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Sample records for serum tartrate-resistant acid

  1. Development of immunoassays for serum tartrate-resistant acid phosphatase isoform 5a.

    PubMed

    Chao, Tsu-Yi; Lee, Su-Huei; Chen, Mary M; Neustadt, David H; Chaudhry, Uzma A; Yam, Lung T; Janckila, Anthony J

    2005-09-01

    Serum tartrate-resistant acid phosphatase (TRACP) consists of 2 structurally related isoforms, TRACP 5a and 5b. TRACP 5b is from bone-resorbing osteoclasts. TRACP 5a may be a macrophage product of inflammation. We used a novel antibody to TRACP 5a to standardize immunoassays for serum TRACP 5a activity and protein. Biotinylated anti-TRACP antibodies were used to immobilize serum TRACP isoforms. TRACP activity was measured using 4-nitrophenyl phosphate as substrate. TRACP 5a protein was measured with an independent peroxidase-conjugated anti-TRACP antibody. Immunoassays were standardized for linearity of serum dose response, sensitivity and precision. Reference ranges for TRACP 5a were established from serum of 50 healthy males and 50 healthy age-matched females. Serum TRACP 5a activity and protein were determined in 29 cases of rheumatoid arthritis. Serum matrix interference in both TRACP 5a assays required dilution to 10% serum to approach linearity. Intra-assay and inter-assay CV% were <10%. Mean serum TRACP 5a activity and protein were significantly higher in healthy men than women. There was a slight, but significant age related increase in both serum TRACP 5a and 5b among females, but not males, from age 20 to 70 years. TRACP 5a activity was positively correlated to TRACP 5a protein in healthy sera. Neither TRACP 5a activity nor protein was correlated strongly to TRACP-5b activity. TRACP 5a protein was significantly increased in 8/29 RA sera, whereas TRACP 5a and 5b activities were not. TRACP 5a activity and protein were not significantly correlated in RA sera. Although TRACP 5a and 5b are related biosynthetically, their circulating levels in healthy humans were independent, suggesting differential regulation of expression. In chronic diseases, increased TRACP 5a may represent pathological processes of inflammation unrelated to bone metabolism.

  2. Biology of tartrate-resistant acid phosphatase.

    PubMed

    Lamp, E C; Drexler, H G

    2000-11-01

    Tartrate-resistant acid phosphatase (TRAP) is a member of the ubiquitously expressed enzyme family of the acid phosphatases. Nearly 30 years ago, TRAP became known to hematologists as cytochemical marker enzyme of hairy cell leukemia. Physiologically, TRAP is primarily a cytochemical marker of macrophages, osteoclasts and dendritic cells. TRAP is localized intracellularly in the lysosomal compartment. Recent data suggest also secretion of TRAP by some cell types, in particular by osteoclasts. Human, mouse and rat TRAP are biochemically well characterized. While the complete genomic sequence of TRAP has been elucidated, only limited information on the genetic details of the gene and its regulation is available. It appears that the intracellular iron content is involved in the regulation of the enzyme. The physiological substrates for this enzyme have not been identified yet and consequently the functional role of TRAP remains completely unknown, though some hypotheses have been forwarded, e.g. involvement in bone resorption and iron homeostasis (transport, metabolism). Taken together, research on the biology of TRAP has been intensive and has led to considerable progress on a number of fronts, including the cloning of the gene. Further studies are, however, still required to determine the role of TRAP in vivo.

  3. The cytochemistry of tartrate-resistant acid phosphatase. Technical considerations.

    PubMed

    Janckila, A J; Li, C Y; Lam, K W; Yam, L T

    1978-07-01

    Cytochemical demonstration of tartrate-resistant acid phosphatase activity is essential for the diagnosis of leukemic reticuloendotheliosis. In order to perform this test correctly and to interpret the results propertly, it is necessary to understand the technical details of the cytochemical methods thoroughly. The method using naphthol--ASBI phosphoric acid--fast garnet GBC is recommended for this purpose, and factors crucial to the cytochemical study, such as fixation, substrate, coupler, pH and temperature of incubation buffer, counterstains, and mounting media are examined and discussed. Conventional methods for acid phosphatase in the presence and absence of L(+) tartaric acid are also critically examined. The naphthol--ASBI phosphoric acid--fast garnet GBC method is sensitive, technically simple and easily reproducible. Its reaction product is highly chromogenic and is most suitable for cytochemical demonstration of acid phosphatase and tartrate-resistant acid phosphatase activity in cytologic preparations. The naphthol--ASBI phosphoric acid--pararosaniline method is highly specific and is best for histochemical demonstration of acid phosphatase and tartrate-resistant acid phosphatase in tissue sections.

  4. Monomeric Tartrate Resistant Acid Phosphatase Induces Insulin Sensitive Obesity

    PubMed Central

    Lång, Pernilla; van Harmelen, Vanessa; Rydén, Mikael; Kaaman, Maria; Parini, Paolo; Carneheim, Claes; Cassady, A. Ian; Hume, David A.; Andersson, Göran; Arner, Peter

    2008-01-01

    Background Obesity is associated with macrophage infiltration of adipose tissue, which may link adipose inflammation to insulin resistance. However, the impact of inflammatory cells in the pathophysiology of obesity remains unclear. Tartrate resistant acid phosphatase (TRAP) is an enzyme expressed by subsets of macrophages and osteoclasts that exists either as an enzymatically inactive monomer or as an active, proteolytically processed dimer. Principal Findings Using mice over expressing TRAP, we show that over-expression of monomeric, but not the dimeric form in adipose tissue leads to early onset spontaneous hyperplastic obesity i.e. many small fat cells. In vitro, recombinant monomeric, but not proteolytically processed TRAP induced proliferation and differentiation of mouse and human adipocyte precursor cells. In humans, monomeric TRAP was highly expressed in the adipose tissue of obese individuals. In both the mouse model and in the obese humans the source of TRAP in adipose tissue was macrophages. In addition, the obese TRAP over expressing mice exhibited signs of a low-grade inflammatory reaction in adipose tissue without evidence of abnormal adipocyte lipolysis, lipogenesis or insulin sensitivity. Conclusion Monomeric TRAP, most likely secreted from adipose tissue macrophages, induces hyperplastic obesity with normal adipocyte lipid metabolism and insulin sensitivity. PMID:18320034

  5. Characterization of four monoclonal antibodies to recombinant human tartrate-resistant acid phosphatase.

    PubMed

    Miyazaki, Takashi; Matsunaga, Toshiyuki; Miyazaki, Shuichi; Hokari, Shigeru; Komoda, Tsugikazu

    2002-06-01

    In this study we produced a recombinant human Tartrate-resistant acid phosphatase (TRAP) enzyme from baculovirus-infected insect cells, generated four monoclonal antibodies (MAbs) 15A4, 13B9, 1C6 and 3G7, to the enzyme, and characterized these antibodies. In the human serum and lung specimen, all four antibodies appeared to have a high specificity for native TRAP enzyme in western blot analysis, immunohistochemical analysis and enzyme immunoassay. These antibodies may react with respective conformational determinants, therefore, they may be useful for detection of active TRAP. Only one of the antibodies, 15A4 also reacted with a denatured epitope, therefore, it is suitable for western blot analysis, enzyme immunoassay and for immunohistochemistry in the rat. Taken together, having characterized properties of four monoclonal antibodies against recombinant human TRAP enzyme may be useful for development of TRAP specific immunoassays in pathology and hematology of the bone. They will certainly be of use for the study of biosynthesis, regulation and function of the TRAP enzyme.

  6. Optimization of the tartrate-resistant acid phosphatase detection by histochemical method

    PubMed Central

    Galvão, M.J.; Santos, A. R.; Ribeiro, M.D.; Ferreira, A.; Nolasco, F.

    2011-01-01

    According to the new kidney disease improving global outcomes (KDIGO) guidelines, the term of renal osteodystrophy, should be used exclusively in reference to the invasive diagnosis of bone abnormalities. Due to the low sensitivity and specificity of biochemical serum markers of bone remodelling, the performance of bone biopsies is highly stimulated in dialysis patients and after kidney transplantation. The tartrate-resistant acid phosphatase (TRACP) is an iso-enzyme of the group of acid phosphatases, which is highly expressed by activated osteoclasts and macrophages. TRACP in osteoclasts is in intracytoplasmic vesicles that transport the products of bone matrix degradation. Being present in activated osteoclasts, the identification of this enzyme by histochemistry in undecalcified bone biopsies is an excellent method to quantify the resorption of bone. Since it is an enzymatic histochemical method for a thermolabile enzyme, the temperature at which it is performed is particularly relevant. This study aimed to determine the optimal temperature for identification of TRACP in activated osteoclasts in undecalcified bone biopsies embedded in methylmethacrylate. We selected 10 cases of undecalcified bone biopsies from hemodialysis patients with the diagnosis of secondary hyperparathyroidism. Sections of 5 µm were stained to identify TRACP at different incubation temperatures (37°, 45°, 60°, 70° and 80°C) for 30 minutes. Activated osteoclasts stained red and trabecular bone (mineralized bone) was contrasted with toluidine blue. This approach also increased the visibility of the trabecular bone resorption areas (Howship lacunae). Unlike what is suggested in the literature and in several international protocols, we found that the best results were obtained with temperatures between 60°C and 70°C. For technical reasons and according to the results of the present study, we recommended that, for an incubation time of 30 min, the reaction should be carried out at 60

  7. [Tartrate-resistant acid phosphatase in free-living Amoeba proteus].

    PubMed

    Sopina, V A

    2002-01-01

    Tartrate-resistant acid phosphatase (TRAP) of Amoeba proteus (strain B) was represented by 3 of 6 bands (= electromorphs) revealed after disc-electrophoresis in polyacrylamide gels with the use of 2-naphthyl phosphate as a substrate at pH 4.0. The presence of MgCl2, CaCl2 or ZnCl2 (50 mM) in the incubation mixture used for gel staining stimulated activities of all 3 TRAP electromorphs or of two of them (in the case of ZnCl2). When gels were treated with MgCl2, CaCl2 or ZnCl2 (10 and 100 mM, 30 min) before their staining activity of TRAP electromorphs also increased. But unlike 1 M MgCl2 or 1 M CaCl2, 1 M ZnCl2 partly inactivated two of the three TRAP electromorphs. EDTA and EGTA (5 mM), and H2O2 (10 mM) completely inhibited TRAP electromorphs after gel treatment for 10, 20 and 30 min, resp. Of 5 tested ions (Mg2+, Ca2+, Fe2+, Fe3+ and Zn2+), only the latter reactivated the TRAP electromorphs previously inactivated by EDTA or EGTA treatment. In addition, after EDTA inactivation, TRAP electromorphs were reactivated better than after EGTA. The resistance of TRAP electromorphs to okadaic acid and phosphatase inhibitor cocktail 1 used in different concentrations is indicative of the absence of PP1 and PP2A among these electromorphs. Mg2+, Ca2+ and Zn2+ dependence of TRAP activity, and the resistance of its electromorphs to vanadate and phosphatase inhibitor cocktail 2 prevents these electromorphs from being classified as PTP. It is suggested that the active center of A. proteus TRAP contains zinc ion, which is essential for catalytic activity of the enzyme. Thus, TRAP of these amoebae is metallophosphatase showing phosphomonoesterase activity in acidic medium. This metalloenzyme differs from both mammalian tartrate-resistant PAPs and tartrate-resistant metallophosphatase of Rana esculenta.

  8. Tartrate-resistant, purple acid phosphatase in Gaucher cells of the spleen. Immuno- and cytochemical analysis.

    PubMed

    Schindelmeiser, J; Radzun, H J; Münstermann, D

    1991-03-01

    Bioptic material from the spleen of a three-year-old boy with a type 1 Gaucher disease was studied by immuno- and cytochemical methods with special regard to the macrophage-derived Gaucher cells. These cells were positive with PAS and Prussian blue staining, and were immuno-positive with the monoclonal 25 F9 antibody, specific to mature, non-inflammatory macrophages. Large Gaucher cells and their postulated small precursor cells revealed strong tartrate-resistant acid phosphatase (TRAP) and unspecific carboxylate esterase activities. Using a polyclonal antibody to bovine spleen purple phosphatase, a lysosomal TRAP from splenic macrophages, the TRAP of the Gaucher cells could be identified to belong to this group of iron-containing, purple acid phosphatases immunocytochemically. The origin of splenic Gaucher cells from blood monocytes and their further development are discussed.

  9. Regulation and expression of type V (tartrate-resistant) acid phosphatase in human mononuclear phagocytes.

    PubMed

    Bevilacqua, M A; Lord, D K; Cross, N C; Whitaker, K B; Moss, D W; Cox, T M

    1991-02-01

    Human type V (tartrate-resistant) acid phosphatase belongs to a unique group of iron-binding proteins that includes uteroferrin and other purple phosphatases. The enzyme is normally restricted to osteoclasts and certain phagocytic cells but its rôle is unknown. We show that phosphatase mRNA is abundant in cells of monohistiocytic phenotype and that enzyme expression in cultured human monocyte-derived macrophages is depressed by gamma-interferon and bacterial lipopolysaccharide, agents that promote functional differentiation in these cells. In contrast, phorbol ester, which stimulates intracellular calcium-mediated events, greatly enhances type V phosphatase expression and mRNA abundance. Lymphokine and phorbol ester-modulated expression of type V acid phosphatase expression thus represents a model system for investigating proliferative responses that are specific to cells of the mononuclear macrophage system.

  10. Ultrastructural localization of a tartrate-resistant acid ATPase in bone.

    PubMed

    Reinholt, F P; Widholm, S M; Ek-Rylander, B; Andersson, G

    1990-10-01

    Osteoclasts are effector cells in bone breakdown, and the active bone resorption is confined to the ruffled border zone of these cells. An acid milieu is maintained in this zone which is probably a prerequisite for bone resorption. Tartrate-resistant acid phosphatase (TRAP) activity has been recognized as a characteristic property of osteoclasts and in several studies proposed as a cytochemical marker of osteoclasts. We have previously isolated and characterized a tartrate-resistant and iron-activated acid ATPase (TrATPase) from rat bone, the enzyme being a member of the TRAP family. In the present study the ultrastructural localization of this enzyme was delineated by employing immunogold technique on low temperature-embedded maxillar rat bone. Intensive immunolabeling was seen on the bone surfaces facing the ruffled border zone while lower amounts of marker were seen in adjacent bone areas, that is, on the bone surfaces facing the clear zone and deeper-into the bone. Within the osteoclasts gold markers were observed mainly in vesicular structures interpreted as lysosomes. Immunolabeling was also observed in the recently described endocytic cells located near osteoblasts and osteoclasts. Also in these cells, the marker was confined to lysosomelike structures. The amount of label in bone facing osteoblasts was low, as was the amount within osteoblasts. Our observation of extracellular localization, in particular accumulation of TrATPase in bone matrix facing the ruffled border area of the osteoclasts, favors the view that the enzyme is exported to areas of active bone resorption, thereby indicating a potential role for the enzyme in this process.

  11. Tartrate-resistant acid phosphatase from human osteoclastomas is translated as a single polypeptide.

    PubMed Central

    Hayman, A R; Dryden, A J; Chambers, T J; Warburton, M J

    1991-01-01

    Tartrate-resistant acid phosphatases have been isolated from a number of sources. These enzymes consist of one subunit (Mr 30,000-40,000) or two dissimilar subunits (Mr 15,000-20,000). Previously we isolated the enzyme from human osteoclastomas, as a two-subunit protein. By Northern blotting and hybridization with radiolabelled oligonucleotides corresponding to the N-terminal sequences of the two subunits, we demonstrate here that the enzyme is transcribed as one mRNA which is translated in vitro to produce a single polypeptide of approx. Mr 33,000. Transcription as a single mRNA species is also the case in other tissues. These results suggest that the osteoclastoma enzyme undergoes post-translational modification in the form of cleavage of a single peptide bond to give a disulphide-bonded two-subunit protein. Images Fig. 1. Fig. 2. Fig. 3. PMID:1872798

  12. Comparative studies of rat recombinant purple acid phosphatase and bone tartrate-resistant acid phosphatase.

    PubMed

    Ek-Rylander, B; Barkhem, T; Ljusberg, J; Ohman, L; Andersson, K K; Andersson, G

    1997-01-15

    The tartrate-resistant acid phosphatase (TRAP) of rat osteoclasts has been shown to exhibit high (85-94%) identity at the amino acid sequence level with the purple acid phosphatase (PAP) from bovine spleen and with pig uteroferrin. These iron-containing purple enzymes contain a binuclear iron centre, with a tyrosinate-to-Fe(III) charge-transfer transition responsible for the purple colour. In the present study, production of rat osteoclast TRAP could be achieved at a level of 4.3 mg/litre of medium using a baculovirus expression system. The enzyme was purified to apparent homogeneity using a combination of cation-exchange, hydrophobic-interaction, lectin-affinity and gel-permeation chromatography steps. The protein as isolated had a purple colour, a specific activity of 428 units/mg of protein and consisted of the single-chain form of molecular mass 34 kDa, with only trace amounts of proteolytically derived subunits. The recombinant enzyme had the ability to dephosphorylate bone matrix phosphoproteins, as previously shown for bone TRAP. Light absorption spectroscopy of the isolated purple enzyme showed a lambda max at 544 nm, which upon reduction with ascorbic acid changed to 515 nm, concomitant with the transition to a pink colour. EPR spectroscopic analysis of the reduced enzyme at 3.6 K revealed a typical mu-hydr(oxo)-bridged mixed-valent Fe(II)Fe(III) signal with g-values at 1.96, 1.74 and 1.60, proving that recombinant rat TRAP belongs to the family of PAPs. To validate the use of recombinant PAP in substituting for the rat bone counterpart in functional studies, various comparative studies were carried out. The enzyme isolated from bone exhibited a lower K(m) for p-nitrophenyl phosphate and was slightly more sensitive to PAP inhibitors such as molybdate, tungstate, arsenate and phosphate. In contrast with the recombinant enzyme, TRAP from bone was isolated predominantly as the proteolytically cleaved, two-subunit, form. Both the recombinant enzyme and rat

  13. Characterization of the mouse tartrate-resistant acid phosphatase (TRAP) gene promoter.

    PubMed

    Reddy, S V; Hundley, J E; Windle, J J; Alcantara, O; Linn, R; Leach, R J; Boldt, D H; Roodman, G D

    1995-04-01

    Tartrate-resistant acid phosphatase (TRAP) is an iron-binding protein that is highly expressed in osteoclasts. To characterize the regulation of TRAP gene expression, progressive 5' and 3' deletions of a 1.8 kb fragment containing the 5'-flanking sequence were fused to a luciferase reporter gene. Two nonoverlapping regions of this 1.8 kb fragment had promoter activity. The upstream promoter (P1) was located within the region from -881 bp to -463 bp relative to the ATG, while the downstream promoter (P2) was located between -363 bp to -1 bp in a region we have previously shown to be an intron in transcripts originating from the upstream promoter. A putative repressor region for the P2 promoter at -1846 bp to -1240 bp and a putative enhancer region at -962 bp to -881 bp relative to the ATG were identified. PCR analysis of promoter-specific transcription of the TRAP gene in various murine tissues showed that both promoters were active in several tissues. Transferrin-bound iron increased P1 promoter activity 2.5-fold and hemin decreased P1 promoter activity, but neither had any effect on P2 activity. These data show that the transcriptional regulation of the TRAP gene is complex and that iron may play a key role in TRAP gene regulation.

  14. Macrophage expression of tartrate-resistant acid phosphatase as a prognostic indicator in colon cancer.

    PubMed

    How, Joan; Brown, Jason R; Saylor, Sasha; Rimm, David L

    2014-08-01

    Recent research has indicated that separate populations of macrophages are associated with differing outcomes in cancer survival. In our study, we examine macrophage expression of tartrate-resistant acid phosphatase (TRAP) and its effect on survival in colon cancer. Immunohistochemical analysis on colorectal adenocarcinomas confirmed macrophage expression of TRAP. Co-localization of TRAP with CD68, a pan-macrophage marker, revealed that TRAP is present in some but not all sub-populations of macrophages. Further co-localization of TRAP with CD163, an M2 marker, revealed that TRAP is expressed by both M2 and non-M2 macrophages. TRAP expression was then measured using the AQUA method of quantitative immunofluorescence in a tissue microarray consisting of 233 colorectal cancer patients seen at Yale-New Haven Hospital. Survival analysis revealed that patients with high TRAP expression have a 22 % increase in 5-year survival (uncorrected log-rank p = 0.025) and a 47 % risk reduction in disease-specific death (p = 0.02). This finding was validated in a second cohort of older cases consisting of 505 colorectal cancer patients. Patients with high TRAP expression in the validation set had a 19 % increase in 5-year survival (log-rank p = 0.0041) and a 52 % risk reduction in death (p = 0.0019). These results provide evidence that macrophage expression of TRAP is associated with improved outcome and implicates TRAP as a potential biomarker in colon cancer.

  15. Macrophage expression of tartrate-resistant acid phosphatase as a prognostic indicator in colon cancer

    PubMed Central

    How, Joan; Brown, Jason R.; Saylor, Sasha; Rimm, David L.

    2014-01-01

    Recent research has indicated that separate populations of macrophages are associated with differing outcomes in cancer survival. In our study, we examine macrophage expression of tartrate resistant acid phosphatase (TRAP) and its effect on survival in colon cancer. Immunohistochemical analysis on colorectal adenocarcinomas confirmed macrophage expression of TRAP. Co-localization of TRAP with CD68, a pan-macrophage marker, revealed that TRAP is present in some but not all subpopulations of macrophages. Further co-localization of TRAP with CD163, an M2 marker, revealed that TRAP is expressed by both M2 and non-M2 macrophages. TRAP expression was then measured using the AQUA method of quantitative immunofluorescence in a tissue microarray consisting of 233 colorectal cancer patients seen at Yale-New Haven Hospital. Survival analysis revealed that patients with high TRAP expression have a 22% increase in 5-year survival (uncorrected log rank p=0.025) and a 47% risk reduction for disease specific death (p=0.02). This finding was validated in a second cohort of older cases consisting of 505 colorectal cancer patients. Patients with high TRAP expression in the validation set had a 19% increase in 5-year survival (log rank p=0.0041) and a 52% risk reduction of death (p=0.0019). These results provide evidence that macrophage expression of TRAP is associated with improved outcome, and implicates TRAP as a potential biomarker in colon cancer. PMID:24429833

  16. Purification and characterization of a tartrate-resistant acid phosphatase from human osteoclastomas.

    PubMed Central

    Hayman, A R; Warburton, M J; Pringle, J A; Coles, B; Chambers, T J

    1989-01-01

    Tartrate-resistant acid phosphatase is one of the major enzymes produced and secreted by osteoclasts. To obtain sufficient enzyme for biochemical characterization, we have purified this enzyme from human osteoclastomas by sequential chromatography on SP-Sephadex, CM-Sephadex, hydroxylapatite, Sephadex G-150 and concanavalin A-Sepharose. The purification over the original tumour extract was about 2000-fold, with a yield of 10%. The enzyme appeared to be homogeneous when assessed by SDS/polyacrylamide-gel electrophoresis. Both gel filtration and SDS/polyacrylamide-gel electrophoresis indicated an Mr of about 30,000. The reduced and alkylated enzyme consists of two subunits with Mrs of 15,000 and 17,500. The N-terminal amino acid sequence of both subunits indicates that there is a high degree of identity between the osteoclastoma enzyme and similar enzymes purified from spleen and uterus. Using 4-methylumbelliferyl phosphate as substrate, the specific activity of the purified enzyme was 387 units.mg-1, and the Km was 284 microns. The pH optimum was 5.7. Unlike similar enzymes purified from human and bovine bone, osteoclastoma acid phosphatase is not activated by reducing agents (2-mercaptoethanol or ascorbic acid). The enzyme contains 4.8 mol of Fe2+/3+, 0.3 mol of Mn2+ and 1.7 mol of Mg2+ per mol of enzyme. Although the enzyme loses 50% of its activity in the presence of EDTA, it is not inhibited by the iron chelator 1,10-phenanthroline. However, the enzyme is activated to a small extent by Mn2+ and Mg2+. Using a variety of substrates and inhibitors, we demonstrate that there are differences between the osteoclastoma acid phosphatase and the enzyme purified from other sources. Images Fig. 1. Fig. 2. Fig. 4. PMID:2775236

  17. Purification and characterization of a tartrate-resistant acid phosphatase from human osteoclastomas.

    PubMed

    Hayman, A R; Warburton, M J; Pringle, J A; Coles, B; Chambers, T J

    1989-07-15

    Tartrate-resistant acid phosphatase is one of the major enzymes produced and secreted by osteoclasts. To obtain sufficient enzyme for biochemical characterization, we have purified this enzyme from human osteoclastomas by sequential chromatography on SP-Sephadex, CM-Sephadex, hydroxylapatite, Sephadex G-150 and concanavalin A-Sepharose. The purification over the original tumour extract was about 2000-fold, with a yield of 10%. The enzyme appeared to be homogeneous when assessed by SDS/polyacrylamide-gel electrophoresis. Both gel filtration and SDS/polyacrylamide-gel electrophoresis indicated an Mr of about 30,000. The reduced and alkylated enzyme consists of two subunits with Mrs of 15,000 and 17,500. The N-terminal amino acid sequence of both subunits indicates that there is a high degree of identity between the osteoclastoma enzyme and similar enzymes purified from spleen and uterus. Using 4-methylumbelliferyl phosphate as substrate, the specific activity of the purified enzyme was 387 units.mg-1, and the Km was 284 microns. The pH optimum was 5.7. Unlike similar enzymes purified from human and bovine bone, osteoclastoma acid phosphatase is not activated by reducing agents (2-mercaptoethanol or ascorbic acid). The enzyme contains 4.8 mol of Fe2+/3+, 0.3 mol of Mn2+ and 1.7 mol of Mg2+ per mol of enzyme. Although the enzyme loses 50% of its activity in the presence of EDTA, it is not inhibited by the iron chelator 1,10-phenanthroline. However, the enzyme is activated to a small extent by Mn2+ and Mg2+. Using a variety of substrates and inhibitors, we demonstrate that there are differences between the osteoclastoma acid phosphatase and the enzyme purified from other sources.

  18. Uteroferrin and intracellular tartrate-resistant acid phosphatases are the products of the same gene.

    PubMed

    Ling, P; Roberts, R M

    1993-04-05

    Uteroferrin (Uf) is a purple acid phosphatase with a bi-iron center. It is the major secretory product of the porcine uterus under the influence of progesterone and supplies iron to the developing fetuses during pregnancy. Tartrate-resistant acid phosphatases (TRAP) are clearly similar to Uf in many of their properties but are generally located intracellularly in lysosomes. To determine whether Uf and intracellular TRAP are distinct gene products, cDNA for the TRAP from pig spleen were compared with Uf cDNA. Although no full-length cDNA for the former were isolated, a TRAP cDNA of 1.1 kilobases was identical in nucleotide sequence to a Uf cDNA (1.42 kilobases) in the region of overlap, which included the entire 3'-end of the transcript and most of the open reading frame. TRAP purified from porcine spleen also had an NH2-terminal amino acid sequence that corresponded to that of Uf purified from uterine secretions and was also similar in sequence to intracellular TRAP isolated from tissues of other species, including ones from human osteoclastomas and spleen. Finally, Southern hybridization analysis with two probes specific for exons 1 and 2 of the Uf gene strongly suggested the presence of only a single gene for acid phosphatases of this class in the pig. A similar analysis performed on human DNA with an exon-specific probe for human TRAP was also consistent with a single gene. It is concluded that the difference in trafficking between a secreted TRAP, such as Uf, and TRAP located in lysosomes is not the result of distinctive primary sequence of the polypeptides and that the variability within species ascribed to such enzymes is most likely the result of minor posttranslational changes.

  19. Expression and distribution of tartrate-resistant purple acid phosphatase in the rat nervous system.

    PubMed

    Lång, P; Schultzberg, M; Andersson, G

    2001-03-01

    Tartrate-resistant purple acid phosphatase (TRAP) of osteoclasts and certain cells of the monocyte-macrophage lineage belongs to the family of purple acid phosphatases (PAPs). We provide here evidence for TRAP/PAP expression in the central and peripheral nervous systems in the rat. TRAP/PAP protein was partially purified and characterized from the trigeminal ganglion, brain, and spinal cord. The TRAP activity (U/mg tissue) in these tissues was about 10-20 times lower than in bone. Reducing agents, e.g. ascorbate and ferric iron, increased the TRAP activity from the neural tissues (nTRAP) and addition of oxidizing agents completely inactivated both bone and nTRAP. The IC(50) for three known oxyanion inhibitors of TRAP/PAP was similar for bone and nTRAP with the same rank order of potency (molybdate > tungstate > phosphate). This indicates that the redox-sensitive binuclear iron center characteristic of mammalian PAPs is present also in nTRAP. Western blots of partially purified nTRAP revealed a band with the expected size of 35 kD. The expression of TRAP in the trigeminal ganglion, brain, and spinal cord was confirmed at the mRNA level by RT-PCR. In situ hybridization histochemistry demonstrated TRAP mRNA expression in small ganglion cells of the trigeminal ganglion, in alpha-motor neurons of the ventral spinal cord, and in Purkinje cells of the cerebellum. TRAP-like immunoreactivity was encountered in the cytoplasm of neuronal cell bodies in specific areas of both the central and the peripheral nervous system. Together, the data demonstrate that active TRAP/PAP is expressed in certain parts of the rat nervous system.

  20. Altered collagen in tartrate-resistant acid phosphatase (TRAP)-deficient mice: a role for TRAP in bone collagen metabolism.

    PubMed

    Roberts, Helen C; Knott, Lynda; Avery, Nicholas C; Cox, Timothy M; Evans, Martin J; Hayman, Alison R

    2007-06-01

    Tartrate-resistant acid phosphatase (TRAP) is an iron-containing protein that is highly expressed by osteoclasts, macrophages, and dendritic cells. The enzyme is secreted by osteoclasts during bone resorption, and serum TRAP activity correlates with resorptive activity in disorders of bone metabolism. TRAP is essential for normal skeletal development. In knockout mice lacking TRAP, bone shape and modeling is altered with increased mineral density. Here, we report the effect of TRAP on the biochemical and biomechanical properties of collagen, the major protein constituting the bone matrix, using these mice. Femurs from TRAP-/- and wild-type mice were used in these studies. The biomechanical properties were investigated using a three-point bending technique. Collagen synthesis was determined by measuring cross-link content using high-performance liquid chromatography and amino acid analysis. Collagen degradation was determined by measuring matrix metalloproteinase-2 (MMP-2) activity. The rates of collagen synthesis and degradation were significantly greater in bones from TRAP-/- mice compared with wild type. At 8 weeks, there was an increase in the intermediate cross-links but no significant difference in animals aged 6 months. There was a significant increase in mature cross-links at both ages. A significant increase in MMP-2 production both pro and active was observed. A significant increase in ultimate stress and Young's modulus of elasticity was needed to fracture the bones from mice deficient in TRAP. We conclude that both synthesis as well as degradation of collagen are increased when TRAP is absent in mice at 8 weeks and 6 months of age, showing that TRAP has an important role in the metabolism of collagen.

  1. Transcriptional regulation of the tartrate-resistant acid phosphatase (TRAP) gene by iron.

    PubMed

    Alcantara, O; Reddy, S V; Roodman, G D; Boldt, D H

    1994-03-01

    Tartrate-resistant acid phosphatase (TRAP) was first identified in cells from patients with hairy cell leukaemia. Subsequently, it has been found in other leukaemias, B-lymphoblastoid cell lines, osteoclasts and subsets of normal lymphocytes, macrophages, and granulocytes. Recent data indicate that TRAP and porcine uteroferrin, a placental iron-transport protein, represent a single gene product. However, the intracellular role of TRAP is unknown. We used a full-length human placental TRAP cDNA probe to examine TRAP expression in human peripheral mononuclear cells (PMCs). TRAP mRNA increased 50-75-fold after 24 h in unstimulated PMC cultures. Cell-fractionation experiments indicated that monocytes were the main cell population accounting for increased TRAP mRNA transcripts, and this was confirmed by histochemical staining for TRAP enzyme activity. Because expression of other iron-binding and -transport proteins is controlled by iron availability, we examined the role of iron in regulating TRAP expression. Increase of TRAP mRNA transcripts in PMCs was inhibited by 50 microM desferrioxamine, a potent iron chelator. The 5' flanking region of the TRAP gene was cloned from a mouse genomic library. In preliminary transient transfection experiments, it was determined that the 5'-flanking region of the TRAP gene contained iron-responsive elements. Therefore, a series of stably transfected HRE H9 cell lines was developed bearing genetic constructs containing various segments of the murine TRAP 5' promoter region driving a luciferase reporter gene. Treatment of transfectants with 100 micrograms/ml iron-saturated human transferrin (FeTF) was performed to assess iron responsiveness of the constructs. Constructs containing a full-length TRAP promoter (comprising base pairs -1846 to +2) responded to FeTF with a 4-5-fold increase of luciferase activity whereas constructs containing only base pairs -363 to +2 of the TRAP promoter did not respond. Constructs containing 1240 or 881

  2. Transcriptional regulation of the tartrate-resistant acid phosphatase (TRAP) gene by iron.

    PubMed Central

    Alcantara, O; Reddy, S V; Roodman, G D; Boldt, D H

    1994-01-01

    Tartrate-resistant acid phosphatase (TRAP) was first identified in cells from patients with hairy cell leukaemia. Subsequently, it has been found in other leukaemias, B-lymphoblastoid cell lines, osteoclasts and subsets of normal lymphocytes, macrophages, and granulocytes. Recent data indicate that TRAP and porcine uteroferrin, a placental iron-transport protein, represent a single gene product. However, the intracellular role of TRAP is unknown. We used a full-length human placental TRAP cDNA probe to examine TRAP expression in human peripheral mononuclear cells (PMCs). TRAP mRNA increased 50-75-fold after 24 h in unstimulated PMC cultures. Cell-fractionation experiments indicated that monocytes were the main cell population accounting for increased TRAP mRNA transcripts, and this was confirmed by histochemical staining for TRAP enzyme activity. Because expression of other iron-binding and -transport proteins is controlled by iron availability, we examined the role of iron in regulating TRAP expression. Increase of TRAP mRNA transcripts in PMCs was inhibited by 50 microM desferrioxamine, a potent iron chelator. The 5' flanking region of the TRAP gene was cloned from a mouse genomic library. In preliminary transient transfection experiments, it was determined that the 5'-flanking region of the TRAP gene contained iron-responsive elements. Therefore, a series of stably transfected HRE H9 cell lines was developed bearing genetic constructs containing various segments of the murine TRAP 5' promoter region driving a luciferase reporter gene. Treatment of transfectants with 100 micrograms/ml iron-saturated human transferrin (FeTF) was performed to assess iron responsiveness of the constructs. Constructs containing a full-length TRAP promoter (comprising base pairs -1846 to +2) responded to FeTF with a 4-5-fold increase of luciferase activity whereas constructs containing only base pairs -363 to +2 of the TRAP promoter did not respond. Constructs containing 1240 or 881

  3. Inhibition by dithionite and reactivation by iron of the tartrate-resistant acid phosphatase in bone of osteopetrotic (ia) rats.

    PubMed

    Hammarström, L E; Anderson, T R; Marks, S C; Toverud, S U

    1983-10-01

    The staining intensity and inhibitor sensitivity of acid phosphatase activity was determined histochemically in various tissues of normal and ia rat pups by the use of freeze-dried whole body sections. Activity was determined using alpha-naphthylphosphate as substrate and hexazonium pararosaniline as coupler. Sections from ia rats (6 and 24 days old) showed markedly higher enzyme activity in bone than sections from normal littermates. However, there were no differences between ia and normal pups in acid phosphatase activity in soft tissues and developing teeth. Preincubation of sections with 1-100 mM sodium dithionite (an iron-binding agent) caused a dose-related inhibition of enzyme activity in bone of ia and normal pups, but only slight inhibition of activity in soft tissues. Partial restoration of the dithionite-inhibited activity in bone was achieved by subsequent preincubation in 1 mM FeCl2. Addition of 100 mM sodium tartrate to the staining solution of non-preincubated sections caused almost complete inhibition of activity in soft tissues and the developing teeth but no inhibition of the activity in bone that was sensitive to sodium dithionite. These data indicate a) that sodium dithionite can be used as a specific histochemical inhibitor of the tartrate-resistant acid phosphatase and b) that the source of increased acid phosphatase activity in bone from ia rats is mostly from the tartrate-resistant acid phosphatase.

  4. Cloning, sequence, and developmental expression of a type 5, tartrate-resistant, acid phosphatase of rat bone.

    PubMed

    Ek-Rylander, B; Bill, P; Norgård, M; Nilsson, S; Andersson, G

    1991-12-25

    Tartrate-resistant acid phosphatase (TRAP) is a characteristic constituent of osteoclasts and some mononuclear preosteoclasts and, therefore, used as a histochemical and biochemical marker for osteoclasts and bone resorption. We now report the isolation of a 1397-base pair (bp) full-length TRAP/tartrate-resistant acid ATPase (TrATPase) cDNA clone from a neonatal rat calvaria lambda gt11 cDNA library. The cDNA clone consists of a 92-bp untranslated 5'-flank, an open reading frame of 981 bp and a 324-bp untranslated 3'-poly(A)-containing region. The deduced protein sequence of 327 amino acids contains a putative cleavable signal sequence of 21 amino acids. The mature polypeptide of 306 amino acids has a calculated Mr of 34,350 Da and a pI of 9.18, and it contains two potential N-glycosylation sites and the lysosomal targeting sequence DKRFQ. At the protein level, the sequence displays 89-94% homology to TRAP enzymes from human placenta, beef spleen, and uteroferrin and identity to the N terminus of purified rat bone TRAP/TrATPase. An N-terminal amino acid segment is strikingly homologous to the corresponding region in lysosomal and prostatic acid phosphatases. The cDNA recognized a 1.5-kilobase mRNA in long bones and calvaria, and in vitro translation using, as template, mRNA transcribed from the full-length insert yielded an immunoprecipitated product of 34 kDa. In neonatal rats, TRAP/TrATPase mRNA was highly expressed in skeletal tissues, with much lower (less than 10%) levels detected in spleen, thymus, liver, skin, brain, kidney, brain, lung, and heart. In situ hybridization demonstrated specific labeling of osteoclasts at endostal surfaces and bone trabeculae of long bones. Thus, despite the apparent similarity of this osteoclastic TRAP/TrATPase with type 5, tartrate-resistant and purple, acid phosphatases expressed in other mammalian tissues, this gene appears to be preferentially expressed at skeletal sites.

  5. Tartrate-resistant acid phosphatase facilitates hydroxyl radical formation and colocalizes with phagocytosed Staphylococcus aureus in alveolar macrophages.

    PubMed

    Räisänen, S R; Halleen, J; Parikka, V; Väänänen, H K

    2001-10-19

    Tartrate-resistant acid phosphatase (TRAP) is an enzyme expressed specifically in osteoclasts and activated macrophages, two phagocytosing cell types originating from the same hematopoietic stem cells. TRAP contains a binuclear iron centre which has been shown to generate reactive oxygen species (ROS). In this study murine macrophage like cell line RAW-264 overexpressing TRAP was shown to produce elevated levels of hydroxyl radicals compared to parental cells. TRAP transfected cells also had reduced growth rate indicating harmful effects of excessive intracellular ROS levels. Using TRAP specific antibody TRAP protein was shown in alveolar macrophages partially colocalize with late endosomal/lysosomal markers Rab7, Lamp 1 and MHC II molecules that bind antigenic peptides. TRAP also colocalized into compartments where Staphylococcus aureus were phagocytosed. These results suggest that TRAP may have an important biological function in the defence mechanism of macrophages by generating intracellular ROS which would be targeted to destroy phagocytosed foreign material. Copyright 2001 Academic Press.

  6. Macrophages overexpressing tartrate-resistant acid phosphatase show altered profile of free radical production and enhanced capacity of bacterial killing.

    PubMed

    Räisänen, Seija R; Alatalo, Sari L; Ylipahkala, Hannele; Halleen, Jussi M; Cassady, A Ian; Hume, David A; Väänänen, H Kalervo

    2005-05-27

    Activated macrophages and osteoclasts express high amounts of tartrate-resistant acid phosphatase (TRACP, acp5). TRACP has a binuclear iron center with a redox-active iron that has been shown to catalyze the formation of reactive oxygen species (ROS) by Fenton's reaction. Previous studies suggest that ROS generated by TRACP may participate in degradation of endocytosed bone matrix products in resorbing osteoclasts and degradation of foreign compounds during antigen presentation in activated macrophages. Here we have compared free radical production in macrophages of TRACP overexpressing (TRACP+) and wild-type (WT) mice. TRACP overexpression increased both ROS levels and superoxide production. Nitric oxide production was increased in activated macrophages of WT mice, but not in TRACP+ mice. Macrophages from TRACP+ mice showed increased capacity of bacterial killing. Recombinant TRACP enzyme was capable of bacterial killing in the presence of hydrogen peroxide. These results suggest that TRACP has an important biological function in immune defense system.

  7. Comparison of tartrate resistant acid phosphatase in a giant cell bone tumor and a spleen infiltrated with hairy cells.

    PubMed

    Lam, K W; Townsend, D; Garza, A; Li, C Y; Yam, L T

    1990-08-01

    Acid phosphatase (E.C.3.1.3.2) in a giant cell bone tumor and a spleen infiltrated with hairy cells was extracted by citrate buffer and then by 0.3 mol/L NaCl. The cationic acid phosphatase in the crude extract was isolated by CM-cellulose chromatography, and further separated by high pressure liquid chromatography. The majority of the tartrate resistant acid phosphatase in the hairy cell spleen was unabsorbed on CM-cellulose and was insensitive to iron. A much larger portion of the acid phosphatase in the bone tumor, than in the spleen, was cationic and was eluted from the column by 0.8 mol/L NaCl. The cationic acid phosphatase was further separated into consecutive peaks of acid phosphatases with different sensitivity to iron. A major portion of acid phosphatase in the giant cell bone tumor was enhanced by iron, while the amounts of iron-enhanced and iron-insensitive acid phosphatase were about the same in the spleen. The differences of the phosphatases in these two types of pathologic specimens indicate the occurrence of two types of enzymes with different biological significance.

  8. Identification of a non-purple tartrate-resistant acid phosphatase: an evolutionary link to Ser/Thr protein phosphatases?

    PubMed Central

    Hadler, Kieran S; Huber, Thomas; Cassady, A Ian; Weber, Jane; Robinson, Jodie; Burrows, Allan; Kelly, Gregory; Guddat, Luke W; Hume, David A; Schenk, Gerhard; Flanagan, Jack U

    2008-01-01

    Background Tartrate-resistant acid phosphatases (TRAcPs), also known as purple acid phosphatases (PAPs), are a family of binuclear metallohydrolases that have been identified in plants, animals and fungi. The human enzyme is a major histochemical marker for the diagnosis of bone-related diseases. TRAcPs can occur as a small form possessing only the ~35 kDa catalytic domain, or a larger ~55 kDa form possessing both a catalytic domain and an additional N-terminal domain of unknown function. Due to its role in bone resorption the 35 kDa TRAcP has become a promising target for the development of anti-osteoporotic chemotherapeutics. Findings A new human gene product encoding a metallohydrolase distantly related to the ~55 kDa plant TRAcP was identified and characterised. The gene product is found in a number of animal species, and is present in all tissues sampled by the RIKEN mouse transcriptome project. Construction of a homology model illustrated that six of the seven metal-coordinating ligands in the active site are identical to that observed in the TRAcP family. However, the tyrosine ligand associated with the charge transfer transition and purple color of TRAcPs is replaced by a histidine. Conlusion The gene product identified here may represent an evolutionary link between TRAcPs and Ser/Thr protein phosphatases. Its biological function is currently unknown but is unlikely to be associated with bone metabolism. PMID:18771593

  9. Identification of a non-purple tartrate-resistant acid phosphatase: an evolutionary link to Ser/Thr protein phosphatases?

    PubMed

    Hadler, Kieran S; Huber, Thomas; Cassady, A Ian; Weber, Jane; Robinson, Jodie; Burrows, Allan; Kelly, Gregory; Guddat, Luke W; Hume, David A; Schenk, Gerhard; Flanagan, Jack U

    2008-09-04

    Tartrate-resistant acid phosphatases (TRAcPs), also known as purple acid phosphatases (PAPs), are a family of binuclear metallohydrolases that have been identified in plants, animals and fungi. The human enzyme is a major histochemical marker for the diagnosis of bone-related diseases. TRAcPs can occur as a small form possessing only the ~35 kDa catalytic domain, or a larger ~55 kDa form possessing both a catalytic domain and an additional N-terminal domain of unknown function. Due to its role in bone resorption the 35 kDa TRAcP has become a promising target for the development of anti-osteoporotic chemotherapeutics. A new human gene product encoding a metallohydrolase distantly related to the ~55 kDa plant TRAcP was identified and characterised. The gene product is found in a number of animal species, and is present in all tissues sampled by the RIKEN mouse transcriptome project. Construction of a homology model illustrated that six of the seven metal-coordinating ligands in the active site are identical to that observed in the TRAcP family. However, the tyrosine ligand associated with the charge transfer transition and purple color of TRAcPs is replaced by a histidine. The gene product identified here may represent an evolutionary link between TRAcPs and Ser/Thr protein phosphatases. Its biological function is currently unknown but is unlikely to be associated with bone metabolism.

  10. Intracellular fragmentation of bone resorption products by reactive oxygen species generated by osteoclastic tartrate-resistant acid phosphatase.

    PubMed

    Halleen, J M; Räisänen, S; Salo, J J; Reddy, S V; Roodman, G D; Hentunen, T A; Lehenkari, P P; Kaija, H; Vihko, P; Väänänen, H K

    1999-08-13

    Tartrate-resistant acid phosphatase (TRAP) is highly expressed in bone-resorbing osteoclasts and activated macrophages. It has been suggested that a redox-active iron in the binuclear iron center of TRAP could have the capacity to react with hydrogen peroxide to produce highly destructive reactive oxygen species (ROS). Here we show that TRAP can generate ROS in vitro and that cells over-expressing TRAP produce higher amounts of intracellular ROS than their parent cells. We further demonstrate that these ROS can be targeted to destroy collagen and other proteins. In resorbing osteoclasts, TRAP was found in transcytotic vesicles transporting matrix degradation products through the cell, suggesting that TRAP-facilitated fragmentation of endocytosed material takes place in a specific cellular compartment. These results suggest that bone matrix degradation occurs not only extracellularly in the resorption lacunae but also intracellularly in the transcytotic vesicles. We propose that proteins containing redox-active iron could represent a novel mechanism of physiological fragmentation of organic molecules. This mechanism could be important in tissue remodeling and as a defense mechanism of phagocytosing cells.

  11. The human tartrate-resistant acid phosphatase (TRAP): involvement of the hemin responsive elements (HRE) in transcriptional regulation.

    PubMed

    Fleckenstein, E C; Dirks, W G; Drexler, H G

    2000-02-01

    The biochemical properties and protein structure of the tartrate-resistant acid phosphatase (TRAP), an iron-containing lysosomal glycoprotein in cells of the mononuclear phagocyte system, are well known. In contrast, little is known about the physiology and genic structure of this unique enzyme. In some diseases, like hairy cell leukemia, Gaucher's disease and osteoclastoma, cytochemically detected TRAP expression is used as a disease-associated marker. In order to begin to elucidate the regulation of this gene we generated different deletion constructs of the TRAP 5'-flanking region, placed them upstream of the luciferase reporter gene and assayed them for their ability to direct luciferase expression in human 293 cells. Treatment of these cells with the iron-modulating reagents transferrin and hemin causes opposite effects on the TRAP promoter activity. Two regulatory GAGGC tandem repeat sequences (the hemin responsive elements, HRE) within the 5'-flanking region of the human TRAP gene were identified. Studies with specific HRE-deletion constructs of the human TRAP 5'-flanking region upstream of the luciferase reporter gene document the functionality of these HRE-sequences which are apparently responsible for mediating transcriptional inhibition upon exposure to hemin. In addition to the previously published functional characterization of the murine TRAP HRE motifs, these results provide the first description of a new iron/hemin-responsive transcriptional regulation in the human TRAP gene.

  12. Effects of proteolysis and reduction on phosphatase and ROS-generating activity of human tartrate-resistant acid phosphatase.

    PubMed

    Fagerlund, Katja M; Ylipahkala, Hannele; Tiitinen, Sari L; Janckila, Anthony J; Hamilton, Susan; Mäentausta, Olli; Väänänen, H Kalervo; Halleen, Jussi M

    2006-05-15

    Osteoclasts and macrophages express high amounts of tartrate-resistant acid phosphatase (TRACP), an enzyme with unknown biological function. TRACP contains a disulfide bond, a protease-sensitive loop peptide, and a redox-active iron that can catalyze formation of reactive oxygen species (ROS). We studied the effects of proteolytic cleavage by trypsin, reduction of the disulfide bond by beta-mercaptoethanol, and reduction of the redox-active iron by ascorbate on the phosphatase and ROS-generating activity of baculovirus-generated recombinant human TRACP. Ascorbate alone and trypsin in combination with beta-mercaptoethanol increased k(cat)/K(m) of the phosphatase activity seven- to ninefold. The pH-optimum was changed from 5.4-5.6 to 6.2-6.4 by ascorbate and trypsin cleavage. Trypsin cleavage increased k(cat)/K(m) of the ROS-generating activity 2.5-fold without affecting the pH-optimum (7.0). These results suggest that the protease-sensitive loop peptide, redox-active iron, and disulfide bond are important regulatory sites in TRACP, and that the phosphatase and ROS-generating activity are performed with different reaction mechanisms.

  13. Molecular cloning of the type 5, iron-containing, tartrate-resistant acid phosphatase from human placenta.

    PubMed

    Ketcham, C M; Roberts, R M; Simmen, R C; Nick, H S

    1989-01-05

    The type 5, iron-containing, tartrate-resistant acid phosphatase (TR-AP) constitutes a relatively minor intracellular isozyme of acid phosphatase in the human that is immunologically related to uteroferrin, a secreted progesterone-induced protein of the porcine uterus. Here, the purification of small amounts of TR-AP from human placenta is described. When a placental lambda gt11 cDNA library was screened with two short 32P-labeled cDNA clones from within the coding region of uteroferrin, a 1412-base pair cDNA was identified that encodes the entire human TR-AP isozyme. This cDNA contains an open reading frame of 969 base pairs, corresponding to a protein of 323 amino acids. A putative signal sequence of 19 amino acids and two potential glycosylation sites are present. The deduced amino acid sequence of the human TR-AP is 85% identical to that of porcine uteroferrin (whose sequence is also reported here in complete form for the first time) and 82% identical to the corresponding regions of a partial amino acid sequence of a bovine spleen phosphoprotein phosphatase. Northern blotting techniques employing a labeled TR-AP cDNA probe revealed the presence of a 1.5-kilobase transcript in white cells from a patient with hairy cell leukemia, in human K562 erythroleukemic cells, and in Epstein-Barr virus-transformed human B-cells, but not in a human T-cell line. Culture of K562 cells in presence of 10(-8) M phorbol 12-myristate 13-acetate ester for 48-72 h enhanced TR-AP activity per cell about 30-fold and led to a corresponding increase in TR-AP mRNA levels.

