与胎儿循环系统中的转铁蛋白相结合,从而参与铁从母体到胎儿的转运过程.

  16. Screening disease-associated proteins from sera of patients with rheumatoid arthritis: a comparative proteomic study

    Institute of Scientific and Technical Information of China (English)

    LI Tian-wang; ZHENG Ben-rong; HUANG Zhi-xiang; LIN Qu; ZHAO Li-ke; LIAO Ze-tao; ZHAO Ji-jun; LIN Zhi-ming; GU Jie-ruo

    2010-01-01

    Background Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation at the synovial membrane. Although great progress has been made recently in exploring the etiology and pathogenesis of RA, its molecular pathological mechanism remains to be further defined and it is still a great challenge in determining the diagnosis and in choosing the appropriate therapy in early patients. This study was performed to screen candidate RA-associated serum proteins by comparative proteomics to provide research clues to early diagnosis and treatment of RA. Methods Sera isolated from 6 RA patients and 6 healthy volunteers were pooled respectively and high-abundance proteins were depleted by Plasma 7 Multiple Affinity Removal System. The protein expression profiles between the two groups were then compared by two-dimensional gel electrophoresis (2-DE) and the proteins over/under-expressed by more than 3-fold were identified by mass spectrometry analysis. To validate the differential expression levels of the identified proteins between the two groups, ELISA was performed in two of the identified proteins in individual sera from 32 RA patients and 32 volunteers. Results Eight proteins which over/under-expressed in sera of RA patients were identified. Among them, chain A of transthyretin (TTR) was under-expressed, while serum amyloid A protein, apolipoprotein A (ApoA)-IV, ApoA-IV precursor, haptoglobin 2, ceruloplasmin (Cp), immunoglobulin superfamily 22 and HT016 were over-expressed. ELISA test confirmed that Cp expressed remarkably higher while TTR obviously lower in RA group compared with volunteer group. Conclusion There were 8 identified proteins differentially expressed between RA group and volunteer group, which might be candidate RA-associated proteins and might be promising diagnostic indicators or therapeutic targets for RA.

  17. The analysis of the acute phase response during the course of Trypanosoma carassii infection in the goldfish (Carassius auratus L.).

    Science.gov (United States)

    Kovacevic, Nikolina; Hagen, Mariel O; Xie, Jiasong; Belosevic, Miodrag

    2015-11-01

    The expression of genes encoding the acute phase proteins (APP) during the course of Trypanasoma carassii infection in the goldfish was determined using quantitative PCR. Significant changes in the mRNA levels of ceruloplasmin (Cp), C-reactive protein (CRP), transferrin (Tf), hemopexin (Hx) and serum amyloid A (SAA) were observed in the kidney, liver and spleen at various days post infection (dpi). Of the five acute phase protein genes examined, CRP and SAA exhibited the highest expression in the tissues during the acute infection. Cp and Tf were up-regulated throughout the acute course of infection in the liver. During the chronic phase of the infection, APP expression in the liver was similar to that in the non-infected control fish. At 7 dpi, Cp, Tf and Hx were down-regulated in the spleen, and Cp and Tf kidney, but their mRNA levels gradually returned to those of control non-infected fish. In contrast, during the chronic phase of the infection, there was an up-regulation of Cp, Hx and Tf in the spleen, and Tf and SAA in the kidney. The goldfish CRP was cloned and functionally characterized. CRP was differentially expressed in normal goldfish immune cells, with highest expression in monocytes and lowest expression in mature macrophages. A recombinant goldfish CRP (rgfCRP) was generated using prokaryotic expression. rgfCRP enhanced complement-mediated killing of trypanosomes in vitro, and the lysis increased after addition of immune serum. rgfCRP did not affect the production of reactive oxygen and nitrogen intermediates by monocytes and macrophages, respectively. PMID:26116443

  18. Metallothionein and antioxidant enzymes in Long-Evans Cinnamon rats treated with zinc.

    Science.gov (United States)

    Medici, Valentina; Santon, Alessandro; Sturniolo, Giacomo Carlo; D'Incà, Renata; Giannetto, Sabrina; Albergoni, Vincenzo; Irato, Paola

    2002-09-01

    The Long-Evans Cinnamon (LEC) rat is a mutant animal model for Wilson's disease. It is known that an abnormal accumulation of Cu and Fe in the liver and low concentrations of both ceruloplasmin and Cu in the serum occur in these rats. The accumulation of Cu is explained by the defective expression of the Cu-transporting P-type ATPase gene, homologous to the gene for Wilson's disease (ATP7B). The aim of this work was to clarify the action mechanism of Zn, and to verify the role that this metal plays in LEC rats in short-term treatment experiments (1 and 2 weeks) on concentrations of Cu, Zn, Fe, metallothionein (MT), 8-hydroxy-2'-deoxyguanosine (oh(8)dG) and on the activity of antioxidant enzymes. It is well known that Zn induces MT and has the ability to prevent redox-active metals, Cu and Fe, binding to and causing oxidative damage at active sites of Zn metalloenzymes and nonspecific binding sites on proteins. Zn administration reduces Cu and Fe transport from mucosal to serosal intestinal sides through competitive mechanisms. Our findings show that treatment with zinc acetate increases tissue Zn and MT contents and decreases Cu and Fe concentrations in the liver and kidneys, even if hepatic Zn and MT concentrations decrease with treatment period. Induction of MT synthesis by Zn contributes to the reduction in free radicals produced by Cu and Fe. We also observed that the superoxide dismutase (SOD)activity in liver decreases with treatment duration in association with the Cu and Fe liver decrease. However, the SOD activity in kidney increases in untreated rats at 2 weeks relative to those untreated for 1 week.

  19. Early weaning alters the acute-phase reaction to an endotoxin challenge in beef calves.

    Science.gov (United States)

    Carroll, J A; Arthington, J D; Chase, C C

    2009-12-01

    Previous research indicates that early weaning before shipment can reduce transportation-induced increases in acute-phase proteins (APP) and can increase feedlot performance in beef calves. These data suggest that the combination of weaning and transport stress may compromise the immune system of calves, thus hindering subsequent performance and health. Therefore, our objective was to determine if the innate immune response of early weaned calves (EW; 80 d of age) differed from normal-weaned calves (NW; 250 d of age) in response to an endotoxin challenge. Eighteen Brahman x Angus calves (8 and 10 EW and NW, respectively; 233 +/- 5 kg of BW) were used. Calves were maintained on pasture with supplement and then moved into individual pens for 1 wk of acclimation before the start of the study. Calves were fitted with an indwelling jugular catheter 1 d before LPS challenge (0 h; 1.0 microg/kg of BW, intravenously). Blood samples were collected at 30-min intervals from -2 to 8 h. Serum samples were stored at -80 degrees C until analyzed for cortisol, tumor necrosis factor-alpha (TNF), IL-1 beta, IL-6, interferon-gamma (IFN), ceruloplasmin, and haptoglobin. Whereas LPS increased serum cortisol (P or= 0.15) was observed. A weaning age x time interaction (P x time interaction (P

  20. Absorption of dietary manganese by dairy cows and the role of plasma proteins and the liver in its homeostasis

    International Nuclear Information System (INIS)

    The concentration of manganese in the systemic blood plasma of cattle is maintained close to 5 μg/1 whether their diet contains 50 or 1000 ppm manganese. The gut absorbs approximately 1% of this dietary manganese irrespective of its dietary concentration. The homeostasis of plasma manganese concentration must therefore be achieved by an excretory method. In vitro experiments have shown that manganese in plasma became bound to two proteins - to α2-macroglobulin, in its divalent Mn2+ state, and to transferrin, in its trivalent Mn3+ state. The proportions of 54Mn bound to these two proteins depended strongly on the temperature of incubation of 54Mn with plasma, and the temperature and pH at which electrophoresis was subsequently performed. 54Mn2+ was bound to transferrin only in the presence of an oxidizing agent such as molecular oxygen, ceruloplasmin or permanganate, and α2-macroglobulin was not involved in this process. In vivo experiments using cows with permanently indwelling mesenteric, portal and hepatic venous cannulae have shown that the liver cleared the portal blood quantitatively of free Mn2+ ions, removed approximately 75% of Mn2+ bound to α2-macroglobulin, but removed practically none of the Mn3+ transferrin complex. These results suggest that manganese may be absorbed through the gut as Mn2+ ions; some of these become bound to α2-macroblobulin while any excess free ions are extracted by the liver and excreted. Some of those bound to α2-macroglobulin enter the systemic circulation and are oxidized, either in the plasma or in tissue, to the Mn3+ state and become bound to transferring, the form in which manganese is circulated for metabolic purposes. (author)

  1. Proteinograma e teores de cobre, ferro e zinco no soro sanguíneo de ovelhas da raça Santa Inês com mastite experimental por Staphylococcus aureus Proteinogram and serum concentrations of copper, iron and zinc in Santa Inês ewes with Staphylococcus aureus experimentally induced mastitis

    Directory of Open Access Journals (Sweden)

    Nivaldo de Azevêdo Costa

    2010-05-01

    ório em razão de sua alta correlação com as proteínas especificas. As alterações nas concentrações séricas de Cu, Fe e Zn sugerem a ação de mediadores inflamatórios, estimulados por S. aureus.The aim of the present study was to evaluate the effect of Staphylococcus aureus experimentally induced mastitis on proteinogram and serum concentrations of cupper, iron and zinc levels of Santa Ines primiparous ewes . The right mammary gland of ten healthy ewes was inoculated with 1,0x10(4 UFC/mL of S. aureus. Clinical examination and determination of serum concentrations of proteins by electrophoresis in polyacrylamide gel (SDS-PAGE, cupper, iron and zinc, as well plasma level of fibrinogen were measured before the inoculation (control and 12h, 24h, 36h, 48h, 60h, 72h, 84h, 96h, 108h, 120h, 132h, 168h, 180h, 288h and 336h after bacteria inoculation. All animals experimentally infected presented clinical mastitis and subsequent loss of mammary gland function. The electrophoretogram allowed the identification of 23 proteins with molecular weights (MW ranged from 26.000 to 185.000 daltons (Da including acute-phase proteins, IgG and IgA. A significant increase (P<0,05 in haptoglobin, ceruloplasmin, IgG and IgA concentrations was observed. Antitrypsin and acid glicoprotein concentrations did not alter. The levels of iron and zinc decreased and the cupper concentration increased . A positive correlation between plasma fibrinogen and serum ceruloplasmin (r=0.74, haptoglobin (r=0.62 and IgA (r=0.62 was also identified. Results showed the importance of ceruloplasmin and haptoglobin as acute-phase proteins in ewes with intramammary infections and confirms fibrinogen as an inflammatory marker because its high correlation with specific proteins. The alterations in the serum levels of Cu, Fe and Zn suggest the action of inflammatory mediators triggered by S. aureus.

  2. Study on the diagnosis of disorders with Parkinson-like symptoms%具有帕金森病样症状相关疾病的诊断探讨

    Institute of Scientific and Technical Information of China (English)

    胡智伟; 邹小冬

    2012-01-01

    Objective To investigate the diagnosis of the disorders with Parkinson-like symptoms (PLS). Methods The clinical data of 78 patients with PLS admitted in our hospital during 2008-01 to 2010-12 were analyzed retrospectively, including medical history, physical examinations, clinical manifestations, blood biochemistry, parathyroxin, ceruloplasmin, levodopa (L-dopa ) test, brain CT scan and MR imaging. The final clinical diagnosis was made according to the diagnostic criteria of PLS related disorders. Results For clinical manifestations, among the 78 patients, there were 74 cases with hypermyotonia, 67 cases with tremor, 65 cases with bradykinesia, 56 cases with abnormal postural reflex, 52 cases with abnormal gait, 5 cases with orthostatic hypotension, 4 cases with vertical gaze palsy, 2 cases with positive K-F corneal ring, 2 cases with visual hallucination, and 1 case with unilateral limb ignorance due to apraxia. The blood biochemistry tests showed abnormal liver function in 5 cases, reduced serum ceruloplasmin level in 2 cases and reduced serum parathyroxin level in 1 case. The CT scan revealed low density in basal ganglia in 59 cases, cerebral atrophy in 35 cases, encephalomalacia in 10 cases, and calcifications existing in the basal ganglia and cerebellar hemisphere in 2 cases. The MR imaging showed abnormal signals in the basal ganglia, the brain stem and the brain whiterfnatter in 65 cases, atrophy in pons and cerebellum in 5 cases, "putamen fissure sign" in 4 cases, "cross sign" in pons in 3 cases, cerebral "hummingbirds sign" in 1 case, high intensity in pallidum on T2 in 2 cases. 31 cases showed poor response to L-dopa treatment. There were 36 cases diagnosed clinically as PD, 28 cases diagnosed as parkinsonian syndrome (PS), 4 cases diagnosed as multiple system atrophy (MSA), 4 cases diagnosed as progressive supranuclear palsy (PSP), 2 cases diagnosed as Lewy body (DLB), 2 cases diagnosed as Wilson disease (WD), 1 case diagnosed as basal ganglia

  3. Valor de alguns exames complementares na Coréia de Sydenha

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    Aron J. Diament

    1972-09-01

    Full Text Available Sixty eight cases of Sydenham's chorea (SC were studied with the purpose of characterizing biologically the choreic individual by means of some laboratorial data. Based on antecedents, on the presence of recent infectious disease, on clinical examination, on electrocardiographs and x-rays of the heart, and according to a modified Jones criteria the patients were initially divided in three groups: aGroup 1 — 30 patients (case 1 to 30 which presented SC associated with active rheumatic fever (RF; b Group 2 — 20 patients (cases 31 to 50 which presented SC associated with a previou or present infectious state without active RF; c Group 3 — 18 patients (cases 51 to 68 which presented "pure" SC, not having anything in their antecedents, or in present history, nor in their physical examinations that could justify calling them "rheumatic" or "infectious". However the analysis of the clinical data, by means of the homogenization tests (qui square or the exact Fisher test and Goodman's contrast test showed the artificiality of this grouping, which could not be longer sustained. From the 68 cases studied the average age group was 9.9 years, with the maximum age being 17 years, and the minimum age being 4.5 years. 47 of the cases were females as compared to 21 males (2.2 to 1; 60 patients were white, 7 dark-skinned and one negro. The average evolution time of the choreic syndrome, at the time of the first consultation, was 6 months and 7 days, with a minimum of 13 days and a maximum of 60 months. The incidence of the outbreak as far as the season of the year is concerned, was as follows: 31 cases between autumn and winter; 14 cases in spring and 22 in summer. The following laboratory examinations have been made: a"classical acute phase serum reagents" (APSR: sedimentation rate, differential blood count, Weltmann reaction, mucoproteins, C reactive protein, antistreptolysin-O titter, electrophoresis of serum proteins; b copper and ceruloplasmin