  14. Polyphosphate-mediated inhibition of tartrate-resistant acid phosphatase and suppression of bone resorption of osteoclasts.

    PubMed

    Harada, Kana; Itoh, Hiromichi; Kawazoe, Yumi; Miyazaki, Shuichi; Doi, Kazuya; Kubo, Takayasu; Akagawa, Yasumasa; Shiba, Toshikazu

    2013-01-01

    Inorganic polyphosphate (poly(P)) has recently been found to play an important role in bone formation. In this study, we found that tartrate-resistant acid phosphatase (TRAP), which is abundantly expressed in osteoclasts, has polyphosphatase activity that degrades poly(P) and yields Pi as well as shorter poly(P) chains. Since the TRAP protein that coprecipitated with anti-TRAP monoclonal antibodies exhibited both polyphosphatase and the original phosphatase activity, poly(P) degradation activity is dependent on TRAP and not on other contaminating enzymes. The ferrous chelator α, α'-bipyridyl, which inhibits the TRAP-mediated production of reactive oxygen species (ROS), had no effect on such poly(P) degradation, suggesting that the degradation is not dependent on ROS. In addition, shorter chain length poly(P) molecules were better substrates than longer chains for TRAP, and poly(P) inhibited the phosphatase activity of TRAP depending on its chain length. The IC50 of poly(P) against the original phosphatase activity of TRAP was 9.8 µM with an average chain length more than 300 phosphate residues, whereas the IC50 of poly(P) with a shorter average chain length of 15 phosphate residues was 8.3 mM. Finally, the pit formation activity of cultured rat osteoclasts differentiated by RANKL and M-CSF were markedly inhibited by poly(P), while no obvious decrease in cell number or differentiation efficiency was observed for poly(P). In particular, the inhibition of pit formation by long chain poly(P) with 300 phosphate residues was stronger than that of shorter chain poly(P). Thus, poly(P) may play an important regulatory role in osteoclastic bone resorption by inhibiting TRAP activity, which is dependent on its chain length.

  15. Increase in tartrate-resistant acid phosphatase of bone at the early stage of ascorbic acid deficiency in the ascorbate-requiring Osteogenic Disorder Shionogi (ODS) rat.

    PubMed

    Goto, A; Tsukamoto, I

    2003-08-01

    The effect of ascorbic acid deficiency on bone metabolism was evaluated using the ascorbate-requiring Osteogenic Disorder Shionogi (ODS) rat model. Ascorbic acid (Asc)-deficient rats gained body weight in a manner similar to Asc-supplemented rats (control) during 3 weeks, but began to lose weight during the 4th week of Asc deficiency. The tartrate-resistant acid phosphatase (TRAP) activity in serum increased to about 2-fold the control value in the rats fed the Asc-free diet for 2, 3, and 4 weeks (AscD2, AscD3, and AscD4), while a decrease in the alkaline phosphatase (ALP) activity was observed only in AscD4 rats. The serum pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP) level significantly increased to 1.3-, 1.4-, and 1.9-fold of that in the controls in AscD2, D3, and D4, respectively. The ALP activity in the distal femur was unchanged in AscD1, D2, and D3, but decreased to 50% of the control level in AscD4 rats. The TRAP activity in the distal femur increased to about 2-fold of that in the controls in the AscD2 and D3 and decreased to the control level in the AscD4 rats. The amount of hydroxyproline in the distal femur significantly decreased to about 80%, 70%, and 60% of the control in AscD2, D3, and D4 rats, respectively. These decreases were associated with a similar reduction in the calcium content of the distal femur. Histochemical analysis of the distal femur showed an increase in TRAP-positive cells in AscD2 and AscD3 rats and a decrease in the trabecular bone in AscD2, D3, and D4 rats. These results suggested that a deficiency of Asc stimulated bone resorption at an early stage, followed by a decrease in bone formation in mature ODS rats which already had a well-developed collagen matrix and fully differentiated osteoblasts.

  16. Tartrate-Resistant Acid Phosphatase 5b in Young Patients With Sickle Cell Disease and Trait Siblings: Relation to Vasculopathy and Bone Mineral Density.

    PubMed

    Mokhtar, Galila Mohamed; Tantawy, Azza Abdel Gawad; Hamed, Ahmed Al-Saeed; Adly, Amira Abdel Moneam; Ismail, Eman Abdel Rahman; Makkeyah, Sara Mostafa

    2017-01-01

    Bone involvement is a frequent cause of acute morbidity in sickle cell disease (SCD). Tartrate-resistant acid phosphatase 5b (TRACP 5b), a bone resorption marker, is produced specifically by activated osteoclasts. We assessed bone mineral density (BMD) in 30 young patients with SCD and 17 asymptomatic patients with sickle cell trait (SCT) compared with 32 healthy controls and determined TRACP 5b levels in relation to vascular complications. Serum ferritin, alkaline phosphatase (ALP), and TRACP 5b were measured. Echocardiography was performed with assessment of BMD using dual energy X-ray absorptiometry (DXA). The BMD was decreased in patients with SCD compared with SCT and controls (P = .005), with no significant difference between the latter 2 groups. Patients with SCD had higher incidence of bone complications than SCT group and controls (P = .03). The SCD group with abnormal DXA scan had higher ferritin and ALP than normal BMD. Serum TRACP 5b was significantly higher in patients with SCD than SCT and controls (P = .003). The TRACP 5b levels were associated with severe vaso-occlusive crisis (P = .022). Patients treated with hydroxyurea and those on chelation therapy had lower TRACP 5b levels than untreated patients. The TRACP 5b level was positively correlated with lactate dehydrogenase, while there was no relation with ferritin, ALP, or BMD. We suggest that bone complications frequently occur in SCD as reflected by low BMD and high ALP and TRACP 5b. Hemolysis and iron overload may be involved in the occurrence of these complications. The lack of correlation between abnormal DXA scan and high TRACP 5b suggests that bone disease in SCD is multifactorial. © The Author(s) 2015.

  17. Purification of a tartrate-resistant acid phosphatase (TrACP) from bovine cortical bone matrix

    SciTech Connect

    Lau, K.H.W.; Freeman, T.K.; Baylink, D.J.

    1986-05-01

    It has been previously demonstrated that a partially purified bovine skeletal TrACP showed protein phosphatase (P'ase) activity that was specific for phosphotyrosyl (Ptyr) proteins. They have now purified TrACP activity from bovine cortical bone matrix to apparent homogeneity. The purification procedures included CM-Sepharose ion-exchange, cellulose phosphate affinity, sephacryl S-300 gel filtration and phenyl sepharose affinity chromatographies. Overall yield was > 25% and purification was approximately 2000-fold with a specific activity of 8.15 umol pNPP hydrolyzed/min/mg protein at 37/sup 0/C. The purified enzyme was judged to be homogeneous based on: (i) appearance as a single protein band on SDS-PAGE (silver staining technique) and (ii) distribution analysis of radioiodinated purified TrACP after SDS-PAGE revealing one band of radioactivity at the same positions as the TrACP protein band. M.W. of TrACP was 34,600 as assessed by gel filtration and 32,500 by SDS-PAGE, suggesting that bovine skeletal TrACP exists as active monomer. Analysis of the purified TrACP by isoelectric focusing showed at least 9 bands of enzyme activities with pIs between 4 and 5, indicating micro-heterogenecity. Substrate specificity analyses revealed that the purified TrACP also hydrolyzed nucleotide tri- and di-phosphates, but not monophosphates or other low M.W. phosphoryl esters, and was also capable of hydrolyzing phosphotyrosine (Tyr(P)) and Ptyr proteins with little activity toward other phosphoamino acids or phosphoseryl proteins. Optimal pH was 5.5 for TrACP activity, 6.0 for Tyr(P) P'ase activity and 7.0 for Ptyr protein P'ase activity. Results of these studies represent the first purification of a skeletal TrACP to apparent homogeneity.

  18. Proteolytic excision of a repressive loop domain in tartrate-resistant acid phosphatase by cathepsin K in osteoclasts.

    PubMed

    Ljusberg, Jenny; Wang, Yunling; Lång, Pernilla; Norgård, Maria; Dodds, Robert; Hultenby, Kjell; Ek-Rylander, Barbro; Andersson, Göran

    2005-08-05

    Tartrate-resistant acid phosphatase (TRAP) is a metallophosphoesterase participating in osteoclast-mediated bone turnover. Activation of TRAP is associated with the redox state of the di-iron metal center as well as with limited proteolytic cleavage in an exposed loop domain. The cysteine proteinases cathepsin B, L, K, and S as well as the matrix metalloproteinase-2, -9, -13, and -14 are expressed by osteoclasts and/or other bone cells and have been implicated in the turnover of bone and cartilage. To identify proteases that could act as activators of TRAP in bone, we report here that cathepsins K and L, in contrast to the matrix metalloproteinases, efficiently cleaved and activated recombinant TRAP in vitro. Activation of TRAP by cathepsin K/L was because of increases in catalytic activity, substrate affinity, and sensitivity to reductants. Processing by cathepsin K occurred sequentially by an initial excision of the loop peptide Gly(143)-Gly(160) followed by the removal of a Val(161)-Ala(162) dipeptide at the N terminus of the C-terminal 16-kDa TRAP subunit. Cathepsin L initially released a shorter Gln(151)-Gly(160) peptide and completed processing at Ser(145) or Gly(143) at the C terminus of the N-terminal 23-kDa TRAP subunit and at Arg(163) at the N terminus of the C-terminal 16-kDa TRAP subunit. Mutation of Ser(145) to Ala partly mimicked the effect of proteolysis on catalytic activity, identifying Ser(145) as well as Asp(146) (Funhoff, E. G., Ljusberg, J., Wang, Y., Andersson, G., and Averill, B. A. (2001) Biochemistry 40, 11614-11622) as repressive amino acids of the loop region to maintain the TRAP enzyme in a catalytically latent state. The C-terminal sequence of TRAP isolated from rat bone was consistent with cathepsin K-mediated processing in vivo. Moreover, cathepsin K, but not cathepsin L, co-localized with TRAP in osteoclast-resorptive compartments, supporting a role for cathepsin K in the extracellular processing of monomeric TRAP in the resorption

  19. Characterization of a tartrate-resistant acid phosphatase (ATPase) from rat bone: hydrodynamic properties and N-terminal amino acid sequence.

    PubMed

    Ek-Rylander, B; Bergman, T; Andersson, G

    1991-04-01

    Certain physicochemical properties of rat bone tartrate-resistant acid ATPase (TrATPase), including the size and shape of the enzyme, potential subunit composition, and detergent binding, have been elucidated. SDS-polyacrylamide gel electrophoresis in combination with immunoblot analysis showed that the bone TrATPase has a molecular weight of 33,000 D and is composed of disulfide-linked polypeptides of 20,000 and 16,000 D. The enzyme contains 1.7 mol Fe per mol enzyme. Hydrodynamic studies allowed calculation of the Stokes radius (24 A), the sedimentation coefficient (3.19S), the partial specific volume (0.748 ml/g), the frictional ratio (0.995), and the axial ratio (1.0). The amount of detergent bound to the protein was determined to 4 mol of Triton X-100 per mol enzyme. The molecular weight of bone TrATPase derived from these parameters was 31,900 D. N-terminal amino acid sequence analysis of the Mr 20,000 subunit indicated a high degree of similarity with TRAP enzymes from spleen, uterus, placenta, hairy cell leukemia, and osteoclastoma. It is concluded that rat bone TrATPase belongs to the type 5 (tartrate-resistant and purple) acid phosphatase family. The similarities in the N-terminal amino acid sequences, iron content, and physicochemical properties of TRAP enzymes indicate a close structural relationship between type 5 acid phosphatases expressed in different tissues. The findings that TrATPase has a spherical shape and binds low amounts of detergent suggest that the enzyme is a soluble protein, compatible with the view that TrATPase is secreted by the osteoclast.

  20. Tartrate-resistant acid phosphatase (TRACP 5b): a biomarker of bone resorption rate in support of drug development: modification, validation and application of the BoneTRAP kit assay.

    PubMed

    Wu, Yuling; Lee, Jean W; Uy, Lennie; Abosaleem, Bassam; Gunn, Han; Ma, Mark; DeSilva, Binodh

    2009-07-12

    A commercial kit assay of tartrate-resistant acid phosphatase (TRACP 5b) used for the diagnosis of bone resorption was modified with a 'Fit-For-Purpose' approach for drug development of anti-resorptive therapeutics. The modifications included changing the standard matrix from buffer to serum, using a consistent bulk reference material to prepare standards and quality controls (QC), and adding sample controls (SC) prepared from authentic sample pools. Method validation experiments were conducted for: inter- and intra-assay accuracy and precision, establishment of SC, range finding of different population groups, selectivity tests, parallelism and stability. The analytical range was 1.00-10.0 U/L and the total errors of lower limit of quantification (LLOQ) and upper limit of quantification (ULOQ) validation samples were 8% and 21%, respectively. Data of range finding experiment showed that serum samples should be collected in tubes instead of bags. Selectivity results showed accurate spike recovery among the majority of test samples from target populations. Samples were demonstrated to be stable for up to four freeze/thaw cycles and for 24 months at -70+/-10 degrees C. Our results show that the modified TRACP 5b method is reliable for the quantification of TRACP 5b in human serum samples to support clinical trials of bone resorptive effect reflected by TRACP 5b activities. The method was robust with similar assay performance characteristics shown in three bioanalytical laboratories.

  1. Terpenes and sterols from the fruits of Prunus mume and their inhibitory effects on osteoclast differentiation by suppressing tartrate-resistant acid phosphatase activity.

    PubMed

    Yan, Xi-Tao; Lee, Sang-Hyun; Li, Wei; Jang, Hae-Dong; Kim, Young-Ho

    2015-02-01

    The fruits of Prunus mume are a common commercial product and a valuable source of food and medicinal material in Eastern Asian countries. Our phytochemical investigation of the P. mume fruit led to the isolation of nine terpenes, including three ursane-type triterpenes (1-3), two cycloartane-type triterpenes (4 and 5), and four tocopherols (10-13), as well as four sterols (6-9). Their structures were elucidated based on extensive spectroscopic analysis, including 1D and 2D NMR and ESI-MS, and the majority of these compounds were isolated from this plant for the first time. The anti-osteoporosis activities of 1-13 were evaluated by measuring their inhibitory effects on tartrate-resistant acid phosphatase (TRAP) activity in receptor activator of nuclear factor κB ligand-induced osteoclastic RAW 264.7 macrophage cells. Compounds 2-7 and 9-12 significantly suppressed TRAP activity down to 47.96 ± 2.45-86.45 ± 3.07 % relative to the control at a concentration of 1 μM. These results suggest that the fruits of P. mume could be an excellent source of anti-osteoporosis phytochemicals that may be developed as natural nutraceuticals and functional foods.

  2. Mice lacking tartrate-resistant acid phosphatase (Acp 5) have disordered macrophage inflammatory responses and reduced clearance of the pathogen, Staphylococcus aureus.

    PubMed

    Bune, A J; Hayman, A R; Evans, M J; Cox, T M

    2001-01-01

    Tartrate-resistant acid phosphatase (TRAP) is a lysosomal di-iron protein of mononuclear phagocytes and osteoclasts. Hitherto, no role for the enzyme in immunity has been identified; however, knockout mice lacking TRAP have a skeletal phenotype caused by an intrinsic osteoclast defect. To investigate a putative function for TRAP in macrophages (Mphi), we investigated proinflammatory responses and systemic microbial clearance in knockout mice compared with age- and gender-matched congenic wild-type mice. Phorbol 12-myristate 13-acetate (PMA)-stimulated and interferon-gamma (IFN-gamma)-induced superoxide formation was enhanced in peritoneal Mphi lacking TRAP; nitrite production in response to stimulation with lipopolysaccharide (LPS) and IFN-gamma was also increased. In addition, secretion of the proinflammatory cytokines, tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta and IL-12, was significantly greater in TRAP-deficient Mphi when stimulated with LPS, with or without addition of either TNF-alpha or IFN-gamma. The activity of tartrate-sensitive (lysosomal) acid phosphatase was increased in Mphi from the knockout mice but activities of the lysosomal hydrolases N-acetyl beta-glucosaminidase and acid beta-glucuronidase were unchanged, indicating selective activation of compensatory acid phosphatase activity. Evidence of impaired Mphi function in vivo was obtained in TRAP knockout mice, which showed delayed clearance of the microbial pathogen, Staphylococcus aureus, after sublethal intraperitoneal inoculation. After microbial challenge, peritoneal exudates obtained from TRAP knockout mice had a reduced population of Mphi. As peritoneal Mphi and neutrophils lacking TRAP were able to phagocytose and kill S. aureus normally in vitro, TRAP may directly or indirectly influence recruitment of Mphi to sites of microbial invasion. Our study shows that TRAP participates in the inflammatory response of the Mphi and influences effector signalling pathways in

  3. The small chemical enzyme inhibitor 5-phenylnicotinic acid/CD13 inhibits cell migration and invasion of tartrate-resistant acid phosphatase/ACP5-overexpressing MDA-MB-231 breast cancer cells.

    PubMed

    Krumpel, Michael; Reithmeier, Anja; Senge, Teresa; Baeumler, Toni Andreas; Frank, Martin; Nyholm, Per-Georg; Ek-Rylander, Barbro; Andersson, Göran

    2015-11-15

    Tartrate-resistant acid phosphatase (TRAP/ACP5/uteroferrin/purple acid phosphatase/PP5) has received considerable attention as a newly discovered proinvasion metastasis driver associated with different malignancies. This renders TRAP an interesting target for novel anti-cancer therapy approaches. TRAP exists as two isoforms, 5a and 5b, where the 5a isoform represents an enzymatically less active monomeric precursor to the more enzymatically active 5b isoform generated by proteolytic excision of a repressive loop domain. Recently, three novel lead compounds were identified by fragment-based screening and demonstrated to be efficient TRAP enzyme inhibitors in vitro. We conclude that one of the three compounds i.e. 5-phenylnicotinic acid (CD13) was efficient as a TRAP inhibitor with Kic values in the low micromolar range towards the TRAP 5b isoform, but was not able to inhibit the TRAP 5a isoform. Structure-based docking revealed similar interactions of CD13 with the active site in both TRAP isoforms. In stably TRAP-overexpressing MDA-MB-231 breast cancer cells, CD13 inhibited intracellular TRAP activity and showed no cytotoxicity at 200 µM. Furthermore, CD13 selectively blocked the TRAP 5b isoform compared to the TRAP 5a in cultured cells, indicating the usefulness of CD13 for assessing the different biological functions of the two TRAP isoforms 5a and 5b in cell systems. Moreover, inhibition of cell migration and invasion of stably TRAP-overexpressing MDA-MB-231 by CD13 was observed. These data establish a proof of principle that a small chemical inhibitor of the TRAP enzyme can block TRAP-dependent functions in cancer cells. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Tartrate-resistant acid phosphatase (TRAP) co-localizes with receptor activator of NF-KB ligand (RANKL) and osteoprotegerin (OPG) in lysosomal-associated membrane protein 1 (LAMP1)-positive vesicles in rat osteoblasts and osteocytes.

    PubMed

    Solberg, L B; Stang, E; Brorson, S-H; Andersson, G; Reinholt, F P

    2015-02-01

    Tartrate-resistant acid phosphatase (TRAP) is well known as an osteoclast marker; however, a recent study from our group demonstrated enhanced number of TRAP + osteocytes as well as enhanced levels of TRAP located to intracellular vesicles in osteoblasts and osteocytes in experimental osteoporosis in rats. Such vesicles were especially abundant in osteoblasts and osteocytes in cancellous bone as well as close to bone surface and intracortical remodeling sites. To further investigate TRAP in osteoblasts and osteocytes, long bones from young, growing rats were examined. Immunofluorescence confocal microscopy displayed co-localization of TRAP with receptor activator of NF-KB ligand (RANKL) and osteoprotegerin (OPG) in hypertrophic chondrocytes and diaphyseal osteocytes with Pearson's correlation coefficient ≥0.8. Transmission electron microscopy showed co-localization of TRAP and RANKL in lysosomal-associated membrane protein 1 (LAMP1) + vesicles in osteoblasts and osteocytes supporting the results obtained by confocal microscopy. Recent in vitro data have demonstrated OPG as a traffic regulator for RANKL to LAMP1 + secretory lysosomes in osteoblasts and osteocytes, which seem to serve as temporary storage compartments for RANKL. Our in situ observations indicate that TRAP is located to RANKL-/OPG-positive secretory lysosomes in osteoblasts and osteocytes, which may have implications for osteocyte regulation of osteoclastogenesis.

  5. Structure of Acid phosphatases.

    PubMed

    Araujo, César L; Vihko, Pirkko T

    2013-01-01

    Acid phosphatases are enzymes that have been studied extensively due to the fact that their dysregulation is associated with pathophysiological conditions. This characteristic has been exploited for the development of diagnostic and therapeutic methods. As an example, prostatic acid phosphatase was the first marker for metastatic prostate cancer diagnosis and the dysregulation of tartrate resistant acid phosphatase is associated with abnormal bone resorption linked to osteoporosis. The pioneering crystallization studies on prostatic acid phosphatase and mammalian tartrate-resistant acid phosphatase conformed significant milestones towards the elucidation of the mechanisms followed by these enzymes (Schneider et al., EMBO J 12:2609-2615, 1993). Acid phosphatases are also found in nonmammalian species such as bacteria, fungi, parasites, and plants, and most of them share structural similarities with mammalian acid phosphatase enzymes. Acid phosphatase (EC 3.1.3.2) enzymes catalyze the hydrolysis of phosphate monoesters following the general equation. Phosphate monoester + H2O -->/<-- alcohol + phosphate. The general classification "acid phosphatase" relies only on the optimum acidic pH for the enzymatic activity in assay conditions using non-physiological substrates. These enzymes accept a wide range of substrates in vitro, ranging from small organic molecules to phosphoproteins, constituting a heterogeneous group of enzymes from the structural point of view. These structural differences account for the divergence in cofactor dependences and behavior against substrates, inhibitors, and activators. In this group only the tartrate-resistant acid phosphatase is a metallo-enzyme whereas the other members do not require metal-ion binding for their catalytic activity. In addition, tartrate-resistant acid phosphatase and erythrocytic acid phosphatase are not inhibited by L-(+)-tartrate ion while the prostatic acid phosphatase is tartrate-sensitive. This is an important

  6. [Serum hyaluronic acid in osteoarthritis].

    PubMed

    Balblanc, J C; Hartmann, D; Noyer, D; Mathieu, P; Conrozier, T; Tron, A M; Piperno, M; Richard, M; Vignon, E

    1993-03-01

    In this prospective study, serum hyaluronate (SH) was assayed using a radiometric method (Pharmacia) in 73 osteoarthritis patients and 39 controls. All assays were performed between 8 h 00 and 9 h 00 a.m. because SH levels exhibit circadian variations. SH levels were significantly higher in patients with osteoarthritis than in controls (92 +/- 66 micrograms/l and 39 +/- 21 micrograms/l, respectively, p = 0.0001). Among 50 patients with osteoarthritis, including 29 with knee involvement and 21 with hip involvement, SH levels were not correlated with morning stiffness, duration of symptoms, Lequesne's algofunctional index, erythrocyte sedimentation rate, C-reactive protein, severity of roentgenographic changes in the affected knee or hip, disease extension, or severity. The lack of any relationship between changes in SH levels and Lequesne's is index values in 25 patients or between SH levels and joint space narrowing evaluated retrospectively in 16 patients, as well as the prompt return to high SH levels after arthroplasty and synovectomy in 14 patients with hip joint osteoarthritis, suggest that this potential marker is not useful for monitoring osteoarthritis in a single joint.

  7. Serum sialic acid and CEA concentrations in human breast cancer.

    PubMed

    Hogan-Ryan, A; Fennelly, J J; Jones, M; Cantwell, B; Duffy, M J

    1980-04-01

    The concentration of bound sialic acid in the sera of 56 normal subjects and 65 subjects with breast cancer was measured, in order to determine (1) whether serum sialic acid concentrations are raised in breast cancer and (2) whether the concentration of sialic acid in serum reflects tumour stage. The amount of sialic acid in serum was compared to serum carcinoembryonic antigen (CEA) values. Urinary hydroxyproline and serum alkaline phosphatase concentrations were used as indicators of bone and liver involvement. Erythrocyte sedimentation rate (ESR) was also measured. Significantly elevated serum sialic acid concentrations were found in breast cancer, and showed correlation with tumour stage. Serum sialic acid values did not correlate with CEA values. The results suggest that measurement of serum sialic acid concentrations may be of adjunctive value in assessing tumour stage.

  8. Relation of serum uric acid to cardiovascular disease.

    PubMed

    Wu, Audrey H; Gladden, James D; Ahmed, Mustafa; Ahmed, Ali; Filippatos, Gerasimos

    2016-06-15

    This review summarizes recent published literature on the association between serum uric acid and cardiovascular disease, a relationship which is complex and not fully elucidated. Uric acid may be a marker for risk, a causative agent in cardiovascular disease, or both. Various biologic factors can influence serum uric acid levels, and serum uric acid level itself is closely related to conditions such as hypertension, dyslipidemia, obesity, and impaired glucose metabolism, that contribute to cardiovascular disease pathophysiology. Serum uric acid levels have been found to be associated with adverse outcomes, including mortality, in the general population. In addition, serum uric acid is associated with increased risk for incident coronary heart disease, heart failure, and atrial fibrillation. In the setting of established systolic heart failure, serum uric acid is positively associated with disease severity and mortality risk. Whether targeting treatment based on uric acid levels might affect clinical outcomes is still being studied. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  9. Reductions in Serum Lipids with a 4-year Decline in Serum Perfluorooctanoic Acid and Perfluorooctanesulfonic Acid

    PubMed Central

    Fitz-Simon, Nicola; Fletcher, Tony; Luster, Michael I.; Steenland, Kyle; Calafat, Antonia M.; Kato, Kayoko; Armstrong, Ben

    2016-01-01

    Background Several epidemiological cross-sectional studies have found positive associations between serum concentrations of lipids and perfluorooctanoic acid (PFOA, or C8). A longitudinal study should be less susceptible to biases from uncontrolled confounding or reverse causality. Methods We investigated the association between within-individual changes in serum PFOA and perfluorooctanesulfonic acid (PFOS) and changes in serum lipid levels (low-density lipoprotein [LDL] cholesterol, high-density lipoprotein cholesterol, total cholesterol, and triglycerides) over a 4.4-year period. The study population consisted of 560 adults living in parts of Ohio and West Virginia where public drinking water had been contaminated with PFOA. They had participated in a cross-sectional study in 2005–2006, and were followed up in 2010, by which time exposure to PFOA had been substantially reduced. Results Overall serum concentrations of PFOA and PFOS fell by half from initial geometric means of 74.8 and 18.5 ng/mL, respectively, with little corresponding change in LDL cholesterol (mean increase 1.8%, standard deviation 26.6%). However, there was a tendency for people with greater declines in serum PFOA or PFOS to have greater LDL decrease. For a person whose serum PFOA fell by half, the predicted fall in LDL cholesterol was 3.6% (95% confidence interval = 1.5–5.7%). The association with a decline in PFOS was even stronger, with a 5% decrease in LDL (2.5–7.4%). Conclusions Our findings from this longitudinal study support previous evidence from cross-sectional studies of positive associations between PFOA and PFOS in serum and LDL cholesterol. PMID:23685825

  10. Reductions in serum lipids with a 4-year decline in serum perfluorooctanoic acid and perfluorooctanesulfonic acid.

    PubMed

    Fitz-Simon, Nicola; Fletcher, Tony; Luster, Michael I; Steenland, Kyle; Calafat, Antonia M; Kato, Kayoko; Armstrong, Ben

    2013-07-01

    Several epidemiological cross-sectional studies have found positive associations between serum concentrations of lipids and perfluorooctanoic acid (PFOA, or C8). A longitudinal study should be less susceptible to biases from uncontrolled confounding or reverse causality. We investigated the association between within-individual changes in serum PFOA and perfluorooctanesulfonic acid (PFOS) and changes in serum lipid levels (low-density lipoprotein [LDL] cholesterol, high-density lipoprotein cholesterol, total cholesterol, and triglycerides) over a 4.4-year period. The study population consisted of 560 adults living in parts of Ohio and West Virginia where public drinking water had been contaminated with PFOA. They had participated in a cross-sectional study in 2005-2006, and were followed up in 2010, by which time exposure to PFOA had been substantially reduced. Overall serum concentrations of PFOA and PFOS fell by half from initial geometric means of 74.8 and 18.5 ng/mL, respectively, with little corresponding change in LDL cholesterol (mean increase 1.8%, standard deviation 26.6%). However, there was a tendency for people with greater declines in serum PFOA or PFOS to have greater LDL decrease. For a person whose serum PFOA fell by half, the predicted fall in LDL cholesterol was 3.6% (95% confidence interval = 1.5-5.7%). The association with a decline in PFOS was even stronger, with a 5% decrease in LDL (2.5-7.4%). Our findings from this longitudinal study support previous evidence from cross-sectional studies of positive associations between PFOA and PFOS in serum and LDL cholesterol.

  11. Serum Uric Acid Levels and Outcomes After Acute Ischemic Stroke.

    PubMed

    Wang, Zhongchao; Lin, Yanlin; Liu, Yuxiu; Chen, Ying; Wang, Bin; Li, Changgui; Yan, Shengli; Wang, Yangang; Zhao, Wenjuan

    2016-04-01

    Previous studies assessing the association between serum uric acid levels and neurological outcome after acute ischemic stroke reported conflicting results. A systematic review and meta-analysis were conducted to assess the impact of serum uric acid levels on outcome after acute ischemic stroke. Pubmed, Embase, Web of Science, and Google scholar were searched through September 26, 2014 to identify eligible published or unpublished studies on the association between serum uric acid levels and outcome after acute ischemic stroke. Hazard ratio (HR) for poor outcome or mean differences of serum uric acid levels with 95% confidence intervals (95% CIs) were pooled using meta-analysis. The primary outcome was occurrence of poor outcomes, while the secondary outcome was the mean differences of serum uric acid levels in patients with good or poor outcomes. Ten eligible studies with a total of 8131 acute ischemic stroke patients were included into the meta-analysis. Compared with low serum uric acid level, high serum uric acid level was associated better outcome after acute ischemic stroke (HR = 0.77, 95% CI 0.68-0.88, P = 0.0001). Sensitivity analysis further identified the prognostic role of serum uric acid levels on outcome after acute ischemic stroke. Patients with good outcomes had a higher serum uric acid level compared with those with poor outcome (mean difference = 30.61 μmol/L, 95% CI 20.13-41.08, P < 0.00001). There was no obvious risk of publication bias in the meta-analysis. This meta-analysis supports that serum uric acid level has a protective effect on neurological outcome after acute ischemic stroke. High uric acid level at the onset is a biomarker of better prognosis in patients with acute ischemic stroke.

  12. Evaluation of serum uric acid levels in psoriasis vulgaris.

    PubMed

    Yilmaz, Emrah; Tamer, Emine; Artüz, Ferda; Külcü Çakmak, Seray; Köktürk, Fürüzan

    2017-04-18

    Psoriasis has been accepted as a systemic disease and it is known to be associated with various disorders including metabolic syndrome. High serum uric acid levels are also associated with the components of metabolic syndrome. In this study, we aimed to determine serum uric acid levels in patients with psoriasis and the association of uric acid levels with disease activity by taking the presence of metabolic syndrome criteria into account, since it is one of the most important factors that affect serum uric acid levels. In this cross-sectional study, we evaluated 70 psoriasis patients and 70 healthy individuals who were matched with the patients according to the presence of metabolic syndrome. We evaluated the demographic features, levels of serum uric acid, Psoriasis Area Severity Index (PASI) scores, presence of psoriatic arthritis, nail involvement, and metabolic syndrome criteria of the patients. Serum uric acid levels of psoriasis patients were significantly higher than those of controls. There was a positive correlation between PASI scores and serum uric acid levels of the patients. As hyperuricemia had a close relationship with psoriasis and PASI scores, we suggest monitoring patients with psoriasis for serum uric acid levels during treatment and follow-up.

  13. Association between serum cobalamin and methylmalonic acid concentrations in dogs.

    PubMed

    Berghoff, Nora; Suchodolski, Jan S; Steiner, Jörg M

    2012-03-01

    The aim of this study was to evaluate the association between serum methylmalonic acid (MMA), a proposed marker of cellular cobalamin deficiency, and serum cobalamin concentrations in dogs. Serum samples from 555 dogs were grouped according to their serum cobalamin concentrations (<150 ng/L to 1000 ng/L). Additionally, serum samples were collected from 43 healthy dogs to calculate a reference interval for canine serum MMA. MMA was measured using a GC/MS method. Groups were compared using a Kruskal-Wallis test with Dunn's post test. Proportions of dogs above the upper limit of the reference interval were calculated and a χ2-test for trend was performed to evaluate the association between serum cobalamin and MMA concentrations. The reference interval for serum MMA was calculated to be 414.7-1192.5 nmol/L. Dogs with serum cobalamin concentrations <251 ng/L had significantly higher MMA concentrations (P<0.05) and the χ2-test for trend showed a trend for increasing serum MMA concentrations with decreasing serum cobalamin concentrations (P<0.0001). Additionally, a number of dogs with normal serum cobalamin concentrations had increased serum MMA concentrations, suggesting that some of these dogs may have cobalamin deficiency on a cellular level. Further studies are warranted to determine if these dogs should receive cobalamin supplementation. Copyright © 2011 Elsevier Ltd. All rights reserved.

  14. KINETICS OF AMINO ACID INCORPORATION INTO SERUM PROTEINS

    PubMed Central

    Green, H.; Anker, H. S.

    1955-01-01

    1. The effect of varying body temperature on the rate of amino acid incorporation into serum protein does not give support to the idea that the rate of this process is adjusted in vivo to restore those protein molecules destroyed by thermal denaturation. The experimentally observed Q10 was about 3.9. 2. When amino acids are injected into the blood of animals in a steady state of serum protein turnover, a period of time elapses before these amino acids can be found in the serum proteins. This has been called transit time. At a given temperature (31°) it is the same in rabbits, turtles, and Limulus (1 hour). In rabbits and turtles it has a Q10 of 3.2. It appears to be specifically related to the process of synthesis (or release) of serum proteins. 3. It was not possible to affect the transit time or the incorporation rate by the administration of amino acid analogues. PMID:13221773

  15. Serum sialic acid enzymatic assay based on microtitre plates: application for measuring capillary serum sialic acid concentrations.

    PubMed

    Simpson, H; Chusney, G D; Crook, M A; Pickup, J C

    1993-06-01

    We have adapted a commercially-available kit for the enzymatic determination of sialic acid so that the reaction can be carried out in microtitre wells and the coloured end product quantitated on an ELISA plate reader. The small volume of serum used allows sialic acid to be measured in capillary blood samples. The assay was based on release of sialic acid from glycoconjugates by neuraminidase, cleavage of sialic acid by N-acetyl neuraminic acid aldolase to pyruvate, and then oxidation of pyruvate to hydrogen peroxide by pyruvate oxidase. Hydrogen peroxide was determined by the red product formed in the presence of peroxidase, 4-aminoantipyrine and N-ethyl-N-2-hydroxyethyl-3-toluidine. The assay was linear to at least 10 mmol/l and unaffected by haemolysis, and by the addition of glucose, 3-hydroxybutyrate, bilirubin and pyruvate. Capillary serum sialic acid concentrations were not significantly different from simultaneously measured venous serum sialic acid levels. Self-collected capillary blood samples were obtained from healthy subjects over 6 h during the day. No variations in serum sialic acid concentrations were found in response to a meal. We conclude that this micro-adaptation of a specific sialic acid assay will be suitable for epidemiological surveys of serum sialic acid collected by patients and normal subjects.

  16. Evaluating the Risk of a Fifth Metatarsal Stress Fracture by Measuring the Serum 25-Hydroxyvitamin D Levels.

    PubMed

    Shimasaki, Yu; Nagao, Masashi; Miyamori, Takayuki; Aoba, Yukihiro; Fukushi, Norifumi; Saita, Yoshitomo; Ikeda, Hiroshi; Kim, Sung-Gon; Nozawa, Masahiko; Kaneko, Kazuo; Yoshimura, Masafumi

    2016-03-01

    The fifth metatarsal bone is a common site of stress fractures in soccer athletes. Although several endocrine risk factors for stress fractures have been proposed, the endocrine risks for fifth metatarsal (5-MT) stress fractures have not been evaluated. To evaluate the endocrine risks of fifth metatarsal stress fractures, we conducted a cumulative case-control study. The present study included 37 athletes, of which 18 had a history of a zone 2 or zone 3 fifth metatarsal stress fracture and 19 controls. We analyzed serum 25-hydroxyvitamin D (25-OHD), serum parathyroid hormone (PTH), as well as biochemical markers of bone turnover by univariate or multivariate analyses. Logistic regression analyses adjusted for multiple confounders revealed that insufficient serum 25-OHD levels less than 30 ng/mL (odds ratio [OR], 23.3), higher serum PTH levels (OR, 1.01), or higher serum bone-specific isoform of alkaline phosphatase levels (OR, 1.10) rather than serum tartrate-resistant acid phosphatase 5b were associated with statistically significantly increased odds of 5-MT stress fractures. A postestimation calculation demonstrated that 25-OHD levels of 10 and 20 ng/mL were associated with 5.1 and 2.9 times greater odds for 5-MT stress fractures, respectively. 25-OHD insufficiency was associated with an increased incidence of 5-MT stress fractures. This insight may be useful for intervening to prevent 5-MT stress fractures. Level III, case-control study. © The Author(s) 2015.

  17. [Does coffee drinking influence serum uric acid concentration?].

    PubMed

    Olak-Białoń, Bogusława; Marcisz, Czesław; Jonderko, Gerard; Olak, Zygfryd; Szymszal, Jan; Orzeł, Arkadiusz

    2004-01-01

    The drinking of coffee, a commonly used beverage, was a subject of many studies, mainly regarded to coffee influence on cardiovascular system. However, only one study indicates that coffee drinking in male adults may lead to decrease in serum uric acid level. Hyperuricaemia is a risk factor of many diseases. The aim of this study was to examine the influence of coffee drinking on serum uric acid concentration. 1955 working persons aged from 18 to 65 years were included into research. There were 571 women among them. We determined energy expenditure during professional work, blood pressure, body mass index, and measured serum levels of uric acid, glucose and creatinine. The amount of coffee and ethanol consumption was evaluated on the ground of an interview. It was showed that persons drinking coffee have lower serum uric acid concentration than non-drinkers, especially among women, who drank more coffee then men. Uricaemia was correlated negatively with number of cups of coffee consumed and positively with body mass index, ethanol consumption and diastolic blood pressure. The author conclude that: 1) among women drinking on an average 10 cups of coffee per week appeared a decrease in serum uric acid concentration and a lower risk of development of hyperuricaemia, 2) elevated serum uric acid concentration is accompanied by elevated blood pressure and increased body mass index.

  18. Nature of mononuclear cells positive for acid phosphatase activity in bone marrow of patients with renal osteodystrophy.

    PubMed Central

    Kaye, M; Henderson, J

    1988-01-01

    Fifty two of 63 patients with renal osteodystrophy had one or more mononuclear cells positive for acid phosphatase in the marrow. These cells are also tartrate resistant and non-specific esterase negative, and are believed to be precursors to osteoclasts and other acid phosphatase positive cells resorbing bone on the trabecular surface. Images Figure PMID:3360955

  19. Altered Serum Uric Acid Level in Lichen Planus Patients

    PubMed Central

    Chakraborti, Goutam; Biswas, Rabindranath; Chakraborti, Sandip; Sen, Pradyot Kumar

    2014-01-01

    Background: Lichen planus (LP) is a common disorder whose etiopathogenesis is not clear. Recently, it has been suggested that increased reactive oxygen species (ROS) play important roles in the underlying mechanism of LP. Objectives: The principal aim of this study was to evaluate serum uric acid (UA) levels as a measure of the antioxidant defense status in LP patients. Methods: Serum UA levels were determined in 58 LP patients and 61 controls. Results: Serum UA levels were significantly decreased in patients with respect to controls. Moreover, serum UA level was decreased according to increasing duration of disease. Conclusions: The results of our study suggest that LP is associated with decrease of UA levels in serum. UA may be a potential, useful biomarker of antioxidant status in LP for elaboration of treatment strategy and monitoring. PMID:25484383

  20. Association between serum folic acid level and erectile dysfunction.

    PubMed

    Karabakan, M; Erkmen, A E; Guzel, O; Aktas, B K; Bozkurt, A; Akdemir, S

    2016-06-01

    This study measured the serum folic acid (FA) level in patients with erectile dysfunction (ED) and evaluated the possible association between the serum FA level and erectile function. The study divided 120 patients with ED into 3 groups of 40 patients each: those with severe, moderate and mild ED. Forty healthy men served as controls. Fasting serum samples were obtained, and the total testosterone, cholesterol and FA levels were measured using chemiluminescent immunoassays. There were no significant differences in the mean age, mean body mass index or mean serum total testosterone and cholesterol levels among the three ED groups and controls (P > 0.05). The mean serum FA concentrations were 7.2 ± 3.7, 7.1 ± 3.2, 10.2 ± 4.6 and 10.7 ± 4.6 ng ml(-1) in the severe, moderate and mild ED and control groups respectively. The mean serum FA concentration was significantly higher in the control group than in the severe and moderate ED groups (both P < 0.001), but not the mild ED group (P = 0.95). Considering the significant differences in the serum FA levels between the control and ED groups, serum FA deficiency might reflect the severity of ED.

  1. Perfluoroalkyl chemicals and elevated serum uric acid in US adults.

    PubMed

    Shankar, Anoop; Xiao, Jie; Ducatman, Alan

    2011-01-01

    Perfluoroalkyl chemicals, including perfluorooctanoic acid and perfluorooctane sulfonate, are man-made chemicals that have been detected in the blood of over 98% of the US population. Serum uric acid is a novel biomarker, even mild elevations of which has been implicated in the development of hypertension, diabetes mellitus, cardiovascular disease, and chronic kidney disease. We examined the relationship of serum perfluoroalkyl chemicals, including perfluorooctanoic acid and perfluorooctane sulfonate, and elevated uric acid levels in a representative sample of US adults. We examined 3883 participants from the 1999-2000 and 2003-2006 National Health and Nutritional Examination Surveys, a representative, multiethnic population-based survey of noninstitutionalized US adults. Serum perfluorooctanoic acid and perfluorooctane sulfonate were analyzed as quartiles. The main outcome was hyperuricemia. We found that serum levels of perfluoroalkyl chemicals, including perfluorooctanoic acid and perfluorooctane sulfonate, were positively associated with hyperuricemia. This association appeared to be independent of confounders such as age, gender, race-ethnicity, body mass index, diabetes, hypertension, and serum cholesterol. Compared with subjects in quartile 1 (referent), the multivariate odds ratio for hyperuricemia among subjects in quartile 4 was 1.97 (95% confidence interval 1.44-2.70, P < 0.0001) for perfluorooctanoic acid and 1.48% (95% confidence interval 0.99-2.22, P = 0.0433) for perfluorooctane sulfonate. This observed association persisted in subgroup analysis by gender and body mass index. Our results demonstrate that elevated levels of perfluoroalkyl chemicals are associated with hyperuricemia even at low perfluoroalkyl chemical exposure levels as seen in the US general population.

  2. Perfluoroalkyl chemicals and elevated serum uric acid in US adults

    PubMed Central

    Shankar, Anoop; Xiao, Jie; Ducatman, Alan

    2011-01-01

    Background: Perfluoroalkyl chemicals, including perfluorooctanoic acid and perfluorooctane sulfonate, are man-made chemicals that have been detected in the blood of over 98% of the US population. Serum uric acid is a novel biomarker, even mild elevations of which has been implicated in the development of hypertension, diabetes mellitus, cardiovascular disease, and chronic kidney disease. We examined the relationship of serum perfluoroalkyl chemicals, including perfluorooctanoic acid and perfluorooctane sulfonate, and elevated uric acid levels in a representative sample of US adults. Methods: We examined 3883 participants from the 1999–2000 and 2003–2006 National Health and Nutritional Examination Surveys, a representative, multiethnic population-based survey of noninstitutionalized US adults. Serum perfluorooctanoic acid and perfluorooctane sulfonate were analyzed as quartiles. The main outcome was hyperuricemia. Results: We found that serum levels of perfluoroalkyl chemicals, including perfluorooctanoic acid and perfluorooctane sulfonate, were positively associated with hyperuricemia. This association appeared to be independent of confounders such as age, gender, race-ethnicity, body mass index, diabetes, hypertension, and serum cholesterol. Compared with subjects in quartile 1 (referent), the multivariate odds ratio for hyperuricemia among subjects in quartile 4 was 1.97 (95% confidence interval 1.44–2.70, P < 0.0001) for perfluorooctanoic acid and 1.48% (95% confidence interval 0.99–2.22, P = 0.0433) for perfluorooctane sulfonate. This observed association persisted in subgroup analysis by gender and body mass index. Conclusion: Our results demonstrate that elevated levels of perfluoroalkyl chemicals are associated with hyperuricemia even at low perfluoroalkyl chemical exposure levels as seen in the US general population. PMID:22003309

  3. Serum free fatty acids level in senile cataract.

    PubMed

    Chang, Dong; Rong, Shengzhong; Zhang, Yannan; Sha, Qian; Liang, Meihua; Zhang, Xuefei; Li, Miaojing; Pan, Hongzhi

    2014-01-01

    To evaluate and compare the levels of free fatty acids between senile cataract patients and normal controls. Fifty consecutive patients with newly diagnosed senile cataract and 50 age- and gender-matched controls were evaluated. Subjects/patients were randomized according to selection criteria. The levels of free fatty acids (FFAs) in serum were measured by gas chromatography-mass spectrometry (GC-MS). Sixteen fatty acids from 14:0 to 24:1 were identified. The values were compared between cataract and control groups by parametric independent sample test and Mann-Whitney U tests. A significant decrease was observed in arachidonic acid (C20:4n-6, ARA), cis-4,7,10,13,16,19-docosahexaenoic acid (C22:6n-3, DHA), tetracosanoic acid (C24: 0), cis-7,10,13,16,19-docosapentaenoic acid (C22:5n-6, DPA), total n-3 long-chain polyunsaturated fatty acids (LC-PUFAs), total n-6 LC-PUFAs, total fatty acids, unsaturated fatty acids (USFAs), polyunsaturated fatty acids (PUFAs), and nonessential fatty acid levels in patients with senile cataract in comparison with healthy persons (p < 0.05). The levels of FFA including DPA, tetracosanoic acid, ARA, and DHA were significantly lower in the senile cataract group compared to that in the normal controls. FFA may be helpful in preventing senile cataract.

  4. Serum free fatty acid biomarkers of lung cancer.

    PubMed

    Liu, Jinbo; Mazzone, Peter J; Cata, Juan P; Kurz, Andrea; Bauer, Maria; Mascha, Edward J; Sessler, Daniel I

    2014-09-01

    Lung cancer is the leading cause of cancer-related mortality. Surgical removal of the tumor at an early stage can be curative. However, lung cancer diagnosis at an early stage remains challenging. There is evidence that free fatty acids play a role in cancer development. Serum samples from 55 patients with lung cancer were propensity matched with samples from 165 similar pulmonary patients without known cancer. Patients were propensity matched on age, sex, smoking history, family history of lung cancer, and chronic diseases that might affect free fatty acid levels. Free fatty acids arachidonic acid (AA) and linoleic acid (LA) and their metabolites hydroxyeicosatetraenoic acids (HETEs)(5-HETE, 11-HETE, 12-HETE, and 15-HETE) were an estimated 1.8- to 3.3-fold greater in 37 patients with adenocarcinoma vs 111 patients without cancer (all P < .001). Areas under the receiver operating characteristic curve were significantly > 0.50, discriminating patients with lung cancer and control subjects for six of eight biomarkers and two of seven phospholipids tested, and ranged between 0.69 and 0.82 (all P < .001) for patients with lung cancer vs control subjects. AA, LA, and 15-HETE had observed sensitivity and specificity > 0.70 at the best cutpoint. Concentrations of free fatty acids and their metabolites were similar in 18 patients with squamous cell carcinoma and 54 control subjects without cancer. Serum fatty acids and their metabolites demonstrate good sensitivity and specificity for the identification of adenocarcinoma of the lung.

  5. Identification of beta-aminoisobutyric acid in uremic serum.

    PubMed

    Gejyo, F; Kinoshita, Y; Ikenaka, T

    1976-08-02

    An unidentified ninhydrin-positive substance found in uremic sera but not found in normal sera was isolated by gel-filtration through Sephadex G-75 followed by high voltage paper electrophoresis (pH 3.5), and identified as beta-aminoisobutyric acid using paper chromatography and automated amino acid analyzer. The quantitative determination of beta-aminoisobutyric acid in serum revealed that the level of beta-aminoisobutyric acid in uremic sera was much higher than that of normal sera. Gas chromatographic determination of the enantiomorphs of beta-aminoisobutyric acid showed that uremic sera contain R- and S-isomers of the amino acid, but with the R-isomer as the dominating form.

  6. Associations between Serum Perfluoroalkyl Acids and LINE-1 DNA Methylation

    PubMed Central

    Watkins, Deborah J.; Wellenius, Gregory A.; Butler, Rondi A.; Bartell, Scott M.; Fletcher, Tony; Kelsey, Karl T.