  4. Valor de alguns exames complementares na Coréia de Sydenha The value of some laboratorial data in Sydenham's chorea

    Directory of Open Access Journals (Sweden)

    Aron J. Diament

    1972-09-01

    Full Text Available Sixty eight cases of Sydenham's chorea (SC were studied with the purpose of characterizing biologically the choreic individual by means of some laboratorial data. Based on antecedents, on the presence of recent infectious disease, on clinical examination, on electrocardiographs and x-rays of the heart, and according to a modified Jones criteria the patients were initially divided in three groups: aGroup 1 — 30 patients (case 1 to 30 which presented SC associated with active rheumatic fever (RF; b Group 2 — 20 patients (cases 31 to 50 which presented SC associated with a previou or present infectious state without active RF; c Group 3 — 18 patients (cases 51 to 68 which presented "pure" SC, not having anything in their antecedents, or in present history, nor in their physical examinations that could justify calling them "rheumatic" or "infectious". However the analysis of the clinical data, by means of the homogenization tests (qui square or the exact Fisher test and Goodman's contrast test showed the artificiality of this grouping, which could not be longer sustained. From the 68 cases studied the average age group was 9.9 years, with the maximum age being 17 years, and the minimum age being 4.5 years. 47 of the cases were females as compared to 21 males (2.2 to 1; 60 patients were white, 7 dark-skinned and one negro. The average evolution time of the choreic syndrome, at the time of the first consultation, was 6 months and 7 days, with a minimum of 13 days and a maximum of 60 months. The incidence of the outbreak as far as the season of the year is concerned, was as follows: 31 cases between autumn and winter; 14 cases in spring and 22 in summer. The following laboratory examinations have been made: a"classical acute phase serum reagents" (APSR: sedimentation rate, differential blood count, Weltmann reaction, mucoproteins, C reactive protein, antistreptolysin-O titter, electrophoresis of serum proteins; b copper and ceruloplasmin

  5. Acute phase response, inflammation and metabolic syndrome biomarkers of Libby asbestos exposure

    International Nuclear Information System (INIS)

    Identification of biomarkers assists in the diagnosis of disease and the assessment of health risks from environmental exposures. We hypothesized that rats exposed to Libby amphibole (LA) would present with a unique serum proteomic profile which could help elucidate epidemiologically-relevant biomarkers. In four experiments spanning varied protocols and temporality, healthy (Wistar Kyoto, WKY; and F344) and cardiovascular compromised (CVD) rat models (spontaneously hypertensive, SH; and SH heart failure, SHHF) were intratracheally instilled with saline (control) or LA. Serum biomarkers of cancer, inflammation, metabolic syndrome (MetS), and the acute phase response (APR) were analyzed. All rat strains exhibited acute increases in α-2-macroglobulin, and α1-acid glycoprotein. Among markers of inflammation, lipocalin-2 was induced in WKY, SH and SHHF and osteopontin only in WKY after LA exposure. While rat strain- and age-related changes were apparent in MetS biomarkers, no LA effects were evident. The cancer marker mesothelin was increased only slightly at 1 month in WKY in one of the studies. Quantitative Intact Proteomic profiling of WKY serum at 1 day or 4 weeks after 4 weekly LA instillations indicated no oxidative protein modifications, however APR proteins were significantly increased. Those included serine protease inhibitor, apolipoprotein E, α-2-HS-glycoprotein, t-kininogen 1 and 2, ceruloplasmin, vitamin D binding protein, serum amyloid P, and more 1 day after last LA exposure. All changes were reversible after a short recovery regardless of the acute or long-term exposures. Thus, LA exposure induces an APR and systemic inflammatory biomarkers that could have implications in systemic and pulmonary disease in individuals exposed to LA. -- Highlights: ► Biomarkers of asbestos exposure are required for disease diagnosis. ► Libby amphibole exposure is associated with increased human mortality. ► Libby amphibole increases circulating proteins involved

  6. Effect of trace minerals and starch on digestibility and rumen fermentation in diets for dairy heifers.

    Science.gov (United States)

    Pino, F; Heinrichs, A J

    2016-04-01

    The objective of this study was to evaluate the effect of different forms of trace minerals (TM) and the use of different starch levels in dairy heifer diets on rumen fermentation and digestibility. Eight rumen cannulated dairy heifers (15.4 ± 0.8 mo of age and 438.31 ± 18.08 kg of body weight) were subjected to a split-plot, 4 × 4 Latin square design with 19-d periods: 15d of adaptation and 4d of sampling. The whole-plot factor was type of TM; organic as proteinates (OTM) or inorganic sulfates (ITM), and the subplot was starch level (3.54, 12.95, 22.25, and 31.73%). Total collection of feces and urine was completed on d 15 to 19 to determine digestibility and TM excretion. Rumen contents were sampled on d 18 to 19 at 0, 1, 2, 4, 8, 12, 16, 20, and 22 h after feeding to measure pH and volatile fatty acid (VFA) concentrations. Plasma samples were collected to evaluate TM concentrations and enzymatic activity for ceruloplasmin, glutathione peroxidase, and superoxide dismutase. Starch level affected pH, individual VFA concentrations, and nutrient excretion. Trace mineral intake was lower for OTM compared with ITM. No effect of TM form on dry matter digestibility was detected, but as level of starch increased, diet dry matter digestibility increased. Rumen pH was lower for diets with OTM, which is consistent with higher total VFA production and butyrate proportion observed for heifers fed OTM diets. These variables may be explained by the higher bioavailability of OTM and faster utilization and fermentation by rumen microorganisms. Heifers that consumed ITM had higher moisture in feces and higher urine excretion, which increased total manure production. Total excretion of TM was not different by treatment. Blood plasma mineral concentration was not different between treatments except for Mn, which was higher for OTM. Enzymatic activity was not affected by treatments. Mineral intake was reduced and blood mineral levels were not different, suggesting enhanced

  7. Malondialdehyde Levels In Wilson′s Disease

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    Sinha Sanjib

    2004-01-01

    Full Text Available Background: Copper ion is a pro-oxidant metal and may be responsible for free radical mediated damage in Wilson′s disease (WD. Estimation of serum malondialdehyde (MDA, a standard test to detect oxidative damage, may support this pathogenesis. Aim: The aim of the study was to analyze the serum levels of MDA and correlate with clinical status in patients of WD. Patients and Methods: Forty five patients, from a large cohort of proven WD at various stages of treatment were evaluated. Their clinical parameters were noted and assessment of disability and handicap were done. The laboratory tests were carried out using standard methods. Results: The mean age of patients was 21.1+9.1 years (range: 6-50 years with M: F ratio of 1.6:1. The mean age at presentation was 14.4+6.9 years (range: 6-42 years and the mean duration of treatment was 14.4+6.9 years (range: 0-24 years. Their mean serum copper and ceruloplasmin levels were 41.4+22.9 g/d1 (range: 4 -103 g/dl and 5.8+3.4 mg/dl (range: 2-18 mg/dl respectively. Thirty eight of them had neurological involvement, four had hepatic form, two had both hepatic and neurological involvement while one was presymptomatic sibling. Patients were assessed using CHU staging (mean: 1.5+0.6, modified schwab and England Activities of Daily Living (MSEADL scale (mean: 94.44+19.55 and Neurologic symptom Score (NSS (mean: 3.96+5.2. The mean serum MDA level was 0.65 + 0.34 moles/1 and only four (9.4% patients had increased levels of MDA (mean: 1.32 + 0.05 moles/1, compared to control (mean: 0.56 + 0.36 moles/1 but it was not statistically significant. No significant correlation was noted between MDA levels and NSS, CHU score, MSEADL score and serum copper level. Conclusion: Increased levels of MDA were detected in only 4 out of 45 patients but those with or without increased MDA levels were not different in their clinical status. These patients were on long term treatment, which might alter the oxidative state. Mechanisms

  8. Alteration of biochemical parameters after supplementation of multivitamins and minerals of sprayers on grape gardens of Western Maharashtra (India

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    Jyotsna A. Patil

    2014-01-01

    , Albumin, Globulin, A/G ratio and Ceruloplasmin were not altered significantly as compared to before vitamin A to Z and multi minerals supplementation. Conclusions: Alteration of these biochemical parameters may be due to ameliorating effects of vitamin A to Z and multi minerals. The vitamins or minerals present in A to Z tablets may improve the hepatocellular damage caused by various pesticides, also beneficial for either decrease free radical formation or increased antioxidant status and increased AChE level may be decreased inhibition of AChE by pesticides of sprayers of grape gardens.

  9. Competition between copper and silver in Fischer rats with a normal copper metabolism and in Long-Evans Cinnamon rats with an abnormal copper metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Sugawara, N.; Sugawara, C. [Sapporo Medical Univ. (Japan). Dept. of Public Health

    2000-07-01

    Long-Evans Cinnamon (LEC) rats inherently lacking in serum ceruloplasmin (CP) activity and biliary Cu excretion were established from a closed colony of Long-Evans rats. These deficiencies, linked to a dysfunction of P-type ATPase, stimulate deposition of Cu and then of Cu metallothionein (MT) in the liver. Male LEC and Fischer rats were injected subcutaneously with Ag (AgNO{sub 3}), which is an antagonist to Cu. They were operated on 24 h after the injection while under anesthesia. Total uptake of Ag into the liver was not stimulated, but its uptake into the MT fraction increased significantly in the LEC rats. Ag injection notably decreased the activity of serum CP in the Fischer rats, but not in the LEC rats. The decrease was accompanied by a reduction of serum Cu. In Fischer rat serum treated with Ag, Ag was detected mainly in the albumin region and partly in the CP fraction. In LEC rat serum, however, the Ag concentration was about 1/20 of that in the Fischer rats, and Ag was not detected in the CP fraction. Ag injection decreased the biliary excretion of Cu in the Fischer rats (0.183-0.052 {mu}g Cu/20 min sampling), but not in the LEC rats (0.014-0.014 {mu}g Cu/20 min sampling). On the other hand, biliary excretion of Ag was much greater in the Fischer rats (1.25 {mu}g Ag/20 min) than in the LEC rats (0.04 {mu}g Ag/20 min). Our results suggest that uptake of Ag into the liver is not dependent on the hepatic Cu content and status, but that biliary excretion of Ag from the liver is affected by these. Hepatic MT is not a transporter of hepatobiliary excretion of Cu and Ag. It seems likely that, unlike Cu excretion, Ag is excreted by not only the CP route but also by another route into the serum. Ag may compete with Cu in the uptake into CP (conversion of apo-CP to holo-CP). (orig.)

  10. Leucogram and serum acute phase protein concentrations in queens submitted to conventional or videolaparoscopic ovariectomy Leucograma e concentrações séricas de proteínas de fase aguda de gatas submetidas à ovariectomia convencional ou por videolaparoscopia

    Directory of Open Access Journals (Sweden)

    A.E. Alves

    2010-02-01

    Full Text Available Thirty health queens were submitted to ovariectomy by conventional technique or by videolaparoscopy. In order to study the intensity of inflammatory response by means of acute phase protein analysis and white blood cell count, serum samples were taken before and until 144 hours after the surgical procedures. The protein concentrations that were significantly increased 24 hours after surgical procedures were: ceruloplasmin, hemopexin, haptoglobin, and α1-acid glycoprotein, 69.8%, 103.5%, 117.3%, and 199.0%, respectively, for conventional ovariectomy; and 22.3%, 46.1%, 79.8%, and 74.6%, respectively, for laparoscopic ovariectomy. Therefore, inflammatory response was more intense in queens submitted to conventional ovariectomy. Results indicate that the increase or decrease in acute phase proteins, as well as in white blood cells count, may be useful in the evaluation of inflammatory response induced by these surgical procedures.Trinta gatas, saudáveis, foram submetidas à ovariectomia pela técnica convencional e por videolaparoscopia. Amostras de sangue foram obtidas com o objetivo de verificar a intensidade da resposta inflamatória por meio da análise das concentrações de proteinas de fase aguda e contagem de leucócitos antes e até 144 horas após procedimento cirúrgico. As proteínas que apresentaram aumento significativo 24 horas após a cirurgia foram: ceruloplasmina, hemopexina, haptoglobina e α1-glicoproteína ácida, 69,8%, 103,5%, 117,3% e 199,0%, respectivamente, para ovariectomia convencional, e 22,3%, 46,1%, 79,8% e 74,6%, respectivamente, para ovariectomia por videolaparoscopia. A resposta inflamatória foi mais evidente nas gatas submetidas à ovariectomia convencional. Os resultados mostram aumento e diminuição na concentração de proteínas de fase aguda e na contagem de leucócitos, podendo ser utilizados na avaliação da resposta inflamatória induzida por procedimentos cirúrgicos.

  11. Acute phase response, inflammation and metabolic syndrome biomarkers of Libby asbestos exposure

    Energy Technology Data Exchange (ETDEWEB)

    Shannahan, Jonathan H. [Curriculum in Toxicology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599 (United States); Alzate, Oscar [Systems Proteomics Center, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599 (United States); Winnik, Witold M.; Andrews, Debora [Proteomics Core, Research Core Unit, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); Schladweiler, Mette C. [Cardiopulmonary and Immunotoxicology Branch, Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); Ghio, Andrew J. [Clinical Research Branch, Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Chapel Hill, NC 27599 (United States); Gavett, Stephen H. [Cardiopulmonary and Immunotoxicology Branch, Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); Kodavanti, Urmila P., E-mail: Kodavanti.Urmila@epa.gov [Cardiopulmonary and Immunotoxicology Branch, Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 (United States)

    2012-04-15

    Identification of biomarkers assists in the diagnosis of disease and the assessment of health risks from environmental exposures. We hypothesized that rats exposed to Libby amphibole (LA) would present with a unique serum proteomic profile which could help elucidate epidemiologically-relevant biomarkers. In four experiments spanning varied protocols and temporality, healthy (Wistar Kyoto, WKY; and F344) and cardiovascular compromised (CVD) rat models (spontaneously hypertensive, SH; and SH heart failure, SHHF) were intratracheally instilled with saline (control) or LA. Serum biomarkers of cancer, inflammation, metabolic syndrome (MetS), and the acute phase response (APR) were analyzed. All rat strains exhibited acute increases in α-2-macroglobulin, and α1-acid glycoprotein. Among markers of inflammation, lipocalin-2 was induced in WKY, SH and SHHF and osteopontin only in WKY after LA exposure. While rat strain- and age-related changes were apparent in MetS biomarkers, no LA effects were evident. The cancer marker mesothelin was increased only slightly at 1 month in WKY in one of the studies. Quantitative Intact Proteomic profiling of WKY serum at 1 day or 4 weeks after 4 weekly LA instillations indicated no oxidative protein modifications, however APR proteins were significantly increased. Those included serine protease inhibitor, apolipoprotein E, α-2-HS-glycoprotein, t-kininogen 1 and 2, ceruloplasmin, vitamin D binding protein, serum amyloid P, and more 1 day after last LA exposure. All changes were reversible after a short recovery regardless of the acute or long-term exposures. Thus, LA exposure induces an APR and systemic inflammatory biomarkers that could have implications in systemic and pulmonary disease in individuals exposed to LA. -- Highlights: ► Biomarkers of asbestos exposure are required for disease diagnosis. ► Libby amphibole exposure is associated with increased human mortality. ► Libby amphibole increases circulating proteins involved

  12. Competition between copper and silver in Fischer rats with a normal copper metabolism and in Long-Evans Cinnamon rats with an abnormal copper metabolism.