    2014-01-01

    Perfluoroalkyl acids (PFAAs) are persistent, synthetic compounds that are used in a number of consumer products. Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) have been associated with cardiovascular risk factors, and changes in gene expression and DNA methylation in animals and cellular systems. However, whether PFAA exposure is associated with LINE-1 DNA methylation, a potential marker of cardiovascular risk, in humans remains unknown. We sought to evaluate the cross-sectional associations between serum PFAAs and LINE-1 DNA methylation in a population highly exposed to PFOA. We measured serum PFAAs twice four to five years apart in 685 adult participants (47% male, mean age ± SD=42 ± 11 years). We measured percent LINE-1 DNA methylation in peripheral blood leukocytes at the second time point (follow-up), and estimated absolute differences in LINE-1 methylation associated with an interquartile (IQR) shift in mean PFAA serum levels. IQR increases in mean serum PFOA, PFOS, perfluorononanoic acid (PFNA), and perfluorohexane sulfonate (PFHxS) were associated with differences of −0.04 (p=0.16), 0.20 (p=0.001), 0.06 (p=0.19), and 0.02 (p=0.57), respectively, in % LINE-1 methylation at follow-up after adjustment for potential confounders. We observed a monotonic increase in LINE-1 DNA methylation across tertiles of PFOS and PFNA (ptrend=0.02 for both associations), but not across tertiles of PFOA or PFHxS (ptrend=0.71 and 0.44, respectively). In summary, serum PFOS was associated with LINE-1 methylation, while serum PFOA, PFHxS, and PFNA were not. Additional research is needed to more precisely determine whether these compounds are epigenetically active. PMID:24263140

  7. Associations between serum perfluoroalkyl acids and LINE-1 DNA methylation.

    PubMed

    Watkins, Deborah J; Wellenius, Gregory A; Butler, Rondi A; Bartell, Scott M; Fletcher, Tony; Kelsey, Karl T

    2014-02-01

    Perfluoroalkyl acids (PFAAs) are persistent, synthetic compounds that are used in a number of consumer products. Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) have been associated with cardiovascular risk factors, and changes in gene expression and DNA methylation in animals and cellular systems. However, whether PFAA exposure is associated with LINE-1 DNA methylation, a potential marker of cardiovascular risk, in humans remains unknown. We sought to evaluate the cross-sectional associations between serum PFAAs and LINE-1 DNA methylation in a population highly exposed to PFOA. We measured serum PFAAs twice four to five years apart in 685 adult participants (47% male, mean age±SD=42±11years). We measured percent LINE-1 DNA methylation in peripheral blood leukocytes at the second time point (follow-up), and estimated absolute differences in LINE-1 methylation associated with an interquartile (IQR) shift in mean PFAA serum levels. IQR increases in mean serum PFOA, PFOS, perfluorononanoic acid (PFNA), and perfluorohexane sulfonate (PFHxS) were associated with differences of -0.04 (p=0.16), 0.20 (p=0.001), 0.06 (p=0.19), and 0.02 (p=0.57), respectively, in % LINE-1 methylation at follow-up after adjustment for potential confounders. We observed a monotonic increase in LINE-1 DNA methylation across tertiles of PFOS and PFNA (ptrend=0.02 for both associations), but not across tertiles of PFOA or PFHxS (ptrend=0.71 and 0.44, respectively). In summary, serum PFOS was associated with LINE-1 methylation, while serum PFOA, PFHxS, and PFNA were not. Additional research is needed to more precisely determine whether these compounds are epigenetically active. © 2013.

  8. Airborne Precursors Predict Maternal Serum Perfluoroalkyl Acid Concentrations.

    PubMed

    Makey, Colleen M; Webster, Thomas F; Martin, Jonathan W; Shoeib, Mahiba; Harner, Tom; Dix-Cooper, Linda; Webster, Glenys M

    2017-07-05

    Human exposure to persistent perfluoroalkyl acids (PFAAs), including perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorooctanesulfonate (PFOS), can occur directly from contaminated food, water, air, and dust. However, precursors to PFAAs (PreFAAs), such as dipolyfluoroalkyl phosphates (diPAPs), fluorotelomer alcohols (FTOHs), perfluorooctyl sulfonamides (FOSAs), and sulfonamidoethanols (FOSEs), which can be biotransformed to PFAAs, may also be a source of exposure. PFAAs were analyzed in 50 maternal sera samples collected in 2007-2008 from participants in Vancouver, Canada, while PFAAs and PreFAAs were measured in matching samples of residential bedroom air collected by passive sampler and in sieved vacuum dust (<150 μm). Concentrations of PreFAAs were higher than for PFAAs in air and dust. Positive associations were discovered between airborne 10:2 FTOH and serum PFOA and PFNA and between airborne MeFOSE and serum PFOS. On average, serum PFOS concentrations were 2.3 ng/mL (95%CI: 0.40, 4.3) higher in participants with airborne MeFOSE concentrations in the highest tertile relative to the lowest tertile. Among all PFAAs, only PFNA in air and vacuum dust predicted serum PFNA. Results suggest that airborne PFAA precursors were a source of PFOA, PFNA, and PFOS exposure in this population.

  9. Sequences Of Amino Acids For Human Serum Albumin

    NASA Technical Reports Server (NTRS)

    Carter, Daniel C.

    1992-01-01

    Sequences of amino acids defined for use in making polypeptides one-third to one-sixth as large as parent human serum albumin molecule. Smaller, chemically stable peptides have diverse applications including service as artificial human serum and as active components of biosensors and chromatographic matrices. In applications involving production of artificial sera from new sequences, little or no concern about viral contaminants. Smaller genetically engineered polypeptides more easily expressed and produced in large quantities, making commercial isolation and production more feasible and profitable.

  10. Binding sites of retinol and retinoic acid with serum albumins.

    PubMed

    Belatik, A; Hotchandani, S; Bariyanga, J; Tajmir-Riahi, H A

    2012-02-01

    Retinoids are effectively transported in the bloodstream via serum albumins. We report the complexation of bovine serum albumin (BSA) with retinol and retinoic acid at physiological conditions, using constant protein concentration and various retinoid contents. FTIR, CD and fluorescence spectroscopic methods and molecular modeling were used to analyze retinoid binding site, the binding constant and the effects of complexation on BSA stability and secondary structure. Structural analysis showed that retinoids bind BSA via hydrophilic and hydrophobic interactions with overall binding constants of K(Ret)(-BSA) = 5.3 (±0.8) × 10(6) M(-1) and K(Retac-BSA) = 2.3 (±0.4) × 10(6) M(-1). The number of bound retinoid molecules (n) was 1.20 (±0.2) for retinol and 1.8 (±0.3) for retinoic acid. Molecular modeling showed the participation of several amino acids in retinoid-BSA complexes stabilized by H-bonding network. The retinoid binding altered BSA conformation with a major reduction of α-helix from 61% (free BSA) to 36% (retinol-BSA) and 26% (retinoic acid-BSA) with an increase in turn and random coil structures indicating a partial protein unfolding. The results indicate that serum albumins are capable of transporting retinoids in vitro and in vivo.

  11. Association of serum uric acid with ischemic stroke.

    PubMed

    Khalil, M I; Islam, M J; Ullah, M A; Khan, R K; Munira, S; Haque, M A; Mamun, M A; Islam, M T; Khan, M H

    2013-04-01

    The present study has examined the association between ischemic stroke and hyperuricemia in Bangladeshi population. This age and sex matched case control study was carried out in the Department of Neurology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh during the period of January 2007 to December 2008. A total of 120 subjects were included in this study, among them 60 were cases and another 60 were controls. Data were collected purposively. Multiple logistic regressions were done to identify the risk factors for ischemic stroke. In this study 68.3% were male and 31.7% were female in both the groups. Male and female ratio of stroke patients was 2.16:1. Mean±SD of serum uric acid level of case and control group was 4.94±1.76 and 3.72±1.09 respectively. Among the case group 76.7% had normal and 23.3% had abnormal serum uric acid level. On the other hand, 93.3% respondents of control group had normal and 6.7% had abnormal serum uric acid (SUA) level. Significant differences was found between case and control group in term of SUA level (p<0.05). Since SUA level is a quantitative numerical variable, an increase in 1mg/dl has a 47.0% (95% CI 1.0% to 2.16%) increase in odds ratio (OR) of having ischemic stroke. This 47.0% is obtained by taking OR for uric acid-1. Elevated serum uric acid level is not significant for ischemic stroke among the Bangladeshi population.

  12. Dietary Sodium Modifies Serum Uric Acid Concentrations in Humans.

    PubMed

    Todd, Alwyn S; Walker, Robert J; MacGinley, Robert J; Kelly, Jaimon; Merriman, Tony R; Major, Tanya J; Johnson, Richard J

    2017-09-07

    Subjects with hypertension are frequently obese or insulin resistant, both conditions in which hyperuricemia is common. Obese and insulin-resistant subjects are also known to have blood pressure that is more sensitive to changes in dietary sodium intake. Whether hyperuricemia is a resulting consequence, moderating or contributing factor to the development of hypertension has not been fully evaluated and very few studies have reported interactions between sodium intake and serum uric acid. We performed further analysis of our randomized controlled clinical trials (Australian New Zealand Clinical Trials Registry #12609000161224 and #12609000292279) designed to assess the effects of modifying sodium intake on concentrations of serum markers, including uric acid. Uric acid and other variables (including blood pressure, renin, and aldosterone) were measured at baseline and 4 weeks following the commencement of low (60 mmol/day), moderate (150 mmol/day), and high (200-250 mmol/day) dietary sodium intake. The median aldosterone-to-renin ratio was 1.90 [pg/ml]/[pg/ml] (range 0.10-11.04). Serum uric acid fell significantly in both the moderate and high interventions compared to the low sodium intervention. This pattern of response occurred when all subjects were analyzed, and when normotensive or hypertensive subjects were analyzed alone. Although previously reported in hypertensive subjects, these data provide evidence in normotensive subjects of an interaction between dietary sodium intake and serum uric acid. As this interaction is present in the absence of hypertension, it is possible it could play a role in hypertension development, and will need to be considered in future trials of dietary sodium intake. The trials were registered with the Australian and New Zealand Clinical Trials Registry as ACTRN12609000161224 and ACTRN1260.

  13. Serum concentration of sialic acids in naturally occurring ovine babesiosis.

    PubMed

    Esmaeilnejad, Bijan; Tavassoli, Mousa; Asri-Rezaei, Siamak; Dalir-Naghadeh, Bahram; Abtahi Froushani, Seyyed Meysam; Arjmand, Jafar; Golabi, Mostafa

    2014-10-01

    This study is designated to assess the effect of the severity of Babesia ovis infection on sialic acid concentration in blood sera in naturally infected sheep. Infected animals (diseased group) comprised 38 Iranian fat-tailed sheep, about 1-3 years old, naturally infected with B. ovis, divided into four subgroups with respect to parasitemia rates (low 0.1-0.3 %, moderate 0.4-0.9 %, high 1-2.5 %, and very high >2.5 %). The parasitological diagnosis was confirmed using PCR analysis. As a control group, ten clinically healthy sheep reared under the same management and environmental conditions were also sampled. Hematological parameters and the concentrations of total sialic acid (TSA), lipid-bound sialic acid (LBSA), and protein-bound sialic acid (PBSA) were measured in both groups. Compared to controls, sialic acid concentrations showed significant increase (p < 0.05) in infected sheep. Parasitemia rate was positively correlated with sialic acid concentrations. This study demonstrated that B. ovis infection induced marked and persistent elevations of serum sialic acid concentrations. It seems that increase of serum sialic acid concentrations during parasitemia alter receptor-ligand interactions, which are known to play important role in immune response. Furthermore, sialic acid would indirectly inhibit the action of leukocytes and consequently promote the evasion of the immune response and persistence of the parasite in the host. This factor could influence the parasite-host cell adhesion, but further detailed biochemical investigations are needed to precisely explain the exact role of sialic acid in invasion process of the parasite to the host cells.

  14. Serum uric acid levels and cardiovascular disease: the Gordian knot

    PubMed Central

    Tugores, Antonio; Rodríguez-González, Fayna

    2016-01-01

    Hyperuricemia is defined as serum uric acid level of more than 7 mg/dL and blood levels of uric acid are causally associated with gout, as implicated by evidence from randomized clinical trials using urate lowering therapies. Uric acid as a cardiovascular risk factor often accompanies metabolic syndrome, hypertension, diabetes, dyslipidemia, chronic renal disease, and obesity. Despite the association of hyperuricemia with cardiovascular risk factors, it has remained controversial as to whether uric acid is an independent predictor of cardiovascular disease. To settle this issue, and in the absence of large randomized controlled trials, Mendelian randomization analysis in which the exposure is defined based on the presence or absence of a specific allele that influences a risk factor of interest have tried to shed light on this. PMID:28066631

  15. Perfluoroalkyl acids in blood serum samples from children in Taiwan.

    PubMed

    Bao, Jia; Lee, Yungling Leo; Chen, Pau-Chung; Jin, Yi-He; Dong, Guang-Hui

    2014-06-01

    Severe perfluoroalkyl acid (PFAA) contamination resulting from the fast-growing semiconductor, electrochemical, and optoelectronic industries has been determined in the river water in the vicinity of the Taipei area, Taiwan, during recent years. However, little is known about body burdens of the PFAA contaminations in local residents, especially children living in the Taipei area recently. In this study, ten target PFAA analytes consisted of three perfluorosulfonates (PFSAs) and seven perfluorocarboxylates (PFCAs) in the blood serum samples, collected from 225 healthy children with an average age of 13.6 years in the Taipei area from 2009 to 2010, were analyzed via high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). As the dominant PFAA contaminant in the blood serum samples from Taiwanese children, perfluorooctane sulfonate (PFOS) contributed 86% of all the target PFAA analytes, while the other nine analytes contributed less than 5% individually. PFOS showed the highest median up to 29 ng/mL, ranging from 0.03 to 148 ng/mL, which was higher than that observed in the serum samples collected from Taiwanese children between 2006 and 2008. Statistically, serum concentrations of perfluorobutane sulfonate (PFBS), perfluorohexane sulfonate (PFHxS), and perfluorooctanoic acid (PFOA) had significantly positive correlations with ages of children (p < 0.05). Furthermore, serum PFBS, PFHxS, and PFOA concentrations in the male children were considerably higher than those in the female children (p = 0.049, p = 0.000, p = 0.000).

  16. Serum fluoride and sialic acid levels in osteosarcoma.

    PubMed

    Sandhu, R; Lal, H; Kundu, Z S; Kharb, S

    2011-12-01

    Osteosarcoma is a rare malignant bone tumor most commonly occurring in children and young adults presenting with painful swelling. Various etiological factors for osteosarcoma are ionizing radiation, family history of bone disorders and cancer, chemicals (fluoride, beryllium, and vinyl chloride), and viruses. Status of fluoride levels in serum of osteosarcoma is still not clear. Recent reports have indicated that there is a link between fluoride exposure and osteosarcoma. Glycoproteins and glycosaminoglycans are an integral part of bone and prolonged exposure to fluoride for long duration has been shown to cause degradation of collagen and ground substance in bones. The present study was planned to analyze serum fluoride, sialic acid, calcium, phosphorus, and alkaline phosphatase levels in 25 patients of osteosarcoma and age- and sex-matched subjects with bone-forming tumours other than osteosarcoma and musculo-skeletal pain (controls, 25 each). Fluoride levels were analyzed by ISE and sialic acid was analyzed by Warren's method. Mean serum fluoride concentration was found to be significantly higher in patients with osteosarcoma as compared to the other two groups. The mean value of flouride in patients with other bone-forming tumors was approximately 50% of the group of osteosarcoma; however, it was significantly higher when compared with patients of group I. Serum sialic acid concentration was found to be significantly raised in patients with osteosarcoma as well as in the group with other bone-forming tumors as compared to the group of controls. There was, however, no significant difference in the group of patients of osteosarcoma when compared with group of patients with other bone-forming tumors. These results showing higher level of fluoride with osteosarcoma compared to others suggesting a role of fluoride in the disease.

  17. Restoration of parathyroid function after change of phosphate binder from calcium carbonate to lanthanum carbonate in hemodialysis patients with suppressed serum parathyroid hormone.

    PubMed

    Inaba, Masaaki; Okuno, Senji; Nagayama, Harumi; Yamada, Shinsuke; Ishimura, Eiji; Imanishi, Yasuo; Shoji, Shigeichi

    2015-03-01

    Control of phosphate is the most critical in the treatment of chronic kidney disease with mineral and bone disorder (CKD-MBD). Because calcium-containing phosphate binder to CKD patients is known to induce adynamic bone disease with ectopic calcification by increasing calcium load, we examined the effect of lanthanum carbonate (LaC), a non-calcium containing phosphate binder, to restore bone turnover in 27 hemodialysis patients with suppressed parathyroid function (serum intact parathyroid hormone [iPTH] ≦ 150 pg/mL). At the initiation of LaC administration, the dose of calcium-containing phosphate binder calcium carbonate (CaC) was withdrawn or reduced based on serum phosphate. After initiation of LaC administration, serum calcium and phosphate decreased significantly by 4 weeks, whereas whole PTH and iPTH increased. A significant and positive correlation between decreases of serum calcium, but not phosphate, with increases of whole PTH and iPTH, suggested that the decline in serum calcium with reduction of calcium load by LaC might increase parathyroid function. Serum bone resorption markers, such as serum tartrate-resistant acid phosphatase 5b, and N-telopeptide of type I collagen increased significantly by 4 weeks after LaC administration, which was followed by increases of serum bone formation markers including serum bone alkaline phosphatase, intact procollagen N-propeptide, and osteocalcin. Therefore, it was suggested that LaC attenuated CaC-induced suppression of parathyroid function and bone turnover by decreasing calcium load. In conclusion, replacement of CaC with LaC, either partially or totally, could increase parathyroid function and resultant bone turnover in hemodialysis patients with serum iPTH ≦ 150 pg/mL. Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  18. The generation of osteoclasts from RAW 264.7 precursors in defined, serum-free conditions.

    PubMed

    Vincent, Cristina; Kogawa, Masakazu; Findlay, David M; Atkins, Gerald J

    2009-01-01

    Osteoclasts are the unique cell type capable of resorbing bone. The discovery of the TNF-ligand family member, RANKL, has allowed more reliable study of these important cells. The mouse monocytic cell line, RAW 264.7, has been shown to readily differentiate into osteoclasts upon exposure to recombinant RANKL. Unlike primary osteoclast precursors, there is no requirement for the addition of macrophage colony stimulating factor (M-CSF). However, to date, their differentiation has always been studied in the context of added foetal calf serum (FCS). FCS is a complex and largely undefined mixture of growth factors and matrix proteins, and varies between batches. For this reason, osteoclastogenesis would ideally be studied in the context of a defined, serum-free medium. RAW 264.7 cells were cultured in serum-replete alpha-MEM or serum-deprived medium (SDM) shown previously to support the growth of human osteoclasts in a co-culture with normal osteoblasts. In SDM, in the presence of recombinant RANKL, RAW 264.7 cells readily differentiated into tartrate resistant acid phosphatase (TRAP) positive multinucleated osteoclast-like cells, a process that was enhanced with the addition of 1alpha,25-dihydroxyvitamin D(3) (1,25D). While the osteoclasts grown in SDM were smaller in size compared with those derived in serum-replete media, their resorptive capacity was significantly increased as indicated by a twofold increase in average resorption pit size. In conclusion, we describe a defined model for studying osteoclast differentiation and activity in the absence of serum, which will be ideal for studying the role of agonistic and antagonistic molecules in this process.

  19. Effects of 25-hydroxycholecalciferol supplementation in maternal diets on milk quality and serum bone status markers of sows and bone quality of piglets.

    PubMed

    Zhou, Hui; Chen, Yuling; Zhuo, Yong; Lv, Gang; Lin, Yan; Feng, Bin; Fang, Zhengfeng; Che, Lianqiang; Li, Jian; Xu, Shengyu; Wu, De

    2017-03-01

    Twenty primiparous sows were allocated to two treatments to evaluate the effects of maternal 25-hydroxycholecalciferol (25OHD3 ) supplementation during gestation and lactation on milk quality and serum bone status markers of sows and bone quality of piglets. Immediately after mating, sows were randomly allotted to one of two diets supplemented with 50 µg/kg 25OHD3 or basal diets without 25OHD3 . Blood and milk samples were obtained. At birth and weaning, 10 piglets from each treatment were killed for bone quality analysis. 25OHD3 -fed sows provided one more piglet at farrowing and 1.17 more piglets at weaning than sows fed basal diets. The contents of solids not-fat, protein, fat or lactose were increased in milk from days 7 and 14 of lactation in 25OHD3 -supplemented sows and 25OHD3 concentrations in milk were increased by dietary 25OHD3 supplementation. Dietary 25OHD3 supplementation increased serum alkaline phosphatase activity but had no effect on serum tartrate-resistant acid phosphatase activity of sows. Maternal 25OHD3 supplementation improved bone strength, density and ash content of newborn piglets rather than those of weaning piglets. In conclusion, 25OHD3 supplementation in maternal diets improved reproductive performance, milk quality and bone status of sows as well as bone quality of newborn piglets. © 2016 Japanese Society of Animal Science.

  20. Dietary, serum and urine ascorbic acid status in male athletes.

    PubMed

    Rokitzki, L; Hinkel, S; Klemp, C; Cufi, D; Keul, J

    1994-10-01

    The ascorbic acid (AA)-status of 14 marathon runners, 12 soccer players, 9 wrestlers, 9 basketball players and 16 controls was determined. A 7-day food weighed record was kept to quantify the AA-intake. In addition, the AA-serum concentrations and urinary ascorbate excretion were measured. The AA-intake of all 44 athletes (median, 26th-75th percentile) was 180.7 (188-239) mg/d, the serum concentration 70.6 (65.7-80.2 mumol/l) and the urine ascorbate excretion 1531 (391-2934) mumol/g creatine. No significant differences could be observed between the various sport groups, or between the sport groups and controls with respect to absolute (mg/d) and relative (mg/g body weight) AA-intake, serum and urine concentrations. Only a few of the athletes had AA-intake below the RDA or serum- or urine levels smaller than the decision limit. The absolute AA-intake (n = 44) from the 7-day record (r = 0.49, p < 0.0009) and the AA-intake on the last day (1-day) prior to urine collection (r = 0.90, p < 0.0000) correlate moderately/strongly with the urinary excretion. Between AA-intake (7-day) and serum concentration there is a correlation of r = 0.59, p < 0.0000. The AA-status of highly trained athletes does not differ significantly from the control group in spite of intensive daily training. Thus, AA-supplementation beyond the normal daily intake does not appear necessary.

  1. Are There Any Promising Biochemical Correlates of Achievement Behavior and Motivation? The Evidence for Serum Uric Acid and Serum Cholesterol

    ERIC Educational Resources Information Center

    Kasl, Stanislav V.

    1974-01-01

    This review examines the available evidence in support of the argument that serum uric acid (SUA) possesses considerable promise as an indicator of one type of biochemical influence on achievement behavior. The evidence arguing for further research into the role of serum cholesterol in achievement behavior is also examined. (Author/JR)

  2. Evening primrose oil in rheumatoid arthritis: changes in serum lipids and fatty acids.

    PubMed Central

    Jäntti, J; Nikkari, T; Solakivi, T; Vapaatalo, H; Isomäki, H

    1989-01-01

    The serum concentration of lipids and composition of fatty acids after overnight fasting were studied in 18 patients with rheumatoid arthritis treated for 12 weeks with either 20 ml of evening primrose oil containing 9% of gamma-linolenic acid or olive oil. The serum concentrations of oleic acid, eicosapentaenoic acid, and apolipoprotein B decreased and those of linoleic acid, gamma-linolenic acid, dihomo-gamma-linolenic acid, and arachidonic acid increased during treatment with evening primrose oil. During olive oil treatment the serum concentration of eicosapentaenoic acid decreased and those of high density lipoprotein-cholesterol and apolipoprotein A-I increased slightly. The decrease in serum eicosapentaenoic acid and the increase in arachidonic acid concentrations induced by evening primrose oil may not be favourable effects in patients with rheumatoid arthritis in the light of the roles of these fatty acids as precursors of eicosanoids. PMID:2649022

  3. Serum hyaluronic acid levels in patients with ankylosing spondylitis.

    PubMed

    Duruöz, Mehmet Tuncay; Turan, Yasemin; Cerrahoglu, Lale; Isbilen, Banu

    2008-05-01

    Our aim in this study was to investigate serum hyaluronic acid (HA) levels and the relationship between clinical parameters in ankylosing spondylitis (AS). Approximately 30 patients with AS and 30 healthy individuals were recruited in this study consecutively. Cross-sectional study was planned, and demographic, clinical, functional, radiological, and laboratory data of patients were evaluated. Disease activity, functional status, and quality of life were assessed, respectively, with Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), and Short-Form 36 (SF-36). Mander Enthesis Index (MEI) was used for evaluation of enthesis involvement. We examined serum concentrations of HA (ng/ml) in patients with AS and controls. The mean ages of patients and control group were 38.3 (SD=10.8) and 42.7 (SD=10.6) years, respectively. The mean of serum HA levels in AS patients was 40.4 (SD=34.8) ng/ml and in controls was 24.9 (SD=20.2). There was significant difference of HA levels between two groups (p=0.04). Furthermore, there was a significant correlation between HA level and distance of hand-floor (r=0.444, p=0.014), modified lumbar Schober's (r= -0.413, p=0.023), distance of chin to chest (r=0.436, p=0.016), right sacroiliit grade (r=0.601, p<0.001), left sacroiliit grade (r=0.610, p<0.001), C reactive protein level (r=0.404, p=0.027), albumin (r= -0.464, p=0.010), C3 (p=0.449, p=0.013), and IgA levels (r=0.369, p=0.045). However, there was no significant correlation between HA levels with MEI, BASFI, BASDAI, and SF-36 (p >or= 0.05). Serum HA level was significantly higher in AS patients than controls. However, there was no significant correlation between serum HA level and disease-specific measures as BASFI and BASDAI; it had significant relation with spinal mobility limitation, sacroiliitis, and laboratory parameters related with acute inflammation. The serum HA level may be a potential biomarker of axial

  4. Inverse Association of Serum Docosahexaenoic Acid With Newly Diagnosed Hypertension

    PubMed Central

    Yang, Bo; Ding, Fang; Wang, Feng-Lei; Yu, Wei; Li, Duo

    2016-01-01

    Abstract Observational studies on circulating fatty acid (FA) and primary prevention of hypertension have yielded inconsistent results, and the association among the Chinese population is not fully clear. The aim of the study was to discern important FAs that can discriminate hypertensive patients from normotensive persons, and investigate associations between the important FAs and risk of hypertension. We conducted a case-control study nested within a community-based cohort of 2447 Chinese participants aged 35 to 79 years who completed a baseline assessment between October 2012 and April 2013. In all, 480 patients with newly diagnosed hypertension were identified at baseline and 480 normotensive individuals were randomly selected as matched normotensive controls. Controls were individually matched to cases by age (±2 y), sex, and recruitment center, with a 1:1 case-to-control ratio. Serum FA profile was compared between cases and controls by orthogonal partial least squares-discriminant analyses. Odds ratio (OR) with 95% confidence interval (CI) for newly diagnosed hypertension was estimated by a conditional logistical analysis. After adjustment for body mass index, education, profession, family history of hypertension, salt intake, heart rate, blood lipids, and fasting glucose levels, serum FA profile in hypertensive patients was typically characterized by higher 16:0 and 16:1n-7, and lower 18:2n-6 and 22:6n-3, compared with normotensive controls. Docosahexaenoic acid (22:6n-3) and palmitoleic acid (16:1n-7) were identified as the important FA contributing most to the intergroup separations. When comparing the highest and lowest quartile of FA composition, newly diagnosed hypertension was negatively associated with 22:6n-3 (OR 0.65; 95% CI, 0.45–0.93; P for trend = 0.02), but positively associated with 16:1n-7 (OR 2.14; 95% CI, 1.46–3.12; P for trend < 0.001). The associations remained pronounced after multiple adjustments and in further stratified

  5. Characterization of hydroxycinnamic acid derivatives binding to bovine serum albumin.

    PubMed

    Jin, Xiao-Ling; Wei, Xia; Qi, Feng-Ming; Yu, Sha-Sha; Zhou, Bo; Bai, Shi

    2012-05-07

    Hydroxycinnamic acid derivatives (HCAs) are a group of naturally occurring polyphenolic compounds which possess various pharmacological activities. In this work, the interactions of bovine serum albumin (BSA) with six HCA derivatives, including chlorogenic acid (CHA), caffeic acid (CFA), m-coumaric acid (m-CA), p-coumaric acid (p-CA), ferulic acid (FA) and sinapic acid (SA) have been investigated by NMR spectroscopic techniques in combination with fluorescence and molecular modeling methods. Competitive STD NMR experiments using warfarin sodium and L-tryptophan as site-selective probes indicated that HCAs bind to site I in the subdomain IIA of BSA. From the analysis of the STD NMR-derived binding epitopes and molecular docking models, it was deduced that CHA, CFA, m-CA and p-CA show similar binding modes and orientation, in which the phenyl ring is in close contact with protein surface, whereas carboxyl group points out of the protein. However, FA and SA showed slightly different binding modes, due to the steric hindrance of methoxy-substituents on the phenyl ring. Relaxation experiments provided detailed information about the relationship between the affinity and structure of HCAs. The binding affinity was the strongest for CHA and ranked in the order CHA > CFA > m-CA ≥ p-CA > FA > SA, which agreed well with the results from fluorescence experiments. Based on our experimental results, we also conclude that HCAs bind to BSA mainly by hydrophobic interaction and hydrogen bonding. This study therefore provides valuable information for elucidating the mechanisms of BSA-HCAs interaction.

  6. Conjugated linoleic acid and calcium co-supplementation improves bone health in ovariectomised mice.

    PubMed

    Park, Yooheon; Kim, Jonggun; Scrimgeour, Angus G; Condlin, Michelle L; Kim, Daeyoung; Park, Yeonhwa

    2013-09-01

    Osteoporosis is a significant health concern for the elderly; conjugated linoleic acid (CLA) has been shown to improve overall bone mass when calcium is included as a co-supplement. However, potential effects of CLA and calcium on bone mass during a period of bone loss have not been reported. The purpose of this study was to determine how dietary calcium modulates the effects of conjugated linoleic acid (CLA) in preventing bone loss, using an ovariectomised mouse model. CLA supplementation significantly prevented ovariectomy-associated weight and fat mass gain, compared to non-supplemented controls. CLA significantly increased bone markers without major changes in bone mineral composition in the femur compared to respective controls. CLA treatment increased serum parathyroid hormone (PTH) significantly (p=0.0172), while serum 1,25-dihydroxyvitamin D3 concentration was not changed by CLA. Meanwhile, CLA significantly reduced femur tartrate resistant acid phosphatase (TRAP) activity, suggesting potential reduction of osteoclastogenesis. The data suggest that CLA, along with dietary calcium, has great potential to be used to prevent bone loss and weight gain associated with menopause. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Conjugated linoleic acid and calcium co-supplementation improves bone health in ovariectomised mice

    PubMed Central

    Park, Yooheon; Kim, Jonggun; Scrimgeour, Angus G.; Condlin, Michelle L.; Kim, Daeyoung; Park, Yeonhwa

    2013-01-01

    Osteoporosis is a significant health concern for the elderly; conjugated linoleic acid (CLA) has been shown to improve overall bone mass when calcium is included as a co-supplement. However, potential effects of CLA and calcium on bone mass during a period of bone loss have not been reported. The purpose of this study was to determine how dietary calcium modulates the effects of conjugated linoleic acid (CLA) in preventing bone loss, using an ovariectomised mouse model. CLA supplementation significantly prevented ovariectomy-associated weight and fat mass gain, compared to non-supplemented controls. CLA significantly increased bone markers without major changes in bone mineral composition in the femur compared to respective controls. CLA treatment increased serum parathyroid hormone (PTH) significantly (p = 0.0172), while serum 1,25-dihydroxyvitamin D3 concentration was not changed by CLA. Meanwhile, CLA significantly reduced femur tartrate resistant acid phosphatase (TRAP) activity, suggesting potential reduction of osteoclastogenesis. The data suggest that CLA, along with dietary calcium, has great potential to be used to prevent bone loss and weight gain associated with menopause. PMID:23578644

  8. Association between Serum Unmetabolized Folic Acid Concentrations and Folic Acid from Fortified Foods.

    PubMed

    Palchetti, Cecília Zanin; Paniz, Clóvis; de Carli, Eduardo; Marchioni, Dirce M; Colli, Célia; Steluti, Josiane; Pfeiffer, Christine M; Fazili, Zia; Guerra-Shinohara, Elvira Maria

    2017-01-01

    To investigate the association between serum unmetabolized folic acid (UMFA) concentrations and folic acid from fortified foods and nutrients known as dietary methyl-group donors (folate, methionine, choline, betaine and vitamins B2, B6 and B12) in participants exposed to mandatory fortification of wheat and maize flours with folic acid. Cross-sectional study carried out with 144 healthy Brazilian participants, both sexes, supplement nonusers. Serum folate, UMFA, vitamin B12 and total plasma homocysteine (tHcy) were biochemically measured. Dietary intake was assessed by 2 non-consecutive 24-hour dietary recalls (24-HRs) and deattenuated energy-adjusted nutrient data were used for statistical analysis. Ninety eight (68.1%) participants were women. Median (interquartile range) age was 35.5 (28.0-52.0) years. Elevated serum folate concentrations (>45 nmol/L) were found in 17 (11.8%), while folate deficiency (<7 nmol/L) in 10 (6.9%) participants. No one had vitamin B12 deficiency (<148 pmol/L). An elevated serum UMFA concentration was defined as > 1 nmol/L (90th percentile). UMFA concentrations were positively correlated with folic acid intake and negatively correlated to choline, methionine and vitamin B6 intakes. Participants in the lowest quartile of UMFA concentrations had lower dietary intake of total folate (DFEs) and folic acid, and higher dietary intake of methionine, choline and vitamin B6 than participants in the highest quartile of UMFA. Folic acid intake (OR [95% CI] = 1.02 [1.01-1.04)] and being a male (OR [95% CI] = 0.40 [0.19-0.87) were associated with increased and reduced odds for UMFA concentrations > 0.55 nmol/L (median values), respectively. UMFA concentrations were directly influenced by folic acid intake from fortified foods in a healthy convenience sample of adult Brazilians exposed to mandatory flour fortification with folic acid.

  9. Association of Renal Manifestations with Serum Uric Acid in Korean Adults with Normal Uric Acid Levels

    PubMed Central

    Jung, Dong-Hyuk; Lee, Yong-Jae; Lee, Hye-Ree; Lee, Jung-Hyun

    2010-01-01

    Several studies have reported that hyperuricemia is associated with the development of hypertension and cardiovascular disease. Increasing evidences also suggest that hyperuricemia may have a pathogenic role in the progression of renal disease. Paradoxically, uric acid is also widely accepted to have antioxidant activity in experimental studies. We aimed to investigate the association between glomerular filtration rate (GFR) and uric acid in healthy individuals with a normal serum level of uric acid. We examined renal function determined by GFR and uric acid in 3,376 subjects (1,896 men; 1,480 women; aged 20-80 yr) who underwent medical examinations at Gangnam Severance Hospital from November 2006 to June 2007. Determinants for renal function and uric acid levels were also investigated. In both men and women, GFR was negatively correlated with systolic and diastolic blood pressures, fasting plasma glucose, total cholesterol, uric acid, log transformed C reactive protein, and log transformed triglycerides. In multivariate regression analysis, total uric acid was found to be an independent factor associated with estimated GFR in both men and women. This result suggests that uric acid appears to contribute to renal impairment in subjects with normal serum level of uric acid. PMID:21165292

  10. Association Between Serum Levels of Uric Acid and Blood Pressure Tracking in Childhood.

    PubMed

    Park, Bohyun; Lee, Hye Ah; Lee, Sung Hee; Park, Bo Mi; Park, Eun Ae; Kim, Hae Soon; Cho, Su Jin; Park, Hyesook

    2017-07-01

    Recent studies suggest that high levels of serum uric acid of very early life are a result of the in-utero environment and may lead to elevated blood pressure (BP) in adulthood. However, serum uric acid levels can change throughout life. We investigated the effect of serum uric acid levels in childhood on the BP tracking and analysed BP according to changes in serum uric acid levels in early life. A total of 449 children from the Ewha Birth and Growth Cohort study underwent at least 2 follow-up examinations. Data were collected across 3 check-up cycles. Serum uric acid levels, BP, and anthropometric characteristics were assessed at 3, 5, and 7 years of age. Children with a serum uric acid level higher than the median values had significantly increased systolic BP (SBP) and diastolic BP at 3 years of age. Baseline serum uric acid levels measured at 3 years of age, significantly affected subsequent BP in the sex and body mass index adjusted longitudinal data analysis (P < 0.05). Considering the changing pattern of serum uric acid over time, subjects with high uric acid levels at both 3 and 5 years of age had the highest SBP at 7 years of age. These findings suggest the importance of maintaining an adequate level of serum uric acids from the early life. Appropriate monitoring and intervention of uric acid levels in a high-risk group can reduce the risk of a future increased BP.

  11. Serum Heme Oxygenase-1 and BMP-7 Are Potential Biomarkers for Bone Metabolism in Patients with Rheumatoid Arthritis and Ankylosing Spondylitis

    PubMed Central

    Yuan, Tong-ling; Chen, Jin; Tong, Yan-li; Zhang, Yan; Liu, Yuan-yuan; Wei, James Cheng-Chung; Liu, Yi; Herrmann, Martin

    2016-01-01

    Backgrounds. Heme oxygenase-1 (HO-1) has been reported to play a regulatory role in osteoclastogenesis. Bone morphogenetic protein (BMP) pathways induce osteoblastic differentiation and bone remodeling. Aims. To identify serum levels of HO-1, BMP-7, and Runt related-transcription factor 2 (Runx2) in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS) and to investigate the relationships between HO-1, BMP-7, Runx2, and other common biomarkers for bone metabolism. Results. Serum levels of HO-1 and BMP-7 were revealed to be significantly higher in patients with RA or AS than in healthy controls (p < 0.01). In RA group, HO-1 was positively correlated with BMP-7, Runx2, and tartrate-resistant acid phosphatase-5b (TRAP-5b) (p < 0.05, resp.), BMP-7 was positively correlated with Runx2 and TRAP-5b (p < 0.05, resp.), and Runx2 was negatively correlated with N-terminal midfragment of osteocalcin (NMID) (p < 0.05). In AS group, we observed identical correlation between HO-1 and BMP-7, but opposite correlations between BMP-7 and TRAP-5b and between Runx2 and NMID, when comparing with the RA cohort. Conclusion. Our findings suggest that HO-1 and BMP-7 are potential biomarkers for bone metabolism in patients with RA and AS. The different correlations between the bone markers point to distinct differences in bone remodeling pathways in the two types of arthritis. PMID:27314037

  12. The nature of human serum insulin-like activity (ILA): characterization of ILA in serum and serum fractions obtained by acid-ethanol extraction and adsorption chromatography

    PubMed Central

    Poffenbarger, Philip L.; Ensinck, John W.; Hepp, Dieter K.; Williams, Robert H.

    1968-01-01

    Studies were undertaken in an attempt to clarify the apparent heterogeneous nature of human serum insulin-like activity. Methods of preparative zone electrophoresis on Pevikon, acid-ethanol extraction of trichloroacetic acid serum protein precipitates, adsorption chromatography on DEAE-cellulose and Dowex 50, gel filtration chromatography, and insulin antiserum immunoreactivity were used. The results establish the presence of a substance in serum with in vitro biological properties similar to insuln but with different physicochemical properties. The major portion of serum ILA measured by bioassay techniques can be attributed to the effects of this substance. Whereas the in vitro biological effects of this substance on muscle and adipose cells were similar to those of crystalline insulin, the substance is distinguished from insulin by: (1) the failure of insulin antiserum to inhibit its in vitro biological effect; (2) a slower electrophoretic mobility (in the gamma-beta globulin zone); and (3) a larger molecular weight, between 40,000 and 50,000 in these studies. It is similar to insulin since both are soluble in acid-ethanol. The results further indicate that previously described insulin-like activity in gamma-beta globulin preparations, the major portion of total serum insulin activity described in acid-ethanol extracts of serum, “bound” insulin, “atypical” insulin, and antibody nonsuppressible insulin-like activity bioassayed in diluted serum are all one and the same substance. PMID:4170389

  13. Equine endurance exercise alters serum branched-chain amino acid and alanine concentrations.

    PubMed

    Trottier, N L; Nielsen, B D; Lang, K J; Ku, P K; Schott, H C

    2002-09-01

    Six 2-year-old Arabian horses were used to determine whether 60 km prolonged endurance exercise (approximately 4 h) alters amino acid concentrations in serum and muscle, and the time required for serum amino acid concentrations to return to basal resting values. Blood and muscle samples were collected throughout exercise and during a 3 day recovery period. Isoleucine concentration in muscle tended to increase and leucine and valine did not change due to exercise. Serum alanine concentrations did not increase immediately after exercise, but increased at 24, 48 and 72 h postexercise. Serum isoleucine, leucine, and valine concentrations decreased after exercise and time required to reach pre-exercising concentrations was 48 h. In conclusion, endurance exercise in the horse decreases serum isoleucine, leucine, and valine concentrations, and increases serum alanine concentration. The decrease in serum branched-chain amino acid concentrations did not correspond to a measurable increase in total muscle branched-chain amino acid concentrations.

  14. Increased Serum Level of Cyclopropaneoctanoic Acid 2-Hexyl in Patients with Hypertriglyceridemia-Related Disorders.

    PubMed

    Mika, Adriana; Stepnowski, Piotr; Chmielewski, Michal; Malgorzewicz, Sylwia; Kaska, Lukasz; Proczko, Monika; Ratnicki-Sklucki, Krzysztof; Sledzinski, Maciej; Sledzinski, Tomasz

    2016-07-01

    We recently reported the presence of various cyclopropane fatty acids-among them, cyclopropaneoctanoic acid 2-hexyl-in the adipose tissue of obese women. The aim of this study was to verify whether the presence of cyclopropaneoctanoic acid 2-hexyl in human serum was associated with obesity or chronic kidney disease (both being related to dyslipidemia), and to find potential associations between the serum level of this compound and specific markers of the these conditions. The serum concentration of cyclopropaneoctanoic acid 2-hexyl was determined by gas chromatography-mass spectrometry (GC-MS) in non-obese controls, obese patients, obese patients after a 3-month low-calorie diet, and individuals with chronic kidney disease. Obese patients and those with chronic kidney disease presented with higher serum levels of cyclopropaneoctanoic acid 2-hexyl than controls. Switching obese individuals to a low-calorie (low-lipid) diet resulted in a reduction in this fatty acid concentration to the level observed in controls. Cyclopropaneoctanoic acid 2-hexyl was also found in foods derived from animal fat. Serum concentrations of triacylglycerols in the analyzed groups followed a pattern similar to that for serum cyclopropaneoctanoic acid 2-hexyl, and these variables were positively correlated with each other among the studied groups. Patients with hypertriglyceridemia-related conditions presented with elevated serum levels of cyclopropaneoctanoic acid 2-hexyl. Our findings suggest that its high serum level is related to high serum triacylglycerol concentrations rather than to body mass or BMI.

  15. Serum uric acid levels during leprosy reaction episodes

    PubMed Central

    Alves-Junior, Eduardo R.; Arruda, Talita A.; Lopes, Jose C.; Fontes, Cor J.F.

    2016-01-01

    Background. Leprosy reactions are acute inflammatory episodes that occur mainly in the multibacillary forms of the disease. The reactions are classified as type 1 (reverse reaction) or type 2 (erythema nodosum leprosum). Leprosy-associated oxidative stress has been widely demonstrated. Several recent studies have shown uric acid (UA) to have antioxidative effects under pathologic conditions. The objective of this study was to assess serum levels of UA in patients with leprosy reactions, with the aim of monitoring their levels before and after treatment, compared with levels in leprosy patients without reactions. Methods. The study included patients aged 18–69 years assisted at a leprosy treatment reference center in the Central Region of Brazil. Patients who were pregnant; were using immunosuppressant drugs or immunobiologicals; or had an autoimmune disease, human immunodeficiency virus infection, acquired immune deficiency syndrome, or tuberculosis were excluded. Upon recruitment, all individuals were clinically assessed for skin lesions and neural or systemic impairment. Some patients had already completed treatment for leprosy, while others were still undergoing treatment or had initiated treatment after being admitted. The treatment of the reactional episode was started only after the initial evaluation. Laboratory assessments were performed upon admission (baseline) and at approximately 30 and 60 days (time points 1 and 2, respectively). Results. A total of 123 leprosy patients were recruited between June 2012 and June 2015; among them, 56, 42, and 25 presented with type 1, type 2, and no reactions, respectively. Serum UA levels were significantly reduced in patients with type 2 leprosy reactions compared with patients in the control group and remained lower in the two subsequent assessments, after initiation of anti-reaction treatments, with similar values to those recorded before the treatment. Discussion. The decreased serum UA levels in patients with

  16. Serum fatty acid binding protein 4, free fatty acids and metabolic risk markers

    PubMed Central

    Karakas, Sidika E.; Almario, Rogelio U.; Kim, Kyoungmi

    2009-01-01

    Fatty acid binding protein (FABP) 4 chaperones free fatty acids (FFA) in the adipocytes during lipolysis. Serum FFA relates to Metabolic Syndrome (METS) and serum FABP4 is emerging as a novel risk marker. In 36 overweight/obese women, serum FABP4 and FFA were measured hourly during 5-hour oral glucose tolerance test (OGTT). Insulin resistance was determined using frequently sampled intravenous GTT (FS-IVGTT). Serum lipids and inflammation markers were measured at fasting. During OGTT, serum FABP4 decreased by 40%, reaching its nadir at 3h (from 45.3±3.1 to 31.9±1.6 ng/mL) and stayed below the baseline at 5 h (35.9±2.2 ng/mL) (p < 0.0001 for both, compared to the baseline). Serum FFA decreased by 10 fold, reaching a nadir at 2h (from 0.611±0.033 to 0.067±0.004 mmol/L), then rebounded to 0.816±0.035 mmol/ L at 5h (p < 0.001 for both, compared to baseline). Both fasting-FABP4 and nadir-FABP4 correlated with obesity. Nadir-FABP4 correlated also with insulin resistance parameters from FS-IVGTT and with inflammation. Nadir-FFA, but not fasting-FFA, correlated with the METS-parameters. In conclusion, fasting-FABP4 related to metabolic risk markers more strongly than fasting-FFA. Nadir-FABP4 and nadir-FFA measured after glucose loading may provide better risk assessment than the fasting values. PMID:19394980

  17. Elevation of serum levels of beta-aminoisobutyric acid in uremic patients and the toxicity of the amino acid.

    PubMed

    Gejyo, F; Kinoshita, Y; Ikenaka, T

    1977-12-01

    A reliable method for the determination of beta-aminoisobutyric acid in serum was developed utilizing an automated amino acid analyzer. The serum concentrations of beta-aminoisobutyric acid were determined in 20 normal subjects and in 71 uremic patients. The mean serum level of beta-aminoisobutyric acid was markedly increased in the uremic patients to 0.856 +/- 0.910 (mean +/- SD) mg/100 ml as compared with a normal value of 0.026 +/- 0.027 mg/100 ml. The distribution of serum beta-aminoisobutyric acid level in uremic patients was wide-spread, and there was no correlation between the serum levels of the amino acid and those of urea nitrogen, creatinine and uric acid. The toxicity of beta-aminoisobutyric acid on mice with acute renal failure induced by uranyl acetate was investigated and compared with that of alpha-amino-n-butyric acid and gamma-amino-n-butyric acid. All mice given more than 4 g/kg body wt of beta-aminoisobutyric acid showed twitching and cramps, and some of them died. However, the control mice given an equivalent dose of alpha-amino-n-butyric acid or gamma-amino-n-butyric acid showed no change. These results suggest that beta-aminoisobutyric acid might be a factor influencing the development and progression of uremic toxemia.

  18. Serum Fatty Acids Are Correlated with Inflammatory Cytokines in Ulcerative Colitis

    PubMed Central

    Wiese, Dawn M.; Horst, Sara N.; Brown, Caroline T.; Allaman, Margaret M.; Hodges, Mallary E.; Slaughter, James C.; Druce, Jennifer P.; Beaulieu, Dawn B.; Schwartz, David A.; Wilson, Keith T.; Coburn, Lori A.

    2016-01-01

    Background and Aims Ulcerative colitis (UC) is associated with increased dietary intake of fat and n-6 polyunsaturated fatty acids (PUFA). Modification of fat metabolism may alter inflammation and disease severity. Our aim was to assess differences in dietary and serum fatty acid levels between control and UC subjects and associations with disease activity and inflammatory cytokines. Methods Dietary histories, serum, and colonic tissue samples were prospectively collected from 137 UC subjects and 38 controls. Both histologic injury and the Mayo Disease Activity Index were assessed. Serum and tissue cytokines were measured by Luminex assay. Serum fatty acids were obtained by gas chromatography. Results UC subjects had increased total fat and oleic acid (OA) intake, but decreased arachidonic acid (AA) intake vs controls. In serum, there was less percent saturated fatty acid (SFA) and AA, with higher monounsaturated fatty acids (MUFA), linoleic acid, OA, eicosapentaenoic acid (EPA), and docosapentaenoic acid (DPA) in UC. Tissue cytokine levels were directly correlated with SFA and inversely correlated with PUFA, EPA, and DPA in UC subjects, but not controls. 5-aminosalicylic acid therapy blunted these associations. Conclusions In summary, we found differences in serum fatty acids in UC subjects that correlated with pro-inflammatory tissue cytokines. We propose that fatty acids may affect cytokine production and thus be immunomodulatory in UC. PMID:27227540

  19. Serum Fatty Acids Are Correlated with Inflammatory Cytokines in Ulcerative Colitis.

    PubMed

    Wiese, Dawn M; Horst, Sara N; Brown, Caroline T; Allaman, Margaret M; Hodges, Mallary E; Slaughter, James C; Druce, Jennifer P; Beaulieu, Dawn B; Schwartz, David A; Wilson, Keith T; Coburn, Lori A

    2016-01-01

    Ulcerative colitis (UC) is associated with increased dietary intake of fat and n-6 polyunsaturated fatty acids (PUFA). Modification of fat metabolism may alter inflammation and disease severity. Our aim was to assess differences in dietary and serum fatty acid levels between control and UC subjects and associations with disease activity and inflammatory cytokines. Dietary histories, serum, and colonic tissue samples were prospectively collected from 137 UC subjects and 38 controls. Both histologic injury and the Mayo Disease Activity Index were assessed. Serum and tissue cytokines were measured by Luminex assay. Serum fatty acids were obtained by gas chromatography. UC subjects had increased total fat and oleic acid (OA) intake, but decreased arachidonic acid (AA) intake vs controls. In serum, there was less percent saturated fatty acid (SFA) and AA, with higher monounsaturated fatty acids (MUFA), linoleic acid, OA, eicosapentaenoic acid (EPA), and docosapentaenoic acid (DPA) in UC. Tissue cytokine levels were directly correlated with SFA and inversely correlated with PUFA, EPA, and DPA in UC subjects, but not controls. 5-aminosalicylic acid therapy blunted these associations. In summary, we found differences in serum fatty acids in UC subjects that correlated with pro-inflammatory tissue cytokines. We propose that fatty acids may affect cytokine production and thus be immunomodulatory in UC.