    Science.gov (United States)

    Sugawara, N; Sugawara, C

    2000-07-01

    Long-Evans Cinnamon (LEC) rats inherently lacking in serum ceruloplasmin (CP) activity and biliary Cu excretion were established from a closed colony of Long-Evans rats. These deficiencies, linked to a dysfunction of P-type ATPase, stimulate deposition of Cu and then of Cu metallothionein (MT) in the liver. Male LEC and Fischer rats were injected subcutaneously with Ag (AgNO3), which is an antagonist to Cu. They were operated on 24 h after the injection while under anesthesia. Total uptake of Ag into the liver was not stimulated, but its uptake into the MT fraction increased significantly in the LEC rats. Ag injection notably decreased the activity of serum CP in the Fischer rats, but not in the LEC rats. The decrease was accompanied by a reduction of serum Cu. In Fischer rat serum treated with Ag, Ag was detected mainly in the albumin region and partly in the CP fraction. In LEC rat serum, however, the Ag concentration was about 1/20 of that in the Fischer rats, and Ag was not detected in the CP fraction. Ag injection decreased the biliary excretion of Cu in the Fischer rats (0.183-0.052 microg Cu/20 min sampling), but not in the LEC rats (0.014-0.014 microg Cu/20 min sampling). On the other hand, biliary excretion of Ag was much greater in the Fischer rats (1.25 microg Ag/20 min) than in the LEC rats (0.04 microg Ag/20 min). Our results suggest that uptake of Ag into the liver is not dependent on the hepatic Cu content and status, but that biliary excretion of Ag from the liver is affected by these. Hepatic MT is not a transporter of hepatobiliary excretion of Cu and Ag. It seems likely that, unlike Cu excretion, Ag is excreted by not only the CP route but also by another route into the serum. Ag may compete with Cu in the uptake into CP (conversion of apo-CP to holo-CP). PMID:10959791

  13. Obesidad y su relación con marcadores de inflamación y ácidos grasos de eritrocito en un grupo de adolescentes obesos Obesity and its relation with markers of inflammation and erythrocyte fatty acids in a group of overweight adolescents

    Directory of Open Access Journals (Sweden)

    M. J. Aguilar Cordero

    2012-02-01

    Full Text Available En la actualidad se acepta que la obesidad constituye un proceso eminentemente inflamatorio. Ello tiene su justificación en las alteraciones descritas en sujetos obesos a nivel de la secreción de ciertas citoquinas tales como ceruloplasmina, leptina, adiponectina e interleuquina 6 (IL-6, entre otras. Asimismo y en modo paralelo, otros trabajos apuntan además hacia alteraciones en la composición de ácidos grasos en la membrana de los eritrocitos de adultos obesos. Los resultados obtenidos en este estudio confirman la existencia de una correlación significativa entre los niveles séricos de algunas de las citokinas estudiadas y el estado nutricional de los sujetos, lo que significa que para la población de escolares valorada, las concentraciones séricas de estas biomoléculas pueden constituir una importante herramienta para predecir el riesgo cardiovascular en la edad adulta. Además, se han encontrado diferencias significativas respecto de la composición en ácidos grasos saturados en la membrana de los eritrocitos.There is a general consensus that obesity is an eminently inflammatory process. This is justified by alterations observed in obese patients, which affect the secretion of certain cytokines such as ceruloplasmin, leptin, adiponectin, and interleukin-6 (IL-6, among others. In a parallel way, other research has also pointed out alterations in the composition of fatty acids in the erythrocyte membrane of overweight adults. The results obtained in our study confirm the existence of a significant correlation between the serum levels of some of the cytokines studied and the nutritional state of the sample studied. This means that for the population of children evaluated in our study, the serum concentrations of these biomolecules can be an important tool for the prediction of cardiovascular risk when they become adults. Furthermore significant differences were found regarding the composition of saturated fatty acids in the

  14. The effect of early weaning on feedlot performance and measures of stress in beef calves.

    Science.gov (United States)

    Arthington, J D; Spears, J W; Miller, D C

    2005-04-01

    Forty crossbred steers (Brahman x English) were categorized into two groups: 1) early weaned (EW; n = 20); and 2) normal weaned (NW; n = 20). Calves were 89 and 300 d of age at the time of EW and NW, respectively; SEM = 4.4. Early-weaned calves were kept on-site (University of Florida, Ona), provided supplement (1% of BW), and grazed on annual and perennial pastures until NW. At the time of normal weaning, all calves were loaded on a commercial livestock trailer and transported to the North Carolina State University Research Feedlot in Butner (approximately 1,200 km). Upon arrival, calves were stratified by BW and randomly allotted to four pens per weaning age treatment. Individual calf BW and blood samples were collected at the time of normal weaning, on arrival at the feedlot (d 1; 24 h following weaning), and on d 3, 7, 14, 21, and 28 of the receiving period. Individual BW was collected at the start and end of the growing and finishing periods, and feed intake by pen was measured daily. As an estimate of stress during the receiving period, plasma was collected and analyzed for the acute-phase proteins, haptoglobin and ceruloplasmin. Early-weaned calves were lighter (P = 0.03) at normal weaning than NW calves (221 vs. 269 kg; SEM = 10.6). By d 28, EW calves tended (P = 0.12) to be lighter than NW calves (242 vs. 282 kg, respectively). Gain:feed was improved for EW compared with NW calves during both the receiving (G:F = 0.157 vs. 0.081) and growing (0.159 vs. 0.136) periods. There tended (P yield grade, marbling score, and LM area, did not differ between treatments. These data imply that EW calves, which are maintained onsite before shipping, may be more tolerant to the stressors associated with transportation and feed yard entry. Early weaned calves, managed within the system described in this study, may have improved G:F.

  15. Global serum glycoform profiling for the investigation of dystroglycanopathies & Congenital Disorders of Glycosylation

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    Wendy E. Heywood

    2016-06-01

    Full Text Available The Congenital Disorders of Glycosylation (CDG are an expanding group of genetic disorders which encompass a spectrum of glycosylation defects of protein and lipids, including N- & O-linked defects and among the latter are the muscular dystroglycanopathies (MD. Initial screening of CDG is usually based on the investigation of the glycoproteins transferrin, and/or apolipoprotein CIII. These biomarkers do not always detect complex or subtle defects present in older patients, therefore there is a need to investigate additional glycoproteins in some cases. We describe a sensitive 2D-Differential Gel Electrophoresis (DIGE method that provides a global analysis of the serum glycoproteome. Patient samples from PMM2-CDG (n = 5, CDG-II (n = 7, MD and known complex N- & O-linked glycosylation defects (n = 3 were analysed by 2D DIGE. Using this technique we demonstrated characteristic changes in mass and charge in PMM2-CDG and in charge in CDG-II for α1-antitrypsin, α1-antichymotrypsin, α2-HS-glycoprotein, ceruloplasmin, and α1-acid glycoproteins 1&2. Analysis of the samples with known N- & O-linked defects identified a lower molecular weight glycoform of C1-esterase inhibitor that was not observed in the N-linked glycosylation disorders indicating the change is likely due to affected O-glycosylation. In addition, we could identify abnormal serum glycoproteins in LARGE and B3GALNT2-deficient muscular dystrophies. The results demonstrate that the glycoform pattern is varied for some CDG patients not all glycoproteins are consistently affected and analysis of more than one protein in complex cases is warranted. 2D DIGE is an ideal method to investigate the global glycoproteome and is a potentially powerful tool and secondary test for aiding the complex diagnosis and sub classification of CDG. The technique has further potential in monitoring patients for future treatment strategies. In an era of shifting emphasis from gel- to mass-spectral based

  16. Epilepsy secondary to Menkes' disease: five cases report and review of literature

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    Pei-yuan ZHANG

    2014-12-01

    Full Text Available Objective To study the clinical features of patients with Menkes' disease (MD that initiate from seizures, and to reinforce the knowledge of etiological diagnosis of secondary epilepsy.  Methods The clinical and laboratory features of 5 MD patients who were admitted from December 1992 to March 2014 were retrospectively analyzed.  Results All cases were male infants including two brothers, and the age of onset was 1-5 months after birth. Their clinical manifestations started from tonic (N = 3 and focal clonic (N = 2 seizures. The focal clonic seizures became more frequent and progressively worsened. Four cases showed abnormal background EEG rhythm; 3 cases revealed interictal focal or multifocal epileptiform discharges over occipital region predominantly; 2 cases revealed epileptic discharge in fit period EEG. All the cases manifested severe mental retardation accompanied with light complexion and curly hair. Low serum copper and ceruloplasmin levels were found in 4 cases and lead to the diagnosis of MD. The exceptional one was made clinical diagnosis of MD due to his typical manifestation and the diagnosis of his elder brother. Three cases received MRI examination, which showed extensive cerebral atrophy and symmetric encephalomalacia foci. One case revealed tortuosity of main artery and diminution of distal artery by MRA. One case was treated with phenobarbital, 2 cases with topiramate, one case with topiramate and levetiracetam and clonazepam. One case died of respiratory failure at 24 h after admission. The other 4 cases were followed up for 1-9 months after being discharged, 3 of whom died, and the left one converted to intractable infantile spasms and severe mental retardation, with interictal EEG changing to hypsarrhythmia.  Conclusions The onset of patients with epilepsy secondary to MD often occurs in early infancy, manifesting tonic and focal clonic seizures predominantly with interictal epileptiform discharges over the posterior

  17. The effect of early weaning on feedlot performance and measures of stress in beef calves.

    Science.gov (United States)

    Arthington, J D; Spears, J W; Miller, D C

    2005-04-01

    Forty crossbred steers (Brahman x English) were categorized into two groups: 1) early weaned (EW; n = 20); and 2) normal weaned (NW; n = 20). Calves were 89 and 300 d of age at the time of EW and NW, respectively; SEM = 4.4. Early-weaned calves were kept on-site (University of Florida, Ona), provided supplement (1% of BW), and grazed on annual and perennial pastures until NW. At the time of normal weaning, all calves were loaded on a commercial livestock trailer and transported to the North Carolina State University Research Feedlot in Butner (approximately 1,200 km). Upon arrival, calves were stratified by BW and randomly allotted to four pens per weaning age treatment. Individual calf BW and blood samples were collected at the time of normal weaning, on arrival at the feedlot (d 1; 24 h following weaning), and on d 3, 7, 14, 21, and 28 of the receiving period. Individual BW was collected at the start and end of the growing and finishing periods, and feed intake by pen was measured daily. As an estimate of stress during the receiving period, plasma was collected and analyzed for the acute-phase proteins, haptoglobin and ceruloplasmin. Early-weaned calves were lighter (P = 0.03) at normal weaning than NW calves (221 vs. 269 kg; SEM = 10.6). By d 28, EW calves tended (P = 0.12) to be lighter than NW calves (242 vs. 282 kg, respectively). Gain:feed was improved for EW compared with NW calves during both the receiving (G:F = 0.157 vs. 0.081) and growing (0.159 vs. 0.136) periods. There tended (P Carcass measures, including backfat thickness, USDA yield grade, marbling score, and LM area, did not differ between treatments. These data imply that EW calves, which are maintained onsite before shipping, may be more tolerant to the stressors associated with transportation and feed yard entry. Early weaned calves, managed within the system described in this study, may have improved G:F.

  18. Increasing the metabolizable protein supply enhanced growth performance and led to variable results on innate and humoral immune response of preconditioning beef steers.

    Science.gov (United States)

    Moriel, P; Artioli, L F A; Poore, M H; Confer, A W; Marques, R S; Cooke, R F

    2015-09-01

    We evaluated the effects of MP supply on growth performance before and after preconditioning and measurements of innate and humoral immune response of beef steers following vaccination. Angus steers ( = 36; BW = 231 ± 21 kg; age = 184 ± 18 d) were weaned on d -6, stratified by BW and age on d 0, and randomly assigned to 1 of 18 drylot pens (2 steers/pen). Treatments were assigned to pens (6 pens/treatment) and consisted of corn silage-based diets formulated to provide 85%, 100%, or 115% of the daily MP requirements of a beef steer gaining 1.1 kg/d from d 0 to 42. Steers were vaccinated against infectious bovine rhinotracheitis virus, bovine viral diarrhea (BVDV) types 1 and 2 viruses, and clostridium on d 14 and 28. Blood samples were collected on d 0, 14, 15, 17, 21, 28, 29, 30, 35, and 42. Body weight did not differ ( ≥ 0.17) among treatments from d 0 to 28. On d 42, 115% MP steers were heaviest, 100% MP steers were intermediate, and 85% MP steers were lightest ( = 0.05; 297, 290, and 278 ± 7 kg, respectively). Overall, ADG and G:F did not differ ( ≥ 0.13) between 100% and 115% MP steers and were least ( treatments ( ≥ 0.46), whereas plasma ceruloplasmin (Cp) concentrations were greatest ( ≤ 0.04) for 85% MP steers, intermediate for 100% MP steers, and least for 115% MP steers on d 30, 35, and 42. Plasma cortisol concentrations were greater ( ≤ 0.03) for 85% vs. 100% and 115% MP steers on d 14 and 28. Liver mRNA expression of Cp and Hp and muscle mRNA expression of m-calpain, mammalian target of rapamycin, and ubiquitin did not differ among treatments ( ≥ 0.17). Serum neutralization titers to BVDV-1b titers were greater ( ≤ 0.02) for 115% vs. 85% and 100% MP steers on d 42 (5.8, 3.0, and 3.7 ± 0.60 log, respectively), whereas mean serum leukotoxin titers were greater for 85% vs. 100% and 115% MP steers (3.1, 2.4, and 2.5 ± 0.21 log, respectively). Preconditioning MP supply did not affect ( ≥ 0.26) ubsequent finishing growth performance and

  19. Global serum glycoform profiling for the investigation of dystroglycanopathies & Congenital Disorders of Glycosylation.

    Science.gov (United States)

    Heywood, Wendy E; Bliss, Emily; Mills, Philippa; Yuzugulen, Jale; Carreno, Gabriela; Clayton, Peter T; Muntoni, Francesco; Worthington, Viki C; Torelli, Silvia; Sebire, Neil J; Mills, Kevin; Grunewald, Stephanie

    2016-06-01

    The Congenital Disorders of Glycosylation (CDG) are an expanding group of genetic disorders which encompass a spectrum of glycosylation defects of protein and lipids, including N- & O-linked defects and among the latter are the muscular dystroglycanopathies (MD). Initial screening of CDG is usually based on the investigation of the glycoproteins transferrin, and/or apolipoprotein CIII. These biomarkers do not always detect complex or subtle defects present in older patients, therefore there is a need to investigate additional glycoproteins in some cases. We describe a sensitive 2D-Differential Gel Electrophoresis (DIGE) method that provides a global analysis of the serum glycoproteome. Patient samples from PMM2-CDG (n = 5), CDG-II (n = 7), MD and known complex N- & O-linked glycosylation defects (n = 3) were analysed by 2D DIGE. Using this technique we demonstrated characteristic changes in mass and charge in PMM2-CDG and in charge in CDG-II for α1-antitrypsin, α1-antichymotrypsin, α2-HS-glycoprotein, ceruloplasmin, and α1-acid glycoproteins 1&2. Analysis of the samples with known N- & O-linked defects identified a lower molecular weight glycoform of C1-esterase inhibitor that was not observed in the N-linked glycosylation disorders indicating the change is likely due to affected O-glycosylation. In addition, we could identify abnormal serum glycoproteins in LARGE and B3GALNT2-deficient muscular dystrophies. The results demonstrate that the glycoform pattern is varied for some CDG patients not all glycoproteins are consistently affected and analysis of more than one protein in complex cases is warranted. 2D DIGE is an ideal method to investigate the global glycoproteome and is a potentially powerful tool and secondary test for aiding the complex diagnosis and sub classification of CDG. The technique has further potential in monitoring patients for future treatment strategies. In an era of shifting emphasis from gel- to mass-spectral based proteomics

  20. Effect of dietary trace mineral concentration and source (inorganic vs. chelated) on performance, mineral status, and fecal mineral excretion in pigs from weaning through finishing.

    Science.gov (United States)

    Creech, B L; Spears, J W; Flowers, W L; Hill, G M; Lloyd, K E; Armstrong, T A; Engle, T E

    2004-07-01

    Two hundred and sixteen weanling gilts (6.65+/-0.08 kg) were used to determine the effects of decreasing supplemental concentrations of Zn, Cu, Fe, and Mn, and trace mineral source (inorganic vs. chelated) on growth performance, mineral status, and fecal mineral concentrations from weaning through development. The study was conducted over three trials with 72 pigs in each trial. Gilts were blocked by weight and randomly assigned to either 1) control, 2) reduced inorganic, or 3) reduced chelated trace minerals. The control diet was supplemented with 25, 150, 180, and 60 mg/kg of Cu, Zn, Fe, and Mn (in sulfate forms), respectively, during the nursery phase and 15, 100, 100, and 40 mg/kg of supplemental Cu, Zn, Fe, and Mn, respectively, during the growing and gilt-developer phases. Reduced inorganic and reduced chelated treatments were supplemented during all phases with 5, 25, 25, and 10 mg/kg of Cu, Zn, Fe, and Mn, respectively. The reduced chelated treatment supplied 50% of the supplemental Cu, Zn, Fe, and Mn in the form of metal proteinates, with the remainder from sulfate forms. Performance by control pigs did not differ from pigs fed the reduced trace mineral treatments during the nursery and grower-development periods. Gain:feed was lower (P < 0.05) for pigs fed the reduced inorganic compared with those fed the reduced chelated treatment during the nursery period. Trace mineral source did not affect performance during the growing or gilt-developer phase. Plasma Zn concentration and alkaline phosphatase activity were higher (P < 0.01) in control pigs than in those receiving reduced trace minerals during the nursery and growing phases. Plasma Cu concentration and ceruloplasmin activity were generally not affected by treatment. Hemoglobin concentrations were lower (P < 0.05) for the reduced inorganic compared with the reduced chelated treatment in the nursery phase. Fecal concentrations of Cu, Zn, and Mn were lower (P < 0.05) in pigs fed reduced trace minerals

  1. Proteinograma sérico de bovinos da raça Curraleir Serum protein concentration in Curraleiro bovine breed

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    R.S. Juliano

    2009-06-01

    Full Text Available Estudou-se o perfil eletroforético das proteínas séricas de bovinos sadios da raça Curraleiro por meio da técnica de eletroforese em gel de acrilamida contendo dodecil sulfato de sódio. Utilizaram-se amostras de soro sanguíneo de 228 bovinos da raça Curraleiro, 51 machos e 177 fêmeas, com idades entre sete meses e 12 anos, pertencentes a dois rebanhos localizados nos Estados de Goiás e Tocantins. Foram quantificadas proteína total e concentração plasmática de fibrinogênio. Verificaram-se variações nas concentrações das diferentes frações proteicas. Foram detectadas 26 proteínas e identificadas 10 delas. A ceruloplasmina esteve ausente em 78,1% dos indivíduos, e a α-antitripsina não foi detectada em nenhum animal. Proteína total, globulina, IgA, IgG e fibrinogênio aumentaram com a idade e houve correlação positiva entre os níveis séricos de haptoglobina e α1-glicoproteína ácida.The eletrophoretic serum protein profile in healthy Curraleiro bovine breed was studied by dodecyl sulphate-polyacrylamide gel electrophoresis. A total of 228 serum samples from Curraleiro cattle, being 51 males and 177 females were analyzed. They were from seven month to 12-year-old and were raised in two farms of Goiás and Tocantins states. Total protein and plasma fibrinogen quantification were performed. It was possible to verify variation in proteins fractions concentration. Twenty-six proteins were detected and ten of them were identified. Ceruloplasmin was absente in 78,10% of animals and α-antitrypsin was not detected. The total protein, globulin, IgA, IgG, and fibrinogen increased with age and there was a positive correlaction between haptoglobin and α1-acid glycoprotein.

  2. Serum protein concentrations, including acute phase proteins, in calves with hepatogenous photosensitization Teores séricos de proteínas, inclusive proteínas de fase aguda, em bovinos com fotossensibilização hepatógena

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    J.J. Fagliari

    2007-12-01

    Full Text Available One hundred 6- to 12-month-old Nelore calves were allotted into control group (G1; 50 healthy calves and photosensitization group (G2; n= 50. Blood samples were collected 12 to 24 hours after the onset of dermatitis (M1, and 15 to 30 days after that (M2, at time of resolution of clinical signs. Serum protein electrophoresis was performed by means of sodium dodecyl sulphate-polyacrylamide gel electrophoresis. Eighteen serum proteins with molecular weights ranging from 16,000 to 189,000 daltons (Da were identified in all calves. In M1 and M2 serum concentrations of proteins with molecular weights of 115,000Da (ceruloplasmin, 61,000Da (a1-antitrypsin, 45,000Da (haptoglobin, and 40,000Da (acid glycoprotein were significantly increased in calves. In conclusion, measurement of serum acute phase protein concentrations may be useful in monitoring the progression of bovine hepatogenous photosensitization, including guide probable alteration on therapeutic procedures.Foram examinados 100 bezerros da raça Nelore com 6 a 12 meses de idade, distribuídos em: grupo controle (G1; 50 bezerros sadios e grupo fotossensibilização (G2; n= 50. As amostras de sangue foram coletadas 12 a 24 horas após o início da dermatite (M1 e 15 a 30 dias após (M2, época da cura das lesões cutâneas. O proteinograma sérico foi obtido por eletroforese em gel de acrilamida. Em todos os bezerros foram identificadas 18 proteínas com pesos moleculares (PM entre 16.000 a 189.000 dáltons (Da. Em M1 e M2, as concentrações séricas das proteínas de PM 115.000Da (ceruloplasmina, 61.000Da (1-antitripsina, 45.000Da (haptoglobina e 40.000Da (glicoproteína ácida foram significativamente maiores em bezerros com fotossensibilização hepatógena em comparação com aquelas dos animais do grupo-controle. A determinação dos teores séricos de proteínas de fase aguda pode ser útil no monitoramento da progressão da fotossensibilização hepatógena em bovinos, inclusive orientando

  3. Involvement of activated leukocytes in the regulation of plasma levels of acute phase proteins in microgravity simulation experiments

    Science.gov (United States)

    Larina, Olga; Bekker, Anna; Turin-Kuzmin, Alexey

    2016-07-01

    Earth-based studies of microgravity effects showed the induction of the mechanisms of acute phase reaction (APR). APR comprises the transition of stress-sensitive protein kinases of macrophages and other responsive cells into the active state and the phosphorylation of transcription factors which in turn stimulate the production of acute-phase reaction cytokines. Leukocyte activation is accompanied by the acceleration of the formation of oxygen radicals which can serve a functional indice of leukocyte cell state. The series of events at acute phase response result in selective changes in the synthesis of a number of secretory blood proteins (acute phase proteins, APPs) in liver cells thus contributing the recovery of homeostasis state in the organism. Earlier experiment with head-down tilt showed the increase in plasma concentrations of two cytokine mediators of acute phase response, tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) being the outcome of the activation of producer cells, foremost, leukocytes. In experiment with 4-day dry immersion chemiluminescent (ChL) reply of the whole blood samples to a test stimulus were studied along with the measurements of plasma levels of APPs, namely, alpha1-antitrypsin (alpha1-AT), alpha1-acid glycoprotein (alpha1-AGP), alpha2-macroglobulin (alpha2-M), ceruloplasmin (Cer), haptoglobin (Hp), C3-complement component (C3), C-reactive protein (CRP). Eight individuals aged 21.2 ± 3.2 years were the test subjects in the investigation. Protein studies showed a noticeable increase in the mean plasma levels of all APPs measured in experiment thus producing the evidence of the activation of acute phase response mechanisms while individual patterns revealed variability during the immersion period. The overall trends were similar to these in the previous immersion series. The augment in the strength of signal in stimulated light emission tests was higher after 1- and 2-day of immersion exposure than before the

  4. Ocular copper deposition associated with monoclonal gammopathy of undetermined significance: case report Depósito ocular de cobre associado a gamopatia monoclonal de significância indeterminada: relato de caso

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    Patrick F. Tzelikis

    2005-08-01

    Full Text Available To report a case of ocular copper deposition in both eyes at the level of Descemet's membrane associated with a monoclonal gammopathy of undetermined significance (MGUS. A 49-year-old white woman had golden-brown metallic dust-like deposits on Descemet's membrane of both eyes. A systemic examination revealed an elevated serum copper, normal serum ceruloplasmin and a normal level of total protein. Serum protein electrophoresis demonstrated a single peak (M-spike in the gamma region (M-protein in serum = 11 g/l. Flow cytometric analysis of the marrow aspirate identified a monoclonal plasma cell population that represents approximately 2% of the total marrow cells consistent with the diagnosis of monoclonal gammopathy of undetermined significance. Copper deposits at the level of Descemet's membrane may be a finding in a patient with monoclonal gammopathy of undetermined significance.Relatar um caso de depósito corneano de cobre em ambos os olhos a nível da membrana de Descemet associado a gamopatia monoclonal de significância indeterminada (GMSI. Paciente feminina, 49 anos, leucodérmica, apresentando depósito corneano de aspecto marrom-ouro a nível da membrana de Descemet em ambos os olhos. Exame sistêmico revelou cobre sérico elevado, ceruloplasmina sérica normal, e proteína total normal. Eletroforese de proteínas séricas demonstrou um pico único na região gama (proteína M = 11 g/l. Análise citométrica de aspirado medular evidenciou uma população de células plasmáticas monoclonais de aproximadamente 2% do total de células medulares consistente com o diagnóstico de gamopatia monoclonal de significância indeterminada. Depósitos de cobre a nível da membrana de Descemet podem ser encontrados em pacientes com gamopatia monoclonal de significância indeterminada.

  5. Maternal rumen-protected methionine supplementation and its effect on blood and liver biomarkers of energy metabolism, inflammation, and oxidative stress in neonatal Holstein calves.

    Science.gov (United States)

    Jacometo, C B; Zhou, Z; Luchini, D; Trevisi, E; Corrêa, M N; Loor, J J

    2016-08-01

    In nonruminants, nutrition during pregnancy can program offspring development, metabolism, and health in later life. Rumen-protected Met (RPM) supplementation during the prepartum period improves liver function and immune response in dairy cows. Our aim was to investigate the effects of RPM during late pregnancy on blood biomarkers (23 targets) and the liver transcriptome (24 genes) in neonatal calves from cows fed RPM at 0.08% of diet dry matter/d (MET) for the last 21 d before calving or controls (CON). Blood (n=12 calves per diet) was collected at birth before receiving colostrum (baseline), 24 h after receiving colostrum, 14, 28, and 50 d (post-weaning) of age. Liver was sampled (n=8 calves per diet) via biopsy on d 4, 14, 28, and 50 of age. Growth and health were not affected by maternal diet. The MET calves had greater overall plasma insulin concentration and lower glucose and ratios of glucose-to-insulin and fatty acids-to-insulin, indicating greater systemic insulin sensitivity. Lower concentration of reactive oxygen metabolites at 14 d of age along with a tendency for lower overall concentration of ceruloplasmin in MET calves indicated a lesser degree of stress. Greater expression on d 4 of fructose-bisphosphatase 1 (FBP1), phosphoenolpyruvate carboxykinase 1 (PCK1), and the facilitated bidirectional glucose transporter SLC2A2 in MET calves indicated alterations in gluconeogenesis and glucose uptake and release. The data agree with the greater expression of the glucocorticoid receptor (GR). Greater expression on d 4 of the insulin receptor (INSR) and insulin-responsive serine/threonine-protein kinase (AKT2) in MET calves indicated alterations in insulin signaling. In that context, the similar expression of sterol regulatory element-binding transcription factor 1 (SREBF1) in CON and MET during the preweaning period followed by the marked upregulation regardless of diet after weaning (d 50) support the idea of changes in hepatic insulin sensitivity during

  6. Doença de Wilson em crianças e adolescentes: diagnóstico e tratamento Wilson's disease in children and adolescents: diagnosis and treatment

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    Stephania de Andrade Sócio

    2010-06-01

    Pediatric Hepatology Ambulatory of the Hospital das Clínicas of Universidade Federal de Minas Gerais, Brazil, from 1985 to 2008. Data were collected by revision of medical charts and during clinical follow-up. RESULTS: Patients were 2.8 to 15.1 years old, with a mean age of 8.8±0.9 years. The disease main presentation was hepatic (53%, followed by the asymptomatic form, diagnosed by family screening. The Kayser-Fleischer ring was observed in 41% of the patients. The ceruloplasmin was altered in 15 out of 17 patients, and the urinary copper varied from 24 to 1000mcg/24h (median: 184mcg/24h. The treatment was stablished with D-penicillamine in all cases. Slight side effects were observed in five children, with no need to interrupt or change medication. Clinical and laboratory responses to treatment, with normalization of aminotransferases levels, were shown in 14 patients after a median of 10.7 months. Although treated, three patients died (one due to fulminant hepatitis and two due to severe hepatic failure. CONCLUSIONS: Wilson's disease is rare in the pediatric group. In children, the main presentation is the liver disease. The diagnosis can be established by reduced ceruloplasmin levels and elevated copper excretion in the 24-hour urine, but it demands high suspicion level. There are good tolerance and response to medical treatment.