  20. Lower serum uric acid level predicts mortality in dialysis patients

    PubMed Central

    Bae, Eunjin; Cho, Hyun-Jeong; Shin, Nara; Kim, Sun Moon; Yang, Seung Hee; Kim, Dong Ki; Kim, Yong-Lim; Kang, Shin-Wook; Yang, Chul Woo; Kim, Nam Ho; Kim, Yon Su; Lee, Hajeong

    2016-01-01

    Abstract We evaluated the impact of serum uric acid (SUA) on mortality in patients with chronic dialysis. A total of 4132 adult patients on dialysis were enrolled prospectively between August 2008 and September 2014. Among them, we included 1738 patients who maintained dialysis for at least 3 months and had available SUA in the database. We categorized the time averaged-SUA (TA-SUA) into 5 groups: <5.5, 5.5–6.4, 6.5–7.4, 7.5–8.4, and ≥8.5 mg/dL. Cox regression analysis was used to calculate the hazard ratio (HR) of all-cause mortality according to SUA group. The mean TA-SUA level was slightly higher in men than in women. Patients with lower TA-SUA level tended to have lower body mass index (BMI), phosphorus, serum albumin level, higher proportion of diabetes mellitus (DM), and higher proportion of malnourishment on the subjective global assessment (SGA). During a median follow-up of 43.9 months, 206 patients died. Patients with the highest SUA had a similar risk to the middle 3 TA-SUA groups, but the lowest TA-SUA group had a significantly elevated HR for mortality. The lowest TA-SUA group was significantly associated with increased all-cause mortality (adjusted HR, 1.720; 95% confidence interval, 1.007–2.937; P = 0.047) even after adjusting for demographic, comorbid, nutritional covariables, and medication use that could affect SUA levels. This association was prominent in patients with well nourishment on the SGA, a preserved serum albumin level, a higher BMI, and concomitant DM although these parameters had no significant interaction in the TA-SUA-mortality relationship except DM. In conclusion, a lower TA-SUA level <5.5 mg/dL predicted all-cause mortality in patients with chronic dialysis. PMID:27310949

  1. Serum sialic acid and glycoprotein levels in some Libyan cancer patients.

    PubMed

    Balo, N N; Ishaq, M

    1991-01-01

    Sialic acid is a common conjugate of some serum glycoproteins and glycolipids. Elevated levels of serum sialic acid and alterations in serum glycoproteins have been observed in certain types of cancer. In this study sialic acid concentration in the sera of patients with various types of cancer was determined. In addition to this, serum glycoproteins were also analysed by electrophoretic method. Our results indicate that serum sialic acid levels are generally raised in all types of cancer studied. This increase was more pronounced in case of lung, bronchogenic, intestinal and breast cancer. Some alterations in the serum glycoprotein profiles were also observed, particularly in bronchogenic and gall bladder cancer where an additional band in the low molecular weight region was present and in lung, breast and lymphoma where a band in the middle molecular weight region was found missing when compared with normals.

  2. Serum uric acid and mortality in chronic kidney disease: A systematic review and meta-analysis.

    PubMed

    Xia, Xi; Luo, Qimei; Li, Bin; Lin, Zhenchuan; Yu, Xueqing; Huang, Fengxian

    2016-09-01

    Studies have shown inconsistent results about the association between serum uric acid levels and mortality in patients with chronic kidney disease (CKD). A systematic literature search in MEDLINE, Web of Science and bibliographies of retrieved articles was performed to identify studies investigating the association between serum uric acid and mortality in patients with CKD. Pooled hazard ratios (HR) and corresponding 95% confidence intervals (CIs) were calculated using random-effects models. A total of 24 studies with 25,453 patients with CKD were included. By meta-analysis, patients with the highest serum uric acid level were associated with a significantly higher risk for mortality (14 studies; HR, 1.52; 95% CI, 1.33-1.73) compared with patients with the lowest serum uric acid level. For dose-response analysis, a linear relationship (8 studies; Pfor non-linearity=0.14) between serum uric acid levels and risk of mortality was found. Overall, an increase of 1mg/dl in serum uric acid level was associated with an 8% increased risk of mortality (21 studies; HR, 1.08; 95% CI, 1.04-1.11). Elevated serum uric acid levels are significantly associated with risk of mortality in patients with CKD. Further randomized controlled trials should attempt to determine whether it improves survival to target serum uric acid in patients with CKD. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Short-term bisphosphonate treatment reduces serum 25(OH) vitamin D3 and alters values of parathyroid hormone, pentosidine, and bone metabolic markers

    PubMed Central

    Kamimura, Mikio; Uchiyama, Shigeharu; Nakamura, Yukio; Ikegami, Shota; Mukaiyama, Keijiro; Kato, Hiroyuki

    2017-01-01

    This study aimed to clarify the effects of short-term bisphosphonate (BP) administration in Japanese osteoporotic patients retrospectively. Daily minodronate (MIN) at 1 mg/day (MIN group) or weekly risedronate (RIS) at 17.5 mg/week (RIS group) was primarily prescribed for each patient. We analyzed the laboratory data of 35 cases (18 of MIN and 17 of RIS) before the start of treatment and at 4 months afterward. The changes in 25(OH)D3, whole parathyroid hormone (PTH), serum pentosidine, and the bone turnover markers urinary cross-linked N-telopeptide of type I collagen (NTX), serum tartrate-resistant acid phosphatase (TRACP)-5b, bone-specific alkaline phosphatase (BAP), and undercarboxylated osteocalcin were evaluated. Overall, serum 25(OH)D3 was significantly decreased from 21.8 to 18.4 ng/mL at 4 months, with a percent change of −14.7%. Whole PTH increased significantly from 23.4 to 30.0 pg/mL, with a percent change of 32.1%. Serum pentosidine rose from 0.0306 to 0.0337 μg/mL, with a percent change of 15.2%. In group comparisons, 25(OH)D3 and pentosidine showed comparable changes in both groups after 4 months of treatment, whereas whole PTH became significantly more increased in the MIN group. All bone turnover markers were significantly decreased at 4 months in both groups. Compared with the RIS group, the MIN group exhibited significantly larger value changes for urinary NTX, serum TRACP-5b, and BAP at the study end point. This study demonstrated that serum 25(OH)D3 became significantly decreased after only 4 months of BP treatment in Japanese osteoporotic patients and confirmed that MIN more strongly inhibited bone turnover as compared with RIS. PMID:28243105

  4. Evaluation of serum beta-carboxy-terminal cross-linking telopeptide of type I collagen as marker of bone resorption in chronic hemodialysis patients.

    PubMed

    Reichel, Helmut; Roth, Heinz-Jürgen; Schmidt-Gayk, Heinrich

    2004-01-01

    The carboxy-terminal cross-linking telopeptide of type I collagen (beta-CrossLaps, beta-CTX) is released into the circulation during degradation of type I collagen and serves as a marker of bone resorption. beta-CTX is known to undergo a diurnal rhythm in normal individuals and to accumulate in chronic renal failure. beta-CTX has a potential role in noninvasive diagnosis of renal bone disease. Serum beta-CTX was compared to parathyroid hormone (PTH) and other biochemical bone markers in 90 unselected hemodialysis patients. Mean beta-CTX was elevated above the normal range (1.72 +/- 0.93 microg/l); there were large individual variations. Serum beta-CTX was significantly correlated with various PTH assays (r >0.56) and with tartrate-resistant acid phosphatase 5b (TRACP 5b, r = 0.629), bone-specific alkaline phosphatase (r = 0.404) and osteocalcin (r = 0.534, all correlations p < 0.001). The correlation between beta-CTX and PTH was significantly higher than the correlation between TRACP 5b and PTH. Several factors which could confound interpretation of serum beta-CTX were assessed in further studies: (i) There was no recognizable influence of the time of blood sampling (morning dialysis shift versus afternoon dialysis shift) on serum beta-CTX. (ii) Serum beta-CTX was not significantly related to residual diuresis of patients. We found a high association between beta-CTX and other established markers of bone and calcium metabolism demonstrating the potential utility of beta-CTX as marker of bone resorption in renal bone disease. However, further studies employing bone histology are still warranted to exactly define the influence of glomerular retention on serum beta-CTX in end-stage renal disease. Copyright 2004 S. Karger AG, Basel.

  5. Synthetic nanoparticles of bovine serum albumin with entrapped salicylic acid

    PubMed Central

    Bronze-Uhle, ES; Costa, BC; Ximenes, VF; Lisboa-Filho, PN

    2017-01-01

    Bovine serum albumin (BSA) is highly water soluble and binds drugs or inorganic substances noncovalently for their effective delivery to various affected areas of the body. Due to the well-defined structure of the protein, containing charged amino acids, albumin nanoparticles (NPs) may allow electrostatic adsorption of negatively or positively charged molecules, such that substantial amounts of drug can be incorporated within the particle, due to different albumin-binding sites. During the synthesis procedure, pH changes significantly. This variation modifies the net charge on the surface of the protein, varying the size and behavior of NPs as the drug delivery system. In this study, the synthesis of BSA NPs, by a desolvation process, was studied with salicylic acid (SA) as the active agent. SA and salicylates are components of various plants and have been used for medication with anti-inflammatory, antibacterial, and antifungal properties. However, when administered orally to adults (usual dose provided by the manufacturer), there is 50% decomposition of salicylates. Thus, there has been a search for some time to develop new systems to improve the bioavailability of SA and salicylates in the human body. Taking this into account, during synthesis, the pH was varied (5.4, 7.4, and 9) to evaluate its influence on the size and release of SA of the formed NPs. The samples were analyzed using field-emission scanning electron microscopy, transmission electron microscopy, Fourier transform infrared, zeta potential, and dynamic light scattering. Through fluorescence, it was possible to analyze the release of SA in vitro in phosphate-buffered saline solution. The results of chemical morphology characterization and in vitro release studies indicated the potential use of these NPs as drug carriers in biological systems requiring a fast release of SA. PMID:28096662

  6. Serum uric acid is associated with coronary artery calcification.

    PubMed

    Grossman, Chagai; Shemesh, Joseph; Koren-Morag, Nira; Bornstein, Gil; Ben-Zvi, Ilan; Grossman, Ehud

    2014-06-01

    Uric acid (UA) is associated with atherosclerosis, and coronary artery calcium (CAC) is a marker of atherosclerosis. The authors studied the association between UA and CAC. A total of 663 asymptomatic patients (564 men; mean age, 55±7 years) were evaluated for the presence of CAC. The study population was divided into three tertiles according to their UA levels, and the prevalence of CAC was compared between the tertiles. CAC was detected in 349 (53%) patients. Levels of UA were significantly higher in those with CAC than in those without CAC (5.6+1.2 vs 5.3+1.3; P=.003). The odds ratio for the presence of CAC in the highest vs lowest UA tertile was 1.72 (95% confidence interval, 1.17-2.51). The highest UA tertile remained associated with the presence of CAC after adjustment for known cardiovascular risk factors. The results show that high serum UA levels are associated with the presence of CAC.

  7. Interaction of perfluorooctanoic acid with human serum albumin

    PubMed Central

    Wu, Ling-Ling; Gao, Hong-Wen; Gao, Nai-Yun; Chen, Fang-Fang; Chen, Ling

    2009-01-01

    Background Recently, perfluorooctanoic acid (PFOA) has become a significant issue in many aspects of environmental ecology, toxicology, pathology and life sciences because it may have serious effects on the endocrine, immune and nervous systems and can lead to embryonic deformities and other diseases. Human serum albumin (HSA) is the major protein component of blood plasma and is called a multifunctional plasma carrier protein because of its ability to bind an unusually broad spectrum of ligands. Results The interaction of PFOA with HSA was investigated in the normal physiological condition by equilibrium dialysis, fluorospectrometry, isothermal titration calorimetry (ITC) and circular dichroism (CD). The non-covalent interaction is resulted from hydrogen bond, van der Waals force and hydrophobic stack. PFOA binding to HSA accorded with two-step binding model with the saturation binding numbers of PFOA, only 1 in the hydrophobic intracavity of HSA and 12 on the exposed outer surface. The interaction of PFOA with HSA is spontaneous and results in change of HSA conformation. The possible binding sites were speculated. Conclusion The present work suggested a characterization method for the intermolecular weak interaction. It is potentially useful for elucidating the toxigenicity of perfluorochemicals when combined with biomolecular function effect, transmembrane transport, toxicological testing and the other experiments. PMID:19442292

  8. Does high serum uric acid level cause aspirin resistance?

    PubMed

    Yildiz, Bekir S; Ozkan, Emel; Esin, Fatma; Alihanoglu, Yusuf I; Ozkan, Hayrettin; Bilgin, Murat; Kilic, Ismail D; Ergin, Ahmet; Kaftan, Havane A; Evrengul, Harun

    2016-06-01

    In patients with coronary artery disease (CAD), though aspirin inhibits platelet activation and reduces atherothrombotic complications, it does not always sufficiently inhibit platelet function, thereby causing a clinical situation known as aspirin resistance. As hyperuricemia activates platelet turnover, aspirin resistance may be specifically induced by increased serum uric acid (SUA) levels. In this study, we thus investigated the association between SUA level and aspirin resistance in patients with CAD. We analyzed 245 consecutive patients with stable angina pectoris (SAP) who in coronary angiography showed more than 50% occlusion in a major coronary artery. According to aspirin resistance, two groups were formed: the aspirin resistance group (Group 1) and the aspirin-sensitive group (Group 2). Compared with those of Group 2, patients with aspirin resistance exhibited significantly higher white blood cell counts, neutrophil counts, neutrophil-to-lymphocyte ratios, SUA levels, high-sensitivity C-reactive protein levels, and fasting blood glucose levels. After multivariate analysis, a high level of SUA emerged as an independent predictor of aspirin resistance. The receiver-operating characteristic analysis provided a cutoff value of 6.45 mg/dl for SUA to predict aspirin resistance with 79% sensitivity and 65% specificity. Hyperuricemia may cause aspirin resistance in patients with CAD and high SUA levels may indicate aspirin-resistant patients. Such levels should thus recommend avoiding heart attack and stroke by adjusting aspirin dosage.

  9. Acute effects of plyometric jumping and intermittent running on serum bone markers in young males.

    PubMed

    Lin, Che-Fu; Huang, Tsang-hai; Tu, Kuo-Cheng; Lin, Linda L; Tu, Yi-Hsuan; Yang, Rong-Sen

    2012-04-01

    The purpose of this study was to investigate whether different modes of single-bout exercise would cause different responses in short-term bone metabolism. 24 untrained male college students (19.1 ± 0.1 years old) were recruited and randomly assigned to three groups: (1) a single-bout plyometric exercise group (the PL group, n = 8), (2) a 200-meter × 10 intermittent running group (the IR group, n = 8) and (3) a sedentary control group, which followed the same time schedule of experimentation without performing any exercise (the CON group, n = 8). Serial blood samples were collected before (baseline) and 5 min, 15 min, 1 h, 3 h, 6 h, 24 h, 48 h, and 72 h after exercise trials. Within 15 min of exercise, the PL and IR groups showed significantly higher serum phosphorus than did the control group (P < 0.05). Osteocalcin levels were significantly higher in the PL group at 5 min and 1 h after exercise (P < 0.05), while serum tartrate-resistant acid phosphatase (TRAP) showed no differences among groups. Exercises with different mechanical impact levels responded differently in serum bone formation markers as shown by osteocalcin. Because the increase in osteocalcin in the PL group was revealed shortly after the exercise bout, the changes might due to an exercise-induced mechanical impact rather than bone cellular activities.

  10. Effect of alpha-linolenic acid-rich Camelina sativa oil on serum fatty acid composition and serum lipids in hypercholesterolemic subjects.

    PubMed

    Karvonen, Henna M; Aro, Antti; Tapola, Niina S; Salminen, Irma; Uusitupa, Matti I j; Sarkkinen, Essi S

    2002-10-01

    Camelina sativa-derived oil (camelina oil) is a good source of alpha-linolenic acid. The proportion of alpha-linolenic acid in serum fatty acids is associated with the risk of cardiovascular diseases. We studied the effects of camelina oil on serum lipids and on the fatty acid composition of total lipids in comparison to rapeseed and olive oils in a parallel, double-blind setting. Sixty-eight hypercholesterolemic subjects aged 28 to 65 years were randomly assigned after a 2-week pretrial period to 1 of 3 oil groups: camelina oil, olive oil, and rapeseed oil. Subjects consumed daily 30 g (actual intake, approximately 33 mL) of test oils for 6 weeks. In the camelina group, the proportion of alpha-linolenic acid in fatty acids of serum lipids was significantly higher (P <.001) compared to the 2 other oil groups at the end of the study: 2.5 times higher compared to the rapeseed oil group and 4 times higher compared to the olive oil group. Respectively the proportions of 2 metabolites of alpha-linolenic acid (eicosapentaenoic and docosapentaenoic acids) increased and differed significantly in the camelina group from those in other groups. During the intervention, the serum low-density lipoprotein (LDL) cholesterol concentration decreased significantly by 12.2% in the camelina oil group, 5.4% in the rapeseed oil group, and 7.7% in the olive oil group. In conclusion, camelina oil significantly elevated the proportions of alpha-linolenic acid and its metabolites in serum of mildly or moderately hypercholesterolemic subjects. Camelina oil's serum cholesterol-lowering effect was comparable to that of rapeseed and olive oils.

  11. Serum biotinidase activity in children treated with valproic acid and carbamazepine.

    PubMed

    Castro-Gago, Manuel; Gómez-Lado, Carmen; Eirís-Puñal, Jesús; Díaz-Mayo, Isabel; Castiñeiras-Ramos, Daisy E

    2010-01-01

    There is evidence that valproic acid causes a reduction of serum biotinidase enzyme activity. We determined the serum concentration of antiepileptic drugs, transaminases, gamma-glutamyl transferase, ammonia, and biotinidase enzyme activity in 57 children treated with valproic acid, in 17 children treated with carbamazepine, and in 75 age- and sex-matched healthy controls. There were no significant differences in the serum biotinidase enzyme activity between the patients treated with valproic acid, the patients treated with carbamazepine, and the control group. Hyperammonemia was detected in 8 patients treated with valproic acid. Hair loss was observed in 3 female patients treated with valproic acid, and the alopecia disappeared with the oral administration of biotin (10 mg/ d) in 3 months. These results suggest that the treatment with valproic acid does not alter the serum biotinidase enzyme activity.

  12. Natural phenolic acids may increase serum estradiol level in ovariectomized rats.

    PubMed

    Zych, Maria; Folwarczna, Joanna; Trzeciak, Henryk I

    2009-01-01

    Natural phenolic acids are commonly present in plants consumed in the diet. Recently we have observed that different natural phenolic acids exert differential effects on the body mass gain in ovariectomized and non-ovariectomized female rats. The aim of the present study was to investigate the effects of ferulic, caffeic, p-coumaric and chlorogenic acids on serum estradiol and total cholesterol levels in ovariectomized and non-ovariectomized rats. The experiments were carried out on 3-month old female Wistar Cmd:(WI)WU rats, divided into following groups (n=8 in each group): non-ovariectomized control rats and non-ovariectomized rats receiving ferulic, caffeic, p-coumaric or chlorogenic acids, sham-operated control rats, ovariectomized control rats and ovariectomized rats receiving the same phenolic acids. The phenolic acids were administered at a dose of 10 mg/kg p.o. daily for 4 weeks. Serum estradiol and total cholesterol levels on the next day after the last administration of the phenolic acids were examined. The phenolic acids did not affect serum estradiol or total cholesterol levels in non-ovariectomized rats. In ovariectomized rats, caffeic acid and to a lesser extent p-coumaric acid increased serum estradiol level, which effect correlated with a decreased body mass gain. All the phenolic acids decreased serum cholesterol level in ovariectomized rats. Concluding, the anti-obesity activity of some phenolic acids may be, at least partially, connected with estrogenic pathways.

  13. Relationship between Acute Phase Proteins and Serum Fatty Acid Composition in Morbidly Obese Patients

    PubMed Central

    Fernandes, Ricardo; Beserra, Bruna Teles Soares; Cunha, Raphael Salles Granato; Hillesheim, Elaine; Camargo, Carolina de Quadros; Pequito, Danielle Cristina Tonello; de Castro, Isabela Coelho; Fernandes, Luiz Cláudio; Nunes, Everson Araújo; Trindade, Erasmo Benício Santos de Moraes

    2013-01-01

    Background. Obesity is considered a low-grade inflammatory state and has been associated with increased acute phase proteins as well as changes in serum fatty acids. Few studies have assessed associations between acute phase proteins and serum fatty acids in morbidly obese patients. Objective. To investigate the relationship between acute phase proteins (C-Reactive Protein, Orosomucoid, and Albumin) and serum fatty acids in morbidly obese patients. Methods. Twenty-two morbidly obese patients were enrolled in this study. Biochemical and clinical data were obtained before bariatric surgery, and fatty acids measured in preoperative serum. Results. Orosomucoid was negatively correlated with lauric acid (P = 0.027) and eicosapentaenoic acid (EPA) (P = 0.037) and positively with arachidonic acid (AA) (P = 0.035), AA/EPA ratio (P = 0.005), and n-6/n-3 polyunsaturated fatty acids ratio (P = 0.035). C-Reactive Protein (CRP) was negatively correlated with lauric acid (P = 0.048), and both CRP and CRP/Albumin ratio were negatively correlated with margaric acid (P = 0.010, P = 0.008, resp.). Albumin was positively correlated with EPA (P = 0.027) and margaric acid (P = 0.008). Other correlations were not statistically significant. Conclusion. Our findings suggest that serum fatty acids are linked to acute phase proteins in morbidly obese patients. PMID:24167354

  14. Serum Collagen Type II Cleavage Epitope and Serum Hyaluronic Acid as Biomarkers for Treatment Monitoring of Dogs with Hip Osteoarthritis

    PubMed Central

    Vilar, José M.; Rubio, Mónica; Spinella, Giuseppe; Cuervo, Belén; Sopena, Joaquín; Cugat, Ramón; Garcia-Balletbó, Montserrat; Dominguez, Juan M.; Granados, Maria; Tvarijonaviciute, Asta; Ceron, José J.; Carrillo, José M.

    2016-01-01

    The aim of this study was to evaluate the use of serum type II collagen cleavage epitope and serum hyaluronic acid as biomarkers for treatment monitoring in osteoarthritic dogs. For this purpose, a treatment model based on mesenchymal stem cells derived from adipose tissue combined with plasma rich in growth factors was used. This clinical study included 10 dogs with hip osteoarthritis. Both analytes were measured in serum at baseline, just before applying the treatment, and 1, 3, and 6 months after treatment. These results were compared with those obtained from force plate analysis using the same animals during the same study period. Levels of type II collagen cleavage epitope decreased and those of hyaluronic acid increased with clinical improvement objectively verified via force plate analysis, suggesting these two biomarkers could be effective as indicators of clinical development of joint disease in dogs. PMID:26886592

  15. Serum Collagen Type II Cleavage Epitope and Serum Hyaluronic Acid as Biomarkers for Treatment Monitoring of Dogs with Hip Osteoarthritis.

    PubMed

    Vilar, José M; Rubio, Mónica; Spinella, Giuseppe; Cuervo, Belén; Sopena, Joaquín; Cugat, Ramón; Garcia-Balletbó, Montserrat; Dominguez, Juan M; Granados, Maria; Tvarijonaviciute, Asta; Ceron, José J; Carrillo, José M

    2016-01-01

    The aim of this study was to evaluate the use of serum type II collagen cleavage epitope and serum hyaluronic acid as biomarkers for treatment monitoring in osteoarthritic dogs. For this purpose, a treatment model based on mesenchymal stem cells derived from adipose tissue combined with plasma rich in growth factors was used. This clinical study included 10 dogs with hip osteoarthritis. Both analytes were measured in serum at baseline, just before applying the treatment, and 1, 3, and 6 months after treatment. These results were compared with those obtained from force plate analysis using the same animals during the same study period. Levels of type II collagen cleavage epitope decreased and those of hyaluronic acid increased with clinical improvement objectively verified via force plate analysis, suggesting these two biomarkers could be effective as indicators of clinical development of joint disease in dogs.

  16. Chronic Depression of Serum Sialic Acid Levels in Alloxan-Induced Diabetes

    DTIC Science & Technology

    1974-10-01

    AFRRI SR74-25 OCTOBER 1974 AFRRI SCIENTIFIC REPORT CHRONIC DEPRESSION OF SERUM SIALIC ACID LEVELS IN ALLOXAN-INDUCED DIABETES R. J. O. Woods...1974 CHRONIC DEPRESSION OF SERUM SIALIC ACID LEVELS IN ALLOXAN-INDUCED DIABETES R. J. O. WOODS P. Z. SOBOCINSKI W. J. CANTERBURY...occurs with no apparent alteration in the level of L-fucose. The depression in sialic acid level may be attributed in part to decreased activities of

  17. Insulin resistance, inflammation, and serum fatty acid composition.

    PubMed

    Fernández-Real, José-Manuel; Broch, Montserrat; Vendrell, Joan; Ricart, Wifredo

    2003-05-01

    Fatty acids (FAs) have been involved in the development of chronic inflammatory conditions such as insulin resistance and obesity. However, the relation among insulin resistance, obesity, inflammatory activity (circulating interleukin [IL]-6) and dietary FAs has been scarcely studied in otherwise healthy subjects. We aimed to study these interactions in 123 overweight (BMI 26.9 +/- 2.4 kg/m(2) [means +/- SD]) subjects and 109 lean (BMI 21.7 +/- 1.7 kg/m(2), P < 0.000001) subjects. IL-6 was measured by immunoassay and FA by gas liquid cromatography. The percentage of saturated FAs (r = 0.30, P = 0.01) and omega-6 FAs (r = -0.32, P = 0.001) were significantly associated with circulating IL-6, whereas the percentage of omega-3 FAs correlated negatively with C-reactive protein in overweight subjects (P = 0.04). Saturated-to-omega-3 and saturated-to-omega-6 FA ratios were significantly and positively associated with C-reactive protein (P < 0.0001) and IL-6 (P < 0.001), respectively. In contrast, none of these associations reached statistical significance in lean subjects. Those subjects in the most insulin-sensitive quintile (homeostasis model assessment value) showed a significantly higher percentage of linoleic acid (C18:2 varpi6) (P = 0.03) and a significantly lower level of araquidic (C20:0) (P = 0.04), behenic (C22:0) (P = 0.009), lignoceric (C24:0) (P = 0.02), and nervonic (C24:1 varpi9) (P = 0.001) FAs than the remaining subjects. In parallel, the most insulin-sensitive subjects showed significantly decreased C-reactive protein (P = 0.03). Serum C-reactive protein was significantly associated with percent linoleic acid and eicosapentaenoic acid in nonsmoking men (P = 0.03 and P = 0.04, respectively) and with docosahexaenoic acid in nonsmoking women (r = -0.46, P < 0.0001). We constructed a multivariant regression analysis to predict circulating IL-6. Age, BMI, waist-to-hip ratio (WHR), smoking status, and the relation of saturated to omega-6 or saturated to omega

  18. Determinants of Serum Glycerophospholipid Fatty Acids in Cystic Fibrosis

    PubMed Central

    Drzymała-Czyż, Sławomira; Krzyżanowska, Patrycja; Koletzko, Berthold; Nowak, Jan; Miśkiewicz-Chotnicka, Anna; Moczko, Jerzy A.; Lisowska, Aleksandra; Walkowiak, Jarosław

    2017-01-01

    The etiology of altered blood fatty acid (FA) composition in cystic fibrosis (CF) is understood only partially. We aimed to investigate the determinants of serum glycerophospholipids’ FAs in CF with regard to the highest number of FAs and in the largest cohort to date. The study comprised 172 CF patients and 30 healthy subjects (HS). We assessed Fas’ profile (gas chromatography/mass spectrometry), CF transmembrane conductance regulator (CFTR) genotype, spirometry, fecal elastase-1, body height and weight Z-scores, liver disease, diabetes and colonization by Pseudomonas aeruginosa. The amounts of saturated FAs (C14:0, C16:0) and monounsaturated FAs (C16:1n-7, C18:1n-9, C20:1n-9, C20:3n-9) were significantly higher in CF patients than in HS. C18:3n-6, C20:3n-6 and C22:4n-6 levels were also higher in CF, but C18:2n-6, C20:2n-6 and C20:4n-6, as well as C22:6n-3, were lower. In a multiple regression analysis, levels of seven FAs were predicted by various sets of factors that included age, genotype, forced expiratory volume in one second, pancreatic status and diabetes. FA composition abnormalities are highly prevalent in CF patients. They seem to be caused by both metabolic disturbances and independent clinical risk factors. Further research into the influence of CFTR mutations on fat metabolism and desaturases’ activity is warranted. PMID:28106773

  19. Appliance-induced osteopenia of dentoalveolar bone in the rat: effect of reduced bone strains on serum bone markers and the multifunctional hormone leptin.

    PubMed

    Vinoth, Jayaseelan K; Patel, Kaval J; Lih, Wei-Song; Seow, Yian-San; Cao, Tong; Meikle, Murray C

    2013-12-01

    To understand, in greater detail, the molecular mechanisms regulating the complex relationship between mechanical strain and alveolar bone metabolism during orthodontic treatment, passive cross-arch palatal springs were bonded to the maxillary molars of 6-wk-old rats, which were killed after 4 and 8 d. Outcome measures included serum assays for markers of bone formation and resorption and for the multifunctional hormone leptin, and histomorphometry of the inter-radicular bone. The concentration of the bone-formation marker alkaline phosphatase (ALP) was significantly reduced at both time points in the appliance group, accompanied by a 50% reduction in inter-radicular bone volume; however, osteocalcin (bone Gla protein) levels remained unaffected. Bone collagen deoxypyridinoline (DPD) crosslinks increased 2.3-fold at 4 d only, indicating a transient increase in bone resorption; in contrast, the level of the osteoclast-specific marker, tartrate-resistant acid phosphatase 5b (TRACP 5b), was unchanged. Leptin levels closely paralleled ALP reductions at both time points, suggesting an important role in the mechanostat negative-feedback loop required to normalize bone mass. These data suggest that an orthodontic appliance, in addition to remodeling the periodontal ligament (PDL)-bone interface, may exert unexpected side-effects on the tooth-supporting alveolar bone, and highlights the importance of recognizing that bone strains can have negative, as well as positive, effects on bone mass.

  20. Markers of bone metabolism in multiple myeloma patients switched from zoledronic acid to denosumab.

    PubMed

    Tatekoshi, Ayumi; Sato, Tsutomu; Ibata, Soushi; Hashimoto, Akari; Kamihara, Yusuke; Horiguchi, Hiroto; Ono, Kaoru; Takada, Kohichi; Iyama, Satoshi; Takimoto, Rishu; Kobune, Masayoshi; Kato, Junji

    2014-11-01

    To date, intravenous drip infusion of zoledronic acid (ZA) has mainly been used for the treatment and prevention of skeletal-related events (SRE) in patients with multiple myeloma (MM). Recently, denosumab, a fully humanized monoclonal antibody against receptor activator of nuclear factor-κB ligand (RANKL), has also become available for the same purpose, but little is known about the impact of switching from ZA to denosumab. Herein, we present a retrospective study on bone metabolic markers in 10 MM patients initially treated with ZA and then switched to denosumab. Consequently, the levels of bone resorption markers, tartrate-resistant acid phosphatase 5b (TRACP-5b) and serum type-I collagen crosslinked N-telopeptide (sNTX), significantly decreased after denosumab treatment, while the levels of bone formation markers, osteocalcin (OC) and bone-specific alkaline phosphatase (BAP), showed no apparent changes. No patient developed severe hypocalcemia with denosumab treatment. In one patient not given chemotherapy, the M-protein level increased after switching from ZA to denosumab and plateaued when ZA was restarted. Based on this finding, we anticipate that switching from ZA to denosumab would exert a stronger suppressive effect on osteoclasts, but the anti-myeloma activity of ZA must be taken into consideration.

  1. Plasma Homocysteine, Serum Folic Acid, Serum Vitamin B12, Serum Vitamin B6, MTHFR, and Risk of Normal-Tension Glaucoma.

    PubMed

    Li, Jinmiao; Xu, Fan; Zeng, Rui; Gong, Haijun; Lan, Yuqing

    2016-02-01

    This meta-analysis aims to comprehensively evaluate the association between total homocysteine (tHcy) levels, serum folic acid, vitamin B12, vitamin B6 levels, methylenetetrahydrofolate reductase (MTHFR) C677T genotype, and risk of normal-tension glaucoma (NTG). A systematic search of the EMBASE and PubMed databases was performed to evaluate plasma tHcy levels, serum folic acid, B vitamins' mean difference, and odds ratios of MTHFR C677T genotype between cases and controls. A total of 7 studies including 458 cases and 555 controls meeting the inclusion criteria were involved in this meta-analysis. There were 4 studies for tHcy (149 cases and 148 controls), 2 studies for vitamin B6, vitamin B12, and folate (90 cases and 82 controls), and 4 studies for MTHFR (343 cases and 449 controls). Overall, the mean plasma tHcy levels, serum folic acids, vitamin B12, and vitamin B6 levels were 1.16 μmol/L [95% confidence interval (CI), -0.13, 2.45], -0.62 μmol/L (95% CI, -1.98, 0.74), 5.81 μmol/L (95% CI, -3.53, 15.14), and -16.79 μmol/L (95% CI, -86.09, 52.51). MTHFR TT genotype was found to be unrelated to NTG risk (odds ratio=1.08; 95% CI, 0.69, 1.69). NTG is not associated with elevated plasma tHcy, serum folic acid, serum vitamin B12, serum vitamin B6, and MTHFR C677T genotype.

  2. Comparative studies on the interaction of caffeic acid, chlorogenic acid and ferulic acid with bovine serum albumin

    NASA Astrophysics Data System (ADS)

    Li, Shuang; Huang, Kelong; Zhong, Ming; Guo, Jun; Wang, Wei-zheng; Zhu, Ronghua

    2010-10-01

    The substitution of the hydrogen on aromatic and esterification of carboxyl group of the phenol compounds plays an important role in their bio-activities. In this paper, caffeic acid (CaA), chlorogenic acid (ChA) and ferulic acid (FA) were selected to investigate the binding to bovine serum albumin (BSA) using UV absorption spectroscopy, fluorescence spectroscopy and synchronous fluorescence spectroscopy. It was found that the methoxyl group substituting for the 3-hydroxyl group of CaA decreased the affinity for BSA and the esterification of carboxyl group of CaA with quinic acid increased the affinities. The affinities of ChA and FA with BSA were more sensitive to the temperature than that of CaA with BSA. Synchronous fluorescence spectroscopy and time-resolved fluorescence indicated that the Stern-Volmer plots largely deviated from linearity at high concentrations and were caused by complete quenching of the tyrosine fluorescence of BSA.

  3. Effects of Sodium Glucose Cotransporter-2 Inhibitors on Serum Uric Acid in Type 2 Diabetes Mellitus.

    PubMed

    Ahmadieh, Hala; Azar, Sami

    2017-07-27

    Hyperuricemia has been linked to metabolic syndrome, cardiovascular disease, and chronic kidney disease. Hyperuricemia and type 2 diabetes mellitus were inter-related, type 2 diabetes mellitus was more at risk of having a higher serum uric acid level, and also individuals with higher serum uric acid had higher risk of developing type 2 diabetes in the future. Insulin resistance seems to play an important role in the causal relationship between metabolic syndrome, type 2 diabetes, and hyperuricemia. Oral diabetic drugs that would have additional beneficial effects on reducing serum uric acid levels are of importance. Selective SGLT2 inhibitors were extensively studied in type 2 diabetes mellitus and were found to have improvement of glycemic control, in addition to their proven metabolic effects on weight and blood pressure. Additional beneficial effect of SGLT2 inhibitors on serum uric acid level reduction is investigated. Recently, data have been accumulating showing that they have additional beneficial effects on serum uric acid reduction. As for the postulated mechanism, serum uric acid decreased in SGLT2 inhibitor users as a result of the increase in the urinary excretion rate of uric acid, due to the inhibition of uric acid reabsorption mediated by the effect of the drug on the GLUT9 isoform 2, located at the collecting duct of the renal tubule.

  4. Serum amino acid concentrations in patients receiving total parenteral nutrition with an amino acid plus dextrose mixture.

    PubMed

    Philcox, J C; Hartley, T F; Worthley, L I; Thomas, D W

    1984-01-01

    The results of monitoring the serum amino acid concentrations during three infusion regimens using a 5:4 mixture of 70% glucose and the synthetic L-amino acid solution, Synthamin 17 (Travasol) are reported. Twelve stabilized patients received continuous total parenteral nutrition (TPN), eight of whom were subsequently placed on a second regimen of cyclical feeding. A separate group of five patients was infused with amino acids, both with and without simultaneous glucose. The serum amino acid concentrations indicated that the supply of valine, leucine, isoleucine, lysine, and histidine, and the synthesis of taurine from the infused methionine was suboptimal, particularly if the period of TPN was prolonged. The synthesis of tyrosine from phenylalanine appeared to be inversely proportional to the infusion rate of the TPN mixture, in particular the glucose component, resulting in depressed tyrosine and increased phenylalanine concentrations in serum during continuous iv nutrition. Cyclical infusions, on the other hand, permitted the tyrosine and phenylalanine concentrations to return to normal during the noninfusion stage of the cycle. Amino acid measurements enabled us to design an amino acids additive mixture which normalized the serum concentrations in three long-term home parenteral nutrition patients. As a result of these investigations serum amino acid measurements are used routinely to monitor the efficacy of TPN and accommodate any specific amino acid requirements of individual patients.

  5. Dietary Acid, Age, and Serum Bicarbonate Levels among Adults in the United States

    PubMed Central

    Amodu, Afolarin

    2013-01-01

    Summary Background and objectives Greater dietary acid has been associated with lower serum bicarbonate levels in patients with CKD. Whether this association extends to the general population and if it is modified by age are unknown. Design, setting, participants, & measurements This study examined the association of the dietary acid load, estimated by net endogenous acid production, with serum bicarbonate levels in adult participants in the National Health and Nutrition Examination Survey 1999–2004. Results The mean serum bicarbonate was 24.9 mEq/L (SEM=0.1), and the mean estimated net endogenous acid production was 57.4 mEq/d (SEM=0.4). Serum bicarbonate was linearly associated with age, such that the oldest participants had the highest serum bicarbonate levels. After multivariable adjustment, participants in the highest quartile of net endogenous acid production had 0.40 mEq/L (95% confidence interval, −0.55 to −0.26) lower serum bicarbonate and a 33% (95% confidence interval, 3 to 72) higher likelihood of acidosis compared with those participants in the lowest quartile. There was a significant interaction by age of the association of net endogenous acid production with serum bicarbonate (P=0.005). Among participants 20–39, 40–59, and ≥60 years old, those participants in the highest net endogenous acid production quartile had 0.26 (95% confidence interval, −0.49 to −0.03), 0.60 (95% confidence interval, −0.92 to −0.29), and 0.49 (95% confidence interval, −0.84 to −0.14) mEq/L lower serum bicarbonate, respectively, compared with participants in the lowest quartile. Conclusion Greater dietary acid is associated with lower serum bicarbonate in the general US population, and the magnitude of this association is greater among middle-aged and elderly persons than younger adults. PMID:24052219

  6. Dietary acid, age, and serum bicarbonate levels among adults in the United States.

    PubMed

    Amodu, Afolarin; Abramowitz, Matthew K

    2013-12-01

    Greater dietary acid has been associated with lower serum bicarbonate levels in patients with CKD. Whether this association extends to the general population and if it is modified by age are unknown. This study examined the association of the dietary acid load, estimated by net endogenous acid production, with serum bicarbonate levels in adult participants in the National Health and Nutrition Examination Survey 1999-2004. The mean serum bicarbonate was 24.9 mEq/L (SEM=0.1), and the mean estimated net endogenous acid production was 57.4 mEq/d (SEM=0.4). Serum bicarbonate was linearly associated with age, such that the oldest participants had the highest serum bicarbonate levels. After multivariable adjustment, participants in the highest quartile of net endogenous acid production had 0.40 mEq/L (95% confidence interval, -0.55 to -0.26) lower serum bicarbonate and a 33% (95% confidence interval, 3 to 72) higher likelihood of acidosis compared with those participants in the lowest quartile. There was a significant interaction by age of the association of net endogenous acid production with serum bicarbonate (P=0.005). Among participants 20-39, 40-59, and ≥60 years old, those participants in the highest net endogenous acid production quartile had 0.26 (95% confidence interval, -0.49 to -0.03), 0.60 (95% confidence interval, -0.92 to -0.29), and 0.49 (95% confidence interval, -0.84 to -0.14) mEq/L lower serum bicarbonate, respectively, compared with participants in the lowest quartile. Greater dietary acid is associated with lower serum bicarbonate in the general US population, and the magnitude of this association is greater among middle-aged and elderly persons than younger adults.

  7. Essential fatty acid intake and serum fatty acid composition among adolescent girls in central Mozambique.

    PubMed

    Freese, Riitta; Korkalo, Liisa; Vessby, Bengt; Tengblad, Siv; Vaara, Elina M; Hauta-alus, Helena; Selvester, Kerry; Mutanen, Marja

    2015-04-14

    Many African diets are low in fat but are currently changing because of nutrition transition. We studied fat and fatty acid (FA) intake and the essential fatty acid (EFA) status of adolescent girls (aged 14-19 years, n 262) in Zambezia Province, central Mozambique. A cross-sectional study was carried out in a city as well as in the towns and rural villages of a coastal and an inland district. Dietary intake and FA sources were studied in a 24 h dietary recall. FA compositions of cholesteryl esters and phospholipids of non-fasting serum samples were analysed by GLC. Fat intake was low (13-18 % of energy) in all areas. Coconut and palm oil were the main sources of fat, and soyabean oil and maize were the main sources of PUFA. Compared to Food and Agriculture Organization/WHO 2010 recommendations, intake of linoleic acid (LA, 18 : 2n-6) was inadequate in the coastal district, and intakes of n-3 PUFA were inadequate in all areas. FA compositions of serum lipids differed between areas. The proportions of LA tended to be highest in the city and lowest in the rural areas. The phospholipid mead (20 : 3n-9):arachidonic acid (20 : 4n-6) ratio did not indicate EFA insufficiency. LA proportions in phospholipids were low, but those of long-chain n-6 and n-3 PUFA were high in comparison with Western adolescents. To conclude, fat sources, FA intake and EFA status differed between adolescent girls living in different types of communities. Fat intake was low, but EFA insufficiency was not indicated.

  8. Influence of cattle temperament on blood serum fatty acid content

    USDA-ARS?s Scientific Manuscript database

    Cattle temperament has been reported to influence blood metabolites. Specifically, temperament was related with increased circulation of serum NEFA, decreased blood urea nitrogen, and reduced insulin sensitivity. Metabolic alterations such as these may impact cattle immune function, performance trai...

  9. Unmetabolized folic acid in serum: acute studies in subjects consuming fortified food and supplements.

    PubMed

    Kelly, P; McPartlin, J; Goggins, M; Weir, D G; Scott, J M

    1997-06-01

    Periconceptual consumption of folic acid has been shown to decrease the incidence of neural tube defects. The strategy of universal fortification of staple foodstuffs with folic acid presents the possibility of life-long exposure to unmetabolized folic acid. Chief among the risks of exposure to folic acid in the circulation is that of masking the diagnosis of cobalamin deficiency in pernicious anemia and the progression of neurologic disease. Other effects are unknown. For instance, the effect of in vivo chronic exposure of adult and fetal cells to the synthetic form of the vitamin has never been investigated at the population level. This study examined the acute appearance of unmetabolized folic acid in serum in response to the consumption of some fortified foodstuffs by young and elderly volunteers. Subjects on a 5-d regimen of fortified ready-to-eat-cereal and bread in addition to their normal diet had a threshold intake of 266 micrograms folic acid per meal at which unaltered folic acid appeared in the serum. Subjects given folic acid in either isotonic saline, milk, or white bread also had a threshold > 200 micrograms. From patterns of food consumption in the United States, the implementation of flour fortification at 1.4 mg/kg is unlikely to lead to folic acid appearance in serum, assuming that consumption is spread throughout the day. Increasing this level of fortification, however, as has been advocated by some agencies, may result in the repeated appearance of folic acid in serum over many years, particularly in consumers in nontargeted populations of large amounts of fortified foods. The "safe level of intake" of 1 mg folate/d set by the US Food and Drug Administration may cause a serum folic acid effect. Furthermore, a repeated serum folic acid response is likely to be found in many women complying with the advice to take 400 micrograms folic acid/d to prevent the occurrence of neural tube defects.

  10. An Endogenous Mediator of Depression of Amino Acids and Trace Metals in Serum during Typhoid Fever

    DTIC Science & Technology

    symptoms after an oral dose of 100,000 virulent Salmonella typhosa. When a 1.0-ml sample of sterile serum from volunteers who were ill with typhoid fever was...leukocytes) was present in the blood during typhoid fever and served as a mediator for the observed depression in zinc and amino acids in serum. The

  11. Serum Uric Acid Level as a Prognostic Marker in Patients With Acute Respiratory Distress Syndrome.

    PubMed

    Lee, Hyun Woo; Choi, Sun Mi; Lee, Jinwoo; Park, Young Sik; Lee, Chang-Hoon; Yim, Jae-Joon; Yoo, Chul-Gyu; Kim, Young Whan; Han, Sung Koo; Lee, Sang-Min

    2017-01-01

    Uric acid acts as both a pathogenic inflammatory mediator and an antioxidative agent. Several studies have shown that uric acid level correlates with the incidence, severity, and prognosis of pulmonary diseases. However, the association between uric acid level and acute respiratory distress syndrome (ARDS) has not been studied. This study was conducted to elucidate how serum uric acid level is related with clinical prognosis of ARDS. A retrospective cohort study with propensity score matching was conducted at a medical intensive care unit of a tertiary teaching hospital. The medical records of patients diagnosed with ARDS admitted from 2005 through 2011 were reviewed. Two hundred thirty-seven patients with ARDS met the inclusion criteria. Patients with a serum uric acid level <3.0 mg/dL were classified into the low uric acid group, and those with a level ≥3 mg/dL were classified into the normal to high uric acid group. We selected 40 patients in each group using propensity score matching. A higher percentage of patients in the low uric acid group experienced clinical improvement in ARDS. More patients died from sepsis in the normal to high uric acid group. Kaplan-Meier analysis showed that a low serum uric acid level was significantly associated with better survival rate. In patients with ARDS, a low serum uric acid level may be a prognostic marker of a low risk of in-hospital mortality.

  12. Evaluation of serum sialic acid, fucose levels and their ratio in oral squamous cell carcinoma

    PubMed Central

    Chinnannavar, Sangamesh Ningappa; Ashok, Lingappa; Vidya, Kodige Chandrashekhar; Setty, Sunil Mysore Kantharaja; Narasimha, Guru Eraiah; Garg, Ranjana

    2015-01-01

    Background: Detection of cancer at the early stage is of utmost importance to decrease the morbidity and mortality of the disease. Apart from the conventional biopsy, minimally invasive methods like serum evaluation are used for screening large populations. Thus, this study aimed to estimate serum levels of sialic acid and fucose and their ratio in oral cancer patients and in healthy control group to evaluate their role in diagnosis. Materials and Methods: Serum samples were collected from 52 healthy controls (group I) and 52 squamous cell carcinoma patients (group II). Estimation of serum levels of sialic acid and fucose and their ratio was performed. This was correlated histopathologically with the grades of carcinoma. Statistical analysis was done by using analysis of variance (ANOVA) test and unpaired “t” test. Results: Results showed that serum levels of sialic acid and fucose were significantly higher in oral cancer patients compared to normal healthy controls (P < 0.001). The sialic acid to fucose ratio was significantly lower in cancer patients than in normal controls (P < 0.01). However, comparison with histological grading, habits, gender, and age group did not show any significant result. Conclusion: The mean serum sialic acid and fucose levels showed an increasing trend from controls to malignant group and their corresponding ratio showed decreasing trend from controls to malignant group. The ratio of sialic acid to fucose can be a useful diagnostic aid for oral cancer patients. PMID:26759796

  13. Effect of canagliflozin on serum uric acid in patients with type 2 diabetes mellitus.

    PubMed

    Davies, M J; Trujillo, A; Vijapurkar, U; Damaraju, C V; Meininger, G

    2015-04-01

    Hyperuricaemia is associated with an increased risk of gout, kidney stones and cardiovascular disease. The present post hoc analysis of pooled data from four placebo-controlled phase III studies assessed the effect of canagliflozin, a sodium-glucose co-transporter 2 inhibitor, on serum uric acid levels in patients with type 2 diabetes mellitus (T2DM) and in a subset of patients with hyperuricaemia [defined as baseline serum uric acid ≥475 µmol/l (∼8 mg/dl)]. At week 26, canagliflozin 100 and 300 mg were associated with a ∼13% reduction in serum uric acid compared with placebo. In the subset of patients with hyperuricaemia, placebo-subtracted percent reductions in serum uric acid were similar to those in the overall cohort. More patients in the hyperuricaemic group achieved a serum uric acid level of <360 µmol/l (∼6 mg/dl) with both canagliflozin 100 mg (23.5%) and 300 mg (32.4%) compared with placebo (3.1%). Incidences of gout and kidney stones were low and similar across groups. In conclusion, canagliflozin treatment decreased serum uric acid in patients with T2DM, including those with baseline hyperuricaemia. © 2015 John Wiley & Sons Ltd.

  14. Evaluation of serum sialic acid, fucose levels and their ratio in oral squamous cell carcinoma.

    PubMed

    Chinnannavar, Sangamesh Ningappa; Ashok, Lingappa; Vidya, Kodige Chandrashekhar; Setty, Sunil Mysore Kantharaja; Narasimha, Guru Eraiah; Garg, Ranjana

    2015-01-01

    Detection of cancer at the early stage is of utmost importance to decrease the morbidity and mortality of the disease. Apart from the conventional biopsy, minimally invasive methods like serum evaluation are used for screening large populations. Thus, this study aimed to estimate serum levels of sialic acid and fucose and their ratio in oral cancer patients and in healthy control group to evaluate their role in diagnosis. Serum samples were collected from 52 healthy controls (group I) and 52 squamous cell carcinoma patients (group II). Estimation of serum levels of sialic acid and fucose and their ratio was performed. This was correlated histopathologically with the grades of carcinoma. Statistical analysis was done by using analysis of variance (ANOVA) test and unpaired "t" test. Results showed that serum levels of sialic acid and fucose were significantly higher in oral cancer patients compared to normal healthy controls (P < 0.001). The sialic acid to fucose ratio was significantly lower in cancer patients than in normal controls (P < 0.01). However, comparison with histological grading, habits, gender, and age group did not show any significant result. The mean serum sialic acid and fucose levels showed an increasing trend from controls to malignant group and their corresponding ratio showed decreasing trend from controls to malignant group. The ratio of sialic acid to fucose can be a useful diagnostic aid for oral cancer patients.