  7. Inflammatory mediators and immune response in Mexican adolescents Mediadores inflamatorios y respuesta inmunitaria en adolescentes mexicanos

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    R. V. Pardo Morales

    2011-10-01

    Full Text Available Introduction: Low-grade inflammation and increased immunity related to cardiovascular diseases have been described in children and adults, however, studies in Mexican adolescents are being done at present. Objective: To evaluate inflammatory proteins and indicators of immunity in adolescents by gender and body mass index. Material and methods: 115 Mexican adolescents, 15-18 years old (36 men, were divided into non-overweight, risk of overweight and overweight by CDC pediatric criteria by body mass index. Serum concentrations of ceruloplasmin, C3 and C4 were quantified by nephelometry; IL-6 and TNF-α from stimulated supernatant were analyzed with Human Th1-Th2 cytokine CBA II kit (BD Biosciences Pharmigen, San Diego, CA, and detected by flow cytometry. Data were analysed by Mann-Whitney U. Results: Gender differences were found in C3 (men: median 118.8, mean rank: 41.0; women: median: 143.9, mean rank: 65.7, p = 0.001 and ceruloplasmin (men: median: 31.01, mean rank: 47.06; women: median: 31.0, mean rank: 62.9, p = 0.015. Differences by BMI were found in C3 (women non-overweight: median: 137.00 mena rank: 36.52; women with risk of overweight/overweight: median: 175.80, mean rank: 57.69, p = 0.002 and C4 (men non-overweight: median: 23.40, mean rank: 16.60; men with risk of overweight/overweight: median: 26.40, mean rank: 26.36, p = 0.028; women non-overweight: median: 24.25, mean rank: 37.16 and women with risk of overweight/overweight: median: 32.80, mean rank: 54.42, p = 0.013. Conclusion: Inflammatory proteins are increased in adolescents with risk of overweight and overweight, particularly in women.Introducción: La inflamación de bajo grado y el aumento en la inmunidad relaciondas con las enfermedades cardiovasculares se han descrito en niños y adultos, sin embargo, estudios en adolescentes mexicanos se están haciendo en la actualidad. Objetivo: Evaluar las proteínas inflamatorias e indicadores de la inmunidad en los adolescentes por g

  8. 29例肝豆状核变性临床病理特点分析%Clinicopathological features of Wilson disease: report of 29 cases

    Institute of Scientific and Technical Information of China (English)

    张玉果; 南月敏; 赵素贤; 王泰龄; 姜君

    2013-01-01

    Objective To summarize the clinicopathological manifestations of Wilson disease(WD) so as to improve its recognition.Methods A total of 29 WD cases were retrospectively analyzed,including clinical presentations,liver function test,serum ceruloplasmin,24 hour urinary copper excretion,ATP7B gene analysis and liver histology.All cases were diagnosed from January 2007 to October 2012 at Third Hospital of Hebei Medical University and China-Japan Friendship Hospital.Results There were 18 males and 11 females with an average age of 25.9 years.The major clinical symptoms included fatigue (n =18,62.1%),abdominal distension (n =4,13.8%) and pruritus (n =4,13.8%).The common physical signs were hepatomegaly (n =11,37.9%),splenomegaly(n =15,51.7%) and ascites (n =4,13.8%).The laboratory examinations included abnormal liver function (n =29,100%),high level of 24-hour urinary copper excretion (n =29,100.0%),low serum ceruloplasmin (n =24,82.8%) and Kayser-Fleischer ring (n =8,27.6%).ATP7B gene mutations were at exons 5,8,11,12,16 and 18.The earliest histologic abnormalities of liver included steatosis (both microvesicular and macrovesicular).Timm's stain showed positive or negative staining.There was no or focal hepatocellular necrosis in liver.During chronic hepatitis phase,the major changes included inflammatory cells infiltration in portal area with biliary epithelium degeneration.The periportal area hepatic cells were swollen,cytoplasm slightly stained and accompanied with some copper particles deposition and cholestic changes.There were many spotty or focal lesion of necrosis in liver.During cirrhotic phase,portal area became enlarged by fibrotic tissue,numerous copper particles deposited in wide fibrous septa and small bile ducts were damaged and became proliferative.Hepatocytes around fibrous interval showed cholestatic changes and contained many copper particles.They diagnosed on the basis of clinical presentation(n =6),clinical presentation and liver

  9. The malarial impact on the nutritional status of Amazonian adult subjects Impacto da malaria no estado nutricional de doentes adultos da Amazônia

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    Paulo C. M. Pereira

    1995-02-01

    Full Text Available The anthropometric (body weight, height, upper arm circumference, triceps and subescapular skinfolds; Quetelet index and arm muscle circunference and blood biochemistry (proteins and lipids parameters were evaluated in 93 males and 27 females, 17-72 years old voluntaries living in the malarial endemic area of Humaita city (southwest Amazon. According to their malarial history they were assembled in four different groups: G1-controls without malarial history (n:30; G2 - controls with malarial history but without actual manifestation of the disease (n:40; G3 - patients with Plasmodium vivax (n:19 and G4 - patients with Plasmodium falciparum (n:31. The malarial status was stablished by clinical and laboratory findings. The overall data of anthropometry and blood biochemistry discriminated the groups differently. The anthropometric data were low sensitive and contrasted only the two extremes (G1>G4 whereas the biochemistry differentiated two big groups, the healthy (G1+G2 and the patients (G3+G4. The nutritional status of the P. falciparum patients was highly depressed for most of the studied indices but none was sensitive enough to differentiate this group from the P. vivax group (G3. On the other hand the two healthy groups could be differentiated through the levels of ceruloplasmin (G1G2. Thus it seems that the malaria-malnourishment state exists and the results could be framed either as a consequence of nutrient sink and/or the infection stress both motivated by the parasite.A avaliação antropométrica (pêso, altura, circunferência branquial, prega cutânea tricipital, prega cutânea subescapular, índice de Quetelet e circunferência muscular do braço e bioquímica (proteínas e lipides foi realizado em 120 indivíduos (93 masculinos e 27 do sexo feminino, de 17 a 72 anos de idade, moradores de área endêmica de malária (Humaitá -AM. De acordo com a história da doença (malária eles foram divididos em 4 grupos: G1 - controle (n = 30

  10. The clinical analysis of 23 patients with hepatolenticular degeneration%肝豆状核变性23例临床分析

    Institute of Scientific and Technical Information of China (English)

    王冬青; 蔺慕会; 龚涛

    2011-01-01

    目的 总结肝豆状核变性的临床特点,以减少误诊、漏诊.方法 回顾性分析23例肝豆状核变性患者的临床表现及诊治过程.结果 平均发病年龄21.5岁,首发症状以神经系统和肝损害症状为主,分别占69.6%(16/23)及26.1%(6/23),其中神经系统症状以肢体震颤、精神异常多见;18例患者临床分型为混合型,占78.3%(18/23),5例为脑型;所有患者均出现角膜色素环(K-F环);所有患者进行了铜代谢的实验室检查,血浆铜蓝蛋白水平降低及24 h尿铜增高常见.青霉胺与硫酸锌联合治疗对78.3%(18/23)的患者有效.结论 肝豆状核变性青少年多发,以神经系统和肝损害症状为主要表现,K-F环阳性率高.青霉胺与硫酸锌联合治疗对大部分肝豆状核变性患者有效.%Objective To summarize the clinical characteristics of hepatolenticular degeneration (Wilson disease, WD) so that to decrease the misdiagnosis and missed diagnosis. Methods The clinical manifestations,diagnosis and treatment process of 23 patients with WD were analyzed retrospectively. Results The mean occurrence age was 21.5. The first-ever symptoms were mainly nervous system and liver lesion, 69.6% (16/23) and 26.1 % (6/23) respectively. Limb tremor and psychiatric disorder were mainly found in nervous system lesion. With disease progress, 18 (78. 3%) patients developed to the mixed type, 5 patients were cerebral type.All patients were found Kayser-Fleischer ring (K-F) in cornea. All patients' parameters of copper metabolism were investigated. Low serum ceruloplasmin levels and elevated 24 h urinary copper excretion were common.Treated with penicillamine associating with zinc sulfate was effective in 18 (78.3%) patients. Conclusions WD often occurs in adolescents. Nervous system and liver lesions are its main manifestations. The incidence of K-F ring is high and the treatment with penicillamine combined zinc sulfate is effective in most patients.

  11. Ecophysiological determinations of antioxidant enzymes and lipoperoxidation in the blood of White Stork Ciconia ciconia from Poland.

    Science.gov (United States)

    Kamiński, Piotr; Kurhalyuk, Nataliya; Jerzak, Leszek; Kasprzak, Mariusz; Tkachenko, Halyna; Klawe, Jacek J; Szady-Grad, Małgorzata; Koim, Beata; Wiśniewska, Ewa

    2009-01-01

    The aim of this study was to investigate the activity of antioxidant enzymes in the blood of White Stork Ciconia ciconia chicks (aged 19-54 days) in Poland in 2006. We took under consideration superoxide dismutase (SOD), catalase (CAT), ceruloplasmine (CP), glutathione peroxidase (GPx), glutathione reductase (GR) and the content of thiobarbituric acid-reactive substances (malondialdehyde) in polluted (copper manufacture), suburban areas, at the Odra meadows, and at swamps near Baltic Sea in the Pomeranian region. We examined the levels of Na, K, Ca, Mg, Fe, Zn, Cu, Mn, Co, Cd, and Pb and compared ecophysiological determinations for developing storks. Blood samples of wing venous were collected from 91 chicks from 33 nests. The degree of activity of antioxidant enzymes studied has been different in White Stork chicks' blood from Poland regions, as a rule. We have stated a relatively high level of CAT, GPx, SOD, and GR activity and malondialdehyde (MDA) content in chicks from polluted areas. However, relative value for GR in storks from Odra meadows was considerably higher (about 112 nmol NADPH(2)/min ml) than those in chicks from other environments (56-84 nmol on average). Relatively high levels of CAT, CP, and GPx (2.7 mkM/min l, 22.2 mg/l, and 3.8 nmol GSH/min ml, respectively) were also stated in chicks nested in swamps near Baltic Sea. Simultaneously, we have stated differences (psmelter (2.2mg/kg), whilst Pb concentration was high in chicks from Głogów (7.2 mg/kg). Cd and Pb levels in blood of chicks were different in individuals from each region (psmelter have the highest level of these elements, whereas the lowest one was stated in chicks from Odra meadows (Cd: 1.45, Pb: 0.84 mg/kg). Thus, Cd could be a useful marker of response for polluted stress. We also observed a relatively high level of Mg in chicks from both Pomeranian (7000 mg/kg) and polluted (about 6000 mg/kg) areas. Potassium, zinc, and cobalt levels were highest in chicks from suburbs (4.65, 10

  12. The evaluation significance of ceruloplasmindetermination in multiple organ dysfunction syndrome (MODS) prognosis%血清铜蓝蛋白测定对MODS预后的评估意义

    Institute of Scientific and Technical Information of China (English)

    胡志华; 陈勉; 陈伟

    2012-01-01

    OBJECTIVE To explore the ceruloplasmin (CP) dynamic change in MODS patients to cause judgment and the value of the prognosis assessment. METHODS Determinedceruloplasmin, high sensitivity C-reactive protein (CRCP), α-acid glycoprotein (AAG) contents of 60 cases of MODS patients (MODS group) , 30 cases of patients with non-MODS (control group) when they were admitted into hospital, and contrasted in the MODS group, evaluated APACHE II and MODS score of all inpatients. RESULTS (1) There were differences in APACHE II, MODS score, CP, CRCP, AAG between MODS group and control group (P< 0.05); (2) comparison within MODS group: CP level was significantly different in patients with 3 and above organ damages and two organ damages (P< 0.05) , and there was no obvious relationship with liver damage. (3) CP and RCRP increased obviously in infection group and non-infection group (P< 0.05). CONCLUSION (1) CP, RCRP, AAG determinations helps early diagnosis in MODS. (2) With the number of organ damage increases, the CP levels increases to different extent, it is helpful to MODS prognostic diagnosis. (3) CP and RCRP monitoring helps preliminary judgment in causes of MODS, and has a certain value to specific therapy of MODS.%目的 探讨血清中铜蓝蛋白动态变化对MODS患者病因判断和预后评估的价值.方法 于入院当天分别检测60例MODS患者(MODS组)、30例非MODS患者(对照组)血清铜蓝蛋白(CP)、超敏C反应蛋白(CRCP)、α-酸性糖蛋白(AAG)乳酸的含量,并对MODS组进行组内比较,入选的住院患者均进行APACHEⅡ和MODS评分.结果 (1) MODS组与对照组相比其APACHEⅡ、MODS评分、血清铜蓝蛋白(CP)、超敏C反应蛋白(CRCP)、α-酸性糖蛋白(AAG)的比较,差异有统计学意义(P<0.05); (2) MODS组内比较:3个及3个以上器官损害与2个器官损害患者铜蓝蛋白水平比较,差异有统计学意义(P<0.05),且与是否有肝损害无明显关系; (3)非感染组与感染组相比较,铜

  13. Biomarcadores del estado inflamatorio: nexo de unión con la obesidad y complicaciones asociadas Inflammatory biomarkers: the link between obesity and associated pathologies

    Directory of Open Access Journals (Sweden)

    M.ª A. Zulet

    2007-10-01

    humanos, así como los factores implicados en su regulación.The objetive of this article is to review biomarkers that have been suggested in recent years as the link between inflammation, obesity and associated co-morbidities, as well as some questions that yet remain unclear. Increasing evidence indicates the important role of inflammation in the etiology of major public health problems. In the last years, several studies have proposed that obesity might be a inflammatory disorder. In addition, oxidative stress has been suggested as a potential inductor of inflammatory status and susceptibility to obesity and related disorders. Several biomarkers are being suggested as the link between obesity, insulin resistance, cardiovascular disease and metabolic syndrome, such as tumor necrosis factor alfa, interleukin-6 and -18, angiotensinogen, transforming grow factor beta, plasminogen activator inhibitor-1, leptin, resistin, C-reactive protein, serum amyloid A, sialic acid, fibrinogen, markers of endothelial dysfunction (von Willebrand factor, ICAMs, VCAMs, complement factor 3, haptoglobin, Zinc-alpha2-glycoprotein, eotaxin, visfatin, apelin, alpha1- antitrypsin, vaspin, omentin, retinol binding protein 4, ceruloplasmin, adiponectin and desnutrin. Some of this biomarkers are good predictors of cardiovascular risk (plasminogen activator inhibitor-1, sialic acid, fribrinogen, complement factor 3, C-reactive protein, adiposity (leptin, visfatin, resistin, haptoglobin and/or insulin resistance (sialic acid, C-reactive protein, plasminogen activator inhibitor-1, von Willebrand factor. However, it is currently unclear the role of many of them concerning inflammatory processes in humans, as well as the factors involved in their regulation.

  14. [The onset of psychiatric disorders and Wilson's disease].

    Science.gov (United States)

    Benhamla, T; Tirouche, Y D; Abaoub-Germain, A; Theodore, F

    2007-12-01

    Wilson's disease is an infrequent, autosomic recessive pathology, resulting from a loss of function of an adenosine triphosphatase (ATP7B or WDNP), secondarily to a change (more than 60 are described currently), insertion or deletion of the ATP7B gene located on the chromosome 13q14.3-q21.1, which involves a reduction or an absence of the transport of copper in the bile and its accumulation in the body, notably the brain. Wilson's disease is transmitted by an autosomic recessive gene located on the long arm of chromosome 13. The prevalence of the heterozygote is evaluated at 1/90 and the homozygote at 1/30,000. Consanguinity, frequent in the socially geographically isolated populations, increases the prevalence of the disease. The toxic quantities of copper, which accumulate in the liver since early childhood and perhaps before, remain concentrated in the body for years. Hence, cytological and histological modifications can be detected in the biopsies, before the appearance of clinical or biological symptoms of hepatic damage. The accumulation of copper in the liver is due to a defect in the biliary excretion of metal and is accompanied invariably by a deficit in ceruloplasmin; protein synthesized from a transferred ATP7B gene, which causes retention of the copper ions in the liver. The detectable cellular anomalies are of two types: hepatic lesions resulting in acute hepatic insufficiency, acute hepatitis and finally advanced cirrhosis and lesions of the central nervous system responsible for the neurological and psychiatric disorders. In approximately 40-50% of the patients, the first manifestation of Wilson's disease affects the central nervous system. Although copper diffuses in the liver towards the blood and then towards other tissues, it has disastrous consequences only in the brain. It can therefore cause either a progressive neurological disease, or psychiatric disorders. Wilson's disease begins in the form of a hepatic, neurological, or psychiatric

  15. 壳聚糖铜对断奶仔猪生长性能、血清生化指标及激素水平的影响

    Institute of Scientific and Technical Information of China (English)

    朱叶萌; 钊守梅; 韩新燕

    2013-01-01

    The study was conducted to observe the effects of chitosan-copper(CS-Cu)on growth performance,serum biochemical and hormone indices of weaning piglets.One hundred and twenty Duroc×Landraee×Yorkshire piglets with(7.8± 0.2)kg body weight were randomly divided into 4 treatment groups and fed with basic diet or basic diet supplemented with 50 mg/kg CS-Cu,100 mg/kg CS-Cu and 200 mg/kg CuSO4 respectively.Feeding trial lasted 30 days.The results showed as follows:compared with the control group,the average daily gain (ADG)of two CS-Cu groups and 200 mg/kg CuSO4 group significantly increased(P < 0.05)and the feed gain ratio(F/G)significantly decreased(P < 0.05),but there was no signifi-cant difference between the 100 mg/kg CS-Cu group and 200 mg/kg CuSO4 group.100 mg/kg CS-Cu group significantly increased(P<0.05)the ceruloplasmin content,total iron binding capacity,alkaline phosphatase activity and insulin activi-ty.The results indicated that efficiency of 100 mg/kg CS-Cu group was similar as 200 mg/kg CuSO 4 group.%为探讨壳聚糖铜(CS-Cu)对断奶仔猪生长性能、血清生化指标和血清激素的影响,选择120头体重(7.8±0.2)kg的“杜×长×大”三元杂交断奶仔猪随机分为4组,对照组饲喂基础日粮,各试验组分别在基础日粮基础上添加50、100 mg/kg CS-Cu和200 mg/kg硫酸铜,预饲期7 d,试验期30 d。结果表明:与对照组相比,50、100 mg/kg CS-Cu组和200 mg/kg硫酸铜组仔猪日增重显著提高(P<0.05),料重比显著降低(P <0.05),但是100 mg/kg CS-Cu组和200 mg/kg硫酸铜组差异不显著(P>0.05)。与对照组相比,100 mg/kg CS-Cu组血清铜蓝蛋白含量、总铁结合力、碱性磷酸酶活性、胰岛素水平显著提高(P<0.05)。结果提示,日粮中添加100 mg/kg CS-Cu与200 mg/kg硫酸铜对提高断奶仔猪日增重和降低料重比具有等同的效果。

  16. Liver lipid content and inflammometabolic indices in peripartal dairy cows are altered in response to prepartal energy intake and postpartal intramammary inflammatory challenge.

    Science.gov (United States)

    Graugnard, D E; Moyes, K M; Trevisi, E; Khan, M J; Keisler, D; Drackley, J K; Bertoni, G; Loor, J J

    2013-02-01

    This study evaluated the effect of feeding a control diet (CON) or a moderate energy diet (overfed, OVE) during the dry period (∼45d) and a postpartum intramammary lipopolysaccharide (LPS) challenge on blood metabolic and inflammatory indices, milk production, and hepatic gene expression. A subset of cows (n=9/diet) in CON (1.34 Mcal/kg of dry matter) and OVE (1.62 Mcal/kg of dry matter) received an intramammary LPS challenge (200 μg; CON-LPS, OVE-LPS, respectively). Liver biopsies were harvested at -14 d from calving, and postpartum at 2.5h post-LPS on d 7, 14, and 30. Prepartum, the OVE group was in more positive energy balance (EB) and had greater body condition score compared with CON. In contrast, during wk 1 postpartum and before the LPS challenge, the OVE group was in greater negative EB than CON. Prepartal diet did not affect postpartal milk production or dry matter intake. At 2h postchallenge on d 7, we observed an increase in serum nonesterified fatty acids (NEFA) and bilirubin and a decrease in hydroxybutyrate, regardless of diet. That was coupled with greater haptoglobin in OVE-LPS compared with CON-LPS. In addition, OVE-LPS cows versus CON nonchallenged, OVE nonchallenged, and CON-LPS had greater liver triacylglycerol (TAG) concentration 2.5h postchallenge on d 7. The concentration of TAG in liver of OVE-LPS remained elevated by 30d postpartum. The liver TAG concentration in OVE-LPS compared with CON-LPS cows was associated with greater serum concentration of NEFA and reactive oxygen metabolites on d 10 and 14 postpartum. Cows in OVE-LPS also had greater concentrations of ceruloplasmin, cholesterol, and vitamin E from d 10 through 21. Among 28 genes associated with fatty acid oxidation, inflammation, oxidative stress, and gluconeogenesis, only SAA3 (which encodes an acute phase protein) was greater in CON-LPS compared with OVE-LPS at 2.5h postchallenge. Expression of HP, which encodes another acute phase protein, was greater in OVE-LPS than in CON

  17. Liver transplantation for Wilson's disease%肝移植治疗肝豆状核变性

    Institute of Scientific and Technical Information of China (English)

    吕少诚; 史宪杰; 梁雨荣; 何蕾; 纪文斌; 芦芳; 陈永卫; 罗英

    2011-01-01

    BACKGROUND: Lh/er transplantation can provide healthy Inzer tissue for Wilson's disease patients to correct their genetic defects, and rt can relive clinical and neuropsychiatric symptoms induced by copper metabolism and cirrhosis. OBJECT P/E: To investigate the effects of liver transplantation on Wilson's disease.METHODS: Seventeen cases were selected. Three cases were treated with cadaveric liver transplantation, and 14 cases were treated with Insing-related Inzer transplantation. In all the cases, artery reconstruction was conducted through end-to-end anastomose between donor hepatic artery and recipient hepatic artery. The duct-to-duct biliary reconstruction was performed. and no support pipe was placed in the biliary duct for drainage during operation.RESULTS AND CONCLUSION: One patient died of hemorrhage p eri op er athsely. Fifteen patients survn/ed more than 1 year and 10 patients survived more than 3 years. Of the eight patients with nervous system dysfunction, srx patients had improved neuropsychic symptoms to various degrees after operation. The Inzer function and serum ceruloplasmin level were improved significantly in the 15 patients undergoing liver transplantation surviving more than 1 year (P < 0.05). It suggests thatlrVer transplantation can correct patients' metabolic defects, isuhich is an effective therapy for Wilson's disease.%背景:肝移植能够为肝豆状核变性患者提供正常的肝组织以纠正其遗传缺陷,改善铜代谢、肝硬化所致的各种临床症状及神经精神症状.目的:观察肝移植治疗肝豆状核变性的效果.方法:选择17例肝豆状核变性患者,3例患者行尸体肝移植,14例患者行亲体肝移植,所有肝移植患者动脉重建采用供肝动脉与受者肝固有动脉端端吻合,胆道重建均采用胆道端端吻合,术中均未放置胆道支架管支撑引流.结果与结论:围手术期死亡1例,生存时间超过1年15例,超过3年10例.8例伴有神

  18. 肝移植治疗Wilson病8例分析%Liver transplantation in treatment of Wilson's disease: a report of 8 cases

    Institute of Scientific and Technical Information of China (English)

    司马辉; 蔡文科; 邵卓; 杨宁; 杨广顺

    2011-01-01

    Objective To determine the efficacy and prognosis of liver transplantation for Wilson's disease (WD). Methods From October 2002 to August 2008, 8 cases (3 men and 5 women) with a mean age of 22.6 years (12 - 42 years) underwent liver transplantation for WD in our department. All the recipients had low serum levels of ceruloplasmin and copper before transplantation, and 5 of them demonstrated the neurological manifestations. Results There were 3 orthotopic liver transplantation (OLT) and 2 living donor liver transplantation (LDLT) in this study. Seven recipients recovered satisfactorily with excellent liver functions, while 1 patient died of acute liver steatosis in 1 month after transplantation. Discharged patients were well followed up for a mean duration of 79.7 months (35- 124 months). Compared to the levels before transplantation, the total bilirubin levels were significantly declined (P0.05). The neurological manifestations were also partly relieved or disappeared after liver transplantation. No K-P loop was found in the patients 12 months after operation. Conclusion OLT and LRLT are effective treatments for patients with WD, which not only improving their copper metabolism but also significantly relieving the severe neurological manifestations and improving life quality. (Shanghai Med J, 2011, 34: 656-659)%目的 探讨Wilson病患者接受肝移植治疗后的效果及预后.方法 回顾性分析2002年10月-2008年8月因Wilson病在第二军医大学附属东方肝胆外科医院接受肝移植手术的8例患者的临床资料,其中男3例,女5例,年龄为12~42岁,平均年龄为(22.6±10.3)岁.术前所有患者的血清铜蓝蛋白和血铜水平均低于正常值(血清铜蓝蛋白为200~600 mg/L,血铜为11~24.4μmol/L),其中5例术前存在神经病学症状.结果 5例患者接受原位肝移植术,3例接受活体肝移植术.除1例患者于术后1个月死于急性肝脂肪变肝功能衰竭外,其余患者术后肝功

  19. A young boy with elevated aminotransferases in physical examination -Two novel missense mutations associated with Wilson's disease were found%男性幼儿体检发现转氨酶升高--发现肝豆状核变性两处新的错义突变

    Institute of Scientific and Technical Information of China (English)

    朱渝; 邓思燕; 万朝敏

    2015-01-01

    1例3岁男性患儿因体检发现肝功能异常5个月入院。患儿无厌食、纳差、黄疸等症状,生长发育正常,肝脾无肿大,实验室检查常规筛查铜蓝蛋白水平(35 mg/L)明显降低,其余嗜肝病毒及巨细胞病毒、EB病毒均为阴性。肌酶正常,血糖、血氨及代谢筛查正常,自身免疫肝病抗体阴性。进一步行眼科检查示K-F环阴性,24 h尿铜水平0.56μmol/L(正常)。对患儿、患儿父母及其妹妹进行ATP7B基因检测,明确患儿和其妹妹具有两处新发现错义突变,为Exon7杂合突变c.2075T>C, p.L692P和Exon13杂合突变c.3044T>C, p.L1015P,各来自父母双方,符合复合杂合突变,基因诊断肝豆状核变性(Wilson)病成立。患儿及其妹妹确诊Wilson病后被嘱低铜饮食,患儿给予青霉胺驱铜治疗及锌剂拮抗铜吸收,其妹妹因尚无临床症状,故给予锌剂治疗。患儿经上述治疗3个月后复查肝功能完全正常。%A 3-year-old boy had abnormal liver function, which was found in physical examination, for 5 months before admission. He had no symptoms such as anorexia, poor appetite, and jaundice, had normal growth and development, and showed no hepatosplenomegaly. Laboratory examination revealed signiifcantly reduced ceruloplasmin (35 mg/L), as well as negative hepatotropic virus, cytomegalovirus, and Epstein-Barr virus. There were normal muscle enzymes, blood glucose, and blood ammonia and negative liver-speciifc autoantibodies. The boy had negative K-F ring and normal 24-hour urine copper (0.56 μmol/L). The ATP7B gene testing for the boy, his sister, and their parents detected two novel missense mutations in the boy and his sister, i.e., compound heterozygous mutations in exon 7 (c.2075T>C, p.L692P) and exon 13 (c.3044T>C, p.L1015P), which were inherited from their father and mother, respectively. Wilson's disease was conifrmed by genetic diagnosis in the boy and his sister. The boy and his