  15. Determination of free fatty acids in human serum by HPLC with fluorescence detection.

    PubMed

    Nishikiori, Minami; Iizuka, Hideaki; Ichiba, Hideaki; Sadamoto, Kiyomi; Fukushima, Takeshi

    2015-04-01

    It has been suggested that serum concentrations of polyunsaturated essential fatty acids correlate with the symptoms or severity of various diseases, including depression and Alzheimer-type dementia, and that determination of serum fatty acids might be important for disease diagnosis. Thus, we developed to analyze serum fatty acids in healthy individuals by using a high-performance liquid chromatography method with fluorescence detection, because free fatty acids have a carboxyl group that can be derivatized with a fluorescent reagent, 4-N,N-dimethylaminosulfonyl-7-N-(2-aminoethyl)amino-2,1,3-benzoxadiazole. This approach could quantify five types of free fatty acids [α-linolenic acid (ALA), palmitoleic acid (PLA), arachidonic acid (AA), linoleic acid (LA) and oleic acid (OA)] in human serum. The detection limits of the method were in the range of 2.29-4.75 fmol (signal-to-noise ratio 3), and absolute concentrations of ALA, PLA, AA, LA and OA were 8.27 ± 1.04, 18.8 ± 2.95, 49.9 ± 4.03, 230 ± 18.1 and 201 ± 22.1 µM, respectively. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  16. Serum fatty acid, lipid profile and dietary intake of Hong Kong Chinese omnivores and vegetarians.

    PubMed

    Lee, H Y; Woo, J; Chen, Z Y; Leung, S F; Peng, X H

    2000-10-01

    To examine the serum fatty acid and lipid profiles and dietary intake of Hong Kong Chinese omnivores and vegetarians with respect to cardiovascular health. Random population survey stratified by age and sex. One-hundred and ninety-four omnivore subjects (81 men, 113 women) age 25-70 y, and 60 ovo-lacto-vegetarian adults (15 men, 45 women) age 30-55 y. Nutrient quantitation was by a food frequency method. Serum fatty acids were analysed by gas chromatography, and serum lipid by standard laboratory methods. Compared with omnivores, vegetarians had higher serum concentrations of polyunsaturated (PUFA) and monosaturated fatty acids (MUFA), and lower saturated fatty acids (SFA), long chain omega-3 and trans fatty acids (TFA). They also had lower serum cholesterol and higher apoA-1 concentrations, but the LDL/HDL ratio was not different. The ratio of polyunsaturated to saturated fatty acids intake was higher in vegetarians. Compared with results from populations with higher incidences of coronary heart disease, while lower myristic and palmitic acid concentrations and higher eicosapentaneoic (EPA) and docosahexanoic acid (DHA) may partly account for the difference in incidence, linoleic acid concentration was higher. Although the Chinese vegetarian diet may be beneficial for heart health in that antioxidant and fibre intakes are higher and saturated fat lower, the low EPA and DHA due to omission from dietary source and suppressed formation by high linoleic acid level, and the presence of TFA in the diet, may exert an opposite effect. There are some favourable features in the serum fatty acid profile in the Hong Kong Chinese population with respect to cardiovascular health, but the consumption of TFA is of concern. The Chinese vegetarian diet also contains some adverse features.

  17. Serum uric acid as prognostic marker of coronary heart disease (CHD).

    PubMed

    Purnima, Samudrala; El-Aal, Bahiga Galal Abd

    A substantial body of epidemiological and experimental evidence suggests the significance of serum uric acid as an important and independent risk factor of cardio vascular and renal diseases especially in patients with diabetes mellitus, hypertension. Hyperuricemia is a risk factor of coronary heart disease. Several studies showed positive association between hyperuricemia and CHD risk factors. To analyze the serum uric acid levels in patients with diabetes and hypertension, which helps in understanding its role as prognostic marker of coronary heart disease. The study was conducted in population of Wadi-Al Dawasir (K.S.A.) aged 20-80 years through random sampling from October 2012 to June 2013. It included 250 samples and the cases were categorized into diabetic and hypertensive. In the cases, purely hypertensive were 52, diabetic were 57 and mixed group included both diabetic and hypertensive patients 65. Fasting blood was collected to analyze lipid profile which included (total cholesterol, triglycerides, high density lipoprotein, low density lipoprotein) and serum uric acid in association with age and heredity was also studied. Patient demographics were recorded. The study revealed significant association of serum uric acid (p<0.014*) and total cholesterol (p<0.007**) triglycerides (p<0.009**) low density lipoprotein (p<0.044*) in hypertensive group. Serum uric acid levels in the mixed group patients with diabetes and hypertension reported serum uric acid (p<0.0037), total cholesterol (p<0.089+) proved to have increased risk of coronary heart disease. When compared to controls (non-diabetic p<0.529) and (non-hypertensive p<0.021*) with respect to serum uric acid levels show the magnitude of risk to coronary heart disease. With progressing age the association of lipid profile and serum uric acid reported (p<0.001**) in diabetics. Significant correlations were found between serum uric acid and risk factors for CHD. This is first study of its kind in this region

  18. Increased Numbers of Nonattached Osteoclasts After Long-Term Zoledronic Acid Therapy in Mice

    PubMed Central

    Kuroshima, Shinichiro; Go, Virginia-Arlene A.

    2012-01-01

    Osteoclasts are key players in the maintenance of bone, which is an endocrine target and organ. Bisphosphonates, used for the management of metastatic bone diseases and osteoporosis, suppress osteoclasts. However, the impact of continuously suppressed osteoclasts is unknown. In this study, mice received zoledronic acid (ZA) for 13 months, nearly half the lifespan of mice, and the effects of continual osteoclast suppression on the bone environment and oral wound healing were determined. ZA therapy suppressed osteoclasts, resulting in significantly more bone mass compared with control. Despite continuous and intense suppression of bone loss in mice receiving ZA, serum calcium levels were maintained in the normal range. No differences were noted in serum tartrate-resistant acid phosphatase (TRAP) 5b levels between ZA-treated and control mice. Histomorphometric analyses of bones revealed that ZA therapy significantly decreased osteoclasts on the bone surface but, instead, substantially increased TRAP+ mononuclear cells and osteoclasts that were not on the bone surface. When oral trauma was induced, such TRAP+ mononuclear and nonattached osteoclasts increased considerably with increased inflammatory cell infiltration in the wounds. As a result, oral wound healing was hindered at the connective tissue level. Healing of the epithelium was unaffected. These findings indicate that the continual suppression of osteoclasts does not affect serum calcium levels and that long-term ZA therapy stimulates nonattached osteoclast and TRAP+ mononuclear cell formation that are expanded rapidly in response to oral trauma. Caution should be exercised when using the serum TRAcP5b to estimate the efficacy of antiresorptive therapy. PMID:22109892

  19. Association of serum uric acid with high-sensitivity C-reactive protein in postmenopausal women.

    PubMed

    Raeisi, A; Ostovar, A; Vahdat, K; Rezaei, P; Darabi, H; Moshtaghi, D; Nabipour, I

    2017-02-01

    To explore the independent correlation between serum uric acid and low-grade inflammation (measured by high-sensitivity C-reactive protein, hs-CRP) in postmenopausal women. A total of 378 healthy Iranian postmenopausal women were randomly selected in a population-based study. Circulating hs-CRP levels were measured by highly specific enzyme-linked immunosorbent assay method and an enzymatic calorimetric method was used to measure serum levels of uric acid. Pearson correlation coefficient, multiple linear regression and logistic regression models were used to analyze the association between uric acid and hs-CRP levels. A statistically significant correlation was seen between serum levels of uric acid and log-transformed circulating hs-CRP (r = 0.25, p < 0.001). After adjustment for age and cardiovascular risk factors (according to NCEP ATP III criteria), circulating hs-CRP levels were significantly associated with serum uric acid levels (β = 0.20, p < 0.001). After adjustment for age and cardiovascular risk factors, hs-CRP levels ≥3 mg/l were significantly associated with higher uric acid levels (odds ratio =1.52, 95% confidence interval 1.18-1.96). Higher serum uric acid levels were positively and independently associated with circulating hs-CRP in healthy postmenopausal women.

  20. Longitudinal profiles of 15 serum bile acids in patients with intrahepatic cholestasis of pregnancy.

    PubMed

    Tribe, Rachel M; Dann, Anthony T; Kenyon, Anna P; Seed, Paul; Shennan, Andrew H; Mallet, Anthony

    2010-03-01

    Increased maternal serum bile acids are implicated in intrahepatic cholestasis of pregnancy. Individual bile acid profiles and their relationship with disease progression, however, remain unknown. The purpose of this prospective study was to determine the temporal changes in bile acids in normal pregnancy and in pregnancies complicated with intrahepatic cholestasis of pregnancy and pruritus gravidarum. A validated method for the evaluation of 15 bile acids (conjugated and unconjugated) in a single serum sample was developed using high-performance liquid chromatography/mass spectrometry (HPLC-MS) with an electrospray interface. Bile acid concentrations were assessed in samples (16 weeks of gestation to 4 weeks postpartum) from women with, or who later developed, intrahepatic cholestasis of pregnancy (n=63) and were compared with those from normal pregnant women (n=26) and from women with pruritus gravidarum (n=43). Intrahepatic cholestasis of pregnancy was associated with a predominant increase in cholic acid conjugated with taurine and glycine, from 24 weeks of pregnancy. Ursodeoxycholic acid (UDCA) treatment (> or =21 days, n=15) significantly reduced serum taurocholic and taurodeoxycholic acid concentrations (P<0.01). Bile acid profiles were similar in normal pregnancy and pregnancy associated with pruritus gravidarum. The bile acid profiles and effects of treatment by UDCA implicate a role for taurine-conjugated bile acids in the syndrome of intrahepatic cholestasis of pregnancy. [corrected] With regard to individual bile acid profiles, pruritus gravidarum is a disorder quite distinct from intrahepatic cholestasis of pregnancy.

  1. Haemodynamic correlates and prognostic significance of serum uric acid in adult patients with Eisenmenger syndrome

    PubMed Central

    Oya, H; Nagaya, N; Satoh, T; Sakamaki, F; Kyotani, S; Fujita, M; Nakanishi, N; Miyatake, K

    2000-01-01

    OBJECTIVE—To assess haemodynamic correlates and prognostic significance of serum uric acid in adult patients with Eisenmenger syndrome.
DESIGN—Retrospective observational study.
SETTING—Tertiary referral centre.
PATIENTS—94 adult patients with Eisenmenger syndrome who were diagnosed between September 1982 and July 1998.
MAIN OUTCOME MEASURES—Serum uric acid was measured in all patients, together with clinical and haemodynamic variables related to mortality.
RESULTS—Serum uric acid was raised in patients with Eisenmenger syndrome compared with age and sex matched control subjects (7.0 v 4.7 mg/dl, p < 0.0001) and increased in proportion to the severity of New York Heart Association functional class. Serum uric acid was positively correlated with mean pulmonary arterial pressure (r = 0.30, p = 0.0052) and total pulmonary resistance index (r = 0.55, p < 0.0001), and negatively correlated with cardiac index (r = −0.50, p < 0.0001). During a mean follow up period of 97 months, 38 patients died of cardiopulmonary causes. Among various clinical, echocardiographic, and laboratory variables, serum uric acid remained predictive in multivariate analysis. Kaplan-Meier survival curves based on median serum uric acid showed that patients with high values had a significantly worse survival rate than those with low values (log-lank test: p = 0.0014 in male patients, p = 0.0034 in female patients).
CONCLUSIONS—Serum uric acid increases in proportion to haemodynamic severity in adult patients with Eisenmenger syndrome and is independently associated with long term mortality.


Keywords: Eisenmenger syndrome; prognosis; uric acid; haemodynamics PMID:10862589

  2. Determination of serum organic acids in puppies with naturally acquired parvoviral enteritis

    PubMed Central

    Nappert, Germain; Dunphy, Elizabeth; Ruben, Dawn; Mann, F. A.

    2002-01-01

    The purpose of the present study was to investigate the acid-base status and the serum concentration of organic acids in puppies with naturally occurring canine parvoviral enteritis. Between July 1999 and July 2000, 25 client-owned puppies admitted to the St. Louis Animal Emergency Clinic South for treatment of enteritis caused by parvovirus infection were used in our study. Control blood samples were collected from 22 healthy puppies less than 9 months of age. Serum organic acid concentrations were quantitatively determined by HPLC. Puppies infected with parvovirus had significantly lower plasma concentrations of sodium, potassium, chloride, and bicarbonate than controls. Although serum L-lactate tended to increase in some puppies with canine parvoviral enteritis, our study demonstrated that most affected puppies developed only mild compensated metabolic acidosis. None of the affected puppies had an elevated serum D-lactate concentration at admission. PMID:11858643

  3. Changes in Serum Free Amino Acids and Muscle Fatigue Experienced during a Half-Ironman Triathlon.

    PubMed

    Areces, Francisco; González-Millán, Cristina; Salinero, Juan José; Abian-Vicen, Javier; Lara, Beatriz; Gallo-Salazar, Cesar; Ruiz-Vicente, Diana; Del Coso, Juan

    2015-01-01

    The aim of this study was to investigate the relationship between changes in serum free amino acids, muscle fatigue and exercise-induced muscle damage during a half-ironman triathlon. Twenty-six experienced triathletes (age = 37.0 ± 6.8 yr; experience = 7.4 ± 3.0 yr) competed in a real half-ironman triathlon in which sector times and total race time were measured by means of chip timing. Before and after the race, a countermovement jump and a maximal isometric force test were performed, and blood samples were withdrawn to measure serum free amino acids concentrations, and serum creatine kinase levels as a blood marker of muscle damage. Total race time was 320 ± 37 min and jump height (-16.3 ± 15.2%, P < 0.001) and isometric force (-14.9 ± 9.8%; P = 0.007) were significantly reduced after the race in all participants. After the race, the serum concentration of creatine kinase increased by 368 ± 187% (P < 0.001). In contrast, the serum concentrations of essential (-27.1 ± 13.0%; P < 0.001) and non-essential amino acids (-24.4 ± 13.1%; P < 0.001) were significantly reduced after the race. The tryptophan/BCAA ratio increased by 42.7 ± 12.7% after the race. Pre-to-post changes in serum free amino acids did not correlate with muscle performance variables or post-race creatine kinase concentration. In summary, during a half-ironman triathlon, serum amino acids concentrations were reduced by > 20%. However, neither the changes in serum free amino acids nor the tryptophan/BCAA ratio were related muscle fatigue or muscle damage during the race.

  4. Changes in Serum Free Amino Acids and Muscle Fatigue Experienced during a Half-Ironman Triathlon

    PubMed Central

    Areces, Francisco; González-Millán, Cristina; Salinero, Juan José; Abian-Vicen, Javier; Lara, Beatriz; Gallo-Salazar, Cesar; Ruiz-Vicente, Diana; Del Coso, Juan

    2015-01-01

    The aim of this study was to investigate the relationship between changes in serum free amino acids, muscle fatigue and exercise-induced muscle damage during a half-ironman triathlon. Twenty-six experienced triathletes (age = 37.0 ± 6.8 yr; experience = 7.4 ± 3.0 yr) competed in a real half-ironman triathlon in which sector times and total race time were measured by means of chip timing. Before and after the race, a countermovement jump and a maximal isometric force test were performed, and blood samples were withdrawn to measure serum free amino acids concentrations, and serum creatine kinase levels as a blood marker of muscle damage. Total race time was 320 ± 37 min and jump height (-16.3 ± 15.2%, P < 0.001) and isometric force (-14.9 ± 9.8%; P = 0.007) were significantly reduced after the race in all participants. After the race, the serum concentration of creatine kinase increased by 368 ± 187% (P < 0.001). In contrast, the serum concentrations of essential (-27.1 ± 13.0%; P < 0.001) and non-essential amino acids (-24.4 ± 13.1%; P < 0.001) were significantly reduced after the race. The tryptophan/BCAA ratio increased by 42.7 ± 12.7% after the race. Pre-to-post changes in serum free amino acids did not correlate with muscle performance variables or post-race creatine kinase concentration. In summary, during a half-ironman triathlon, serum amino acids concentrations were reduced by > 20%. However, neither the changes in serum free amino acids nor the tryptophan/BCAA ratio were related muscle fatigue or muscle damage during the race. PMID:26372162

  5. Association of fatty acids in serum phospholipids with hay fever, specific and total immunoglobulin E.

    PubMed

    Kompauer, Iris; Demmelmair, Hans; Koletzko, Berthold; Bolte, Gabriele; Linseisen, Jakob; Heinrich, Joachim

    2005-04-01

    The dietary intake of certain fatty acids might contribute to the development of allergic diseases such as hay fever and asthma. We investigated the association between the concentrations of fifteen fatty acids in serum phospholipids, as a marker of dietary intake and metabolism, and hay fever, allergic sensitisation and total IgE in adults. Data from a population-based cross-sectional study on respiratory health, including the measurement of fatty acids in the serum phospholipids of 740 adults between 20 and 64 years of age, were analysed. Positive associations were found between hay fever and arachidonic acid, and allergic sensitisation and oleic acid. No other fatty acids showed any association with hay fever or allergic sensitisation. Elevated levels of total IgE were not related to fatty acids. Concentrations of long-chain n-3 fatty acids, trans fatty acids or saturated fatty acids in serum phospholipids were not associated with allergic diseases in adults in this study. The present result on the association between hay fever and arachidonic acid is consistent with current hypotheses but warrants further research.

  6. The effect of diet on the fatty acid compositions of serum, brain, brain mitochondria and myelin in the rat

    PubMed Central

    Rathbone, L.

    1965-01-01

    1. Three groups of female rats (8–12 weeks old) were maintained respectively on a linoleic acid-rich diet, a linoleic acid-poor predominantly saturated-fatty acid diet and a normal diet. Changes in the fatty acid compositions of serum, brain, brain mitochondria-rich fraction and myelin were observed. 2. Of the serum fatty acids, linoleic acid showed the greatest change in the percentage of the total acids in response to diet; the change in the proportion of oleic acid was considerable. The percentages of arachidonic acid in serum fatty acids in the groups on the linoleic acid-rich and linoleic acid-poor diets were similar, but higher than those in the normal group. 3. Changes in the proportions of linoleic acid, arachidonic acid and docosahexaenoic acid occurred in brain fatty acids that to some extent paralleled those occurring in the serum. Changes in the proportions of most other acids in the serum fatty acids were not accompanied by corresponding changes in the brain fatty acids. 4. The percentage fatty acid compositions of a mitochondria-rich fraction and myelin are given, and changes in the relative proportions of linoleic acid, arachidonic acid and possibly some docosapolyenoic acids were demonstrated to occur as a result of diet. 5. The results are discussed in relation to the possible aetiology of multiple sclerosis. PMID:5881652

  7. Serum uric acid levels and hormone therapy type: a retrospective cohort study of postmenopausal women.

    PubMed

    Jung, Jae H; Song, Gwan G; Lee, Young H; Kim, Jae-Hoon; Hyun, Myung H; Choi, Sung J

    2017-08-07

    Serum uric acid levels increase in postmenopausal women, but decrease when hormone therapy (HT) is administered. No study has, however, evaluated the effects of different types of HT on serum uric acid levels. We therefore examined whether estrogen therapy (ET), estrogen plus progestogen therapy (EPT), and tibolone use affected serum uric acid levels in this population. We performed a retrospective cohort study of postmenopausal women. From 2005 to 2015, postmenopausal women who had undergone blood uric acid-level testing at least twice were enrolled. Participants were grouped according to HT regimen: ET, EPT, or tibolone. The nonhormone therapy group did not receive HT. Differences in serum uric acid levels were examined in each group. Our analysis was adjusted to accommodate different follow-up intervals for individual participants. Multiple variables were adjusted using the Tukey-Kramer method. Age, body mass index, hypertension, diabetes mellitus, dyslipidemia, estimated glomerular filtration rate, alcohol consumption, smoking status, and comedications were also adjusted. After adjusting for multiple variables, the serum uric acid level increased to 0.87 ± 0.27 mg/dL (least squares mean ± standard error) in the nonhormone therapy group, and serum uric levels in the EPT group were found to be significantly lower (-0.38 ± 0.29 mg/dL, P < 0.001). The serum uric acid levels in the ET and tibolone groups did not, however, differ significantly from the nonhormone therapy group level. We attribute our findings to the effects of progestogen, rather than estrogen.

  8. Serum N-terminal telopeptide of type I collagen as an early marker of fracture nonunion in rabbits

    PubMed Central

    Lin, Jian-Ping; Shi, Zhan-Jun; Shen, Ning-Jiang; Wang, Jian; Li, Zao-Min; Xiao, Jun

    2016-01-01

    The aim of the present study was to establish an experimental animal model of fracture nonunion, and to investigate the changes in serum biomarker concentrations in fracture nonunion. A total of 20 purebred New Zealand rabbits were divided into two group: A bone defect group and a bone fracture group. In the bone defect group, a 15-mm section of bone (including the periosteum) was removed from the mid-radius, and the medullary cavities were closed with bone wax. In the bone fracture group, the mid-radius was fractured. X-rays were taken and blood samples were collected preoperatively and at 2, 3, 4, 5, 6, 7, 8, 10 and 12 weeks after the surgical procedure. The serum concentrations of osteocalcin (OC) and bone-specific alkaline phosphatase (BSAP) served as markers of bone formation, and those of C-terminal telopeptide of type I collagen (CTX), N-terminal telopeptide of type I collagen (NTX) and tartrate-resistant acid phosphatase 5b (TRACP 5b) served as markers of bone resorption. The concentration levels of the markers were measured using a biotin double-antibody sandwich enzyme-linked immunosorbent assay. In the bone defect group, bone callus was observed on X-ray at 2 weeks in three rabbits and the bone calluses stabilized at 5 weeks; however, none of the bones had healed at 8 weeks. In the bone fracture group, the fracture line was distorted at 2 weeks and bone calluses formed at 6–8 weeks. In the bone defect group, the serum BSAP and TRACP 5b concentrations increased following the surgical procedure, peaked at 4 weeks, began to decrease at 5 weeks and stabilized after 6 weeks. The serum OC concentrations did not change significantly following the surgical procedure. The serum CTX concentrations fluctuated during the first 4 weeks, peaked at 5 weeks, then decreased and stabilized after 6 weeks. The serum NTX concentrations fluctuated during the first 4 weeks, were significantly lower at 5 weeks compared with the other time points and stabilized after 6 weeks

  9. Comparative Serum Fatty Acid Profiles of Captive and Free-Ranging Cheetahs (Acinonyx jubatus) in Namibia

    PubMed Central

    Wachter, Bettina; Heinrich, Sonja K.; Reyers, Fred; Mienie, Lodewyk J.

    2016-01-01

    Cheetahs (Acinonyx jubatus) are highly specialised large felids, currently listed as vulnerable on the IUCN red data list. In captivity, they are known to suffer from a range of chronic non-infectious diseases. Although low heterozygosity and the stress of captivity have been suggested as possible causal factors, recent studies have started to focus on the contribution of potential dietary factors in the pathogenesis of these diseases. Fatty acids are an important component of the diet, not only providing a source of metabolisable energy, but serving other important functions in hormone production, cellular signalling as well as providing structural components in biological membranes. To develop a better understanding of lipid metabolism in cheetahs, we compared the total serum fatty acid profiles of 35 captive cheetahs to those of 43 free-ranging individuals in Namibia using gas chromatography-mass spectrometry. The unsaturated fatty acid concentrations differed most remarkably between the groups, with all of the polyunsaturated and monounsaturated fatty acids, except arachidonic acid and hypogeic acid, detected at significantly lower concentrations in the serum of the free-ranging animals. The influence of age and sex on the individual fatty acid concentrations was less notable. This study represents the first evaluation of the serum fatty acids of free-ranging cheetahs, providing critical information on the normal fatty acid profiles of free-living, healthy individuals of this species. The results raise several important questions about the potential impact of dietary fatty acid composition on the health of cheetahs in captivity. PMID:27992457

  10. Serum Paraoxonase 1 Activity Is Associated with Fatty Acid Composition of High Density Lipoprotein

    PubMed Central

    Boshtam, Maryam; Pourfarzam, Morteza; Ani, Mohsen; Naderi, Gholam Ali; Basati, Gholam; Mansourian, Marjan; Dinani, Narges Jafari; Asgary, Seddigheh; Abdi, Soheila

    2013-01-01

    Introduction. Cardioprotective effect of high density lipoprotein (HDL) is, in part, dependent on its related enzyme, paraoxonase 1 (PON1). Fatty acid composition of HDL could affect its size and structure. On the other hand, PON1 activity is directly related to the structure of HDL. This study was designed to investigate the association between serum PON1 activity and fatty acid composition of HDL in healthy men. Methods. One hundred and forty healthy men participated in this research. HDL was separated by sequential ultracentrifugation, and its fatty acid composition was analyzed by gas chromatography. PON1 activity was measured spectrophotometrically using paraxon as substrate. Results. Serum PON1 activity was directly correlated with the amount of stearic acid and dihomo-gamma-linolenic acid (DGLA). PON1/HDL-C was directly correlated with the amount of miristic acid, stearic acid, and DGLA and was inversely correlated with total amount of ω6 fatty acids of HDL. Conclusion. The fatty acid composition of HDL could affect the activity of its associated enzyme, PON1. As dietary fats are the major determinants of serum lipids and lipoprotein composition, consuming some special dietary fatty acids may improve the activity of PON1 and thereby have beneficial effects on health. PMID:24167374

  11. Comparative Serum Fatty Acid Profiles of Captive and Free-Ranging Cheetahs (Acinonyx jubatus) in Namibia.

    PubMed

    Tordiffe, Adrian S W; Wachter, Bettina; Heinrich, Sonja K; Reyers, Fred; Mienie, Lodewyk J

    2016-01-01

    Cheetahs (Acinonyx jubatus) are highly specialised large felids, currently listed as vulnerable on the IUCN red data list. In captivity, they are known to suffer from a range of chronic non-infectious diseases. Although low heterozygosity and the stress of captivity have been suggested as possible causal factors, recent studies have started to focus on the contribution of potential dietary factors in the pathogenesis of these diseases. Fatty acids are an important component of the diet, not only providing a source of metabolisable energy, but serving other important functions in hormone production, cellular signalling as well as providing structural components in biological membranes. To develop a better understanding of lipid metabolism in cheetahs, we compared the total serum fatty acid profiles of 35 captive cheetahs to those of 43 free-ranging individuals in Namibia using gas chromatography-mass spectrometry. The unsaturated fatty acid concentrations differed most remarkably between the groups, with all of the polyunsaturated and monounsaturated fatty acids, except arachidonic acid and hypogeic acid, detected at significantly lower concentrations in the serum of the free-ranging animals. The influence of age and sex on the individual fatty acid concentrations was less notable. This study represents the first evaluation of the serum fatty acids of free-ranging cheetahs, providing critical information on the normal fatty acid profiles of free-living, healthy individuals of this species. The results raise several important questions about the potential impact of dietary fatty acid composition on the health of cheetahs in captivity.

  12. The evaluation of serum homocysteine, folic acid, and vitamin B12 in patients complicated with preeclampsia.

    PubMed

    Shahbazian, Nahid; Jafari, Razieh Mohammad; Haghnia, Sahar

    2016-10-01

    Increased plasma homocysteine may be associated with adverse pregnancy outcomes, such as preeclampsia. The aim of this study was to determine the plasma homocysteine, serum folate, and vitamin B12 levels in preeclamptic pregnant women. This case-control study was conducted in 2016 in Ahwaz on 51 pregnant women with preeclampsia and 51 healthy pregnant women of the same gestational age, who served as controls. The case group also was subdivided into severe and non-severe preeclampsia. Patients' data were collected through a questionnaire and medical records. Serum homocysteine, folic acid, and vitamin B12 were analyzed using chemiluminescent assay. The results were compared between two groups. Statistical analyses were done using IBM-SPSS 20.0. A Kolmogorov-Smirnov test, independent samples t-test, Mann-Whitney test, and Chi-square test were used for data analysis. No different demographic characteristics were found among the groups. Pregnant women complicated with preeclampsia displayed significantly higher serum homocysteine levels (p < 0.001) and lower serum folate (p = 0.005) and vitamin B12 levels (p < 0.001) compared to controls. A statistically significant inverse correlation was evident between serum homocysteine and serum folate levels in preeclamptic patients (p = 0.005; r = -0.389). In addition, an inverse correlation was identified between homocysteine and serum vitamin B12, but it was not statistically significant (p = 0.160; r = -0.200). Significant differences occurred in serum homocysteine and folate levels between the severe and non-severe subgroups (p < 0.001, p < 0.001). Women complicated with preeclampsia displayed higher maternal serum homocysteine and lower serum folate and vitamin B12. Further studies are needed to confirm if the prescription of folic acid and vitamin B12 in women with a deficiency of these vitamins could decrease the level of serum homocysteine and, therefore, reduce the risk of preeclampsia or, if it occurred, its severity.

  13. In vitro study of caffeic acid-bovine serum albumin interaction.

    PubMed

    Adzet, T; Camarasa, J; Escubedo, E; Merlos, M

    1988-01-01

    Caffeic acid, a natural product with pharmacological properties, such as DOPA-decarboxylase and 5-lipooxygenase inhibition, has been tested in vitro for its binding ratio to bovine serum albumin. This study was carried out by means of four analytical methods. Equilibrium dialysis has been proved to be the most reliable in determination of total binding sites, while acid precipitation has been evaluated as a model of irreversible binding. A binding ratio between 61 and 95% was observed, also varying according the caffeic acid and albumin concentration, pH and protein conformation. Binding constants were calculated by mathematical fitting to a hyperbolic plot. Other cinnamic acids non-o-diphenolic (ferulic acid, m- and p-coumaric acids) have been proved to have a binding ratio to bovine serum albumin of less than 10%.

  14. Investigation of competitive binding of ibuprofen and salicylic acid with serum albumin by affinity capillary electrophoresis.

    PubMed

    Li, Zhu-Mei; Wei, Chuan-Wan; Zhang, Yintang; Wang, Di-Shan; Liu, You-Nian

    2011-07-01

    Ibuprofen and salicylic acid, two typical non-steroidal anti-inflammatory drugs, are used commonly as analgesic drug in clinical medicine and sometimes are co-administered. When the drugs are co-administered, the drug-drug interactions may occur, and can lead to alter the safety and efficacy of drugs, resulting in variations in drug response of the co-administered drugs. Affinity capillary electrophoresis (ACE) was employed to investigate the competitive binding of ibuprofen and salicylic acid on serum albumin. Mobility ratio, derivatives from mobility shift method, was used to deduce the binding constant (K(b)). The binding constants of ibuprofen with HSA are 2.97×10⁶ M⁻¹ and 7.07×10⁴ M⁻¹, respectively; while for salicylic acid, the binding constant is 5.99×10⁴ M⁻¹. The competitive binding of the two drugs was investigated by addition of excessive ibuprofen into the solutions containing constant concentrations of salicylic acid and serum albumin. The results confirmed that ibuprofen and salicylic acid have different high-affinity binding site, but share some low-affinity binding sites on the serum albumin; and ibuprofen is able to partially replace salicylic acid from the preformed binary complexes of serum albumin and salicylic acid. Copyright © 2011 Elsevier B.V. All rights reserved.

  15. Reversible binding of ethacrynic acid to human serum albumin: difference circular dichroism study.

    PubMed

    Bertucci, C; Nanni, B; Salvadori, P

    1999-01-01

    The reversible binding of ethacrynic acid was characterized by a difference circular dichroism method. A 2/1 stoichiometry was determined for the [drug]/[HSA] (human serum albumin) complex. The reversible binding of ethacrynic acid to HSA determines direct competition with ligands that selectivity bind to site II and to the fatty acid site. Furthermore, indirect competition was shown for ligands for site I (anti-cooperative) and to site III (cooperative).

  16. The effect of hemodialysis and hemoperfusion on serum valproic acid concentration.

    PubMed

    Kandrotas, R J; Love, J M; Gal, P; Oles, K S

    1990-09-01

    We report a patient with dialysis-induced encephalopathy who was taking divalproex sodium for a seizure disorder. Her serum valproic acid concentration appeared to be in the low therapeutic range at 54 mg/l yet she continued to have seizure activity. The elimination half-life and apparent clearance of valproic acid were the same for both a dialysis and nondialysis day, indicating that hemodialysis/hemoperfusion has little effect on the overall removal of valproic acid from the body.

  17. Spectroscopic Evidence for Complexing of Acetic Acid with Bovine Serum Albumin, Gramicidin, and Dimethylformamide

    PubMed Central

    Cann, John R.

    1961-01-01

    Acetic acid has a major effect on the absorption spectra of bovine serum albumin, gramicidin, and dimethylformamide in the region, 255 to 200 mμ. Increasing the concentration of acetic acid causes progressively decreasing absorbency accompanied by a large and progressively increasing red shift of the absorption maximum. The decrease in absorbency is interpreted in terms of a reversible complexing of acetic acid with these molecules and the red shift in terms of a non-specific solvent effect. PMID:13876221

  18. Serum vitamin B12, folic acid, and homocysteine levels in children with febrile seizure.

    PubMed

    Özkale, Yasemin; Erol, İlknur; Kılıçarslan, Buket; Özkale, Murat; Saygı, Semra; Sarıtürk, Çağla; Sezgin, Nurzen

    2015-01-01

    The aim of this study is to investigate the associations between febrile seizure and serum levels of vitamin B12, folic acid, and homocysteine. One hundred and four children who presented with febrile seizure and 75 controls who presented with febrile illness unaccompanied by seizure were enrolled into the study. Mean levels of vitamin B12, folic acid and homocysteine were compared between two groups. Mean vitamin B12 level in the febrile seizure group was significantly lower than the control group. The febrile seizure patients with 3 or more had significantly lower serum folic acid than the subgroups with two or one episode only. Serum concentrations of folic acid were significantly lower in the febrile seizure subgroup with body temperature 37.5-39.0˚C at time of convulsion. Low serum vitamin B12 may reduce a child's threshold for seizure and may be a risk factor for febrile seizure. Low serum folic acid level may be predisposed to recurrent febrile seizure.

  19. [Determination of cinnamic acid and glycyrrhizic acid in rat serum and its pharmacokinetics after oral administration of Dangguisini decoction].

    PubMed

    Gao, Yu-Qin; Wu, Jie; Jiang, Ren-Wang; Zhao, Guo-Ping

    2011-03-01

    To mensurate concentrations and pharmacokinetics of cinnamic acid and glycyrrhizic acid in rats after oral adiministration Dangguisini decoction. To Determine serum concentration of cinnamic acid and glycyrrhizic acid by High-Performance Liquid Chromatography and calculate its parameter of pharmacokinetics in rats after oral administration of Dangguisini decoction via 3P97 software. Parameters of Pharmacokinetics of cinnamic acid and glycyrrhizic acid were Cmax 9.2008 (mg/L), AUC 304.0734 (mg/L) x min and Cmax 51.1330(mg/L), AUC 21476.9688 (mg/L) x min respectively in rats after oral administration of Dangguisini decoction. Absorption of cinnamic acid is quick and its metabolize is quick too, but metabolism of glycyrrhizic acid is oppositely slow in rats after oral administration of Dangguisini decoction.

  20. [Effect of nuts enrich in monounsaturated acid on serum lipid of hyperlipidemia rats].

    PubMed

    Yan, Shaofang; Xiao, Ying; Wang, Junbo; Liang, Xuejun

    2003-03-01

    In order to observe the regulatory effect of monounsaturated acid-enriched almond and macadamia nuts on blood lipid-level (TC, TG, HDL-C), the hyperlipidemia Wistar rats were used as the model and a diet containing almond and macadamia at the doses of between 12.5% and 25.0% was given for six weeks. The results showed that the level of the serum TC and TG in each study group was significantly lower than that of high fat chow control group (P < 0.05). There was a significant increase (P < 0.05) in the serum HDL-C level in the high fat chow group with high-dose macadamias compared with that in the high fat chow control group. The findings suggested that nuts enrich in monounsaturated acid could decrease the level of serum TC and TG and macadamias could increased the level of serum HDL-C in the hyperlipidemia rats.

  1. Influence of myristic acid on furosemide binding to bovine serum albumin. Comparison with furosemide-human serum albumin complex

    NASA Astrophysics Data System (ADS)

    Bojko, B.; Sułkowska, A.; Maciążek-Jurczyk, M.; Równicka, J.; Sułkowski, W. W.

    2010-06-01

    Fluorescence studies on furosemide (FUR) binding to bovine serum albumin (BSA) showed the existence of three or four binding sites in the tertiary structure of the protein. Two of them are located in subdomain IIA, while the others in subdomains IB and/or IIIA. Furosemide binding in subdomain IB is postulated on the basis of run of Stern-Volmer plot indicating the existence of two populations of tryptophans involved in the interaction with FUR. In turn, the significant participation of tyrosil residues in complex formation leads to the consideration of the subdomain IIIA as furosemide low-affinity binding site. The effect of increasing concentration of fatty acid on FUR binding in all studied binding sites was also investigated and compared with the previous results obtained for human serum albumin (HSA). For BSA the lesser impact of fatty acid on affinity between drug and albumin was observed. This is probably a result of more significant role of tyrosines in the complex formation and different polarity of microenvironment of the fluorophores when compared HSA and BSA. The most distinct differences between FUR-BSA and FUR-HSA binding parameters are observed when third fatty acid molecule is bound with the protein and rotation of domains I and II occurs. However these structural changes mostly affect FUR low affinity binding sites.

  2. Influence of myristic acid on furosemide binding to bovine serum albumin. Comparison with furosemide-human serum albumin complex.

    PubMed

    Bojko, B; Sułkowska, A; Maciazek-Jurczyk, M; Równicka, J; Sułkowski, W W

    2010-06-01

    Fluorescence studies on furosemide (FUR) binding to bovine serum albumin (BSA) showed the existence of three or four binding sites in the tertiary structure of the protein. Two of them are located in subdomain IIA, while the others in subdomains IB and/or IIIA. Furosemide binding in subdomain IB is postulated on the basis of run of Stern-Volmer plot indicating the existence of two populations of tryptophans involved in the interaction with FUR. In turn, the significant participation of tyrosil residues in complex formation leads to the consideration of the subdomain IIIA as furosemide low-affinity binding site. The effect of increasing concentration of fatty acid on FUR binding in all studied binding sites was also investigated and compared with the previous results obtained for human serum albumin (HSA). For BSA the lesser impact of fatty acid on affinity between drug and albumin was observed. This is probably a result of more significant role of tyrosines in the complex formation and different polarity of microenvironment of the fluorophores when compared HSA and BSA. The most distinct differences between FUR-BSA and FUR-HSA binding parameters are observed when third fatty acid molecule is bound with the protein and rotation of domains I and II occurs. However these structural changes mostly affect FUR low affinity binding sites. Copyright 2010 Elsevier B.V. All rights reserved.

  3. Determination of binding affinities of retinoids to retinoic acid-binding protein and serum albumin

    PubMed Central

    Sani, Brahma P.; Titus, Belinda C.; Banerjee, Chandra K.

    1978-01-01

    Binding affinities of retinoic acid and its synthetic analogues to intracellular retinoic acid-binding protein, which is a possible candidate for mediating their biological function, and to serum albumin, the plasma transport protein, were evaluated. A quantitative method involving elimination of interfering serum albumin by immunoprecipitation was developed to measure the binding efficiency of these retinoids, some of which are active in modifying epithelial differentiation and preventing tumorigenesis. Two cyclopentenyl analogues of retinoic acid and 13-cis-retinoic acid showed, like retinoic acid, a binding efficiency of 100% for the cellular binding protein. With the phenyl, dichlorophenyl and trimethylmethoxyphenyl analogues of retinoic acid, the binding efficiency increased as the substituents on the aromatic ring increased; thus the trimethylmethoxyphenyl analogue binds almost as efficiently as retinoic acid itself. However, the trimethylmethoxyphenyl analogue with a sulphur atom on the side chain has a much decreased binding affinity. The correlation noticed between the binding efficiency of these retinoids and their biological activity in differentiation and/or in the control of tumorigenesis particularly enhances the confidence in the present method of determining the relative binding efficiencies. None of the vitamins, hormones and cofactors tested, showed appreciable affinity for the retinoic acid-binding site. Studies on binding of retinoic acid and its analogues to serum albumin indicate that no correlation exists between binding affinity for albumin and their biological potency. PMID:666734

  4. Serum uric acid concentrations and risk of frailty in older adults.

    PubMed

    García-Esquinas, Esther; Guallar-Castillón, Pilar; Carnicero, José Antonio; Buño, Antonio; García-García, Francisco José; Rodríguez-Mañas, Leocadio; Rodríguez-Artalejo, Fernando

    2016-09-01

    To evaluate for the first time the longitudinal relationship between serum uric acid concentrations and risk of frailty. Prospective cohort study of 2198 non-institutionalized individuals aged ≥60years recruited in 2008-2010. At baseline, information was obtained on socio-demographic factors, health behaviors and morbidity, while serum uric acid was determined in 12-h fasting blood samples. Study participants were followed-up through 2012 to assess incident frailty, defined as ≥2 of the following 4 Fried criteria: exhaustion, muscle weakness, low physical activity, and slow walking speed. During a mean 3.5-year follow-up, 256 cases of incident frailty were identified. After multivariate adjustment, the odds ratios (95% confidence interval) of frailty comparing the second and third tertiles of uric acid to the lowest tertile were, respectively: 1.18 (0.83-1.68) and 1.57 (1.11-2.22); p-linear trend=0.01. The corresponding result for a 1mg/dL increase in serum uric acid concentration was 1.12 (1.00-1.24). Similar associations were observed across subgroups defined by sex, age, body mass index, and physical activity. As regards each frailty component, the odds ratios (95% confidence interval) per 1mg/dL increase in serum uric acid were 1.10 (0.99-1.23) for low physical activity, 1.08 (0.95-1.23) for low walking speed, 1.08 (0.67-1.73) for exhaustion and 0.91 (0.81-1.02) for weakness. Serum uric acid concentrations are positively associated with the risk of frailty in older adults. Further studies are needed to evaluate whether specific dietary recommendations or pharmacological strategies aimed at lowering serum uric acid would be beneficial to prevent the development of this syndrome. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Zoledronic acid acutely increases sclerostin serum levels in women with postmenopausal osteoporosis.

    PubMed

    Catalano, Antonino; Morabito, Nancy; Basile, Giorgio; Brancatelli, Santa; Cucinotta, Domenico; Lasco, Antonino

    2013-05-01

    Sclerostin is a circulating inhibitor of the Wnt-signaling pathway produced by osteocytes, which acts as a negative regulator of bone formation. Effects of zoledronic acid on sclerostin serum levels in postmenopausal osteoporosis are unknown. The purpose of this study was to evaluate sclerostin serum levels after zoledronic acid administration and correlate variations with bone turnover markers. We conducted a prospective intervention study in an ambulatory care setting. Forty women (mean age 62.6 ± 4.9 years) with postmenopausal osteoporosis were enrolled in this study and randomized into 2 groups to receive zoledronic acid (5 mg) or placebo. At baseline and then at 2, 7, 30, and 360 days after zoledronic acid or placebo administration, serum levels of sclerostin, bone-specific alkaline phosphatase (BSAP), as a bone formation marker, and serum C-telopeptide of type 1 collagen (CTX), as a bone resorption marker, were measured. Sclerostin serum levels increased by day 2, reached a peak at day 7 (3-fold baseline, P < .001), and then decreased at day 30 and returned near to baseline after 360 days in the zoledronic acid group. Both CTX and BSAP were reduced, and a significant negative correlation was observed between the percentage changes of sclerostin and the variation in BSAP and CTX at all time points in the zoledronic acid group (P < .05). No changes were observed in the placebo group. Our data demonstrate that zoledronic acid increases sclerostin serum levels and that sclerostin could play a role in coupling bone resorption to bone formation.

  6. Effects of folic acid supplementation on serum homocysteine and lipoprotein (a) levels during pregnancy

    PubMed Central

    Hekmati Azar Mehrabani, Zohreh; Ghorbanihaghjo, Amir; Sayyah Melli, Manizheh; Hamzeh-Mivehroud, Maryam; Fathi Maroufi, Nazila; Bargahi, Nasrin; Bannazadeh Amirkhiz, Maryam; Rashtchizadeh, Nadereh

    2015-01-01

    Introduction:There are many ideas concerning the etiology and pathogenesis of preeclampsia including endothelial dysfunction, inflammation and angiogenesis. Elevated levels of total homocysteine (Hcy) and lipoprotein (a) [Lp(a)] are risk factors for endothelial dysfunction. This study aimed to evaluate the effect of high dose folic acid (FA) on serum Hcy and Lp(a) concentrations with respect to methylenetetrahydrofolate reductase (MTHFR) polymorphisms 677C→T during pregnancy. Methods: In a prospective uncontrolled intervention, 90 pregnant women received 5 mg FA supplementation before pregnancy till 36th week of pregnancy. The MTHFR polymorphisms 677C→T, serum lactate dehydrogenase activity, urine protein and creatinine concentrations were measured before starting folic acid administration. Serum levels of Hcy and Lp(a) were determined before and after completion of folic acid supplementation period. Results: Supplementation of the patients with FA for 36 week decreased the median (minimum– maximum) levels of serum Hcy from 11.40 μmol/L (4.40-28.70) to 9.70 (1.60-20.80) μmol/L (p=0.001). There was no significant change in serum Lp(a) after FA supplementation (p=0.17). The overall prevalence of genotypes in pregnant women that were under study for MTHFR C677T polymorphism was 53.3% CC, 26.7% CT and 20.0% TT. There was no correlation between decreasing level of serum Hcy in the patients receiving FA and MTHFR polymorphisms. Conclusion:Although FA supplementation decreased serum levels of Hcy in different MTHFR genotypes, serum Lp(a) was not changed by FA supplements. Our data suggests that FA supplementation effects on serum Hcy is MTHFR genotype independent in pregnant women. PMID:26929921

  7. Different Serum Free Fatty Acid Profiles in NAFLD Subjects and Healthy Controls after Oral Fat Load.

    PubMed

    Gambino, Roberto; Bugianesi, Elisabetta; Rosso, Chiara; Mezzabotta, Lavinia; Pinach, Silvia; Alemanno, Natalina; Saba, Francesca; Cassader, Maurizio

    2016-03-31

    Free fatty acid (FFA) metabolism can impact on metabolic conditions, such as obesity and nonalcoholic fatty liver disease (NAFLD). This work studied the increase in total FFA shown in NAFLD subjects to possibly characterize which fatty acids significantly accounted for the whole increase. 21 patients with NAFLD were selected according to specified criteria. The control group consisted of nine healthy subjects. All subjects underwent an oral standard fat load. Triglycerides; cholesterol; FFA; glucose and insulin were measured every 2 h with the determination of fatty acid composition of FFA. higher serum FFA levels in NAFLD subjects are mainly due to levels of oleic, palmitic and linoleic acids at different times. Significant increases were shown for docosahexaenoic acid, linolenic acid, eicosatrienoic acid, and arachidonic acid, although this was just on one occasion. In the postprandial phase, homeostatic model assessment HOMA index positively correlated with the ω3/ω6 ratio in NAFLD patients. the higher serum levels of FFA in NAFLD subjects are mainly due to levels of oleic and palmitic acids which are the most abundant circulating free fatty acids. This is almost exactly corresponded with significant increases in linoleic acid. An imbalance in the n-3/n-6 fatty acids ratio could modulate postprandial responses with more pronounced effects in insulin-resistant subjects, such as NAFLD patients.

  8. Different Serum Free Fatty Acid Profiles in NAFLD Subjects and Healthy Controls after Oral Fat Load

    PubMed Central

    Gambino, Roberto; Bugianesi, Elisabetta; Rosso, Chiara; Mezzabotta, Lavinia; Pinach, Silvia; Alemanno, Natalina; Saba, Francesca; Cassader, Maurizio

    2016-01-01

    Background: Free fatty acid (FFA) metabolism can impact on metabolic conditions, such as obesity and nonalcoholic fatty liver disease (NAFLD). This work studied the increase in total FFA shown in NAFLD subjects to possibly characterize which fatty acids significantly accounted for the whole increase. Methods: 21 patients with NAFLD were selected according to specified criteria. The control group consisted of nine healthy subjects. All subjects underwent an oral standard fat load. Triglycerides; cholesterol; FFA; glucose and insulin were measured every 2 h with the determination of fatty acid composition of FFA. Results: higher serum FFA levels in NAFLD subjects are mainly due to levels of oleic, palmitic and linoleic acids at different times. Significant increases were shown for docosahexaenoic acid, linolenic acid, eicosatrienoic acid, and arachidonic acid, although this was just on one occasion. In the postprandial phase, homeostatic model assessment HOMA index positively correlated with the ω3/ω6 ratio in NAFLD patients. Conclusions: the higher serum levels of FFA in NAFLD subjects are mainly due to levels of oleic and palmitic acids which are the most abundant circulating free fatty acids. This is almost exactly corresponded with significant increases in linoleic acid. An imbalance in the n-3/n-6 fatty acids ratio could modulate postprandial responses with more pronounced effects in insulin-resistant subjects, such as NAFLD patients. PMID:27043543

  9. Assessment of Folic Acid Supplementation in Pregnant Women by Estimation of Serum Levels of Tetrahydrofolic Acid, Dihydrofolate Reductase, and Homocysteine.

    PubMed

    Naithani, Manisha; Saxena, Vartika; Mirza, Anissa Atif; Kumari, Ranjeeta; Sharma, Kapil; Bharadwaj, Jyoti

    2016-01-01

    Background. Status of folic acid use in pregnant women of the hilly regions in North India was little known. This study was carried out to assess the folic acid use and estimate folate metabolites in pregnant women of this region. Materials and Methods. This cross-sectional study is comprised of 76 pregnant women, whose folic acid supplementation was assessed by a questionnaire and serum levels of homocysteine, tetrahydrofolic acid (THFA), and dihydrofolate reductase (DHFR) were estimated using Enzyme Linked Immunoassays. Results. The study data revealed awareness of folic acid use during pregnancy was present in 46.1% and 23.7% were taking folic acid supplements. The study depicted that there was no statistically significant difference between serum levels of THFA and DHFR in pregnant women with and without folic acid supplements (p = 0.790). Hyperhomocysteinemia was present in 15.78% of the participants. Conclusion. Less awareness about folic acid supplementation and low use of folic acid by pregnant women were observed in this region. Sufficient dietary ingestion may suffice for the escalated requirements in pregnancy, but since this cannot be ensured, hence folic acid supplementation should be made as an integral part of education and reproductive health programs for its better metabolic use, growth, and development of fetus.