  20. 肝豆状核变性的遗传学研究进展%Genetic Research Advances of Wilson Disease

    Institute of Scientific and Technical Information of China (English)

    杨华荣; 宋治; 邓昊

    2009-01-01

    Wilson disease (WD) , an autosomal recessive disorder of copper transport, is characterized by excessive accumulation of intracellular copper in liver and extrahepatic tissues because of impaired biliary copper excretion and disturbed incorporation of copper into ceruloplasmin, subsequently presence clinical manifestations such as liver cirrhosis, lenticular degeneration and Kayser-Fleischer comeal rings. Mutations in the ATP7B gene are responsible for WD and more than 515 variants (379 probable disease-causing) have now been reported in patients with WD. The disease is distributed widely in different ethnic and geographical populations.The mutations include missense, nonsense, deletions, insertions, substitutions and splice mutations, etc. Missense mutation His1069GIn in exon 14 is the most common type of mutation in European patients, whereas,missense mutation Arg778Leu in exon 8 is the most frequently observed mutation type in Aisan patients. Gene mutation analysis contributes to accurate and definitive diagnosis, and early treatment. Animal models of genetic defects will help to carry out experimental treatment and elucidate pathological genetic mechanisms of this disease. The known genetic research advances in Wilson's disease are reviewed in this article.%肝豆状核变性(Wilson's disease,WD)是一种铜转运障碍的常染色体隐性遗传病,以胆汁铜排泄及血浆铜蓝蛋白合成障碍而导致肝和肝外组织铜的过度蓄积为特征,进而出现肝硬化、豆状核变性和角膜的K-F环等一系列异常临床表现.WD是由ATP7B基因突变引起的,基因变异超过515种(至少379种可能为致病突变),广泛分布不同人种和地域,包括错义突变、无义突变、缺失突变、插入突变、置换突变和剪接突变等.其中最常见的突变类型欧洲患者为14号外显子His1069Gln错义突变,亚洲患者为位于8号外显子的Arg778Leu错义突变.基因突变分析有利于准确诊断及早期治疗,遗传

  1. Genetic characterization of a brangus-ibage cattle population: biochemical polymorphisms and reproductive efficiency Caracterização genética de uma população de bovinos brangus-ibagé: polimorfismos bioquímicos e eficiência reprodutiva

    Directory of Open Access Journals (Sweden)

    Luiz Ernani Henkes

    2000-10-01

    Full Text Available Biochemical techniques were used to investigate the genetic variability in a Brangus-Ibage population by determining allele frequencies of 18 blood protein systems: Hemogloin beta-Chain (Hb, Albumin (Alb, Amylase (Am, Transferrin (Tf, Carbonic Anhydrase (CA, Ceruloplasmin (Cp, Malic Enzyme (ME, Diaphorase I and II (Dia I and Dia II, Slow Alpha 2 Macroglobulin (Ap, Acid Phosphatase (ACP, Esterase B and D (EstB and EstD, Phosphogluconate Dehydrogenase (PGD, Glucose-6-Phosphate Dehydrogenase (G-6-PD, Glucose-Phosphate-Isomerase (GPI, Superoxide Dismutase (SOD and Glyoxalase I (GLO. The percentage of polymorphic loci were estimated at 0.27, the mean number of alleles was 1.33 and the mean heterozygosity was 0.07. There was a good agreement between expected and observed heterozygosity values. The population was in agreement with Hardy-Weinberg expectations in all systems. Reproductive records allowed to estimate three parameters of reproductive efficiency: mean age at first calving (1152.15 ± 166.60 days, mean calving interval (539.23 ± 124.10 days and mean weight at first calving (391.02 ± 37.59kg. No relationship was found between reproductive efficiency and genetic systems.Técnicas bioquímicas foram utilizadas para determinar a variabilidade genética numa população de bovinos da raça Brangus-Ibagé com relação a 18 sistemas protéicos sangüíneos: Hemoglobina - Cadeia beta (Hb, Albumina (Alb, Amilase (Am, Transferrina (Tf, Anidrase Carbônica (CA, Ceruloplasmina (Cp, Enzima Málica (ME, Diaforase I and II (Dia I and Dia II, Macroglobulina alfa2 lenta (Ap, Fosfatase Ácida (ACP, Esterase B and D (EstB and EstD, Fosfogliconato Desidrogenase (PGD, Glicose-6-Fosfato Desidrogenase (G-6-PD, Glicose-Fosfato-Isomerase (GPI, Superóxido Dismutase (SOD e Glioxalase I (GLO. O percentual de locos polimórficos foi estimado em 0,27, o número médio de alelos foi 1,33 e a heterozigosidade média foi de 0,07. Houve boa concordância entre a

  2. Vitamin D3 transactivates the zinc and manganese transporter SLC30A10 via the Vitamin D receptor.

    Science.gov (United States)

    Claro da Silva, Tatiana; Hiller, Christian; Gai, Zhibo; Kullak-Ublick, Gerd A

    2016-10-01

    Vitamin D3 regulates genes critical for human health and its deficiency is associated with an increased risk for osteoporosis, cancer, diabetes, multiple sclerosis, hypertension, inflammatory and immunological diseases. To study the impact of vitamin D3 on genes relevant for the transport and metabolism of nutrients and drugs, we employed next-generation sequencing (NGS) and analyzed global gene expression of the human-derived Caco-2 cell line treated with 500nM vitamin D3. Genes involved in neuropeptide signaling, inflammation, cell adhesion and morphogenesis were differentially expressed. Notably, genes implicated in zinc, manganese and iron homeostasis were largely increased by vitamin D3 treatment. An ∼10-fold increase in ceruloplasmin and ∼4-fold increase in haptoglobin gene expression suggested a possible association between vitamin D and iron homeostasis. SLC30A10, the gene encoding the zinc and manganese transporter ZnT10, was the chiefly affected transporter, with ∼15-fold increase in expression. SLC30A10 is critical for zinc and manganese homeostasis and mutations in this gene, resulting in impaired ZnT10 function or expression, cause manganese intoxication, with Parkinson-like symptoms. Our NGS results were validated by real-time PCR in Caco-2 cells, as well as in duodenal biopsies taken from healthy human subjects treated with 0.5μg vitamin D3 daily for 10 days. In addition to increasing gene expression of SLC30A10 and the positive control TRPV6, vitamin D3 also increased ZnT10 protein expression, as indicated by Western blot and cytofluorescence. In silico identification of potential vitamin D responsive elements (VDREs) in the 5'-flanking region of the SLC30A10 promoter and dual-luciferase reporter assay showed enhanced promoter activity in the presence of vitamin D receptor (VDR) and retinoid X receptor (RXR) constructs, as well as vitamin D3, but not when one of these factors was absent. Electrophoretic mobility shift assay (EMSA) and

  3. 癌症患者血中微量元素与氧化应激的相关分析%Correlation between oxidative stress and trace elements in blood of patients with cancer

    Institute of Scientific and Technical Information of China (English)

    俸家富; 李少林

    2006-01-01

    (TAOP) levels were measured with phenanthroline colorimetry. Albumin concentration was determined with bromcresol purple. Serum transferrin (Trf) and ceruloplasmin (CER)concentrations were determined with immunonephelometry. The concentrations of Cu, Zn, Fe, and Se were measured with flame atomic absorption spectroscopy.MAIN OUTCOME MEASURES: MDA (as lipid peroxidation marker),trace elements copper, zinc, iron, and selenium and their transport proteins (albumin, transferrin and ceruloplasmin); antioxidation status markers: the concentrations of XOD, GSH, GSHPx, vitamin C, and vitamin E, and total antioxidant power levels.RESULTS: It was shown that lipid peroxidation ( measured as MDA)was significantly higher in cancer patients than in healthy controls [(5.21±1.05) nmol/L vs (4.04±0.68) nmol/L,P < 0.001], and the TAOP level was significantly decreased in cancer patients than in the health controls[(4.34±0.980) U/L vs (5.87±0.93) U/L,P < 0.001]. There were not obvious changes of antioxidation components (XOD, GSH, GSHPx, vitamin C,and vitamin E). Serum albumin concentration was found to be significantly lower in the cancer patients than in the health controls [(34.19±6.94)g/L vs (42.34±4.89) g/L ,P < 0.001], and serum ceruloplasmin concentration was found to be significantly higher in the cancer patients than in the health controls [(0.371 ±0.031) g/L vs (0.346±0.026) g/L,P < 0.05] butserum transferrin concentration remained unaltered (P > 0.05). As com pared with the healthy controls, serum copper level was significantly increased[(19.27±4.74) μmol/L vs (14.29±2.71) μmol/L, P < 0.001], serum selenium levels was significantly decreased[(1.175±0.333 0 μmol/L vs (1.413±0.446) μmol/L,P < 0.001)]. However, the concentrations of zinc and iron remained unchanged. Correlation was observed between copper and MDA levels (r=0.281, P=0.003) in the cancer patients but not in the healthy controls. Moreover, a correlation was also observed between serum iron and

  4. 肝移植新术式——双多米诺供肝交叉辅助式肝移植治疗代谢性肝脏疾病%Conceptual innovation: cross-auxiliary double domino donor liver transplantation

    Institute of Scientific and Technical Information of China (English)

    朱志军; 魏林; 孙丽莹; 张忠涛; 贾继东; 曲伟; 曾志贵; 刘颖; 张梁

    2014-01-01

    outflow tract and domino liver transplantation were completed in stage-1; domino liver-2 resection,vascular preparation and transplantation were done in stage-2.Result The recipient obtain normal liver function,ceruloplasmin oxidase activity,blood copper and urine copper level after stage-1; and also with normal blood ammonia after stage-2.Abdominal Ultrasound showed that the blood flow of artery,portal vein and hepatic vein were all normal.Conclusion As a conceptual change in a liver transplant,two domino donors from different liver-based metabolic disorder patients can implement a metabolic function complementary each other in the same recipient.The recipient can obtain ideal liver function and quality of life by overcoming the surgical technical problems.

  5. 轻型肝豆状核变性诊断标准的再评估%Re-evaluation of the diagnostic criteria in mild Wilson Disease

    Institute of Scientific and Technical Information of China (English)

    葛欣; 王廉文

    2014-01-01

    Objective With the development of children 's health care policy, mild Wilson Disease as the first symptom of pa-tients is increasing.In this study, we assessed the reliability of the 2001 international general standards of the Wilson Disease diagnos -tic score.Methods Twenty -one cases of Wilson Disease in children (11 cases were boys, 10 cases were girls, average age was 3 ~10.8 years) included in the study, other 21 cases with liver disease were age-matched and gender-matched.There were no clinical symptoms, only with abnormal liver function in laboratory tests .All the patients with Wilson Disease were all confirmed through genetic diagnosis.Results Receiver operating characteristic (ROC) curve analysis showed that at 20 mg /L threshold, the sensitivity of cer-uloplasmin was 93.4% (95% CI : 81.2% ~98.8%), the specificity was 81.8 (95% CI : 71.6% ~93.6%); urinary copper diag-nostic threshold was 40μg/L/24h, the sensitivity was 75.9% (95% CI :61.7% ~92.4%); the specificity was 89.9% (95% CI :73.7% ~96.6%).WD scoring diagnostic system of the positive and negative predictive values as high as 93% and 91.6%.Penicil-lamine load test in Wilson Disease and control groups , no significant difference between the ROC curve showed a sensitivity of only 10%.Conclusions WD scoring diagnostic system in the mild Wilson Disease patients still has a high diagnostic specificity , but peni-cillamine load test does not have diagnostic significance in some patients .%目的:探讨 WD 评分标准诊断系统在轻型肝豆状核变性(wilson disease,WD)疾病中的诊断价值,为临床提供诊断依据。方法本医院门诊纳入21例年龄3~10.8岁的肝豆状核变性患儿(男11例,女10例),收集年龄、性别匹配的肝脏疾病患儿21例,两组均无临床症状,仅有肝功能异常的实验室检查。所有肝豆状核变性的患者,所有诊断均通过基因诊断确诊。结果接受者操作特征曲线(ROC)分析表明,在20

  6. Quadro seroproteico como auxílio diagnóstico na anemia hemolítica imunomediada em cães Serum proteic profile as diagnosis aids in immune-mediated hemolytic anemia in dogs

    Directory of Open Access Journals (Sweden)

    Patrícia Mendes Pereira

    2010-04-01

    maior nestes. Tais achados analisados em conjunto agregam informações adicionais úteis à elucidação das AHIMs em cães.This assay aimed to determine the serum protein - via polyacrylamide gel electrophoresis, which contained duodecil sodium sulfate (SDS-PAGE - in 120 dogs, with different breeds and ages, seen by the Veterinary Hospital "Governor Laudo Natel." These animals were grouped into five experimental groups: Group 1 - group control with 20 dogs, group 2 - 28 dogs with regenerative anemia; group 3 - 27 dogs with arregenarative; anemia group 4 - 10 dogs with primary immune-mediated hemolytic anemia (AHIM 1.rd; group 5 - 35 dogs with secondary immune-mediated hemolytic anemia (AHIM 2.rd. The technique allowed the SDS-PAGE fractionation of 24 protein, whose molecular weights (PM ranged from 18,000 to 165,000 daltons (Da. The dogs with 1st and 2nd AHIM showed 24 protein fractions in their tracks electrophoretic, while other groups of dogs showed 23 fractions of protein, whose molecular protein weight of 68,000Da was not found. Thus, twenty-three proteins were common to proteinograms of the five experimental groups. From these, it was possible to identify eleven protein fractions nominally, and others were identified by their molecular weights. For control dogs, the anemic (groups 2, 3, 4 and 5 showed higher concentrations of serum transferrin and between them, the animals carrying the primary IMHA. All groups of dogs showed anemic levels of serum haptoglobin and phosphorylase significantly higher than the control dogs, while the serum ceruloplasmin was lower in anemic dogs. These findings provide additional information to the elucidation of the AHIMs in dogs.