  10. Assessment of Folic Acid Supplementation in Pregnant Women by Estimation of Serum Levels of Tetrahydrofolic Acid, Dihydrofolate Reductase, and Homocysteine

    PubMed Central

    Saxena, Vartika; Mirza, Anissa Atif; Kumari, Ranjeeta; Sharma, Kapil; Bharadwaj, Jyoti

    2016-01-01

    Background. Status of folic acid use in pregnant women of the hilly regions in North India was little known. This study was carried out to assess the folic acid use and estimate folate metabolites in pregnant women of this region. Materials and Methods. This cross-sectional study is comprised of 76 pregnant women, whose folic acid supplementation was assessed by a questionnaire and serum levels of homocysteine, tetrahydrofolic acid (THFA), and dihydrofolate reductase (DHFR) were estimated using Enzyme Linked Immunoassays. Results. The study data revealed awareness of folic acid use during pregnancy was present in 46.1% and 23.7% were taking folic acid supplements. The study depicted that there was no statistically significant difference between serum levels of THFA and DHFR in pregnant women with and without folic acid supplements (p = 0.790). Hyperhomocysteinemia was present in 15.78% of the participants. Conclusion. Less awareness about folic acid supplementation and low use of folic acid by pregnant women were observed in this region. Sufficient dietary ingestion may suffice for the escalated requirements in pregnancy, but since this cannot be ensured, hence folic acid supplementation should be made as an integral part of education and reproductive health programs for its better metabolic use, growth, and development of fetus. PMID:27064332

  11. Effect of excitatory amino acids on serum TSH and thyroid hormone levels in freely moving rats.

    PubMed

    Alfonso, M; Durán, R; Arufe, M C

    2000-01-01

    The actions of glutamate (L-Glu), and glutamate receptor agonists on serum thyroid hormones (T4 and T3) and TSH levels have been studied in conscious and freely moving adult male rats. The excitatory amino acids (EAA), L-Glu, N-methyl-D-aspartate (NMDA), kainic acid (KA) and domoic acid (Dom) were administered intraperitoneally. Blood samples were collected through a cannula implanted in the rats jugular 0--60 min after injection. Thyroid hormone concentrations were measured by enzyme immunoassay, and thyrotrophin (TSH) concentrations were determined by radioimmunoassay. The results showed that L-Glu (20 and 25 mg/kg) and NMDA (25 mg/kg) increased serum thyroxine (T4), triiodothyronine (T3) and TSH concentrations. Serum thyroid hormone levels increased 30 min after treatment, while serum TSH levels increased 5 min after i.p. administration, in both cases serum levels remained elevated during one hour. Injection of the non-NMDA glutamatergic agonists KA (30 mg/kg) and Dom (1 mg/kg) produced an increase in serum thyroid hormones and TSH levels. These results suggest the importance of EAAs in the regulation of hormone secretion from the pituitary-thyroid axis, as well as the importance of the NMDA and non-NMDA receptors in this stimulatory effect.

  12. Serum iron, vitamin B12 and folic acid levels in Parkinson's disease.

    PubMed

    Madenci, Gulizar; Bilen, Sule; Arli, Berna; Saka, Mustafa; Ak, Fikri

    2012-07-01

    We aimed to investigate possible associations between systemic iron metabolism deficiency and Parkinson's disease, and also to research any possible correlations between stage of the disease and vitamin B12 and folic acid levels. 33 male and 27 female patients diagnosed with idiopathic Parkinson's disease and 22 male and 20 female age- and sex-matched controls were enrolled in the study. Having the diagnosis of secondary Parkinsonism or Parkinson plus syndromes, and for the females, not being in the menopausal stage were considered as exclusion criteria. Recordings of blood samples of both groups collected after 8 h fasts were assessed in terms of serum iron, ferritin levels and iron-binding capacity, vitamin B12 and folic acid levels. The Hoehn and Yahr scale was used to determine the stage of the disease. No statistically significant difference was found with respect to mean serum iron, median serum ferritin levels and median serum iron-binding capacity between the groups. A statistically significant but inverse correlation was found between symptoms' duration and serum iron and ferritin levels. There was no statistically significant difference between the groups with respect to vitamin B12 and folic acid levels. However, a statistically significant but inverse correlation was determined between the patients' vitamin B12 levels and the Hoehn and Yahr scores. As Parkinson's disease progresses, serum iron, ferritin and vitamin B12 levels may decrease. The lower levels of these parameters may be the cause of the progression or may be the result of it.

  13. Association between Serum Uric Acid and Non-Alcoholic Fatty Liver Disease: A Meta-Analysis.

    PubMed

    Darmawan, Guntur; Hamijoyo, Laniyati; Hasan, Irsan

    2017-04-01

    non-alcoholic fatty liver disease (NAFLD) is known to be associated with some metabolic disorders. Recent studies suggested the role of uric acid in NAFLD through oxidative stress and inflammatory process. This study is aimed to evaluate the association between serum uric acid and NAFLD. a systematic literature review was conducted using Pubmed and Cochrane library. The quality of all studies was assessed using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE). All data were analyzed using REVIEW MANAGER 5.3. eleven studies from America and Asia involving 100,275 subjects were included. The pooled adjusted OR for NAFLD was 1.92 (95% CI: 1.66-2.23; p<0.00001). Subgroup analyses were done based on study design, gender, non-diabetic subjects, non-obese subjects. All subgroup analyses showed statistically significant adjusted OR and most of which having low to moderate heterogeneity. Two studies revealed relationship between increased serum uric acid levels and severity of NAFLD. No publication bias was observed. our study demonstrated association between serum uric acid level and NAFLD. This finding brings a new insight of uric acid in clinical practice. Increased in serum uric acid levels might serve as a trigger for physician to screen for NAFLD.

  14. Radiotherapy improves serum fatty acids and lipid profile in breast cancer.

    PubMed

    Shaikh, Sana; Channa, Naseem Aslam; Talpur, Farha Naz; Younis, Muhammad; Tabassum, Naila

    2017-05-18

    Breast cancer is a disease with diverse clinical symptoms, molecular profiles, and its nature to response its therapeutic treatments. Radiotherapy (RT), along with surgery and chemotherapy is a part of treatment in breast cancer. The aim of present study was to investigate pre and post treatment effects of radiotherapy in serum fatty acids and its lipids profile in patients with breast cancer. In this comparative as well as follow up study, Serum fatty acids were performed by gas chromatography to investigate fatty acids and Microlab for analysis of lipid profile. Among serum free and total fatty acids the major saturated fatty acids (SFAs) in serum lipids of breast cancer patients (pre and post treated) were stearic acid (18:0) and palmitic acid (16:0). These fatty acids contributed about 35-50% of total fatty acids. The decreased concentrations of linoleic acid (C18:2) and arachidonic acid (C20:4) with a lower ratio of C18:2/C18:1 was found in pretreated breast cancer patients as compared to controls. The n-3/n-6 ratio of breast cancer patients was decreased before treatment but it was 35% increased after treatment. In addition, plasma activity of D6 desaturase was increased in the breast cancer patients, while the activity of D5 desaturase was decreased. Increased levels of SFAs, monounsaturated fatty acids (MUFAs) and decreased polyunsaturated fatty acids (PUFAs) levels in breast cancer patients (pre and post treated) as compared to controls. Serum total cholesterol (TC) (224.4 mg/dL) and low density lipoprotein cholesterol (LDL-C) (142.9 mg/dL) were significantly increased in pretreated breast cancer patients but after the radiotherapy treatment, the TC (150.2 mg/dL) and LDL-C (89.8 mg/dL) were decreased. It seems that RT would have played a potential role in the treatment of BC. After RT the serum levels of PUFAs, TC, and LDL-C are improved. Our study reinforces the important role of RT in the management of BC. The level of PUFAs, TC, and LDL-C can be

  15. Comparison study between fasting total serum bile acid and post prandial bile acid in hepatic diseases: a preliminary study.

    PubMed

    Boonyapisit, S; Lekhakula, S; Amornkittichareon, B; Shumnumsirivath, D

    1994-01-01

    Fasting bile acid, two-hour post prandial bile acid and other liver function tests (Bili, AST, ALT, ALB, Glob, ALP) were measured in 22 normal and 28 liver diseased patients. In normal volunteers, the mean value of fasting total serum bile acid (FTBA) and postprandial serum bile acid (PTBA) were 3.08 mumole/L (S.D. 1.65) range 0.21-6.26 mumol/L, and 8.07 mumole/L (S.D. 2.99) range 4.06-15.65 mumole/L. Comparison between FTBA, PTBA and other liver function tests in various liver diseases from this study the PTBA was not statistically significant superior to FTBA. Therefore, it is not necessary to do the PTBA at this time until more data is available.

  16. Serum uric acid levels and long-term outcomes in chronic kidney disease.

    PubMed

    Miyaoka, Tokiko; Mochizuki, Toshio; Takei, Takashi; Tsuchiya, Ken; Nitta, Kosaku

    2014-07-01

    Hyperuricemia is common in chronic kidney disease (CKD), but data regarding the relationship between serum uric acid levels and the long-term outcomes of CKD patients have been limited. The present study evaluated the associations between baseline serum uric acid levels with mortality and end-stage renal disease (ESRD). The subjects of this study were 551 stage 2-4 CKD patients. Cox proportional hazards models were used to evaluate the relationship between serum uric acid tertiles and all-cause mortality, cardiovascular disease (CVD) mortality, 50 % reduction in estimated glomerular filtration rate (eGFR), and development of ESRD, initially without adjustment, and then after adjusting for several groups of covariates. The mean age of the study subjects was 58.5 years, 59.3 % were men, and 10.0 % had diabetes. The mean eGFR was 42.02 ± 18.52 ml/min/1.73 m(2). In all subjects, the mean serum uric acid level was 6.57 ± 1.35 mg/dl, and 52.2 % of study subjects were on hypouricemic therapy (allopurinol; 48.3 %) at baseline. Thirty-one patients (6.1 %) died during a follow-up period of approximately 6 years. There was no significant association between serum uric acid level and all-cause mortality, CVD mortality, development of ESRD and 50 % reduction in eGFR in the unadjusted Cox models. In the adjusted models, hyperuricemia was found to be associated with all-cause mortality and CVD mortality after adjustment with CVD risk factors, kidney disease factors, and allopurinol, but not associated with development of ESRD and 50 % reduction in eGFR. The results of this study showed that hyperuricemia but not serum uric acid levels were associated with all-cause mortality, CVD mortality after adjustments with CVD risk factors, kidney disease factors, and allopurinol in stage 2-4 CKD patients.

  17. Even- and odd-chain saturated fatty acids in serum phospholipids are differentially associated with adipokines

    PubMed Central

    Sato, Masao; Yasuda, Kazuki; Kashima, Kentaro; Tanaka, Shoji; Hayashi, Takuya; Shirouchi, Bungo; Akter, Shamima; Kashino, Ikuko; Hayabuchi, Hitomi; Mizoue, Tetsuya

    2017-01-01

    Background Saturated fatty acids are generally thought to have detrimental effects on health. However, a recent study showed that even- and odd-chain saturated fatty acids had opposite associations with type 2 diabetes. Limited studies of Western populations examined the associations of circulating saturated fatty acids with adipokines, an important role in glucose metabolism. Objective We examined the associations of saturated fatty acids in serum phospholipids with circulating levels of adipokines among a Japanese population. Design A cross-sectional study was conducted among 484 Japanese employees (284 men and 200 women) aged 20–65 years. The serum fatty acid composition in the phospholipid fraction was measured by gas-chromatography. Serum leptin, adiponectin, plasminogen activator inhibitor-1 (PAI-1), resistin, and visfatin were measured using a Luminex suspension bead-based multiplexed array. Multiple linear regression analysis was performed to assess the association between saturated fatty acids and adipokines, with adjustment for potential confounding variables. Results Even- and odd-chain saturated fatty acids were differentially associated with adipokines. Higher levels of even-chain saturated fatty acids (14:0 myristic, 16:0 palmitic, and 18:0 stearic acids) were associated with higher levels of resistin (P for trend = 0.048) and lower levels of adiponectin (P for trend = 0.003). By contrast, odd-chain saturated fatty acids (15:0 pentadecanoic and 17:0 heptadecanoic acids) showed inverse associations with leptin and PAI-1 (P for trend = 0.048 and 0.02, respectively). Visfatin was positively associated with both even- and odd-chain saturated fatty acids. Conclusions The results suggest that even- and odd-chain saturated fatty acids are differentially associated with adipokine profile. PMID:28552966

  18. Effects of coffee consumption on serum uric acid: systematic review and meta-analysis.

    PubMed

    Park, Kyu Yong; Kim, Hyun Jung; Ahn, Hyeong Sik; Kim, Sun Hee; Park, Eun Ji; Yim, Shin-Young; Jun, Jae-Bum

    2016-04-01

    Study results on the effects of coffee consumption on serum uric acid (UA) have been conflicting. The aim of this study is to analyze the literature regarding the effect of coffee consumption on serum UA. We searched MEDLINE, EMBASE, the Cochrane library, and KoreaMed for all articles published before January 2015. Studies with quantitative data on coffee consumption and serum UA level were included. Coffee consumption and serum UA level were identified with/without the risk of gout. Nine studies published between 1999 and 2014 were included, containing a total of 175,310 subjects. Meta-analysis demonstrated that coffee has a significantly lowering effect on serum UA, where there are gender differences in the amount of coffee required to lower serum UA. Women (4-6 cups/day) need more coffee to lower serum UA than men (1-3 cups/day). Meta-analysis showed that coffee intake of 1 cup/day or more was significantly associated with reduction of the risk of gout, with a negative correlation with the amount of daily coffee intake for both genders. This is the first systematic review on the effects of coffee consumption on serum UA. Based on our study, moderate coffee intake might be advocated for primary prevention of hyperuricemia and gout in both genders. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Association of androgen with gender difference in serum adipocyte fatty acid binding protein levels

    PubMed Central

    Hu, Xiang; Ma, Xiaojing; Pan, Xiaoping; Luo, Yuqi; Xu, Yiting; Xiong, Qin; Bao, Yuqian; Jia, Weiping

    2016-01-01

    Clinical investigations have indicated women have higher levels of adipocyte fatty acid binding protein (A-FABP) than men. The present study aimed to identify factors related to gender difference in serum A-FABP levels. A total of 507 participants (194 men, 132 premenopausal women, and 181 postmenopausal women) were enrolled in the present study. Serum A-FABP levels increased in the order from men to premenopausal women to postmenopausal women in both body mass index categories (<25.0 and ≥25.0 kg/m2; all P < 0.05). Multiple stepwise regression analyses showed that after adjustment for factors related to serum A-FABP levels, the trunk fat mass was an independent and positive factor of serum A-FABP levels. For men, total testosterone was associated independently and inversely with serum A-FABP levels. For pre- and postmenopausal women, bioavailable testosterone and total testosterone were independent and positive factors associated with serum A-FABP levels, respectively. The present study demonstrated that the androgen was correlated with the serum A-FABP levels negatively in men, but positively in women. With these effects on the fat content, especially trunk fat, androgen might contribute to the gender difference in serum A-FABP levels. PMID:27270834

  20. Serum uric acid is associated with apathy in early, drug-naïve Parkinson's disease.

    PubMed

    Picillo, Marina; Santangelo, Gabriella; Moccia, Marcello; Erro, Roberto; Amboni, Marianna; Prestipino, Elio; Longo, Katia; Vitale, Carmine; Spina, Emanuele; Orefice, Giuseppe; Barone, Paolo; Pellecchia, Maria Teresa

    2016-04-01

    Both low serum uric acid (UA) levels and apathy are considered biomarkers of cognitive decline and dementia in Parkinson's disease (PD). There is an urgent need to combine different biomarkers to predict disease course in PD. Data on the relationship between serum UA levels and apathy in PD are lacking. The aim of this study is to evaluate the relationship between serum UA levels and pure apathy in early, drug-naïve PD patients. Forty-nine early, drug-naïve PD patients were enrolled and stratified into two groups using the median serum UA levels at diagnosis (Group 1 serum UA ≤ 4.8 mg/dl; Group 2 serum UA > 4.8 mg/dl). The cohort was followed for the first 2 years of disease. Apathy was evaluated with the Apathy Evaluation Scale (AES). Patients with lower serum UA levels presented significant higher AES score compared to patients with higher serum UA levels. Regression analysis showed that baseline serum UA levels were significant determinants of AES scores at both baseline and 2-year follow up, irrespective of gender, age, attention/executive functions and dopamine replacement therapy when applicable. This is the first study showing a link between serum UA levels and apathy in non-demented, non-depressed, early, drug-naïve PD, being lower serum UA levels associated with greater apathy. Further follow up of our patients and replication of this observation in independent cohorts are needed to establish if this combination of biomarkers may help in characterizing a subgroup of PD patients at diagnosis.

  1. Serum Phospholipid Docosahexaenoic Acid Is Inversely Associated with Arterial Stiffness in Metabolically Healthy Men

    PubMed Central

    Lee, Mi-Hyang; Kwon, Nayeon; Yoon, So Ra

    2016-01-01

    We hypothesized that lower proportion of serum phospholipid docosahexaenoic acid (DHA) is inversely associated with increased cardiovascular risk and vascular function in metabolically healthy men. To elucidate it, we first compared serum phospholipid free fatty acid (FA) compositions and cardiovascular risk parameters between healthy men (n = 499) and male patients with coronary artery disease (CAD, n = 111) (30-69 years) without metabolic syndrome, and then further-analyzed the association of serum phospholipid DHA composition with arterial stiffness expressed by brachial-ankle pulse wave velocity (ba-PWV) in metabolically healthy men. Basic parameters, lipid profiles, fasting glycemic status, adiponectin, high sensitivity C-reactive protein (hs-CRP) and LDL particle size, and serum phospholipid FA compositions were significantly different between the two subject groups. Serum phospholipid DHA was highly correlated with most of long-chain FAs. Metabolically healthy men were subdivided into tertile groups according to serum phospholipid DHA proportion: lower (< 2.061%), middle (2.061%-3.235%) and higher (> 3.235%). Fasting glucose, insulin resistance, hs-CRP and ba-PWVs were significantly higher and adiponectin and LDL particle size were significantly lower in the lower-DHA group than the higher-DHA group after adjusted for confounding factors. In metabolically healthy men, multiple stepwise regression analysis revealed that serum phospholipid DHA mainly contributed to arterial stiffness (β′-coefficients = -0.127, p = 0.006) together with age, systolic blood pressure, triglyceride (r = 0.548, p = 0.023). Lower proportion of serum phospholipid DHA was associated with increased cardiovascular risk and arterial stiffness in metabolically healthy men. It suggests that maintaining higher proportion of serum phospholipid DHA may be beneficial for reducing cardiovascular risk including arterial stiffness in metabolically healthy men. PMID:27482523

  2. Serum Phospholipid Docosahexaenoic Acid Is Inversely Associated with Arterial Stiffness in Metabolically Healthy Men.

    PubMed

    Lee, Mi-Hyang; Kwon, Nayeon; Yoon, So Ra; Kim, Oh Yoen

    2016-07-01

    We hypothesized that lower proportion of serum phospholipid docosahexaenoic acid (DHA) is inversely associated with increased cardiovascular risk and vascular function in metabolically healthy men. To elucidate it, we first compared serum phospholipid free fatty acid (FA) compositions and cardiovascular risk parameters between healthy men (n = 499) and male patients with coronary artery disease (CAD, n = 111) (30-69 years) without metabolic syndrome, and then further-analyzed the association of serum phospholipid DHA composition with arterial stiffness expressed by brachial-ankle pulse wave velocity (ba-PWV) in metabolically healthy men. Basic parameters, lipid profiles, fasting glycemic status, adiponectin, high sensitivity C-reactive protein (hs-CRP) and LDL particle size, and serum phospholipid FA compositions were significantly different between the two subject groups. Serum phospholipid DHA was highly correlated with most of long-chain FAs. Metabolically healthy men were subdivided into tertile groups according to serum phospholipid DHA proportion: lower (< 2.061%), middle (2.061%-3.235%) and higher (> 3.235%). Fasting glucose, insulin resistance, hs-CRP and ba-PWVs were significantly higher and adiponectin and LDL particle size were significantly lower in the lower-DHA group than the higher-DHA group after adjusted for confounding factors. In metabolically healthy men, multiple stepwise regression analysis revealed that serum phospholipid DHA mainly contributed to arterial stiffness (β'-coefficients = -0.127, p = 0.006) together with age, systolic blood pressure, triglyceride (r = 0.548, p = 0.023). Lower proportion of serum phospholipid DHA was associated with increased cardiovascular risk and arterial stiffness in metabolically healthy men. It suggests that maintaining higher proportion of serum phospholipid DHA may be beneficial for reducing cardiovascular risk including arterial stiffness in metabolically healthy men.

  3. A multicenter study of the association of serum uric acid, serum creatinine, and diuretic use in hypertensive patients.

    PubMed

    Lin, Chung-Sheng; Hung, Yi-Jen; Chen, Gau-Yang; Tzeng, Thing-Fong; Lee, Du-Yi; Chen, Cheng-Yun; Huang, Wen-Pin; Huang, Chin-Hsung

    2011-05-05

    Individuals with hypertension and hyperuricemia have an increased risk of coronary artery disease and cerebral vascular disease as compared to patients with normal uric acid levels. Our aim is to determine the prevalence of hyperuricemia in hypertensive patients in Taiwan, and whether serum uric acid (SUA) is associated with changes in renal function in patients with hypertension. We studied 2145 hypertensive patients receiving medical treatment, assessed the prevalence of hyperuricemia, and determined the independent risk factors for SUA. Simple correlation and multiple regression analyses were applied to identify the independent risk factors for SUA increase. Logistic regression analysis was used to estimate the association between 4 quartiles of SUA level and correspondent serum creatinine (SCr) concentrations. Hypertensive subjects had a high prevalence of hyperuricemia (men, 35%; women, 43%). SUA was significantly associated with the independent risk factors of SCr, diuretic usage, and diabetes (inversely related) in both genders, whereas β-blocker usage and body mass index were only associated in men. Multiple logistic regression models showed that in the non-diuretic user group the highest SUA quartile entailed >4 times greater risk for SCr elevation than the lowest. In the diuretic user group, a >2 times greater risk was noted. Hyperuricemia hypertensive subjects demonstrated a corresponding elevation of SUA and SCr irrespective of diuretic use. Elevation of SUA, in addition to SCr, may represent a progression of renal function impairment. Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.

  4. Total Serum Bilirubin Predicts Fat-Soluble Vitamin Deficiency Better Than Serum Bile Acids in Infants with Biliary Atresia

    PubMed Central

    Venkat, Veena L.; Shneider, Benjamin L.; Magee, John C.; Turmelle, Yumirle; Arnon, Ronen; Bezerra, Jorge A.; Hertel, Paula M.; Karpen, Saul J; Kerkar, Nanda; Loomes, Kathleen M.; Molleston, Jean; Murray, Karen F.; Ng, Vicky L.; Raghunathan, Trivellore; Rosenthal, Philip; Schwartz, Kathleen; Sherker, Averell H.; Sokol, Ronald J.; Teckman, Jeffrey; Wang, Kasper; Whitington, Peter F.; Heubi, James E.

    2014-01-01

    Objective Fat soluble vitamin (FSV) deficiency is a well-recognized consequence of cholestatic liver disease and reduced intestinal intraluminal bile acids. We hypothesized that serum bile acids (SBA) would predict biochemical FSV deficiency better than serum total bilirubin level (TB) in infants with biliary atresia. Methods Infants enrolled in the Trial of Corticosteroid Therapy in Infants with Biliary Atresia (START) after hepatoportoenterostomy were the subjects of this investigation. Infants received standardized FSV supplementation and monitoring of TB, SBA and vitamin levels at 1, 3 and 6 months. A logistic regression model was used with the binary indicator variable insufficient/sufficient as the outcome variable. Linear and non-parametric correlations were made between specific vitamin measurement levels and either TB or SBA. Results The degree of correlation for any particular vitamin at a specific time point was higher with TB than SBA (higher for TB in 31 circumstances versus 3 circumstances for SBA). Receiver operating characteristic (ROC) shows that TB performed better than SBA (AUC 0.998 vs. 0.821). Including both TB and SBA did not perform better than TB alone (AUC 0.998). Conclusion We found that TB was a better predictor of FSV deficiency than SBA in infants with biliary atresia. The role of SBA as a surrogate marker of FSV deficiency in other cholestatic liver diseases, such as PFIC, alpha-one antitrypsin deficiency and Alagille syndrome where the pathophysiology is dominated by intrahepatic cholestasis, warrants further study. PMID:25419594

  5. Serum uric acid and acute kidney injury: A mini review.

    PubMed

    Hahn, Kai; Kanbay, Mehmet; Lanaspa, Miguel A; Johnson, Richard J; Ejaz, A Ahsan

    2017-09-01

    Acute kidney injury causes great morbidity and mortality in both the community and hospital settings. Understanding the etiological factors and the pathophysiological principles resulting in acute kidney injury is essential in prompting appropriate therapies. Recently hyperuricemia has been recognized as a potentially modifiable risk factor for acute kidney injury, including that associated with cardiovascular surgery, radiocontrast administration, rhabdomyolysis, and associated with heat stress. This review discussed the evidence that repeated episodes of acute kidney injury from heat stress and dehydration may also underlie the pathogenesis of the chronic kidney disease epidemic that is occurring in Central America (Mesoamerican nephropathy). Potential mechanisms for how uric acid might contribute to acute kidney injury are also discussed, including systemic effects on renal microvasculature and hemodynamics, and local crystalline and noncrystalline effects on the renal tubules. Pilot clinical trials also show potential benefits of lowering uric acid on acute kidney injury associated with a variety of insults. In summary, there is mounting evidence that hyperuricemia may have a significant role in the development of acute kidney injury. Prospective, placebo controlled, randomized trials are needed to determine the potential benefit of uric acid lowering therapy on kidney and cardio-metabolic diseases.

  6. Association of Elevated first Trimester Serum Uric Acid Levels with Development of GDM

    PubMed Central

    C, Rasika; Ghose, Seetesh

    2014-01-01

    Background: Early intervention and appropriate treatment in patients with GDM will help in preventing the adverse maternal and fetal outcome and protect them from long term complications. Several studies have shown the association of hyperuricemia with GDM. This study was undertaken to find out the association of elevated first trimester uric acid with development of GDM. Materials and Methods: This prospective observational study was conducted in Mahatma Gandhi Medical Collage and Research Institute, Pondicherry, India, between November 2010 and May 2012. A total of 70 pregnant women were included and parameters like age, parity, BMI, history of DM, serum uric acid at <15 weeks and at 24 to 28 weeks and one step test at 24 to 28 weeks were noted and compared. Results: There was no significant correlation between the demographic variables and GDM, but a moderate significance noted between the family history of DM and one step test (p=0.048). Though there is a proportional increase in the serum uric acid with increase in the BMI, it was not statistically significant. A significant correlation was seen between BMI and risk of development of GDM (p= 0.001). Though there is a significant correlation between serum uric acid at <15 weeks and at 24 to 28 weeks, serum uric acid at <15 weeks of gestation is a better predictor of GGI and GDM (Pearson’s correlation = 0.735). Conclusion: There is increase in the risk of development of GDM with increased levels of serum uric acid in the first trimester. Uric acid levels at <15 weeks of gestation is more significantly associated with risk of development of GDM than it’s levels at 24 to 28 weeks of gestation. PMID:25653992

  7. Association of Elevated first Trimester Serum Uric Acid Levels with Development of GDM.

    PubMed

    C, Rasika; Samal, Sunita; Ghose, Seetesh

    2014-12-01

    Early intervention and appropriate treatment in patients with GDM will help in preventing the adverse maternal and fetal outcome and protect them from long term complications. Several studies have shown the association of hyperuricemia with GDM. This study was undertaken to find out the association of elevated first trimester uric acid with development of GDM. This prospective observational study was conducted in Mahatma Gandhi Medical Collage and Research Institute, Pondicherry, India, between November 2010 and May 2012. A total of 70 pregnant women were included and parameters like age, parity, BMI, history of DM, serum uric acid at <15 weeks and at 24 to 28 weeks and one step test at 24 to 28 weeks were noted and compared. There was no significant correlation between the demographic variables and GDM, but a moderate significance noted between the family history of DM and one step test (p=0.048). Though there is a proportional increase in the serum uric acid with increase in the BMI, it was not statistically significant. A significant correlation was seen between BMI and risk of development of GDM (p= 0.001). Though there is a significant correlation between serum uric acid at <15 weeks and at 24 to 28 weeks, serum uric acid at <15 weeks of gestation is a better predictor of GGI and GDM (Pearson's correlation = 0.735). There is increase in the risk of development of GDM with increased levels of serum uric acid in the first trimester. Uric acid levels at <15 weeks of gestation is more significantly associated with risk of development of GDM than it's levels at 24 to 28 weeks of gestation.

  8. Serum from patients with pernicious anaemia blocks gastrin stimulation of acid secretion by parietal cells.

    PubMed Central

    de Aizpurua, H J; Ungar, B; Toh, B H

    1985-01-01

    We examined 51 sera from patients with pernicious anaemia for their capacity to block maximal gastrin stimulation of acid secretion by isolated rodent gastric parietal cells. 14C-aminopyrine accumulation was used as the index of acid secretion in vitro. Sera from patients with pernicious anaemia gave significantly (P less than 0.005) more block of maximal gastrin stimulation of acid secretion (61.7 +/- 37.8%) than sera from 10 patients with systemic lupus erythematosus (19.6 +/- 17.7%), 10 with scleroderma (34.2 +/- 22.3%), five with rheumatoid arthritis (22.4 +/- 15.6%) or 30 from healthy persons (27.4 +/- 12.8%). Maximal histamine stimulation of acid secretion was not inhibited. The blocking factor was present in serum IgG fractions, and serum and IgG fractions gave parallel dose-response and dilution curves. The serum block was abolished by absorption with gastric mucosal cells and correlated with the presence of parietal cell surface autoantibody. We conclude that serum immunoglobulin in pernicious anaemia can block gastrin stimulation of acid secretion and suggest that this block may be mediated by competition with gastrin for surface receptors on parietal cells. PMID:4042425

  9. Associations of birth weight with serum long chain polyunsaturated fatty acids in adolescents; the HELENA study.

    PubMed

    Labayen, Idoia; Moreno, Luis A; Ruiz, Jonatan R; Ortega, Francisco B; Sjostrom, Michael; Huybrechts, Inge; Gonzalez-Gross, Marcela; Spinneker, André; De Henauw, Stefaan; Manios, Yannis; Molnar, Dénés; Leclercq, Catherine; Gottrand, Frédéric

    2011-07-01

    Nutritional factors in early life may have long-term physiologic effects in humans. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) play important roles in protecting against cardiovascular disease (CVD) risk. Our aim was to examine the association of birth weight (BW) with serum long chain polyunsaturated fatty acids (LCPUFA) profile in adolescents. A total of 772 European adolescents (56.3% females) aged 14.7 ± 1.2 years were included in this study. Information on BW and gestational age was obtained from parental records. DHA, EPA and arachidonic acid (AA) concentrations were measured in serum phospholipids. Alfa-linolenic (ALA), linoleic (LA), AA, EPA and DHA intakes assessed by a computer based 24h dietary recall. Gender, gestational age, pubertal status, body mass index, center and total energy and LCPUFA intakes were used as confounders in all the analyses. BW was significantly associated with serum DHA and EPA (both adjusted P<0.05) independently of potential confounders including their main dietetic source. We did not observe any significant relationship between BW and serum AA levels. Our findings suggest that early metabolic changes, as a result from prenatal environmental influences, could affect long chain polyunsaturated fatty acid metabolism later in life. These results may contribute to explain the relationship between early nutrition and growth and later metabolic disorders as CVD. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  10. Time trends of perfluorinated alkyl acids in serum from Danish pregnant women 2008-2013.

    PubMed

    Bjerregaard-Olesen, Christian; Bach, Cathrine C; Long, Manhai; Ghisari, Mandana; Bossi, Rossana; Bech, Bodil H; Nohr, Ellen A; Henriksen, Tine B; Olsen, Jørn; Bonefeld-Jørgensen, Eva C

    2016-05-01

    We aimed to estimate the levels and time trends of perfluorinated alkyl acids (PFAAs) in serum of 1533 Danish pregnant nulliparous women between 2008 and 2013. The selection criterion of only including nulliparous women was chosen to avoid confounding from parity. The serum samples were analyzed for sixteen PFAAs using solid phase extraction and liquid chromatography tandem mass spectrometry (LC-MS/MS). We investigated the time trends for seven PFAAs, which were detected in more than 50% of the samples: perfluorohexane sulfonate (PFHxS), perfluoroheptane sulfonate (PFHpS), perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnA). We found that the serum levels of all seven PFAAs decreased during the period from 2008 to 2013; on average PFHxS decreased with 7.0% per year, PFHpS with 14.8%, PFOS with 9.3%, PFOA with 9.1%, PFNA with 6.2%, PFDA with 6.3%, and PFUnA with 7.1% per year. Adjustment for maternal age, body mass index (BMI), educational level and gestational age at blood sampling did not change the time trends much. To our knowledge, we are the first to report decreasing trends of PFNA, PFDA and PFUnA since year 2000, thereby indicating that the phase-out of these compounds are beginning to show an effect on human serum levels. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. The associations of serum uric acid level and hyperuricemia with knee osteoarthritis.

    PubMed

    Ding, Xiang; Zeng, Chao; Wei, Jie; Li, Hui; Yang, Tuo; Zhang, Yi; Xiong, Yi-Lin; Gao, Shu-Guang; Li, Yu-Sheng; Lei, Guang-Hua

    2016-04-01

    To examine the cross-sectional associations of the serum uric acid level and hyperuricemia (HU) with the radiographic features of osteoarthritis (OA), including osteophytes (OST) and joint space narrowing (JSN), a total of 4685 subjects were included in this study. Blood samples were drawn from all subjects. Serum uric acid and some other indexes were detected. OST and JSN were assessed for each subject according to the Osteoarthritis Research Society International (OARSI) atlas. A multivariable logistic analysis model was applied to test the target associations after adjusting a number of potential confounding factors. The prevalence of OST was increased in the highest tertile of uric acid compared to the lowest in female subjects (OR 1.46, 95 % CI 1.07-1.99, P for trend = 0.02). Meanwhile, a positive association between OST and HU was observed in female subjects (OR 1.43, 95 % CI 1.01-2.03, P = 0.05). However, serum uric acid and HU were not significantly associated with JSN in male subjects. The findings of this study indicated that the serum uric acid concentration and prevalence of HU are positively associated with OST of the knee in the female population. Level of evidence Cross-sectional study, Level III.

  12. Serum bile acids and their conjugates in breast-fed infants with prolonged jaundice.

    PubMed

    Tazawa, Y; Yamada, M; Nakagawa, M; Konno, T; Tada, K

    1985-05-01

    Serum bile acids and their conjugates were analysed in 20 breast-fed infants with prolonged jaundice. The mean total bile acid levels in serum were increased in the breast-fed infants with jaundice, as compared with those in either breast- or bottle-fed infants without jaundice. However, there were no significant differences between the groups. All the breast-fed infants examined, regardless of association with jaundice, had a bile acid pattern dominated by taurine conjugates (the ratio of glycine- to taurine-conjugated bile acid, G/T ratio, less than 1.00). In contrast, the bottle-fed infants without jaundice had a pattern dominated by glycine conjugates (G/T ratio, more than 1.00). Among the breast-fed infants with jaundice, the mean G/T ratio in those who had serum bilirubin levels over 10 mg/100 ml was significantly lower than that in those who had serum bilirubin levels of less than 10 mg/100 ml. The altered bile acid metabolism might be associated with the pathology of breast milk jaundice.

  13. Odd-numbered perfluorocarboxylates predominate over perfluorooctanoic acid in serum samples from Japan, Korea and Vietnam.

    PubMed

    Harada, Kouji H; Hitomi, Toshiaki; Niisoe, Tamon; Takanaka, Katsunobu; Kamiyama, Sigetosi; Watanabe, Takao; Moon, Chan-seok; Yang, Hye-ran; Hung, Nguyen Ngoc; Koizumi, Akio

    2011-10-01

    Perfluorooctanoic acid (PFOA) has recently attracted attention as a potential health risk following environmental contamination. However, information detailing exposure to perfluorinated carboxylic acids (PFCAs) other than PFOA is limited. We measured the concentrations of PFCAs (from perfluorohexanoic acid to perfluorotetradecanoic acid) in serum samples obtained from patients in Japan (Sendai, Takayama, Kyoto and Osaka) between 2002 and 2009, Korea (Busan and Seoul) between 1994 and 2008 and Vietnam (Hanoi) in 2007/2008. Total PFCA levels (geometric mean) were increased from 8.9 ng mL(-1) to 10.3 ng mL(-1) in Japan; from 7.0 ng mL(-1) to 9.2 ng mL(-1) in Korea; and were estimated at 4.7 ng mL(-1) in Vietnam. PFCAs of greater length than PFOA were significantly increased in Sendai, Takayama and Kyoto, Japan, and levels of long-chain PFCAs exceeded PFOA levels in serum. Among these PFCAs, perfluoroundecanoic acid (PFUnDA) was the predominant component (28.5%), followed by perfluorononanoic acid (PFNA 17.5%), perfluorodecanoic acid (PFDA 7.9%), perfluorotridecanoic acid (PFTrDA 6.1%) and perfluorododecanoic acid (PFDoDA 1.8%). Odd-numbered PFCAs (PFNA, PFUnDA and PFTrDA) were also observed in Korea and Vietnam and their presence increased significantly in Korea between 1994 and 2007/2008. The proportion of long-chain PFCAs in serum was relatively high compared to reports in Western countries. Further investigations into the sources and exposure routes are needed to predict the future trajectory of these serum PFCA levels. Copyright © 2011 Elsevier Ltd. All rights reserved.

  14. Fish protein decreases serum cholesterol in rats by inhibition of cholesterol and bile acid absorption.

    PubMed

    Hosomi, Ryota; Fukunaga, Kenji; Arai, Hirofumi; Kanda, Seiji; Nishiyama, Toshimasa; Yoshida, Munehiro

    2011-05-01

    Fish protein has been shown to decrease serum cholesterol content by inhibiting absorption of cholesterol and bile acid in laboratory animals, though the mechanism underlying this effect is not yet fully understood. The purpose of this study was to elucidate the mechanism underlying the inhibition of cholesterol and bile acid absorption following fish protein intake. Male Wistar rats were divided into 2 dietary groups of 7 rats each, 1 group receiving a diet consisting of 20% casein and the other receiving a diet consisting of 10% casein and 10% fish protein. Both experimental diets also contained 0.5% cholesterol and 0.1% sodium cholate. After the rats had been on their respective diets for 4 wk, their serum and liver cholesterol contents and fecal cholesterol, bile acid, and nitrogen excretion contents were measured. Fish protein consumption decreased serum and liver cholesterol content and increased fecal cholesterol and bile acid excretion and simultaneously increased fecal nitrogen excretion. In addition, fish protein hydrolyzate prepared by in vitro digestion had lower micellar solubility of cholesterol and higher binding capacity for bile acids compared with casein hydrolyzate. These results suggest that the hypocholesterolemic effect of fish protein is mediated by increased fecal cholesterol and bile acid excretion, which is due to the digestion products of fish protein having reduced micellar solubility of cholesterol and increased bile acid binding capacity.

  15. Effect of losartan on serum uric acid in hypertension treated with a diuretic: the COMFORT study.

    PubMed

    Matsumura, Kiyoshi; Arima, Hisatomi; Tominaga, Mitsuhiro; Ohtsubo, Toshio; Sasaguri, Toshiyuki; Fujii, Koji; Fukuhara, Masayo; Uezono, Keiko; Morinaga, Yuki; Ohta, Yuko; Otonari, Takatoshi; Kawasaki, Junya; Kato, Isao; Tsuchihashi, Takuya

    2015-01-01

    It has been shown that losartan, an angiotensin II receptor blocker (ARB), reduces serum uric acid levels. However, the effects of losartan on serum uric acid levels in the patients treated with a thiazide diuretic have not been fully elucidated. We have investigated the effects of losartan compared with other ARBs on blood variables and blood pressure control in hypertensive patients treated with a thiazide diuretic using data from the COMFORT study. The present analysis included a total of 118 hypertensive subjects on combination treatment with ARBs except for losartan and a diuretic who were randomly assigned to a daily regimen of a combination pill (losartan 50 mg/hydrochlorothiazide 12.5 mg) or to continuation of two pills, an ARB except for losartan and a diuretic. Blood pressures were evaluated at 1, 3, and 6 months after randomization and changes in blood variables including serum uric acid were evaluated during 6 months treatment period. Mean follow-up blood pressure levels were not different between the combination pill (losartan treatment) group and the control (ARBs except for losartan) group. On the other hand, serum uric acid significantly decreased in the combination pill group compared with the control group (-0.44 versus + 0.10 mg/dl; p = 0.01), although hematocrit, serum creatinine, sodium and potassium were not different between the groups. These results suggest that the treatment regimen switched from a combination therapy of ARBs except for losartan and a diuretic to a combination pill (losartan/ hydrochlorothiazide) decreases serum uric acid without affecting blood pressure control.

  16. [Correlation between serum uric acid level and acute renal injury after coronary artery bypass grafting].

    PubMed

    Xu, D Q; Du, J; Zheng, Z; Tang, Y; Zou, L; Zhang, Y H; Zhang, H T

    2017-07-11

    Objective: To evaluate whether early postoperative serum uric acid level can predict postoperative acute renal injury (AKI) among patients undergoing coronary artery bypass grafting (CABG). Methods: The study retrospectively enrolled 1 306 patients undergoing CABG in Fuwai Hospital between September 2012 and December 2013. The patients were divided into 5 groups by the concentrations of serum uric acid measured on the morning of the first postoperative day, and uric acid categories were as follow: less than 195 μmol/L (Q1 group, 262 cases), 195-236 μmol/L (Q2 group, 263 cases), 237-280 μmol/L (Q3 group, 260 cases), 281-336 μmol/L (Q4 group, 261 cases), more than 336 μmol/L (Q5 group, 260 cases). The primary end points were AKI (RIFLE criteria), severe AKI (AKI≥stage Ⅰ), postoperative continuous renal replacement therapy (CRRT) requirement, in-hospital death, length of stay in hospital and intensive care unit(ICU). The area under the receiver-operating characteristic (ROC) curve (AUC) was used to determine the ability of the early postoperative serum uric acid level as a risk factor for postoperative AKI prediction. Results: Among the 1 306 patients enrolled in the study, AKI was found in 335 patients (25.65%). After adjusting for variables that were different between the 5 groups, the Q5 group had significantly higher risk of AKI, AKI≥ stage Ⅰ and the requirement of CRRT (P<0.01). The ROC for the outcome of postoperative AKI had an AUC of 0.648 (95% CI: 0.612-0.683) when serum creatinine levels alone were used and 0.722 (95% CI: 0.688-0.755) when serum uric acid levels alone were used (both P<0.001). Early postoperative serum uric acid was a better predictor than serum creatinine(P<0.001). Conclusion: The serum uric acid concentration within 12 hours after operation is an independent predictor of postoperative AKI in patients undergoing CABG, which could be used to identify patients at high risk for AKI.

  17. Serum Cobalamin and Methylmalonic Acid Concentrations in Hyperthyroid Cats Before and After Radioiodine Treatment.

    PubMed

    Geesaman, B M; Whitehouse, W H; Viviano, K R

    2016-01-01

    Hyperthyroidism, the most common endocrine disorder in cats, has been associated with low serum cobalamin concentrations. Whether this is a functional cobalamin deficiency of clinical importance has not been assessed. Cats with hyperthyroidism experience a functional cobalamin deficiency which correlates with their clinical catabolic state and is reversible with return of the euthyroid state. Thirty-nine client-owned hyperthyroid cats. Prospective observational study. Serum cobalamin, methylmalonic acid, and clinical scores were determined in each hyperthyroid cat at enrollment and when euthyroid (60 days after radioiodine treatment). Five of the 39 hyperthyroid cats (13%) had a low serum cobalamin concentration ranging from <150 to 290 ng/L. Serum cobalamin concentrations normalized to >350 ng/L in 2 of the hypocobalaminemic cats once euthyroid. None of the hyperthyroid/hypocobalaminemic cats had increased serum methylmalonic acid concentrations (175-601 nmol/L). In cats with clinical and biochemical hyperthyroidism, there was no correlation between serum cobalamin concentrations with total T4 concentration (P = .12) or clinical scores including body weight (P = .11) and BCS (P = .54). In this population of hyperthyroid cats, the prevalence of hypocobalaminemia was low. Specifically, hyperthyroid cats, in which concurrent gastrointestinal disease is unlikely. Hypocobalaminemia is not a functional deficiency requiring supplementation in hyperthyroid cats without gastrointestinal disease. Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  18. Viral Nucleic Acids in the Serum Are Dependent on Blood Sampling Site in Patients with Clinical Suspicion of Myocarditis.

    PubMed

    Pawlak, Agnieszka; Przybylski, Maciej; Durlik, Marek; Gil, Katarzyna; Nasierowska-Guttmejer, Anna M; Byczkowska, Katarzyna; Ziemba, Andrzej; Gil, Robert J

    2016-01-01

    The meaning of viral nucleic acids in the myocardium in many cases is difficult for clinical interpretation, whereas the presence of viral nucleic acids in the serum is a marker of active infection. We determined the diagnostic value of viral nucleic acids in ventricular serum and peripheral serum samples in comparison with endomyocardial biopsy (EMB) specimens in patients with clinically suspected myocarditis. The viral nucleic acid evaluation was performed in serum samples and EMB specimens by real-time PCR in 70 patients (age: 47 ± 16 years). The biopsy specimens were examined by histo- and immunohistochemistry to detect inflammatory response. The viral nucleic acids were detected in ventricular and peripheral serum, and EMB samples of 10 (14%), 14 (20%), and 32 (46%) patients, respectively. Notably, viral nucleic acids of the same virus as in the EMB sample were present more often in ventricular than in peripheral serum (60 vs. 7%, p = 0.01). A significant concurrence was observed between the positive and the negative results of viral nucleic acids present in EMB and ventricular serum (p = 0.0001). The detection of the same viral nucleic acid type in the myocardium and in ventricular serum being significantly more frequent than in the peripheral serum may suggest that the site of the blood collection is important for more precise and reliable confirmation of the active viral replication in the heart. © 2017 S. Karger AG, Basel.

  19. Dietary Acid Load is Associated With Serum Bicarbonate but not Insulin Sensitivity in Chronic Kidney Disease.

    PubMed

    Ikizler, Halil O; Zelnick, Leila; Ruzinski, John; Curtin, Laura; Utzschneider, Kristina M; Kestenbaum, Bryan; Himmelfarb, Jonathan; de Boer, Ian H

    2016-03-01

    In chronic kidney disease (CKD), dietary acid may promote metabolic acidosis and insulin resistance, which in turn may contribute to adverse clinical health outcomes. We examined associations between dietary acid load, serum bicarbonate, and insulin sensitivity in CKD. In a cross-sectional study, we collected 3-day prospective food diaries to quantify dietary acid load as net endogenous acid production (NEAP, the nonvolatile acid load produced by the diet's acid balance) and potential renal acid load (PRAL). We measured urine net acid excretion (NAE) in 24-hour urine samples. Insulin sensitivity was measured by hyperinsulinemic euglycemic clamp. Forty-two patients with CKD Stages 3 to 5 attending nephrology clinics in the Pacific Northwest and 21 control subjects (estimated glomerular filtration rate [eGFR] ≥ 60 mL/minute/1.73 m(2)). Serum bicarbonate and insulin sensitivity (SIclamp). Mean age was 60.8 ± 13.6 years, and 54% of participants were men. Mean eGFR and serum bicarbonate concentrations were 34.4 ± 13.1 mL/minute/1.73 m(2) and 24.1 ± 2.9 mEq/L for participants with CKD and 88.6 ± 14.5 mL/minute/1.73 m(2) and 26.3 ± 1.8 mEq/L for control subjects, respectively. Mean NEAP, PRAL, and NAE were 58.2 ± 24.3, 9.7 ± 18.4, and 32.1 ± 19.8 mEq/day, respectively. Considering all participants, dietary acid load was significantly, inversely associated with serum bicarbonate, adjusting for age, gender, race, eGFR, body mass index, and diuretic use: -1.2 mEq/L per standard deviation (SD) NEAP (95% confidence interval [CI] -1.8 to -0.6, P < .0001); -0.9 mEq/L bicarbonate per SD PRAL (95% CI -1.5 to -0.4, P = .0005); -0.7 mEq/L bicarbonate per SD NAE (95% CI -1.2 to -0.1, P = .01). These associations were similar in participants with and without CKD. However, neither NEAP and PRAL nor NAE was significantly associated with SIclamp. Serum bicarbonate was also not significantly associated with SIclamp. In CKD, dietary acid load is associated with serum bicarbonate

  20. Tuna extract reduces serum uric acid in gout-free subjects with insignificantly high serum uric acid: A randomized controlled trial

    PubMed Central

    Kubomura, Daiki; Yamada, Masanori; Masui, Ayano

    2016-01-01

    Long-term reduction of serum urate levels is vital in the treatment of gout. However, it is difficult to convince gout-free individuals of the necessity of treatment as few appropriate over-the-counter remedies and dietary supplements are available. Therefore, the present study aimed to investigate the antihyperuricemic efficacy and safety of a tuna extract containing the imidazole compounds to evaluate its potential as a functional food ingredient. A randomized, 4-week, double-blind, placebo-controlled study was conducted. A total of 48 male gout-free subjects with insignificantly high serum uric acid were randomly assigned to low- and high-dose tuna extract groups or a placebo group. The efficacy of the extract was assessed by measuring serum uric acid levels. Furthermore, a safety assessment was performed by physical parameters, hematology, blood biochemistry and urinalysis. The results indicated that the uric acid level was decreased at week 4 during the intervention in the tuna extract groups (low and high dose, −0.23 and −0.34 mg/dl, respectively) compared to the placebo group (−0.07 mg/dl). At week 4 after the intervention, a significant reduction in uric acid levels (−0.41 mg/dl; P<0.05) was observed in the high-dose tuna extract group compared with the placebo group (+0.11 mg/dl). No dose-related adverse events were observed during and following the intervention. Therefore, the present results suggest that oral administration of tuna extract containing the imidazole compounds has hypouricemic activity with no undesirable side effects. PMID:27446553

  1. Serum Glial Fibrillary Acidic Protein as a Specific Marker for Necrotizing Meningoencephalitis in Pug Dogs

    PubMed Central

    MIYAKE, Hizuru; INOUE, Akiko; TANAKA, Miho; MATSUKI, Naoaki

    2013-01-01

    ABSTRACT To evaluate the ability of serum glial fibrillary acidic protein (GFAP) concentration as a diagnostic marker for canine central nervous system (CNS) disorders, sera from dogs with various CNS (n=47) and non-CNS (n=56) disorders were measured for GFAP by using an ELISA kit. Healthy Beagles (n=15) and Pug dogs (n=12) were also examined as controls. Interestingly, only Pug dogs with necrotizing meningoencephalitis (NME) showed elevated serum GFAP concentrations (<0.01 to 1.14 ng/ml), while other breeds of dogs with NME did not. Among the Pug dogs with NME, serum GFAP concentrations did not correlate with their clinical features, such as ages or survival times. Our data indicate the usefulness of serum GFAP as a novel marker for Pug dogs with NME. PMID:23856761

  2. Serum cobalamin and methylmalonic acid concentrations in dogs with chronic gastrointestinal disease.

    PubMed

    Berghoff, Nora; Parnell, Nolie K; Hill, Steve L; Suchodolski, Jan S; Steiner, Jörg M

    2013-01-01

    To determine the prevalence of hypocobalaminemia or methylmalonic acidemia (or both) in dogs with chronic gastrointestinal disease. Serum samples from 56 dogs with chronic gastrointestinal disease and 43 control dogs. Serum cobalamin and methylmalonic acid (MMA) concentrations were measured in all samples and compared between groups. A correlation between serum cobalamin and MMA concentrations and the canine chronic enteropathy clinical activity index was evaluated via the Spearman rank correlation. 20 of 56 (36%) dogs with gastrointestinal disease had hypocobalaminemia. Serum cobalamin concentrations were significantly lower in dogs with gastrointestinal disease than in control dogs. Five of 56 (9%) dogs with chronic gastrointestinal disease and 5 of 20 (25%) hypocobalaminemic dogs had increased MMA concentrations. There was a significant negative correlation (Spearman r = -0.450) between serum cobalamin and MMA concentrations in dogs with gastrointestinal disease. No correlation was found between the canine chronic enteropathy clinical activity index and serum cobalamin or MMA concentrations. These data indicated the prevalence of hypocobalaminemia in dogs with chronic gastrointestinal disease was 20 of 56 (36%). Five of 20 (25%) hypocobalaminemic dogs had increased serum MMA concentrations, which indicated that although hypocobalaminemia was common in these dogs, it did not always appear to be associated with a deficiency of cobalamin on a cellular level. Hypocobalaminemia is a risk factor for negative outcome in dogs with chronic gastrointestinal disease and should be considered in every patient with corresponding clinical signs.