  7. Doença de Creutzfeldt-Jakob forma Heidenhain: relato de caso com achados de ressonância magnética e DWI Creutzfeldt-Jakob disease, Heidenhain variant: case report with MRI (DWI findings

    Directory of Open Access Journals (Sweden)

    Walter Oleschko Arruda

    2004-06-01

    -old white woman, was admitted in our service with a month history of progressive, bilateral cortical blindness. After admission, she developed right partial motor seizures( right facial, upper and lower limbs, she became progressively aphasic( mixed aphasia. Seizures were controlled with phenytoin, but she developed choreoathetotic movements on her right dimidium, with partial control after introduction of chlorpromazine 25 mg q/d. She could no longer stand up or walk due to severe ataxia. The first EEG (October, 2001 showed left hemisphere severe seizure activity (status epilepticus partialis. She was delivered home with enteral nutrition, phenytoin , chlorpromazine and mepacrine 100 mg qd. The following laboratorial tests were negative or normal: blood series, platelets, ESR, kidney and liver function, copper, ceruloplasmin, VDRL, HIV, HTLV-1, lactate, and cerebral DSA (performed in other service.A spinal tap with normal opening pressure was perform and CSF examination was normal. CSF 14-3-3 protein was positive, CSF specific neuronal enolase 7.5 ng/ml(normal. Genetic study of PRNP gene did not disclosed any known mutation. A MRI (October, 2001 showed areas of hyperintense signal (T2 and FLAIR without Gd-enhancement on T1, in the left temporal lobe and in both occipital lobes; basal ganglia have a normal appearance. DWI imaging showed bright areas at the same sites. An EEG (March, 2002 disclosed a periodical sharp triphasic waves pattern, suggestive of CJD. A second MRI (April, 2002 showed mild generalized atrophy, no ventricular dilatation, and the hyperintense sites disappeared. She remained clinically stable and under use of chlorpromazine and mepacrine until she died due to pulmonary complications on April, 2003.

  8. Citrin缺陷所致婴儿肝内胆汁淤积症43例分析%Intrahepatic cholestasis caused by citrin deficiency:a clinical analysis of 43 infants

    Institute of Scientific and Technical Information of China (English)

    姜涛; 姚蔚; 欧阳文献; 谭艳芳; 李双杰

    2014-01-01

    Objective To analyze the clinical characteristics and prognosis of neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD)in infants.Methods The clinical data of 43 infants with NICCD in our hospital from July 201 1 to April 2014 were collected.The diagnosis was confirmed by tandem mass spectrometry (MS-MS)analysis of blood,gas chromatography-mass spectrometry (GC-MS)a-nalysis of urine,and genetic testing,and an analysis was performed with reference to clinical manifestations and laboratory results.Results Most patients with NICCD developed jaundice early,with a round,fat face,hepatomegaly,and growth retardation.Laboratory examina-tions showed increased bilirubin,total bile acids,blood lactic acid,alpha-fetoprotein,and procalcitonin in all patients,increased alanine aminotransferase,gamma-glutamyl transpeptidase,and blood ammonia,decreased albumin and blood glucose,and dyslipidemia and coag-ulation disorders in most patients,and abnormal liver fibrosis markers (20/24)and low ceruloplasmin (17/20)in some patients.Abdomi-nal ultrasound showed hepatomegaly in 32 patients.MS-MS analysis of blood samples revealed distinctive elevation of methionine,citrul-line,tyrosine,threonine,and a variety of acyl carnitine in most patients.GC-MS analysis of urine samples revealed elevated galactose and galactitol in 20 patients,elevated 4-hydroxyphenyllactic acid and 4-hydroxyphenylpyruvic acid in 10 patients,and no abnormalities in 6 patients.Genetic testing revealed 851del4,1638ins23,and IVS6+5G>A mutations,especially 851del4 mutation.After being treated by giving lactose-free diet,strengthening medium-chain fatty acid diet,protecting the liver,and relieving cholestasis,most patients had nor-malized indices 2 months later,2 cases had liver cirrhosis,and 7 cases died.Conclusion The clinical manifestations of NICCD vary in children.MS-MS analysis of blood,GC-MS analysis of urine,and genetic testing should be performed early in children with clinically suspected NICCD

  9. Clinical Diagnosis of the Diseases with Atypical Parkinsonian Disorders%非典型帕金森病相关疾病的临床诊断思路

    Institute of Scientific and Technical Information of China (English)

    胡智伟; 王浩; 邹小东; 王百辰; 呙登俊

    2013-01-01

    and levodopa (L-dopa) tests.The final clinical diagnosis was made according to the diagnostic criterias of APD related diseases.Results For clinical manifestations,among the 48 patients,there were 42 cases with hypermytoma,40 cases with tremor,39 cases with bradykinesia,32 cases with abnormal postural reflex,29 cases with abnormal gait,13 cases with orthostatic hypotension,12 cases with tendon hyperreflexia,11 cases with cognitive impairment,10 cases with vertical gaze palsy,10 cases with bulbar palsy,8 cases with ataxia,8 cases with positive pathologic reflexes,7 cases with K-F corneal ring,5 cases with visual hallucination and 3 cases with unilateral limb ignorance duo to apraxia.Laboratory tests showed abnormal liver function in 9 cases,thrombocytopenia in 8 cases,reduced serum ceruloplasmin levels in 7 cases and abnormal coagulation monitoring in 5 cases.The CT scan revealed low density in basal ganglia in 19 cases,ventricular dilatation in 17 cases and cerebral atrophy in 14 cases.The MR imaging showed abnormal signals in the basal ganglia in 30 cases,ventricle expand in 20 cases,diffusive cerebral atrophy in 18 cases,atrophy in pons and cerebellum in 15 cases,hippocampal atrophy in 7 cases,high intensity in pallidum on T2 in 4 cases,“putamen fissure sign” in 8 cases,“cross sign” in pons in 7 cases and “hummingbird sign”in midbrain in 6 cases.Fourty-six cases showed poor response to L-dopa treatment.Montreal Cognitive Assessment Scale (MoCA) total scores < 26 in 23 cases.There were 18 cases diagnosed clinically as multiple system atrophy(MSA),10 cases diagnosed as progressive supranuclear palsy (PSP),7 cases diagnosed as Wilson disease(WD),6 cases diagnosed as dementia with Lewy bodies (DLB),5 cases diagnosed as Alzheimer' s disease (AD) with Parkinsonism syndrome (PS) and 2 cases diagnosed as corticobasal degeneration (CBD).Conclusion Although APD related diseases have some similarity in clinical manifestations,but their clinical characteristics

  10. Electrophoresis of Serum Proteins in Patients with Hepatitis B Virus - associated Hepatocellular Carcinoma%HBSAg阳性原发性肝癌患者血清蛋白电泳图谱分析

    Institute of Scientific and Technical Information of China (English)

    高国生; 徐晓珍

    2012-01-01

    . Meantime, serum albumin (ALB),α1-antitrypsin(AAT), al-phafetoprotein (AFP), haptoglobin(Hp), Ceruloplasmin (Gp),transferrin(TRF), complement C3(C3), immu no globulin G(IgG), immu-noglobulin A(IgA),immunoglobulin M(IgM) and C-reactive protein(CRP) were detected. Then a statistical analysis was made on these results. Results In all groups,the percent of albumin in patients with hepatitis B virus-associated hepatocellular carcinoma was lowest, and the difference compared with healthy adults and patients with chronic hepatitis B had statistical significant (P<0.05). The percent of α1-globin was highest, and the difference compared with healthy adults and patients with posthepatitic cirrhosis had statistical significance(P<0.05), The percent of α2-globin was higher than other patients. And the level of serum AAT,AFP, Cp and CRP was significantly higher than that in other groups (P<0.05). The level of serum Hp and C3 was significantly higher than that in other patients (just a little lower than that in healthy adults).Conclusion The changes of serum protein electrophoresis in patients with hepatitis B virus-associated hepatocellular carcinoma were mainly presented with the decreased level in albumin and increased percent of α1 and α2-glo-bins. Increased percent of α-globins markedly related with increased positive acute phase proteins and AFP. Serum protein electrophoresis combined with detection of specific proteins was important for the diagnosis of disease and the assessment of disease progression.

  11. Radicais livres de oxigênio e exercício: mecanismos de formação e adaptação ao treinamento físico Radicales libres de oxigeno y ejercicio: mecanismos de formación y adaptación al entrenamiento Oxygen free radicals and exercise: mechanisms of synthesis and adaptation to the physical training

    Directory of Open Access Journals (Sweden)

    Cláudia Dornelles Schneider

    2004-08-01

    formación de los RLO y de adaptación al estrés oxidativo crónico provocado por el entrenamiento físico.The interest about the mechanisms of generation and adaptation of oxygen free radicals (OFR to exercise has increased significantly from the demonstration of its relation with the oxygen intake. The OFR are formed through the incomplete reduction of oxygen, generating species presenting high reactivity to other biomolecules, especially lipids and proteins of the cell membranes and even DNA. The injuries caused by the oxidative stress present accumulative effects, being related to several diseases such as cancer, arteriosclerosis and diabetes. The acute physical exercise furthers the increase on the formation of OFR in function of the increment on the oxygen intake. However, the physical training generates adaptations able to soften the harmful effects caused by OFR. These adaptations are related to several systems, among which the most important are the enzymatic system, composed by the superoxide dysmutase, catalase and glutathione peroxidase; and the non-enzymatic system, composed by the ceruloplasmine, the sexual hormones, co-enzyme Q, uric acid, thermal shock proteins, among others. Such adaptations, despite the controversies about the mechanisms involved, further a higher tissue resistance and oxidative challenges such as those provided by long-duration high intensity exercises. The evaluations techniques of the oxidative stress, most times are not able to detect injuries in short-duration exercises. Thus, studies of physical efforts performed for long periods or until exhaustion have been conducted. New lesion markers by OFR action have been discovered and new techniques for its determination have been created. The objective of this work is discuss the formation mechanisms of OFR and the adaptations to the chronic oxidative stress caused by physical training.

  12. 铅对大鼠铜稳态失衡的影响及槲皮素的干预作用%Disorder of copper homeostasis induced by lead exposure among mice and intervention effect of quercetin

    Institute of Scientific and Technical Information of China (English)

    杨辉; 闫立成; 曹福源; 赵会新; 王雅洁; 郭璇; 孟维静; 李清钊; 张艳淑

    2013-01-01

    受损情况好转.结论 铅暴露能引起机体铜稳态失调,槲皮素对铅引起的损伤有一定缓解作用.%Objective To investigate the effect of lead exposure on copper and copper metalloenzyme and the intervention effect of quercetin.Methods Twenty-four specific pathogen-free male Sprague-Dawley rats of good health were randomly divided into control group (n=8),lead acetate group (n=8),and lead acetate+ quercetin group (n=8).The rats in lead acetate group were poisoned by drinking water with 1 g/L lead acetate for 8 weeks,while the rats in control group were fed by drinking water with sodium acetate of the same volume for 8 weeks; the rats in lead acetate+quercetin group were intraperitoneally injected with quercetin (30 mg· kg1 ·d-1) for 8 weeks while drinking water with lead acetate.The Morris water maze was used to test the learning and memory abilities of rats.The lead and copper levels in the serum,hippocampus,cortex,and bone were measured by graphite furnace atomic absorption spectrometry.The level of advanced glycation end products,activity of Cu/Zn superoxide dismutase (SOD),and content and activity of ceruloplasmin (CP) in the hippocampus and serum were measured using a test kit.HE staining was performed to observe the pathological changes in the hippocampus.Results The Morris water maze test showed that the latency in lead acetate group (52.50± 12.04 s) was significantly longer than that in control group (28.08±7.31 s) (P<0.05),and the number of platform crossings was significantly lower in the lead acetate group than in the control group.Compared with those in the control group,the lead levels in the cortex and hippocampus in lead acetate group increased 2.72-fold and 3.79-fold,and the copper in the cortex and hippocampus,and serum free copper levels in lead acetate group increased 1.15-fold,1.48-fold,and 6.44-fold.Compared with the control group,the lead acetate group had a lower content of CP in the hippocampus (1.23±0.40 U/mg pro vs 0.78±0.08 U/mg pro) and

  13. Mutation and Copy Number Variation Analysis of ATP7A Gene in Patients with Menkes Disease%Menkes病临床及ATP7A基因突变和拷贝数改变分析

    Institute of Scientific and Technical Information of China (English)

    黄琼辉; 王静敏; 吴晔; 邓艳华; 熊晖; 张月华; 杨艳玲; 姜玉武

    2012-01-01

    Objective To analyze ATP7A gene mutations and copy number variation( CNV) in 13 Chinese patients with classical Menkes disease (MD) and discuss the relationship of genotype and phenotype. Methods Thirteen patients clinically diagnosed Menkes disease were included. All 23 exons and exon - intron boundaries of ATP7A gene were amplified by polymerase chain reaction ( PCR) and directly se-quenced for genomic DNA. The mutation had been proved by DNA restriction enzyme digestion of PCR - amplified fragments. Multiplex liga-tion - dependent probe amplification( MLPA) assays were performed to detect ATP7 A copy number variation. Results All of 13 patients were boys. The symptoms onset occurred between 3 days to 7 months. The manifestations were typical hair changes, seizures, hypotonia, neurodevelo-pmental delays and inguinal hernias. Twelve cases(100% ,n = 12)patients had low serum ceruloplasmin concentration;6 cases(75% ,n = 8) patients had low serum copper concentration;4 cases ( 100% , n = 4) patients had " corkscrew" appearance of cerebral vessels in MR angiography. Five patients had been found dead before 14 months old during follow - up. One patient was 47XXY/46XY chimerism;Six mutations were identified in 8 of 13 patients through DNA sequencing,including 2 missense mutations ( c. 3028A > C,c. 2179G > A) ;2 frame - shift mutations (one complicated deletion mutation:c. 2589delTGAAGGA + c. 2598delTT + c.2601delT + c. 2603delT + c. 2605delGTAGATGA, one simple deletion:c. 3045delT) and 2 splicing mutations (e.4005 +1G >C,c. 3658 + 1G > A); three of these were novel. MLPA assays identified one case with deletion covered whole exon 10 which was proved by long -fragment PCR as c.2173 -346_2407 -346del,p. F725_ K802 del. With the same mutations c. 2179G > A( p. G727R) ,P1 which was 47XXY/46XY,had earlier onset and heavier clinical symptoms than P2 which was the normal karyotype. Conclusions MLPA is a rapid and reliable technique to detect the big fragment or whole gene