  3. Association between serum uric acid and bone health in general population: a large and multicentre study

    PubMed Central

    Hong, Dun; Liu, Wenyue; Huang, Kangmao; Mo, Jian; Yu, Hejun; Wu, Shengjie; Fan, Shunwu

    2015-01-01

    Previous studies proposed that serum uric acid (UA), an endogenous antioxidant, could be a protective factor against bone loss. However, recently, a study with a population of US adults did not note the protective effects of serum UA. Therefore, the exact association between serum UA and bone health remains unclear. We performed a retrospective consecutive cohort study in a Chinese population to examine the association between serum UA and bone health. This cross-sectional study included 17,735 individuals who underwent lumbar spine bone mineral density (BMD) measurements as part of a health examination. In covariance analyses (multivariable-adjusted), a high serum UA level was associated with a high BMD, T-score, and Z-score. In binary logistic regression analyses (multivariable-adjusted), a high serum UA level was associated with low odds ratios (ORs) for at least osteopenia and osteoporosis in male (age ≥50 years) (OR = 0.72–0.60 and OR = 0.49–0.39, respectively) and postmenopausal female participants (OR = 0.61–0.51 and OR = 0.66–0.49, respectively). In conclusion, serum UA is associated with BMD, the T-score, and the Z-score, and has a strong protective effect against at least osteopenia and osteoporosis. PMID:26496032

  4. The influence of fatty acids on theophylline binding to human serum albumin. Comparative fluorescence study

    NASA Astrophysics Data System (ADS)

    Maciążek-Jurczyk, M.; Sułkowska, A.; Bojko, B.; Równicka-Zubik, J.; Szkudlarek-Haśnik, A.; Zubik-Skupień, I.; Góra, A.; Dubas, M.; Korzonek-Szlacheta, I.; Wielkoszyński, T.; Żurawiński, W.; Sosada, K.

    2012-04-01

    Theophylline, popular diuretic, is used to treat asthma and bronchospasm. In blood it forms complexes with albumin, which is also the main transporter of fatty acids. The aim of the present study was to describe the influence of fatty acids (FA) on binding of theophylline (Th) to human serum albumin (HSA) in the high affinity binding sites. Binding parameters have been obtained on the basis of the fluorescence analysis. The data obtained for the complex of Th and natural human serum albumin (nHSA) obtained from blood of obese patients qualified for surgical removal of stomach was compared with our previous studies on the influence of FA on the complex of Th and commercially available defatted human serum albumin (dHSA).

  5. Polyacrylic acids-bovine serum albumin complexation: Structure and dynamics.

    PubMed

    Othman, Mohamed; Aschi, Adel; Gharbi, Abdelhafidh

    2016-01-01

    The study of the mixture of BSA with polyacrylic acids at different masses versus pH allowed highlighting the existence of two regimes of weak and strong complexation. These complexes were studied in diluted regime concentration, by turbidimetry, dynamic light scattering (DLS), zeta-potential measurements and nuclear magnetic resonance (NMR). We have followed the pH effect on the structure and properties of the complex. This allowed refining the interpretation of the phase diagram and understanding the observed phenomena. The NMR measurements allowed probing the dynamics of the constituents versus the pH. The computational method was used to precisely determine the electrostatic potential of BSA and how the polyelectrolyte binds to it at different pH.

  6. Serum Uric Acid, Hyperuricemia and Body Mass Index in Children and Adolescents with Intellectual Disabilities

    ERIC Educational Resources Information Center

    Lin, Jin-Ding; Lin, Pei-Ying; Lin, Lan-Ping; Hsu, Shang-Wei; Yen, Chia-Feng; Fang, Wen-Hui; Wu, Sheng-Ru; Chien, Wu-Chien; Loh, Ching-Hui; Chu, Cordia M.

    2009-01-01

    The aims of the preset study were to describe the profile of serum uric acid, the prevalence of hyperuricemia and its risk factors among children and adolescents with intellectual disabilities. We conducted a cross-sectional study of 941 children and adolescents with intellectual disabilities (aged 4-18 years) who participated in annual health…

  7. Serum Uric Acid, Hyperuricemia and Body Mass Index in Children and Adolescents with Intellectual Disabilities

    ERIC Educational Resources Information Center

    Lin, Jin-Ding; Lin, Pei-Ying; Lin, Lan-Ping; Hsu, Shang-Wei; Yen, Chia-Feng; Fang, Wen-Hui; Wu, Sheng-Ru; Chien, Wu-Chien; Loh, Ching-Hui; Chu, Cordia M.

    2009-01-01

    The aims of the preset study were to describe the profile of serum uric acid, the prevalence of hyperuricemia and its risk factors among children and adolescents with intellectual disabilities. We conducted a cross-sectional study of 941 children and adolescents with intellectual disabilities (aged 4-18 years) who participated in annual health…

  8. Positive association between metabolic syndrome and serum uric acid in Wuhan.

    PubMed

    Fu, Yuan-Qing; Yang, Hong; Zheng, Ju-Sheng; Zeng, Xiao-Yun; Zeng, Wen; Fan, Zhi-Fen; Chen, Min; Wang, Ling; Li, Duo

    2017-03-01

    The objective was to determine whether serum uric acid concentrations were associated with metabolic syndrome in a population from Wuhan. 5,628 subjects (2,838 men, 2,790 women) aged 18-80 years were recruited in Wuhan, China. Biochemical parameters of venous blood were measured by standard methods and metabolic syndrome was defined by Chinese Diabetes Society criteria. Association analysis was performed by logistic regression. 8.2% of the included subjects were confirmed as having metabolic syndrome and 14.4% were confirmed as having hyperuricemia. After multivariable adjustment, logistic regression showed the odds ratios of metabolic syndrome for subjects in the highest quartile of serum uric acid concentration was 2.84 (95% CI: 2.09-3.86) compared with those in the lowest quartile and no gender difference was found. For each component of metabolic syndrome, subjects in the highest quartile of serum uric acid concentrations had increased multivariable odds ratios for high BMI (OR: 3.29, 95% CI: 2.71-3.98), for hypertension (OR: 3.54, 95% CI: 2.93-3.86), for dyslipidemia (OR: 2.49, 95% CI: 1.98-3.14), but not for hyperglycemia (OR: 1.21, 95% CI: 0.87-1.67). Odd ratio of metabolic syndrome was significantly positively associated with serum uric acid concentration among the present sample of 5,628 subjects in Wuhan.

  9. Phenolic acids are in vivo atheroprotective compounds appearing in serum of rats after blueberry consumption

    USDA-ARS?s Scientific Manuscript database

    Blueberries (BB) have recently been shown to have cardio-protective effects and prevention of atherosclerosis in rodent models. However, the bioactive compounds in BB responsible for these effects have not yet been characterized. Seven phenolic acids were identified as metabolites in serum of rats ...

  10. Dietary fructose in relation to blood pressure and serum uric acid in adolescent boys and girls.

    PubMed

    Bobridge, K S; Haines, G L; Mori, T A; Beilin, L J; Oddy, W H; Sherriff, J; O'Sullivan, T A

    2013-04-01

    Evidence that fructose intake may modify blood pressure is generally limited to adult populations. This study examined cross-sectional associations between dietary intake of fructose, serum uric acid and blood pressure in 814 adolescents aged 13-15 years participating in the Western Australian Pregnancy Cohort (Raine) Study. Energy-adjusted fructose intake was derived from 3-day food records, serum uric acid concentration was assessed using fasting blood and resting blood pressure was determined using repeated oscillometric readings. In multivariate linear regression models, we did not see a significant association between fructose and blood pressure in boys or girls. In boys, fructose intake was independently associated with serum uric acid (P<0.01), and serum uric acid was independently associated with systolic blood pressure (P<0.01) and mean arterial pressure (P<0.001). Although there are independent associations, there is no direct relationship between fructose intake and blood pressure. Our data suggest that gender may influence these relationships in adolescence, with significant associations observed more frequently in boys than girls.

  11. Bacillus anthracis Overcomes an Amino Acid Auxotrophy by Cleaving Host Serum Proteins

    PubMed Central

    Terwilliger, Austen; Swick, Michelle C.; Pflughoeft, Kathryn J.; Pomerantsev, Andrei; Lyons, C. Rick; Koehler, Theresa M.

    2015-01-01

    ABSTRACT Bacteria sustain an infection by acquiring nutrients from the host to support replication. The host sequesters these nutrients as a growth-restricting strategy, a concept termed “nutritional immunity.” Historically, the study of nutritional immunity has centered on iron uptake because many bacteria target hemoglobin, an abundant circulating protein, as an iron source. Left unresolved are the mechanisms that bacteria use to attain other nutrients from host sources, including amino acids. We employed a novel medium designed to mimic the chemical composition of human serum, and we show here that Bacillus anthracis, the causative agent of anthrax disease, proteolyzes human hemoglobin to liberate essential amino acids which enhance its growth. This property can be traced to the actions of InhA1, a secreted metalloprotease, and extends to at least three other serum proteins, including serum albumin. The results suggest that we must also consider proteolysis of key host proteins to be a way for bacterial pathogens to attain essential nutrients, and we provide an experimental framework to determine the host and bacterial factors involved in this process. IMPORTANCE The mechanisms by which bacterial pathogens acquire nutrients during infection are poorly understood. Here we used a novel defined medium that approximates the chemical composition of human blood serum, blood serum mimic (BSM), to better model the nutritional environment that pathogens encounter during bacteremia. Removing essential amino acids from BSM revealed that two of the most abundant proteins in blood—hemoglobin and serum albumin—can satiate the amino acid requirement for Bacillus anthracis, the causative agent of anthrax. We further demonstrate that hemoglobin is proteolyzed by the secreted protease InhA1. These studies highlight that common blood proteins can be a nutrient source for bacteria. They also challenge the historical view that hemoglobin is solely an iron source for

  12. The nature of osteoporotic low back pain without acute vertebral fracture: A prospective multicenter study on the analgesic effect of monthly minodronic acid hydrate.

    PubMed

    Fujimoto, Kazuki; Inage, Kazuhide; Orita, Sumihisa; Yamashita, Masaomi; Abe, Koki; Yamagata, Masatsune; Sainoh, Takeshi; Akazawa, Tsutomu; Kinoshita, Tomoaki; Nemoto, Tetsuharu; Hirayama, Jiro; Murata, Yasuaki; Kotani, Toshiaki; Aoki, Yasuchika; Eguchi, Yawara; Sakuma, Takeshi; Aihara, Takahito; Ishikawa, Tetsuhiro; Suseki, Kaoru; Hanaoka, Eiji; Yamauchi, Kazuyo; Kubota, Gou; Suzuki, Miyako; Sato, Jun; Shiga, Yasuhiro; Kanamoto, Hirohito; Inoue, Masahiro; Kinoshita, Hideyuki; Koda, Masao; Furuya, Takeo; Takahashi, Kazuhisa; Ohtori, Seiji

    2017-07-01

    Patients with osteoporosis but no evidence of fracture can sometimes report low back pain. However, few studies have evaluated the nature of osteoporotic low back pain in a clinical situation. Therefore, the aim of this study was to examine the nature of osteoporotic low back pain without fracture, and the analgesic effect of minodronic acid hydrate on such pain. The current study examined 136 patients with osteoporotic low back pain and no lower extremity symptoms. The following factors were evaluated before and after minodronic acid hydrate administration: the nature of osteoporotic low back pain was evaluated using the painDETECT questionnaire, numeric rating scale (NRS) score for low back pain at rest and in motion, bone mineral density (BMD) of the lumbar spine, and the serum concentration of tartrate-resistant acid phosphatase 5b (TRACP-5b) as a bone metabolism marker. A total of 113 patients were enrolled. The painDETECT questionnaire revealed the percentage of patients with nociceptive pain and neuropathic or mixed pain was approximately 85% and 15%, respectively. the average NRS scores for low back pain at rest decreased significantly 2 months after treatment (p = 0.01), while those in motion decreased significantly 1 month after treatment (p = 0.04). The average lumbar spine BMD tended to increase after treatment, but not significantly. On the other hand, the changes in the average serum concentration of TRACP-5b did significantly decrease 1 month after treatment. There was a significant positive correlation between the rate of NRS score improvement for low back pain at rest, and the rate of improvement in serum concentration of TRACP-5b (p < 0.05). Osteoporotic low back pain consisted of 85% nociceptive pain and 15% neuropathic or mixed pain. The pain is strongly related to pain at rest rather than that in motion. Copyright © 2017 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.

  13. C-Reactive Protein, Sialic Acid and Adenosine Deaminase Levels in Serum and Pleural Fluid from Patients with Pleural Effusion

    PubMed Central

    Kim, Ji Woon; Yang, In Ae; Oh, Eun A; Rhyoo, Young Gun; Jang, Young Ho; Ryang, Dong Wook; Yoo, JooYong

    1988-01-01

    Laboratory analysis of pleural fluids is essential to determine underlying diseases. The authors evaluated the clinical significance of C-reactive protein (C-RP), sialic acid (SA), and adenosine deaminase (ADA) determinations in sera and pleural fluids from 37 patients with pleural effusion. (FP12)C-RP and sialic acid levels and ADA activities were higher in exudates than in transudates of pleural fluids. Serum and pleural fluid C-RP levels were high in patients with pyothorax. Determinations of serum sialic acid and the pleural fluid to serum ratio were useful for the differential diagnosis of pulmonary tuberculosis and malignancy. ADA activities of pleural fluid and serum are useful for the differentiation of malignancy from tuberculosis and nonspecific pyothorax. C-RP concentrations of pleural fluid correlated to serum levels. However, concentrations of sialic acid and ADA activities were not correlated to serum levels and only correlated to protein concentrations of pleural fluids. PMID:3154188

  14. Association of Serum Phospholipid Fatty Acids with Breast Cancer Risk among Postmenopausal Cigarette Smokers

    PubMed Central

    Takata, Yumie; King, Irena B.; Neuhouser, Marian L.; Schaffer, Steve; Barnett, Matt; Thornquist, Mark; Peters, Ulrike; Goodman, Gary E.

    2009-01-01

    Objective To examine the association between breast cancer risk and the fatty acid composition of phospholipids in prediagnostic serum samples. Methods We analyzed the fatty acid composition in 130 incident postmenopausal breast cancer cases and 257 matched controls nested within the β-Carotene and Retinol Efficacy Trial Cohort. The fatty acid composition was measured by gas chromatography. Multivariate-adjusted odds ratios and corresponding 95% confidence intervals for the risk of breast cancer were estimated using logistic regression. Stratified analysis was conducted by smoking status. Results There were no associations with breast cancer risk for total saturated, monounsaturated, n-3, n-6, or trans fatty acids among all women. For individual fatty acids, we observed an inverse association with the trans linoleic acid, 18:2n6tt (p trend = 0.0002). Among current smokers, long-chain saturated fatty acids (22:0 and 24:0) and total 16:1 trans fatty acids were positively associated with the risk of breast cancer, whereas these fatty acids showed no association among former smokers. Conclusion Overall, we observed no significant association between serum phospholipid fatty acids and breast cancer risk, except for the trans linoleic acid isomer 18:2n6tt, which was unexpected. Our finding of a positive association of long-chain saturated fatty acids (22:0 and 24:0) and total 16:1 trans fatty acids with the risk of breast cancer only in current smokers may suggest an effect modification by smoking status. Our findings need to be replicated in future epidemiologic studies. PMID:19255861

  15. Serum Bile Acids in Repaired Tetralogy of Fallot: A Marker for Liver and Heart?

    PubMed

    Grangl, Gernot; Zöhrer, Evelyn; Köstenberger, Martin; Jud, Alexandra; Fauler, Günter; Scharnagl, Hubert; Stojakovic, Tatjana; Marterer, Robert; Gamillscheg, Andreas; Jahnel, Jörg

    2015-01-01

    Patients with repaired tetralogy of Fallot may develop chronic right ventricular dysfunction and hepatic congestion over time. We hypothesized that bile acid metabolism is altered in repaired tetralogy of Fallot patients and therefore sought to correlate right ventricular indices with serum bile acid levels. Indexed right ventricular end diastolic volume, as assessed by cardiac magnetic-resonance imaging, was classified as <100ml/m2 (Group 1, n = 5), 100-150ml/m2 (Group 2, n = 18), and >150ml/m2 (Group 3, n = 6) in 29 patients with repaired tetralogy of Fallot. Pulmonary regurgitation fraction and right ventricular ejection fraction were calculated. The serum bile acid profile, including 15 species, in these patients was determined by liquid chromatography coupled with mass spectrometry. Serum bile acid levels increased from Group 1 to Group 3 (2.5 ± 0.7; 4.1 ± 2.5; 6.0 ± 2.8 μmol/l, respectively) with significantly increased bile acid values in Group 3 compared to Group 1 (p≤0.05). In Group 3, but not in Group 1 and 2, a significant increase in glycine-conjugated bile acids was observed. Pulmonary regurgitation fraction increased (12 ± 1; 28 ± 16; 43 ± 3%, Groups 1-3, respectively) and right ventricular ejection fraction decreased (48.4 ± 6.4; 48.5 ± 6.5; 42.1 ± 5.3%, Groups 1-3, respectively) with rising indexed right ventricular end diastolic volume. These preliminary results suggest that serum bile acid levels are positively correlated with indexed right ventricular end-diastolic volume in patients with repaired tetralogy of Fallot; however, this needs to be confirmed in a larger patient cohort.

  16. Serum nitrite and nitrate levels in epileptic children using valproic acid or carbamazepine.

    PubMed

    Karabiber, Hamza; Yakinci, Cengiz; Durmaz, Yasar; Temel, Ismail; Mehmet, Nihayet

    2004-01-01

    In experimental epilepsy studies, nitric oxide was found to act as both proconvulsant and anticonvulsant. The objective of this study was to investigate the effects of valproic acid and carbamazepine on serum levels of nitrite and nitrate, which are the metabolites of nitric oxide. To achieve this goal, serum nitrite and nitrate levels were determined in active epileptic 34 children using valproic acid and 23 children using carbamazepine and in non-active epileptic 38 children (control group) not using any antiepileptic drug. In the valproic acid group serum nitrite and nitrate levels were 2.66 +/- 2.11 micromol/l and 69.35 +/- 23.20 micromol/l, 1.89 +/- 1.01 micromol/l and 49.39 +/- 10.61 micromol/l in the carbamazepine group, and 1.22 +/- 0.55 micromol/l, 29.53 +/- 10.05 micromol in the control group, respectively. Nitrite and nitrate levels were significantly high in both valproic acid and carbamazepine groups compared to the control group (P < 0.01). When valproic acid and carbamazepine groups were compared to each other, level of nitrate was found statistically higher in the valproic acid group in relation to the carbamazepine group (P < 0.01), however, there was no statistically significant difference in the levels of nitrite (P > 0.05). No relation could be found between serum drug levels and nitrite and nitrate levels. According to these results, it can be suggested that valproic acid and carbamazepine might have antiepileptic effects through nitric oxide.

  17. Serum hyaluronic acid predicts protein-energy malnutrition in chronic hepatitis C

    PubMed Central

    Nishikawa, Hiroki; Enomoto, Hirayuki; Yoh, Kazunori; Iwata, Yoshinori; Hasegawa, Kunihiro; Nakano, Chikage; Takata, Ryo; Kishino, Kyohei; Shimono, Yoshihiro; Sakai, Yoshiyuki; Nishimura, Takashi; Aizawa, Nobuhiro; Ikeda, Naoto; Takashima, Tomoyuki; Ishii, Akio; Iijima, Hiroko; Nishiguchi, Shuhei

    2016-01-01

    Abstract Serum hyaluronic acid (HA) is a well-established marker of fibrosis in patients with chronic liver disease (CLD). However, the relationship between serum HA level and protein-energy malnutrition (PEM) in patients with CLD is an unknown. We aimed to examine the relationship between serum HA level and PEM in patients with chronic hepatitis C (CHC) compared with the relationships of other serum markers of fibrosis. A total of 298 CHC subjects were analyzed. We defined patients with serum albumin level of ≤3.5 g/dL and nonprotein respiratory quotient <0.85 using indirect calorimetry as having PEM. We investigated the effect of serum HA level on the presence of PEM. Receiver operating characteristic curve (ROC) analysis was performed for calculating the area under the ROC (AUROC) for serum HA level, platelet count, aspartate aminotransferase (AST) to platelet ratio index, FIB-4 index, AST to alanine aminotransferase ratio, and Forns index for the presence of PEM. The median serum HA level in this study was 148.0 ng/mL (range: 9.0–6340.0 ng/mL). In terms of the degree of liver function (chronic hepatitis, Child-Pugh A, B, and C), the analyzed patients were well stratified according to serum HA level (overall significance, P < 0.0001). The median value (range) of serum HA level in patients with PEM (n = 61) was 389.0 ng/mL (43.6–6340.0 ng/mL) and that in patients without PEM (n = 237) was 103.0 ng/mL (9.0–783.0 ng/mL) (P < 0.0001). Among 6 fibrosis markers, serum HA level yielded the highest AUROC with a level of 0.849 at an optimal cut-off value of 151.0 ng/mL (sensitivity 93.4%; specificity 62.0%; P < 0.0001). In the multivariate analysis, serum HA level was found to be a significant prognostic factor related to the presence of PEM (P = 0.0001). In conclusion, serum HA level can be a useful predictor of PEM in patients with CHC. PMID:27311000

  18. Impact of serum uric acid, albumin and their interaction on Parkinson's disease.

    PubMed

    Wang, Lijun; Hu, Wei; Wang, Jun; Fang, Fangfang; Cheng, Guanliang; Jiang, Yuzhang; Xiao, Hang; Wan, Qi

    2017-02-01

    The study aimed to investigate the correlation between Parkinson's disease (PD) and serum levels of uric acid (UA), albumin and their interaction. A cross-sectional study was conducted to evaluate the relationship of serum UA, albumin with PD. A total of 96 PD patients and 108 healthy controls were recruited at Huai'an First People's Hospital, Nanjing Medical University. Baseline data included age, gender, body mass index (BMI), disease duration, Hoehn and Yahr scale (H&Y) stage, serum UA and albumin levels. The levels of serum UA and albumin were significantly lower in PD patients than those in controls (P = 0.001; P = 0.000). Serum albumin levels were strikingly different in H&Y group (P = 0.004). Multivariable logistic regression showed that the levels of serum UA (P = 0.001, adjusted OR 0.993, 95% CI 0.988-0.997) and albumin (P = 0.000, adjusted OR 0.513, 95% CI 0.425-0.620) were independent risk factors in PD. The receiver operating characteristic (ROC) curve analyses showed that the area under curve (AUC) for serum UA and albumin was 0.669 (95% CI 0.594-0.744) and 0.883 (95% CI 0.835-0.931), respectively. The combination of serum albumin and UA improved the AUC to 0.898 (95% CI 0.854-0.942). Serum UA and albumin levels significantly decreased in PD patients and were independent risk factors for PD. More studies are needed to confirm our findings.

  19. Determination of Selected Amino Acids in Serum of Patients with Liver Disease.

    PubMed

    Kanďár, Roman; Drábková, Petra; Toiflová, Tereza; Čegan, Alexander

    2016-01-01

    The determination of amino acids can be a reliable approach for extended diagnosis of liver diseases. This is because liver disease can be a cause of impaired amino acid metabolism. Therefore, a method for the determination of serum amino acids, applicable for clinical purposes, is necessary. The aim of this study was to find differences in the levels of selected amino acids between patients with liver disease and a control group. Samples of peripheral venous blood were obtained from a group of patients with liver disease (n = 131, 59 women at an average age of 60 years and 72 men at an average age of 52 years) and a control group (n = 105, 47 women at an average age of 62 years and 58 men at an average age of 58 years). Before the separation, the amino acids were derivatized with naphthalene-2,3-dicarboxaldehyde. For the separation, reverse phase column was used. The effluent was monitored with a fluorescence detector. There were significant differences in the concentrations of some amino acids between the patients and the control group, but also between women and men. Correlations between some amino acids and markers of liver blood tests and lipid metabolism were observed. A simple, relatively rapid and selective HPLC method with fluorescence detection for the determination of selected amino acids in serum has been developed.

  20. Interactions of hybrid gold-tannic acid nanoparticles with human serum albumin.

    PubMed

    Sekowski, Szymon; Tomaszewska, Emilia; Soliwoda, Katarzyna; Celichowski, Grzegorz; Grobelny, Jaroslaw

    2017-01-01

    Nanoparticles present a wide spectrum of chemical, biological, and physical properties which result in their usage in many branches of science. We present an investigation of the interaction between human serum albumin and hybrid gold-tannic acid nanoparticles synthesized via a chemical reduction method. The results obtained demonstrate that tannic acid can be a very effective reducing and stabilizing agent and allows monodisperse hybrid gold nanomaterial to be obtained. The synthesized hybrid gold-tannic acid nanoparticles strongly interact with human serum albumin by formation of protein-corona complexes. The strength of the interaction with albumin depends on the number of tannic acid molecules on the surface of the nanoparticles and the presence of citric acid. Nanoparticles of large size and rich in tannic acid react more strongly with the protein [K SV = (8.00 ± 0.2) × 10(5) M(-1)] compared with smaller ones [K SV = (6.83 ± 0.5) × 10(4) M(-1)] containing citric acid and low concentration of tannic acid.

  1. Tryptophan concentrations in rat brain. Failure to correlate with free serum tryptophan or its ratio to the sum of other serum neutral amino acids.

    PubMed Central

    Fernstrom, J D; Hirsch, M J; Faller, D V

    1976-01-01

    Groups of rats were deprived of food overnight and then given free access to diets designed to raise (carbohydrate) or lower (carbohydrate and large neutral amino acids) brain tryptophan concentrations. Similar diets were supplemented with 40% fat and fed to other groups. All animals were killed 2h after food presentation. Sera from animals fed carbohydrate plus fat contained 2.5 times as much free tryptophan concentrations did not differ. Similarly, sera from rats fed on carbohydrate, large neutral amino acids, and 40% fat contained 5 times as much free tryptophan as those from rats given this meal without fat, but brain tryptophan concentrations increased by only 26%. Correlations were made between brain tryptophan and (1) free serum tryptophan, (2) the ratio of free serum tryptophan to the sum of the other large neutral amino acids in serum that compete with it for uptake into the brain, (3) total serum tryptophan or (4) the ratio of total serum tryptophan to the sum of its circulating competitors. The r values for correlations (3) and (4) (i.e. those involving total serum tryptophan) were appreciably higher than those for correlations (1) and (2). Brain tyrosine concentrations also were found to correlate well with the ratio of serum tyrosine to the sum of its competitors. Competition for uptake into the brain among large neutral amino acids (represented here by serum ratios) thus appears to determine the changes in the brain concentrations of these amino acids under physiological conditions(i.e. after food consumption). Total, not free, serum tryptophan is the relevant index for predicting brain tryptophan concentrations. PMID:1016241

  2. Serum uric acid concentrations and SLC2A9 genetic variation in Hispanic children: The Viva La Familia Study

    USDA-ARS?s Scientific Manuscript database

    Elevated concentrations of serum uric acid are associated with increased risk of gout and renal and cardiovascular diseases. Genetic studies in adults have consistently identified associations of solute carrier family 2, member 9 (SLC2A9), polymorphisms with variation in serum uric acid. However, it...

  3. The evaluation of serum homocysteine, folic acid, and vitamin B12 in patients complicated with preeclampsia

    PubMed Central

    Shahbazian, Nahid; Jafari, Razieh Mohammad; Haghnia, Sahar

    2016-01-01

    Introduction Increased plasma homocysteine may be associated with adverse pregnancy outcomes, such as preeclampsia. The aim of this study was to determine the plasma homocysteine, serum folate, and vitamin B12 levels in preeclamptic pregnant women. Methods This case-control study was conducted in 2016 in Ahwaz on 51 pregnant women with preeclampsia and 51 healthy pregnant women of the same gestational age, who served as controls. The case group also was subdivided into severe and non-severe preeclampsia. Patients’ data were collected through a questionnaire and medical records. Serum homocysteine, folic acid, and vitamin B12 were analyzed using chemiluminescent assay. The results were compared between two groups. Statistical analyses were done using IBM-SPSS 20.0. A Kolmogorov-Smirnov test, independent samples t-test, Mann-Whitney test, and Chi-square test were used for data analysis. Results No different demographic characteristics were found among the groups. Pregnant women complicated with preeclampsia displayed significantly higher serum homocysteine levels (p < 0.001) and lower serum folate (p = 0.005) and vitamin B12 levels (p < 0.001) compared to controls. A statistically significant inverse correlation was evident between serum homocysteine and serum folate levels in preeclamptic patients (p = 0.005; r = −0.389). In addition, an inverse correlation was identified between homocysteine and serum vitamin B12, but it was not statistically significant (p = 0.160; r = −0.200). Significant differences occurred in serum homocysteine and folate levels between the severe and non-severe subgroups (p < 0.001, p < 0.001). Conclusion Women complicated with preeclampsia displayed higher maternal serum homocysteine and lower serum folate and vitamin B12. Further studies are needed to confirm if the prescription of folic acid and vitamin B12 in women with a deficiency of these vitamins could decrease the level of serum homocysteine and, therefore, reduce the risk of

  4. Fluorescence spectroscopy and molecular simulation on the interaction of caffeic acid with human serum albumin.

    PubMed

    Xiang, Yuhong; Duan, Lili; Ma, Qiang; Lv, Zizheng; Ruohua, Zhu; Zhang, Zhuoyong

    2016-12-01

    Fluorescence spectroscopy and molecular simulation were explored to study the interaction between caffeic acid and human serum albumin (HSA). The experimental results indicated that the fluorescence quenching mechanism between caffeic acid and HSA is a static quenching, which was proved again by the analysis of fluorescence lifetime by time-correlated single photon counting. The binding process is spontaneous and the hydrophobic force is the main force between caffeic acid and HSA. In addition, the binding of caffeic acid to HSA was modeled by molecular dynamics simulations. The root mean square deviations, root mean square fluctuations, radius of gyration and the number of hydrogen bonds of the molecular dynamic (MD) simulation process were analyzed. Both experimental and modeling results demonstrated strong binding between HSA and caffeic acid. HSA had a slight conformational change when it binds with caffeic acid. The obtained information is useful for HSA drug design. Copyright © 2016 John Wiley & Sons, Ltd.

  5. Elucidating the influence of gold nanoparticles on the binding of salvianolic acid B and rosmarinic acid to bovine serum albumin.

    PubMed

    Peng, Xin; Qi, Wei; Huang, Renliang; Su, Rongxin; He, Zhimin

    2015-01-01

    Salvianolic acid B and rosmarinic acid are two main water-soluble active ingredients from Salvia miltiorrhiza with important pharmacological activities and clinical applications. The interactions between salvianolic acid B (or rosmarinic acid) and bovine serum albumin (BSA) in the presence and absence of gold nanoparticles (Au NPs) with three different sizes were investigated by using biophysical methods for the first time. Experimental results proved that two components quenched the fluorescence of BSA mainly through a static mechanism irrespective of the absence or presence of Au NPs. The presence of Au NPs decreased the binding constants of salvianolic acid B with BSA from 27.82% to 10.08%, while Au NPs increased the affinities of rosmarinic acid for BSA from 0.4% to 14.32%. The conformational change of BSA in the presence of Au NPs (caused by a noncompetitive binding between Au NPs and drugs at different albumin sites) induced changeable affinity and binding distance between drugs and BSA compared with no Au NPs. The competitive experiments revealed that the site I (subdomain IIA) of BSA was the primary binding site for salvianolic acid B and rosmarinic acid. Additionally, two compounds may induce conformational and micro-environmental changes of BSA. The results would provide valuable binding information between salvianolic acid B (or rosmarinic acid) and BSA, and also indicated that the Au NPs could alter the interaction mechanism and binding capability of drugs to BSA, which might be beneficial to understanding the pharmacokinetics and biological activities of the two drugs.

  6. Effect of intragastric infusions of ethanol and wine on serum gastrin concentration and gastric acid secretion.

    PubMed

    Peterson, W L; Barnett, C; Walsh, J H

    1986-12-01

    The effects of ethanol and wine on serum gastrin concentration and gastric acid secretion were evaluated in 13 normal volunteers. Solutions studied were pure ethanol (5%, 12%, and 36%), red wine, and white wine. Each solution contained 28 g of ethanol and each was administered as a slow, steady intragastric infusion to simulate normal ingestion of beverages. When compared to saline (control), none of the pure ethanol solutions increased serum gastrin concentration or gastric acid secretion significantly. In contrast, red and white wine (12% ethanol vol/vol) were potent stimulants of gastrin release and acid secretion when compared either to saline or pure 12% ethanol. Mean (+/- SEM) peak serum gastrin increases with 300 ml of red wine, white wine, saline, and pure 12% ethanol were 253 +/- 125, 182 +/- 91, 13 +/- 2, and 11 +/- 3 pg/ml, respectively (p less than 0.05 for red and white wine versus saline or 12% ethanol), and the mean peak acid outputs were 28.6 +/- 2.8, 27.9 +/- 1.9, 9.3 +/- 2.0, and 11.9 +/- 1.3 mmol/h, respectively (p less than 0.05 for red and white wine versus saline or 12% ethanol). We conclude that red and white wine stimulate gastric acid secretion, probably by enhanced release of gastrin, and that this effect is not due to the ethanol content of wine.

  7. Effects of a honeybee sting on the serum free amino acid profile in humans.

    PubMed

    Matysiak, Jan; Dereziński, Paweł; Klupczyńska, Agnieszka; Matysiak, Joanna; Kaczmarek, Elżbieta; Kokot, Zenon J

    2014-01-01

    The aim of this study was to assess the response to a honeybee venom by analyzing serum levels of 34 free amino acids. Another goal of this study was to apply complex analytic-bioinformatic-clinical strategy based on up-to-date achievements of mass spectrometry in metabolomic profiling. The amino acid profiles were determined using hybrid triple quadrupole/linear ion trap mass spectrometer coupled with a liquid chromatography instrument. Serum samples were collected from 27 beekeepers within 3 hours after they were stung and after a minimum of 6 weeks following the last sting. The differences in amino acid profiles were evaluated using MetaboAnalyst and ROCCET web portals. Chemometric tests showed statistically significant differences in the levels of L-glutamine (Gln), L-glutamic acid (Glu), L-methionine (Met) and 3-methyl-L-histidine (3MHis) between the two analyzed groups of serum samples. Gln and Glu appeared to be the most important metabolites for distinguishing the beekeepers tested shortly after a bee sting from those tested at least 6 weeks later. The role of some amino acids in the response of an organism to the honeybee sting was also discussed. This study indicated that proposed methodology may allow to identify the individuals just after the sting and those who were stung at least 6 weeks earlier. The results we obtained will contribute to better understanding of the human body response to the honeybee sting.

  8. Effects of a Honeybee Sting on the Serum Free Amino Acid Profile in Humans

    PubMed Central

    Matysiak, Jan; Dereziński, Paweł; Klupczyńska, Agnieszka; Matysiak, Joanna; Kaczmarek, Elżbieta; Kokot, Zenon J.

    2014-01-01

    The aim of this study was to assess the response to a honeybee venom by analyzing serum levels of 34 free amino acids. Another goal of this study was to apply complex analytic-bioinformatic-clinical strategy based on up-to-date achievements of mass spectrometry in metabolomic profiling. The amino acid profiles were determined using hybrid triple quadrupole/linear ion trap mass spectrometer coupled with a liquid chromatography instrument. Serum samples were collected from 27 beekeepers within 3 hours after they were stung and after a minimum of 6 weeks following the last sting. The differences in amino acid profiles were evaluated using MetaboAnalyst and ROCCET web portals. Chemometric tests showed statistically significant differences in the levels of L-glutamine (Gln), L-glutamic acid (Glu), L-methionine (Met) and 3-methyl-L-histidine (3MHis) between the two analyzed groups of serum samples. Gln and Glu appeared to be the most important metabolites for distinguishing the beekeepers tested shortly after a bee sting from those tested at least 6 weeks later. The role of some amino acids in the response of an organism to the honeybee sting was also discussed. This study indicated that proposed methodology may allow to identify the individuals just after the sting and those who were stung at least 6 weeks earlier. The results we obtained will contribute to better understanding of the human body response to the honeybee sting. PMID:25072247

  9. Inverse Association Between Serum Uric Acid Levels and Alzheimer's Disease Risk.

    PubMed

    Du, Na; Xu, Donghua; Hou, Xu; Song, Xuejia; Liu, Cancan; Chen, Ying; Wang, Yangang; Li, Xin

    2016-05-01

    The association between Alzheimer's disease and uric acid levels had gained great interest in recent years, but there was still lack of definite evidence. A systematic review and meta-analysis of relevant studies was performed to comprehensively estimate the association. Relevant studies published before October 26, 2014, were searched in PubMed, Embase, and China Biology Medicine (CBM) databases. Study-specific data were combined using random-effects or fixed-effects models of meta-analysis according to between-study heterogeneity. Twenty-four studies (21 case-control and 3 cohort studies) were finally included into the meta-analysis. Those 21 case-control studies included a total of 1128 cases of Alzheimer's disease and 2498 controls without Alzheimer's disease. Those 3 cohort studies included a total of 7327 participants. Meta-analysis showed that patients with Alzheimer's disease had lower levels of uric acid than healthy controls (weighted mean difference (WMD) = -0.77 mg/dl, 95% CI -2.28 to -0.36, P = 0.0002). High serum uric acid levels were significantly associated with decreased risk of Alzheimer's disease (risk ratio (RR) = 0.66, 95% CI 0.52-0.85, P = 0.001). There was low risk of publication bias in the meta-analysis. There is an inverse association between serum uric acid levels and Alzheimer's disease. High serum uric acid level is a protective factor of Alzheimer's disease.

  10. Changes of serum albumin affinity for aspirin induced by fatty acid.

    PubMed

    Bojko, B; Sułkowska, A; Maciazek, M; Równicka, J; Njau, F; Sułkowski, W W

    2008-05-01

    Saturated fatty acids such as myristic acid play an important role in the pathogenesis of cardiovascular disorders. Using the quenching fluorescence method we examined the influence of myristate on the changes of transporting protein affinity towards aspirin-the most popular anticoagulant. Our results showed that the presence of the myristic acid alters the stability of the anticoagulant-albumin complex. The ranges of [myristate]/[albumin] molar ratio at which the stability of drug-protein complex increases or decreases were determined. The differences in interaction between ligands and human or bovine serum albumins were identified. The competition in binding of ligands with these albumins was also described.

  11. Interlaboratory Analytical Comparison of Fatty Acid Concentrations in Serum or Plasma

    PubMed Central

    Schantz, Michele M.; Powers, Carissa D.; Schleicher, Rosemary L.; Betz, Joseph M.; Wise, Stephen A.

    2016-01-01

    The National Institute of Standards and Technology, in collaboration with the National Institutes of Health Office of Dietary Supplements and the Centers for Disease Control and Prevention, is conducting an accuracy-based program for improving the comparability of individual fatty acid measurements in serum and plasma. To date, two exercises of the Fatty Acid Quality Assurance Program (FAQAP) were conducted with 11 and 14 participants, respectively. The results from these two exercises indicate the need to improve the within-lab repeatability and between-lab reproducibility thus providing more confidence in the comparability of fatty acid measurements. PMID:27662814

  12. The influence of valproic acid and carbamazepine treatment on serum biotin and zinc levels and on biotinidase activity.

    PubMed

    Castro-Gago, Manuel; Pérez-Gay, Laura; Gómez-Lado, Carmen; Castiñeiras-Ramos, Daisy E; Otero-Martínez, Santiago; Rodríguez-Segade, Santiago

    2011-12-01

    We determined the serum concentration of biotin, zinc, antiepileptic drugs, and biotinidase enzyme activity in 20 children treated with valproic acid, in 10 children treated with carbamazepine, and in 75 age- and sex-matched healthy controls. There were no significant differences in the serum levels of biotin, and biotinidase enzyme activity between the patients treated with valproic acid, the patients treated with carbamazepine, and the control group. Zinc serum levels were lower in the patients treated with valproic acid and with carbamazepine than in the control group, but within the normal range. Hair loss was observed in 3 patients treated with valproic acid, with normal serum levels of biotin, zinc, and biotinidase activity, and the alopecia disappeared with the oral administration of biotin (10 mg/d) in 3 months. These results suggest that the treatment with valproic acid does not alter the serum levels of biotin, zinc, and biotinidase enzyme activity.

  13. Mouse serum paraoxonase-1 lactonase activity is specific for medium-chain length fatty acid lactones.

    PubMed

    Connelly, Philip W; Picardo, Clive M; Potter, Philip M; Teiber, John F; Maguire, Graham F; Ng, Dominic S

    2011-01-01

    Recent studies suggest that paraoxonase-1 (PON1), complexed with high-density lipoproteins, is the major lactonase in the circulation. Using 5-hydroxy eicosatetraenoate δ-lactone (5-HETEL) as the substrate, we observed lactonase activity in serum from Pon1-/- mice. However, 6-12 carbon fatty acid γ- and δ-lactones were not hydrolyzed in serum from Pon1-/- mice. Serum from both wild-type and Pon1-/- mice contained a lactonase activity towards 5-HETEL and 3-oxo-dodecanoyl-homoserine lactone that was resistant to inactivation by EDTA. This lactonase activity was sensitive to the serine esterase inhibitor phenyl methyl sulfonyl fluoride and co-eluted with carboxylesterase activity by size-exclusion chromatography. Analysis of serum from the Es1e mouse strain, which has a deficiency in the carboxylesterase, ES-1, proved that this activity was due to ES-1. PON1 activity predominated at early time points (30 s), whereas both PON1 and ES-1 contributed equally at later time points (15 min). When both PON1 and ES-1 were inhibited, 5-HETEL was stable in mouse serum. Thus, while long-chain fatty acid lactones are substrates for PON1, they can be hydrolyzed by ES-1 at neutral pH. In contrast, medium-chain length fatty acid lactones are stable in mouse serum in the absence of PON1, suggesting that PON1 plays a specific role in the metabolism of these compounds. Copyright © 2010 Elsevier B.V. All rights reserved.

  14. Serum uric acid levels in patients with myasthenia gravis are inversely correlated with disability

    PubMed Central

    Yang, Dehao; Weng, Yiyun; Lin, Haihua; Xie, Feiyan; Yin, Fang; Lou, Kangliang; Zhou, Xuan; Han, Yixiang; Li, Xiang

    2016-01-01

    Uric acid (UA), the final product of purine metabolism, has been reported to be reduced in patients with various neurological disorders and is considered to be a possible indicator for monitoring the disability and progression of multiple sclerosis. However, it remains unclear whether there is a close relationship between UA and myasthenia gravis (MG), or whether UA is primarily deficient or secondarily reduced because of its peroxynitrite scavenging activity. We investigated the correlation between serum UA levels and the clinical characteristics of MG. We assessed 338 serum UA levels obtained in 135 patients with MG, 47 patients with multiple sclerosis, and 156 healthy controls. In addition, we compared serum UA levels when MG patients were stratified according to disease activity and classifications performed by the Myasthenia Gravis Foundation of America, age of onset, duration, and thymus histology (by means of MRI or computed tomography). MG patients had significantly lower serum UA levels than the controls (P<0.001). Moreover, UA levels in patients with MG were inversely correlated with disease activity and disease progression (P=0.013). However, UA levels did not correlate significantly with disease duration, age of onset, and thymus histology. Our findings suggest that serum level of UA was reduced in patients with MG and serum UA might be considered a surrogate biomarker of MG disability and progression. PMID:26836463

  15. Serum uric acid and nigral iron deposition in Parkinson's disease: a pilot study.

    PubMed

    Kim, Tae-Hyoung; Lee, Jae-Hyeok

    2014-01-01

    Uric acid (UA) is an endogenous antioxidant which is known to reduce oxidative stress and also chelate iron ion. Recent studies have provided evidence that UA may play a neuroprotective role in Parkinson's disease (PD). However, it is unknown whether UA relates to nigral iron deposition, which is a characteristic pathophysiological alteration in PD. The aim of this study was to determine the potential relationship of these two markers in patients with PD. A total of 30 patients of PD and 25 age- and gender- matched healthy controls underwent 3-Tesla MRI and laboratory tests including serum UA levels. We assessed iron levels by measuring phase shift values using susceptibility-weighted image. Mean phase shift values of the substantia nigra (SN), red nucleus, head of the caudate nucleus, globus pallidus, putamen, thalamus, and frontal white matter were calculated and correlated with serum UA levels. Serum UA levels were significantly decreased in the PD patients than in the controls. Phase shift values in bilateral SN were significantly increased in the PD patients than in the controls. There was no significant correlation between serum UA levels and nigral phase shift values. As previous studies, low serum UA level and increased nigral iron content in the PD was reconfirmed in this study. However, we failed to find the relationship between these two markers. Our data suggest that serum UA may not be important determinant of nigral iron deposition in PD.

  16. Human Growth Factor Cream and Hyaluronic Acid Serum in Conjunction with Micro Laser Peel

    PubMed Central

    Katz, Bruce E.; Cohen, Joel L.; Biron, Julie

    2010-01-01

    The present study investigated the use of a novel hyaluronic acid serum in combination with a cream comprising a mixture of human growth factors in conjunction with the micro laser peel procedure for skin rejuvenation. After preconditioning the face with the hyaluronic acid serum followed by the cream twice daily for one month, 15 female volunteers between 35 to 65 years of age with demonstrable facial wrinkling received a micro laser peel on the entire face using an erbium-doped yttrium aluminium garnet laser. Immediately following the laser procedure, the subjects applied the test products twice daily until the second laser peel one month later. Immediately following the second procedure, the subjects reapplied the test products for another month. In the large majority of subjects, erythema or edema, crusts or erosions, and transitory stinging or burning sensations after the micro laser peel were minimal or mild when the skin was treated with the serum followed by the cream. The micro laser peel in conjunction with the test products helped to significantly improve hyperpigmentation, wrinkles, and texture as compared to before treatment. This study with the micro laser peel device demonstrated that a novel hyaluronic acid serum combined with the human growth factor cream can be successfully used for skin rejuvenation in conjunction with light-to-medium invasive laser skin treatments. PMID:21203354

  17. Pyruvic acid levels in serum and saliva: A new course for oral cancer screening?

    PubMed Central

    Bhat, Manohara A; Prasad, KVV; Trivedi, Dheeraj; Rajeev, BR; Battur, Hemanth

    2016-01-01

    Objective: Cancerous cells show increased glycolysis rate. This will increase overall levels of pyruvate as it is one of the end products of glycolysis. The present on-going study is to estimate the levels of pyruvate in saliva and serum among healthy and oral cancer subjects. Settings and Design: Hospital-based cross-sectional comparative study. Methodology: A total of 50 subjects among healthy and oral cancer subjects were selected based on clinical and histological criteria. Saliva and serum samples were collected and subjected to pyruvate level estimation using biochemical analysis. Statistical Analysis: Descriptive analysis and Mann-Whitney test were used to find the statistical difference between the two independent groups. Results: Serum pyruvic acid levels of the healthy group were 1.09 ± 0.14 and for oral cancer, it was 2.95 ± 0.59 and salivary level were 3.49 ± 0.47 and 1.32 ± 0.10 respectively. Mann-Whitney test showed statistically significant difference in serum and salivary pyruvate level in between two groups (P < 0.000 respectively). Conclusion: The present study showed noticeable variation in the level of pyruvic acid among healthy and oral cancer subjects. This generates the hypothesis that estimation of the pyruvic acid can be a new tool to screening of the cancer. PMID:27194870

  18. Age-related change of cefazolin binding to rat serum proteins and its relation to the molar ratio of free fatty acid to serum albumin.

    PubMed

    Terasaki, T; Imaeda, N; Nishide, K; Tsuji, A

    1986-01-01

    The binding of cefazolin to rat sera has been studied as a function of age. A significant difference was observed in the cefazolin binding to serum protein among 1-, 2-, 3-, 5-, 7-, 50- and 100-week-old rats. There was a good correlation between the dissociation constants of cefazolin binding and the molar ratio of free fatty acid to albumin concentration in sera. This suggests that both changes of concentration of albumin and free fatty acid, which could be a major endogenous inhibitor of cefazolin binding, play an important role in the age-related changes of the serum protein binding. Removal of free fatty acid in 1- and 2-week-old rat sera showed marked increases of the cefazolin binding. On the contrary, addition of oleic acid to 7-week-old rat serum produced significant reduction of cefazolin binding to rat serum protein. Accordingly, free fatty acid could effectively inhibit the cefazolin binding in the physiological concentration range with increasing age, and the age-related changes of cefazolin binding to rat serum protein appear to be due to the fluctuation of the molar ratios of free fatty acid to albumin concentration in sera.

  19. Association of cognitive function and serum uric acid: Are cardiovascular diseases a mediator among women?

    PubMed

    Perna, Laura; Mons, Ute; Schöttker, Ben; Brenner, Hermann

    2016-08-01

    Several studies reported an association between concentrations of serum uric acid and cognitive function, but the evidence is contradictory. It is known that uric acid is associated with cardiovascular diseases, especially among women. Stratifying by sex and history of cardiovascular disease may clarify whether uric acid is an independent risk factor for cognitive dysfunction. A population-based study was conducted in the German State of Saarland. A subgroup of participants aged ≥70years underwent a comprehensive assessment of cognitive function. Linear regression models and restricted cubic spline functions were used to assess association of uric acid with cognitive performance in 1144 study participants. High levels of uric acid were associated with worse cognitive performance among women (-0.57; 95% CI: -1.10 to -0.04) but not among men (-0.12; 95% CI: -0.64 to 0.39). The association was much stronger among the subgroup of women with cardiovascular diseases (-1.91; 95% CI: -3.15 to -0.67) and also revealed a dose-response relationship in this subgroup. Serum uric acid showed an inverse association with cognitive function among women and the association was amplified by the presence of cardiovascular disease. These results highlight the importance of stratifying by sex and cardiovascular disease in future studies on uric acid and cognition. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Spectroscopic studies on the interaction of cinnamic acid and its hydroxyl derivatives with human serum albumin

    NASA Astrophysics Data System (ADS)

    Min, Jiang; Meng-Xia, Xie; Dong, Zheng; Yuan, Liu; Xiao-Yu, Li; Xing, Chen

    2004-04-01

    Cinnamic acid and its derivatives possess various biological effects in remedy of many diseases. Interaction of cinnamic acid and its hydroxyl derivatives, p-coumaric acid and caffeic acid, with human serum albumin (HSA), and concomitant changes in its conformation were studied using fluorescence and Fourier transform infrared spectroscopic methods. Fluorescence data revealed the presence of one binding site on HSA for cinnamic acid and its hydroxyl derivatives, and their binding constants ( KA) are caffeic acid> p-coumaric acid> cinnamic acid when Cdrug/ CHSA ranging from 1 to 10. The changes of the secondary structure of HSA after interacting with the three drugs are estimated, respectively by combining the curve-fitting results of amid I and amid III bands. The α-helix structure has a decrease of ≈9, 5 and 3% after HSA interacted with caffeic acid, p-coumaric acid and cinnamic acid, respectively. It was found that the hydroxyls substituted on aromatic ring of the drugs play an important role in the changes of protein's secondary structure. Combining the result of fluorescence quenching and the changes of secondary structure of HSA after interaction with the three drugs, the drug-HSA interaction mode was discussed.

  1. Association of the folic acid consumption and its serum levels with preeclampsia in pregnant women

    PubMed Central

    Salehi-PourMehr, Hanieh; Mohamad-Alizadeh, Sakineh; Malakouti, Jamileh; Farshbaf-Khalili, Azizeh

    2012-01-01

    Background and Objectives: Preeclampsia is one of the main causes of maternal and fetal mortality. Despite numerous studies, its etiology is unknown. Recently there has been attention towards Folic acid. This study examined the association of Folic acid consumption and its serum levels with Preeclampsia. Materials and Methods: A case-control study conducted in Tabriz- Alzahra hospital. 52 preeclamptic women in 34-42 weeks and 52 normotensive pregnant women were studied from Jun to Nov 2009. Data was gathered through interview with the women and review of their medical records. Folic acid serum levels were measured by electrochemiluminescence method on Elecsys-2010 system using the Roche brand kit. Data were analyzed by t-test, chi-square, exact fisher and logistic regression. Results: 46% of women in the case group and 71% in the control group regularly consumed Folic acid supplements before and during the first trimester of pregnancy. Frequency of correct pattern of Folic acid consumption in the case group were significantly lower than control group (P = 0.02). Findings about frequency of main food groups’ consumption containing folic acid indicated that the only mean difference between two groups was in relation to fruits (P = 0.002). The mean of Folic Acid serum levels in preeclamptic group was significantly lower than non- preeclamptic group [10.9 (3.9) vs. 13.6 (4.0) ng/ml, P = 0.001]. Conclusion: it is recommended all health care providers educate clients especially high risk women about regular and timely consumption of supplements as well as food groups containing Folic acid specially fruits and its possible role in prevention of preeclampsia. PMID:23922590

  2. Correlation of serum uric acid with heart rate variability in hypertension.

    PubMed

    Kunikullaya, K U; Purushottam, N; Prakash, V; Mohan, S; Chinnaswamy, R

    2015-01-01

    Autonomic dysfunction with dominant sympathetic tone is a common finding among hypertensives and prehypertensives. Uric acid is one of the independent predictors of hypertension. There are very few studies which have shown a relationship between the autonomic tone and uric acid generation pathway among prehypertensives and hypertensives. Aim of the study was to estimate and correlate serum uric acid levels with autonomic function as measured by heart rate variability (HRV) among prehypertensives and hypertensives. Cross-sectional study of three groups, prehypertensives, hypertensives and normotensives, classified according to Joint National Committee VII criteria, with 35 subjects in each group were included in this study. Serum uric acid levels were estimated by using colorimetric assay kit. HRV was analyzed after recording lead II Electrocardiogram using RMS Vagus HRV software (RMS, India). One-way ANOVA and Pearson's correlation was done using SPSS 18.0 software. Mean uric acid levels were 5.62±2.21mg/dL in normal subjects, 7.06±2.87mg/dL in prehypertensives and 9.77±2.04mg/dL in hypertensives. There was statistically significant negative correlation between uric acid and time domain parameters of HRV in the whole sample and among prehypertensives and positive correlation with low frequency power (LF) in ms(2) and n.u. Serum uric acid levels were high in prehypertensives and hypertensives as compared to normal subjects. Further, there was statistically significant correlation seen between uric acid levels and sympathetic domain parameters particularly among prehypertensives. Copyright © 2015 SEHLELHA. Published by Elsevier España, S.L.U. All rights reserved.

  3. Examining confounding by diet in the association between perfluoroalkyl acids and serum cholesterol in pregnancy.

    PubMed

    Skuladottir, Margret; Ramel, Alfons; Rytter, Dorte; Haug, Line Småstuen; Sabaredzovic, Azemira; Bech, Bodil Hammer; Henriksen, Tine Brink; Olsen, Sjurdur F; Halldorsson, Thorhallur I

    2015-11-01

    Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) have consistently been associated with higher cholesterol levels in cross sectional studies. Concerns have, however, been raised about potential confounding by diet and clinical relevance. To examine the association between concentrations of PFOS and PFOA and total cholesterol in serum during pregnancy taking into considerations confounding by diet. 854 Danish women who gave birth in 1988-89 and provided a blood sample and reported their diet in week 30 of gestation. Mean serum PFOS, PFOA and total cholesterol concentrations were 22.3 ng/mL, 4.1 ng/mL and 7.3 mmol/L, respectively. Maternal diet was a significant predictor of serum PFOS and PFOA concentrations. In particular intake of meat and meat products was positively associated while intake of vegetables was inversely associated (P for trend <0.01) with relative difference between the highest and lowest quartile in PFOS and PFOA concentrations ranging between 6% and 25% of mean values. After adjustment for dietary factors both PFOA and PFOS were positively and similarly associated with serum cholesterol (P for trend ≤0.01). For example, the mean increase in serum cholesterol was 0.39 mmol/L (95%CI: 0.09, 0.68) when comparing women in the highest to lowest quintile of PFOA concentrations. In comparison the mean increase in serum cholesterol was 0.61 mmol/L (95%CI: 0.17, 1.05) when comparing women in the highest to lowest quintile of saturated fat intake. In this study associations between PFOS and PFOA with serum cholesterol appeared unrelated to dietary intake and were similar in magnitude as the associations between saturated fat intake and serum cholesterol. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Dietary acid load is associated with serum bicarbonate but not insulin sensitivity in chronic kidney disease

    PubMed Central

    Ikizler, H. Omer; Zelnick, Leila; Ruzinski, John; Curtin, Laura; Utzschneider, Kristina M.; Kestenbaum, Bryan; Himmelfarb, Jonathan; de Boer, Ian H.

    2015-01-01

    Objective In chronic kidney disease (CKD), dietary acid may promote metabolic acidosis and insulin resistance, which in turn may contribute to adverse clinical health outcomes. We examined associations between dietary acid load, serum bicarbonate, and insulin sensitivity in CKD. Design In a cross-sectional study, we collected 3-day prospective food diaries to quantify dietary acid load as net endogenous acid production (NEAP, the nonvolatile acid load produced by the diet’s acid balance) and potential renal acid load (PRAL). We measured urine net acid excretion (NAE) in 24-hour urine samples. Insulin sensitivity was measured by hyperinsulinemic euglycemic clamp. Subjects 42 patients with CKD stages 3–5 attending nephrology clinics in the Pacific Northwest and 21 control subjects (eGFR ≥60mL/min/1.73m2). Main outcome measures Serum bicarbonate and insulin sensitivity (SIclamp). Results Mean age was 60.8±13.6 years and 54% of participants were men. Mean eGFR and serum bicarbonate concentrations were 34.4±13.1 mL/min/1.73m2 and 24.1±2.9 mEq/L for participants with CKD and 88.6±14.5 mL/min/1.73m2 and 26.3±1.8 mEq/L for control subjects, respectively. Mean NEAP, PRAL, and NAE were 58.2±24.3, 9.7±18.4, and 32.1±19.8 mEq/day, respectively. Considering all participants, dietary acid load was significantly, inversely associated with serum bicarbonate, adjusting for age, sex, race, eGFR, BMI, and diuretic use: −1.2 mEq/L per SD NEAP (95% CI −1.8, −0.6, p<0.0001); −0.9 mEq/L bicarbonate per SD PRAL (95% CI −1.5, −0.4, p=0.0005); −0.7 mEq/L bicarbonate per SD NAE (95% CI −1.2, −0.1, p=0.01). These associations were similar in participants with and without CKD. However, neither NEAP, PRAL, nor NAE was significantly associated with SIclamp. Serum bicarbonate was also not significantly associated with SIclamp. Conclusions In CKD, dietary acid load is associated with serum bicarbonate, suggesting that acidosis may be improved by dietary changes, but

  5. Physicochemical aspects of the energetics of binding of sulphanilic acid with bovine serum albumin

    NASA Astrophysics Data System (ADS)

    Banipal, Tarlok S.; Kaur, Amandeep; Banipal, Parampaul K.

    2017-01-01

    The thermodynamic study of the binding of sulphanilic acid with model transport protein bovine serum albumin is a promising approach in the area of synthesizing new sulfa drugs with improved therapeutic effect. Thus, such binding studies play an important role in the rational drug design process. The binding between sulphanilic acid and bovine serum albumin has been studied using calorimetry, light scattering in combination with spectroscopic and microscopic techniques. The calorimetric data reveals the presence of two sequential nature of binding sites where the first binding site has stronger affinity ( 104 M- 1) and second binding site has weaker affinity ( 103 M- 1). However, the spectroscopic (absorption and fluorescence) results suggest the presence of single low affinity binding site ( 103 M- 1) on protein. The contribution of polar and non-polar interactions to the binding process has been explored in the presence of various additives. It is found that sulphanilic acid binds with high affinity at Sudlow site II and with low affinity at Sudlow site I of protein. Light scattering and circular dichroism measurements have been used to study the effect on the molecular topology and conformation of protein, respectively. Thus these studies provide important insights into the binding of sulphanilic acid with bovine serum albumin both quantitatively and qualitatively.

  6. Serum homocysteine, vitamin B12, folic acid levels and methylenetetrahydrofolate reductase (MTHFR) gene polymorphism in vitiligo.

    PubMed

    Yasar, Ali; Gunduz, Kamer; Onur, Ece; Calkan, Mehmet

    2012-01-01

    The aim of this study was to determine serum vitamin B12, folic acid and homocysteine (Hcy) levels as well as MTHFR (C677, A1298C) gene polymorphisms in patients with vitiligo, and to compare the results with healthy controls. Forty patients with vitiligo and 40 age and sex matched healthy subjects were studied. Serum vitamin B12 and folate levels were determined by enzyme-linked immunosorbent assay. Plasma Hcy levels and MTHFR polymorphisms were determined by chemiluminescence and real time PCR methods, respectively. Mean serum vitamin B12 and Hcy levels were not significantly different while folic acid levels were significantly lower in the control group. There was no significant relationship between disease activity and vitamin B12, folic acid and homocystein levels. No significant difference in C677T gene polymorphism was detected. Heterozygote A1298C gene polymorphism in the patient group was statistically higher than the control group. There was no significant relationship between MTHFR gene polymorphisms and vitamin B12, folic acid and homocysteine levels. In conclusion, vitamin B12, folate and Hcy levels are not altered in vitiligo and MTHFR gene mutations (C677T and A1298C) do not seem to create susceptibility for vitiligo.

  7. Physicochemical aspects of the energetics of binding of sulphanilic acid with bovine serum albumin.

    PubMed

    Banipal, Tarlok S; Kaur, Amandeep; Banipal, Parampaul K

    2017-01-05

    The thermodynamic study of the binding of sulphanilic acid with model transport protein bovine serum albumin is a promising approach in the area of synthesizing new sulfa drugs with improved therapeutic effect. Thus, such binding studies play an important role in the rational drug design process. The binding between sulphanilic acid and bovine serum albumin has been studied using calorimetry, light scattering in combination with spectroscopic and microscopic techniques. The calorimetric data reveals the presence of two sequential nature of binding sites where the first binding site has stronger affinity (~10(4)M(-1)) and second binding site has weaker affinity (~10(3)M(-1)). However, the spectroscopic (absorption and fluorescence) results suggest the presence of single low affinity binding site (~10(3)M(-1)) on protein. The contribution of polar and non-polar interactions to the binding process has been explored in the presence of various additives. It is found that sulphanilic acid binds with high affinity at Sudlow site II and with low affinity at Sudlow site I of protein. Light scattering and circular dichroism measurements have been used to study the effect on the molecular topology and conformation of protein, respectively. Thus these studies provide important insights into the binding of sulphanilic acid with bovine serum albumin both quantitatively and qualitatively. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Industrial Trans Fatty Acid and Serum Cholesterol: The Allowable Dietary Level

    PubMed Central

    Sugano, Michihiro

    2017-01-01

    Trans fatty acid (TFA) from partially hydrogenated oil is regarded as the worst dietary fatty acid per gram due to its role in coronary heart disease. TFA consumption is decreasing worldwide, but some but not all observational studies indicate that TFA intake has little relevance to serum cholesterol levels in populations with low TFA intake (<1% E [percentage of total energy intake], serum cholesterol level. To establish allowable level, we must consider not only the dietary level of TFAs, but also the composition of dietary fats simultaneously consumed, that is, saturated and unsaturated fatty acids. These fatty acids strengthen or counteract the adverse effect of TFAs on serum cholesterol levels. In this review we describe the complex situation of the cardiovascular effects of industrial TFAs. The relationship between dietary industrial TFAs and concentration of plasma cholesterol should be evaluated from the viewpoint of dietary patterns rather than TFAs alone. PMID:28951788

  9. Serum folic acid and RFC A80G polymorphism in Alzheimer's disease and vascular dementia.

    PubMed

    Mansoori, Nasim; Tripathi, Manjari; Alam, Rizwan; Luthra, Kalpana; Sharma, Sumit; Lakshmy, Ramakrishnan; Kalaivani, Mani; Mukhopadhyay, Asok K

    2014-02-01

    Low level of vitamin B12 and folic acid has been reported to play an important role in the pathogenesis of Alzheimer's disease (AD) and vascular dementia (VaD). Serum folic acid and vitamin B12 were assayed in 80 AD and 50 VaD cases and in 120 healthy controls. The reduced folate carrier (RFC1) gene, rs1051266, which encodes the RFC 1, protein was analyzed for polymorphism by polymerase chain reaction-restriction fragment length polymorphism. It was observed that the patients having folic acid <8.45 ng/mL had 2.4 (95% confidence interval [CI]: 1.4-4.5) times higher odds of having AD and 2.1 (95% CI: 1.1-4.2) times higher odds of having VaD than patients having folic acid ≥8.45 ng/mL. Serum vitamin B12 level did not show any such statistically significant effect in altering the odds. No direct association was found between variant (G) allele or genotype of rs1051266 with AD and VaD cases. On serum folate level no association was observed with gene polymorphism.

  10. Serum uric acid levels and mortality in the Japanese population: the Yamagata (Takahata) study.

    PubMed

    Kamei, Keita; Konta, Tsuneo; Ichikawa, Kazunobu; Sato, Hiroko; Suzuki, Natsuko; Kabasawa, Asami; Suzuki, Kazuko; Hirayama, Atsushi; Shibata, Yoko; Watanabe, Tetsu; Kato, Takeo; Ueno, Yoshiyuki; Kayama, Takamasa; Kubota, Isao

    2016-12-01

    Serum uric acid level is regulated by gender, dietary habit, genetic predisposition, and renal function, and is associated with the development of renal and cardiovascular diseases. This study prospectively investigated the association between serum uric acid levels and mortality in a community-based population. Three thousand four hundred and eighty-seven subjects regardless of the antihyperuricemic medication (45 % male; mean age 62 years old) from the Takahata town in Japan participated in this study and were followed up for 8 years (median 7.5 years). We examined the association between serum uric acid levels at baseline and the all-cause and cardiovascular mortality, respectively, in this population. One hundred seventy-nine subjects died during the follow-up period, with 49 deaths attributed to cardiovascular causes. Kaplan-Meier analysis revealed that the all-cause mortality was significantly higher along with the increase in serum uric acid levels at baseline among female (Log-rank P < 0.01), but not male subjects (P = 0.97). Cox-proportional hazard model analysis with adjustment for possible confounders including age, renal function, and comorbidities revealed that hyperuricemia (uric acid ≥7.0 mg/dL) was an independent risk factor for all-cause and cardiovascular mortality, respectively, in female [hazard ratio (HR) 5.92, 95 % confidence interval (CI) 2.10-14.6 for all-cause mortality, and HR 10.7, 95 % CI 1.76-50.2 for cardiovascular mortality], but not male subjects. Hyperuricemia was an independent risk for all-cause and cardiovascular mortality in female, but not among the male subjects in a community-based population.

  11. Serum uric acid concentrations are directly associated with the presence of benign multiple sclerosis.

    PubMed

    Simental-Mendía, Esteban; Simental-Mendía, Luis E; Guerrero-Romero, Fernando

    2017-06-28

    It has been reported that patients with multiple sclerosis (MS) exhibit lower serum uric acid levels; however, the association between uric acid concentrations and benign MS (BMS) has not been assessed. Hence, the objective of the present study was to determine whether the serum concentrations of uric acid are associated with the presence of BMS. Men and non-pregnant women over 16 years of age with diagnosis of MS were enrolled in a cross-sectional study. Expanded Disability Status Scale score < 3, progression of disease ≤10 years, diabetes, renal or hepatic diseases, gout, malignancy, alcohol intake, and treatment with thiazide diuretics and/or acetylsalicylic acid were exclusion criteria. According to subtype of disease, the eligible patients were allocated into groups with BMS and other varieties of MS. A logistic regression analysis was conducted in order to evaluate the association between serum concentrations of uric acid and BMS. A total of 106 patients were included, 39 in the group with BMS and 67 in the group with other varieties of MS. The logistic regression analysis adjusted by age, sex, and disease duration showed that increased concentrations of uric acid, indeed within the physiological levels, are significantly associated with the presence of BMS (OR = 2.60; 95% CI: 1.55-4.38, p < 0.001). The results of the present study suggest that elevated concentrations of uric acid, indeed within the physiological range, are likely linked to the presence of BMS.

  12. Spectrometric determination of clinically relevant fatty acids in the blood serum

    NASA Astrophysics Data System (ADS)

    Kalinin, A. V.; Krasheninnikov, V. N.; Sviridov, A. P.; Titov, V. N.

    2017-01-01

    The content of fatty acid (FA) triglycerides in food and biological media is predicting traditionally using gas and liquid chromatographic methods. Named techniques aren't available for clinical labs due to their complexity. So, our objective was to develop the method and apparatus for rapid assay of a few clinically important FA as the saturated palmitic, mono unsaturated oleic and others in serum using near infrared spectrometer. As a result, the applicability of the FT spectrometer in the wavelength range of 0.9 -1.8 μ to analyze these FA in serum without sample preparation was confirmed. Besides, measurement specifications were determined and a correlations of the absorption spectra and contents of total triglycerides and cholesterol, palmitic, oleic, linoleic and arachidonic FA in serum were established

  13. Determination of salicylic acid in human serum with capillary zone electrophoresis.

    PubMed

    Goto, Y; Makino, K; Kataoka, Y; Shuto, H; Oishi, R

    1998-03-20

    The determination of salicylic acid (SA), a metabolite of aspirin, in human serum was developed using capillary zone electrophoresis (CZE) with diode array detection. The reproducibility of separation and quantification with CZE analysis of the extract of SA from human serum was appropriate for the intra- and inter-day assay coefficients. A high correlation was revealed between the serum SA levels in volunteers determined by CZE and those determined by a fluorescence polarization immunoassay (r=0.973, n = 12), although the former values were slightly higher than the latter. There were no peaks interfering with the assay of SA by internal standard method. This CZE method could provide a simple and efficient method for monitoring SA in patients.

  14. Spectrometric determination of clinically relevant fatty acids in the blood serum

    NASA Astrophysics Data System (ADS)

    Kalinin, A. V.; Krasheninnikov, V. N.; Sviridov, A. P.; Titov, V. N.

    2016-12-01

    The content of fatty acid (FA) triglycerides in food and biological media is predicting traditionally using gas and liquid chromatographic methods. Named techniques aren't available for clinical labs due to their complexity. So, our objective was to develop the method and apparatus for rapid assay of a few clinically important FA as the saturated palmitic, mono unsaturated oleic and others in serum using near infrared spectrometer. As a result, the applicability of the FT spectrometer in the wavelength range of 0.9 -1.8 μ to analyze these FA in serum without sample preparation was confirmed. Besides, measurement specifications were determined and a correlations of the absorption spectra and contents of total triglycerides and cholesterol, palmitic, oleic, linoleic and arachidonic FA in serum were established

  15. Effect of seven fluoroquinolones on the determination of serum creatinine by the picric acid and enzymatic methods.

    PubMed

    Massoomi, F; Mathews, H G; Destache, C J

    1993-05-01

    To investigate in vitro the interaction of seven fluoroquinolone antibiotics with the determination of serum creatinine by the picric acid and enzymatic methods. This blind, in vitro study assayed duplicate serum samples for creatinine by the picric acid and enzymatic methods with averaged spiked concentrations of 2.71, 13.56, 27.12, and 108.47 mumol/L of ciprofloxacin, fleroxacin, lomefloxacin, ofloxacin, 1-ofloxacin, sparfloxacin, and temafloxacin. Cefoxitin (in concentrations of 233.9, 1169.6, 1754.4, and 2339.2 mumol/L) was used as a positive control for the picric acid assay. University-affiliated hospital, Department of Pharmaceutical Services and Clinical Chemistry section of the Department of Pathology. The serum creatinine samples spiked with the seven substituted fluoroquinolones and cefoxitin were assayed by both the picric acid and enzymatic assays. Statistical analysis compared the spiked samples with blank serum by Student's t-test and concentration ranges were compared by analysis of variance. A statistically significant interference with serum creatinine was p < 0.05. None of the substituted fluoroquinolones interfered significantly with the determination of serum creatinine by either method. Cefoxitin significantly interfered with the determination of serum creatinine by the picric acid method. Fluoroquinolones do not interfere with the determination of serum creatinine by either the picric acid or enzymatic method.

  16. Serum Sialic Acid Concentration and Content in ApoB-Containing Lipoproteins in Liver Diseases.

    PubMed

    Gudowska, Monika; Gruszewska, Ewa; Cylwik, Bogdan; Panasiuk, Anatol; Filisiak, Robert; Szmitkowski, Maciej; Chrostek, Lech

    2016-01-01

    The great significance for the metabolism of lipoproteins is the composition of carbohydrate chain of apolipoproteins, where sialic acid (SA) is located. In VILDL and LDL sialic acid is attached to apolipoprotein B. The sialylation of serum proteins including apolipoprotein B can be affected in the course of liver diseases. Therefore, the aim of this study was to assess the effect of liver diseases on the concentration and content of SA in ApoB-containing lipoproteins. The tested group consisted of 165 patients (118 males, 47 females) with liver diseases: alcoholic cirrhosis, non-alcoholic cirrhosis, chronic hepatitis, toxic hepatitis, chronic viral hepatitis, and liver cancer. ApoB-containing lipoproteins were isolated by a turbidimetric procedure and SA concentration was measured according to an enzymatic method. There was a significant increase in the serum concentration of SA in ApoB-containing lipoproteins in viral hepatitis. Although the serum concentration of ApoB was not significantly different between specific liver diseases, the serum levels of SA in ApoB-containing lipoproteins appeared to be different. There is an association between SA concentration and triglycerides in alcoholic cirrhosis and viral hepatitis. Also, in viral hepatitis SA concentration correlated negatively with HDL-cholesterol. The content of SA in ApoB-containing lipoproteins in alcoholic cirrhosis and viral hepatitis was significantly higher than that in the control group, but did not differ between diseases. This study may explain the variations in serum lipids and lipoproteins in liver diseases. It seems that the reason for these abnormalities is the changes in the concentration of sialic acid in ApoB-containing lipoproteins.

  17. The effect of ongoing blood loss on human serum concentrations of perfluorinated acids.

    PubMed

    Lorber, M; Eaglesham, G E; Hobson, P; Toms, L-M L; Mueller, J F; Thompson, J S

    2015-01-01

    Perfluorinated alkyl acids (PFAAs) have been detected in serum at low concentrations in background populations. Higher concentrations haven been observed in adult males compared to females, with a possible explanation that menstruation offers females an additional elimination route. In this study, we examined the significance of blood loss as an elimination route of PFAAs. Pooled serum samples were collected from individuals undergoing a medical procedure involving ongoing blood withdrawal called venesection. Concentrations from male venesection patients were approximately 40% lower than males in the general population for perfluorohexane sulfonate (PFHxS), perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA). A simple pharmacokinetic model was used to test the hypothesis that blood loss could explain why adult males have higher concentrations of PFAAs than females, and why males undergoing venesections had lower concentrations compared to males in the general population. The model application generally supported these hypotheses showing that venesection might reduce blood serum concentrations by 37% (PFOA) and 53% (PFOS) compared to the observed difference of 44% and 37%. Menstruation was modeled to show a 22% reduction in PFOA serum concentrations compared to a 24% difference in concentrations between males and females in the background population. Uncertainties in the modeling and the data are identified and discussed. Published by Elsevier Ltd.

  18. Human placental transfer of perfluoroalkyl acid precursors: Levels and profiles in paired maternal and cord serum.

    PubMed

    Yang, Lin; Wang, Zhen; Shi, Yu; Li, Jingguang; Wang, Yuxin; Zhao, Yunfeng; Wu, Yongning; Cai, Zongwei

    2016-02-01

    Perfluoroalkyl acids (PFAAs) precursors, the indirect source of PFAA exposure, have been observed in environmental and human samples. However, the maternal-fetal transfer of these chemicals has not been well examined. In this study, 50 paired maternal and cord serum samples collected in Jiangsu province of China were analyzed for fifteen PFAA precursors. Among the detected PFAAs, 6:2 fluorotelomer sulfonate (6:2 FTS), N-methyl- and N-ethyl-perfluorooctanesulfonamidoacetates had comparable detection rate in both maternal and cord sera, while the mean concentrations and detection rates of 8:2 FTS and perfluorooctane sulfonamide (PFOSA) were higher in maternal sera compared to cord sera (Mann-Whitney U test, P < 0.05). Analysis of variance and least significant difference tests showed that the youngest maternal age group (21-24 years old) had the highest concentration of 6:2 FTS in cord sera. Maternal serum PFOSA was found significantly correlated with the cord serum perfluorooctanesulfonate (PFOS) (Spearman test, r = 0.361, P = 0.010), indicating that maternal serum PFOSA might be an indirect source of PFOS in fetuses. The obtained results suggested the potential prenatal exposure and human placental transfer of perfluoroalkyl acid precursors. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Impact of nutrition on serum levels of docosahexaenoic acid among Omani children with autism.

    PubMed

    Al-Farsi, Yahya M; Waly, Mostafa I; Deth, Richard C; Al-Sharbati, Marwan M; Al-Shafaee, Mohammed; Al-Farsi, Omar; Al-Khaduri, Maha M; Al-Adawi, Samir; Hodgson, Nathaniel W; Gupta, Ishita; Ouhtit, Allal

    2013-09-01

    Autism is a lifelong neurodevelopmental disorder of early childhood. Dietary supplementation of the ω-3 fatty acid (docosahexaenoic acid [DHA]) during prenatal and postnatal life is considered a protective dietary intervention strategy to minimize the risk for autism spectrum disorder (ASD). To our knowledge, no relevant studies have been conducted in the Middle East investigating the status of DHA among children with autism during early childhood. The aim of this study was to investigate the serum levels and dietary intake status of DHA among Omani children recently diagnosed with ASD. The present case-control study involved 80 Omani children (<5 y), 40 cases and 40 controls matched for age and sex. A semi-quantitative food frequency questionnaire was used to assess dietary intake of all the participants, while serum levels of DHA were measured using high-performance liquid chromatography. Our results showed that children with ASD had lower dietary consumption of foodstuff containing DHA, as well as lower serum levels of DHA than controls. The present finding from Oman supports the view of other studies that there are low serum levels of DHA among children with ASD. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. Serum Uric Acid Levels in Patients with Alzheimer's Disease: A Meta-Analysis

    PubMed Central

    Chen, Xueping; Guo, Xiaoyan; Huang, Rui; Chen, Yongping; Zheng, Zhenzhen; Shang, Huifang

    2014-01-01

    Background Serum uric acid (UA) could exert neuro-protective effects against Alzheimer's disease (AD) via its antioxidant capacities. Many studies investigated serum UA levels in AD patients, but to date, results from these observational studies are conflicting. Methods We conducted a meta-analysis to compare serum UA levels between AD patients and healthy controls by the random-effects model. Studies were identified by searching PubMed, ISI Web of Science, EMBASE, and the Cochrane library databases from 1966 through July 2013 using the Medical Subject Headings and keywords without restriction in languages. Only case-control studies were included if they had data on serum UA levels in AD patients and healthy controls. Begg's funnel plot and Egger's regression test were applied to assess the potential publication bias. Sensitivity analyses and meta-regression were conducted to explore possible explanations for heterogeneity. Results A total of 11 studies met the inclusion criteria including 2708 participants were abstracted. Serum UA levels were not significantly different in AD patients compared to healthy controls (standardized mean difference (SMD) = −0.50; 95% confidence interval (CI): −1.23 to 0.22). Little evidence of publication bias was observed. Sensitivity analyses showed that the combined SMD was consistent every time omitting any one study, except only one study which greatly influenced the overall results. Meta-regression showed that year of publication, race, sample size, and mean age were not significant sources of heterogeneity. Conclusion Our meta-analysis of case-control studies suggests that serum UA levels do not differ significantly in AD patients, but there may be a trend toward decreased UA in AD after an appropriate interpretation. More well-designed investigations are needed to demonstrate the potential change of serum UA levels in AD patients. PMID:24714617

  1. Serum homocysteine and methylmalonic acid concentrations in Chinese Shar-Pei dogs with cobalamin deficiency.

    PubMed

    Grützner, Niels; Heilmann, Romy M; Stupka, Kenneth C; Rangachari, Venkat R; Weber, Katja; Holzenburg, Andreas; Suchodolski, Jan S; Steiner, Jörg M

    2013-08-01

    Cobalamin deficiency is suspected to be hereditary in Chinese Shar-Pei dogs (Shar-Peis), and inherited causes of cobalamin deficiency may affect the cellular processing of cobalamin. In humans, a defect of the two main cobalamin-dependent intracellular enzymes (i.e., methionine synthase and methylmalonyl-CoA mutase) may lead to hyperhomocysteinemia and hypermethylmalonic acidemia. The aim of this retrospective study was to evaluate serum homocysteine (HCY) and methylmalonic acid (MMA) concentrations in cobalamin-deficient Shar-Peis and dogs of six other breeds. Serum samples (n=297) from cobalamin-deficient dogs (Shar-Peis, German Shepherd dogs, Labrador Retrievers, Yorkshire Terriers, Boxers, Cocker Spaniels, and Beagles) were analyzed for serum HCY and MMA concentrations. A Fisher's exact test was used to evaluate if cobalamin deficiency in Shar-Peis is associated with hyperhomocysteinemia. Serum HCY and MMA concentrations were higher in cobalamin-deficient Shar-Peis compared to cobalamin-deficient dogs of the six other breeds (P<0.0001). Hyperhomocysteinemia was associated with cobalamin deficiency in Shar-Peis (P=0.009). In addition, serum HCY and MMA concentrations did not differ between cobalamin-deficient German Shepherd dogs with and without exocrine pancreatic insufficiency (EPI), a potential cause of secondary cobalamin deficiency. These findings suggest that the function of the two intracellular cobalamin-dependent enzymes is impaired in Shar-Peis with cobalamin deficiency. Published by Elsevier Ltd.

  2. High serum uric acid concentration predicts poor survival in patients with breast cancer.

    PubMed

    Yue, Cai-Feng; Feng, Pin-Ning; Yao, Zhen-Rong; Yu, Xue-Gao; Lin, Wen-Bin; Qian, Yuan-Min; Guo, Yun-Miao; Li, Lai-Sheng; Liu, Min

    2017-08-26

    Uric acid is a product of purine metabolism. Recently, uric acid has gained much attraction in cancer. In this study, we aim to investigate the clinicopathological and prognostic significance of serum uric acid concentration in breast cancer patients. A total of 443 female patients with histopathologically diagnosed breast cancer were included. After a mean follow-up time of 56months, survival was analysed using the Kaplan-Meier method. To further evaluate the prognostic significance of uric acid concentrations, univariate and multivariate Cox regression analyses were applied. Of the clinicopathological parameters, uric acid concentration was associated with age, body mass index, ER status and PR status. Univariate analysis identified that patients with increased uric acid concentration had a significantly inferior overall survival (HR 2.13, 95% CI 1.15-3.94, p=0.016). In multivariate analysis, we found that high uric acid concentration is an independent prognostic factor predicting death, but insufficient to predict local relapse or distant metastasis. Kaplan-Meier analysis indicated that high uric acid concentration is related to the poor overall survival (p=0.013). High uric acid concentration predicts poor survival in patients with breast cancer, and might serve as a potential marker for appropriate management of breast cancer patients. Copyright © 2017. Published by Elsevier B.V.

  3. Estimate of serum immunoglobulin G concentration using refractometry with or without caprylic acid fractionation.

    PubMed

    Morrill, K M; Polo, J; Lago, A; Campbell, J; Quigley, J; Tyler, H

    2013-07-01

    Objectives of this study were to develop a rapid calf-side test to determine serum IgG concentrations using caprylic acid (CA) fractionation, followed by refractometry of the IgG-rich supernatant and compare the accuracy of this method with results obtained using refractometry using raw serum. Serum samples (n=200) were obtained from 1-d-old calves, frozen (-20°C), and shipped to the laboratory. Samples were allowed to thaw for 1h at room temperature. Fractionation with CA was conducted by adding 1mL of serum to a tube containing 45, 60, or 75µL of CA and 0.5, 1.0, or 1.5mL of 0.06 M acetic acid. The tube contents were mixed well, allowed to react for 1 min, and then centrifuged at 3,300 × g for 0, 10, or 20 min at 25°C. The %Brix and refractive index of the fractionated supernatant were determined using a digital refractometer. Nonfractionated serum was analyzed for %Brix (BRn), refractive index (nDn), and IgG concentration by radial immunodiffusion. The mean serum IgG concentration was 19.0 mg/mL [standard deviation (SD)=9.7], with a range of 3.5 to 47.0 mg/mL. The mean serum BRn was 8.6 (SD=0.91), with a range of 6.8 to 11.0. The mean serum nDn was 1.34566 (SD=0.00140), with a range of 1.34300 to 1.34930. Serum nDn was positively correlated with IgG concentration (correlation coefficient=0.86; n=185). Fractionated samples treated with 1mL 0.6 M acetic acid and 60µL of CA and not centrifuged before analysis resulted in a strong relationship between the refractive index of the fractionated supernatant and IgG (correlation coefficient=0.80; n=45). Regression was used to determine cut points indicative of 10, 12, and 14 mg of IgG/mL to determine the sensitivity and specificity of refractometry to identify failure of passive transfer (serum IgG <10 mg/mL at 24 h old). The nDn were 1.34414, 1.34448, and 1.34480 to predict 10, 12, and 14 mg of IgG/mL of serum, respectively. The BRn cut points were 7.6, 7.8, and 8.0, respectively. The nDn cut points of 1.34448 and

  4. Methylmalonic acid quantification in low serum volumes by UPLC-MS/MS.

    PubMed

    Pedersen, Theresa L; Keyes, William R; Shahab-Ferdows, Setareh; Allen, Lindsay H; Newman, John W

    2011-06-01

    Methylmalonic acid (MMA) is a metabolic intermediate transformed to succinic acid (SA) by a vitamin B(12)-dependent catalytic step, and is broadly used as a clinical biomarker of functional vitamin B12 status. However, reported methods use between 100 and 1000 μL of serum or plasma making them sub-optimal for sample-limited studies, including those with neonates and infants. LC-MS/MS based protocols to measure MMA as n-butyl esters in the presence of tri-deuterated MMA (MMA-d(3)) were modified for use with 25 μL of human serum by scaling down sample processing volumes and analysis by UPLC-MS/MS. Plasma-based calibration solutions were found to be unnecessary, and chromatographic resolution and peak shape of SA and MMA was optimized in <4 min with isocratic 53:47 methanol/1.67 mM (pH 6.5) ammonium formate. Additionally, 1-cyclohexyl-urido-3-dodecanoic acid (CUDA) was included as internal standard allowing direct assessment of MMA recovery. Sample concentrations in the low normal range produced a signal:noise of >100:1. MMA intra- and inter-assay variability was under 10%. MMA-d(3) surrogate recovery averaged 93±14%. MMA stability exceeded three years in frozen samples and was unaffected by up to five freeze/thaw cycles. In conclusion, we report that methylmalonic acid can be measured with 25 μL of serum using water based standards. The assay signal:noise per concentration indicates that the method could perform as implemented with as little as 5 μL of serum. The reported method is applicable for studies of functional B12 status in sample limited experiments including investigations of nutritional status in neonates and in studies where low normal MMA levels are expected.

  5. Gas chromatographic/mass spectrometric determination of lysergic acid diethylamide (LSD) in serum samples.

    PubMed

    Musshoff, F; Daldrup, T

    1997-08-04

    A sensitive method for the detection and quantification of lysergic acid diethylamide (LSD) in serum samples is described. After liquid-liquid extraction the trimethylsilyl derivative of LSD is detected by gas chromatography-mass spectrometry. Experiments with spiked samples resulted in a recovery of 76%, the coefficient of variation was 9.3%. Excellent linearity was obtained over the range 0.1-10 ng ml-1. Additionally experiments demonstrating the light sensitivity of LSD are presented together with casuistics.

  6. Total and lipid-bound serum sialic acid in benign and malignant breast disease.

    PubMed

    Romppanen, J; Eskelinen, M; Tikanoja, S; Mononen, I

    1997-01-01

    Elevation in the total sialic acid (TSA), TSA/total protein (TSA/TP) and lipid-bound sialic acid (LASA) concentration in serum occurs in breast cancer and we have studied the applicability of the assays in classification of undefined breast tumors. Sialic acid was determined by HPLC and the statistical evaluation included the receiver operating characteristic (ROC) and Youden's index analyses. In cancer patients, the serum LASA and TSA concentration was significantly higher (p < 0.05) than in patients with benign breast disease and all the markers were significantly higher (p < 0.0001) than in normal controls. All the markers had a low accuracy (AUCs < 0.75) in differentiating between breast cancer and benign breast disease and at the specificity level of 0.95 the corresponding sensitivities were 0.32 (TSA), 0.14 (TSA/TP) and 0.23 (LASA). The results indicate that both breast cancer and benign breast disease cause elevation of TSA, TSA/TP and LASA values in serum and do not provide reliable classification of undefined breast tumors.

  7. [Molecular docking of chlorogenic acid, 3,4-di-O-caffeoylquinic acid and 3,5-di-O-caffeoylquinic acid with human serum albumin].

    PubMed

    Zhou, Jing; Ma, Hong-yue; Fan, Xin-sheng; Xiao, Wei; Wang, Tuan-jie

    2012-10-01

    To investigate the mechanism of binding of human serum albumin (HSA) with potential sensitinogen, including chlorogenic acid and two isochlorogenic acids (3,4-di-O-caffeoylquinic acid and 3,5-di-O-caffeoylquinic acid). By using the docking algorithm of computer-aided molecular design and the Molegro Virtual Docker, the crystal structures of HSA with warfarin and diazepam (Protein Data Bank ID: 2BXD and 2BXF) were selected as molecular docking receptors of HSA sites I and II. According to docking scores, key residues and H-bond, the molecular docking mode was selected and confirmed. The molecular docking of chlorogenic acid and two isochlorogenic acids on sites I and II was compared based on the above design. The results from molecular docking indicated that chlorogenic acid, 3,4-di-O-caffeoylquinic acid and 3,5-di-O-caffeoylquinic acid could bind to HSA site I by high affinity scores of -112.3, -155.3 and -153.1, respectively. They could bind to site II on HSA by high affinity scores of -101.7, -138.5 and -133.4, respectively. In site I, two isochlorogenic acids interacted with the key apolar side-chains of Leu238 and Ala291 by higher affinity scores than chlorogenic acid. Furthermore, the H-bonds of isochlorogenic acids with polar residues inside the pocket and at the entrance of the pocket were different from chlorogenic acid. Moreover, the second coffee acyl of isochlorogenic acid occupied the right-hand apolar compartment in the pocket of HSA site I. In site I, the second coffee acyl of isochlorogenic acid formed the H-bonds with polar side-chains, which contributed isochlorogenic acid to binding with site II of HSA. The isochlorogenic acids with two coffee acyls have higher binding abilities with HSA than chlorogenic acid with one coffee acyl, suggesting that isochlorogenic acids binding with HSA may be sensitinogen.

  8. Quantification of total content of non-esterified fatty acids bound to human serum albumin.

    PubMed

    Pavićević, Ivan D; Jovanović, Vesna B; Takić, Marija M; Aćimović, Jelena M; Penezić, Ana Z; Mandić, Ljuba M

    2016-09-10

    Non-esterified fatty acids bound to the human serum albumin (HSA) contribute to several HSAs properties of special concern in pathologies, for instance to the reactivity of the free HSA-Cys34 thiol group (important antioxidative thiol pool in plasma), and to the affinity for binding of molecules and ions (for example cobalt as a prominent biomarker in heart ischemia). Therefore, the method for determination of FAs bound to HSA was developed. FAs were released from HSA (previously isolated from serum by ammonium sulfate precipitation) using acidic copper(II) sulfate in phosphoric acid, extracted by n-heptane-chloroform (4:1, v/v) mixture, spotted on TL silica-gel and then developed with n-heptane-chloroform-acetic acid (5:3:0.3, v/v/v). Common office flatbed scanner and software solution for densitometric image analysis, developed in R, were used. The linearity of calibration curve in concentration range from 0.1 to 5.0mmol/L stearic acid was achieved. The method was proved to be precise (with RSD of 1.4-4.7%) and accurate. Accuracy was examined by standard addition method (recoveries 97.2-102.5%) and by comparison to results of GC. The method is sample saving, technically less demanding, and cheap, and therefore suitable for determination of FAs/HSA ratio when elevated concentrations of free FAs are reliable diagnostic/risk parameter of pathological states. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Location and binding mechanism of an ESIPT probe 3-hydroxy-2-naphthoic acid in unsaturated fatty acid bound serum albumins.

    PubMed

    Ghorai, Shyamal Kr; Tripathy, Debi Ranjan; Dasgupta, Swagata; Ghosh, Sanjib

    2014-02-05

    The binding site and the binding mechanism of 3-hydroxy-2-naphthoic acid (3HNA) in oleic acid (OA) bound serum albumins (bovine serum albumin (BSA) and human serum albumin (HSA)) have been determined using steady state and time resolved emission of tryptophan residues (Trp) in proteins and the ESIPT emission of 3HNA. Time resolved anisotropy of the probe 3HNA and low temperature phosphorescence of Trp residues of BSA in OA bound BSA at 77K reveals a drastic change of the binding site of 3HNA in the ternary system compared to that in the free protein. 3HNA binds near Trp213 in the ternary system whereas 3HNA binds near Trp134 in the free protein. The structure of OA bound BSA generated using docking methodology exhibits U-bend configuration of all bound OA. The docked pose of 3HNA in the free protein and in OA bound albumins (ternary systems) and the concomitant perturbation of the structure of proteins around the binding region of 3HNA corroborate the enhanced ESIPT emission of 3HNA and the energy transfer efficiency from the donor Trp213 of BSA to 3HNA acceptor in 3HNA-OA-BSA system.

  10. A Study of Reverse Causation: Examining the Associations of Perfluorooctanoic Acid Serum Levels with Two Outcomes.

    PubMed

    Dhingra, Radhika; Winquist, Andrea; Darrow, Lyndsey A; Klein, Mitchel; Steenland, Kyle

    2017-03-01

    Impaired kidney function and earlier menopause were associated with perfluorooctanoic acid (PFOA) serum levels in previous cross-sectional studies. Reverse causation, whereby health outcomes increase serum PFOA, may underlie these associations. We compared measured (subject to reverse causation) versus modeled (unaffected by reverse causation) serum PFOA in association with these outcomes to examine the possible role of reverse causation in these associations. In cross-sectional analyses, we analyzed PFOA in relation to self-reported menopause among women (n = 9,192) 30-65 years old and in relation to kidney function among adults > 20 years old (n = 29,499) in a highly exposed Mid-Ohio Valley cohort. Estimated glomerular filtration rate (eGFR, a marker of kidney function) and serum PFOA concentration were measured in blood samples collected during 2005-2006. Retrospective year-specific serum PFOA estimates were modeled independently of measured PFOA based on residential history and plant emissions. Using measured and modeled PFOA in 2005 or 2006 (predictor variables), cross-sectional associations were assessed for eGFR and menopause (yes/no). We also analyzed measured PFOA (dependent variable) in relation to the number of years since menopause. Menopause and eGFR were significantly associated with measured (trend tests: p = 0.013, p = 0.0005, respectively) but not with modeled serum PFOA (p = 0.50, p = 0.76, respectively). Measured PFOA levels increased for the first 7 years after menopause (trend test, p < 0.0001), providing further evidence that the observed association between measured PFOA and menopause is subject to reverse causation for this outcome. Our results support the conjecture that in previous studies, earlier menopause and reduced kidney function are the causes rather than the results of increased measured serum PFOA. These results suggest caution in using biomarkers in cross-sectional studies. Citation: Dhingra R, Winquist A, Darrow LA, Klein M

  11. A Study of Reverse Causation: Examining the Associations of Perfluorooctanoic Acid Serum Levels with Two Outcomes

    PubMed Central

    Dhingra, Radhika; Winquist, Andrea; Darrow, Lyndsey A.; Klein, Mitchel; Steenland, Kyle

    2016-01-01

    Background: Impaired kidney function and earlier menopause were associated with perfluorooctanoic acid (PFOA) serum levels in previous cross-sectional studies. Reverse causation, whereby health outcomes increase serum PFOA, may underlie these associations. Objective: We compared measured (subject to reverse causation) versus modeled (unaffected by reverse causation) serum PFOA in association with these outcomes to examine the possible role of reverse causation in these associations. Methods: In cross-sectional analyses, we analyzed PFOA in relation to self-reported menopause among women (n = 9,192) 30–65 years old and in relation to kidney function among adults > 20 years old (n = 29,499) in a highly exposed Mid-Ohio Valley cohort. Estimated glomerular filtration rate (eGFR, a marker of kidney function) and serum PFOA concentration were measured in blood samples collected during 2005–2006. Retrospective year-specific serum PFOA estimates were modeled independently of measured PFOA based on residential history and plant emissions. Using measured and modeled PFOA in 2005 or 2006 (predictor variables), cross-sectional associations were assessed for eGFR and menopause (yes/no). We also analyzed measured PFOA (dependent variable) in relation to the number of years since menopause. Results: Menopause and eGFR were significantly associated with measured (trend tests: p = 0.013, p = 0.0005, respectively) but not with modeled serum PFOA (p = 0.50, p = 0.76, respectively). Measured PFOA levels increased for the first 7 years after menopause (trend test, p < 0.0001), providing further evidence that the observed association between measured PFOA and menopause is subject to reverse causation for this outcome. Conclusion: Our results support the conjecture that in previous studies, earlier menopause and reduced kidney function are the causes rather than the results of increased measured serum PFOA. These results suggest caution in using biomarkers in cross-sectional studies

  12. Influence of diet transition on serum calcium and phosphorus and fatty acids in zoo giraffe (Giraffa camelopardalis).

    PubMed

    Koutsos, E A; Armstrong, D; Ball, R; Dikeman, C; Hetherington, J; Simmons, L; Valdes, E V; Griffin, M

    2011-01-01

    In response to new recommendations for feeding giraffe in zoos, giraffe (n = 6) were transitioned from a typical hoofstock diet to diets containing reduced starch, protein, Ca and P and added n3 fatty acids. This diet was fed as a 50:50 mix with alfalfa and grass hay. Over the next 4 years, serum Ca, P, and fatty acids were measured every 6 months (summer and winter). Serum Ca was not affected by season (P = 0.67) or by diet (P = 0.12). Serum P was not affected season (P = 0.14), but was reduced by diet (P<0.01), and serum Ca:P was also increased by diet (P<0.01). The ratio of serum Ca:P tended to be affected by season (P = 0.07), in which animals tended to have greater Ca:P during the summer vs. the winter. The diet transition resulted in reduced serum saturated fatty acids (including lauric, myristic, palmitic, arachidic, and behenic acids), and increases in n6 fatty acids (including linolenic and arachidonic acids) and n3 fatty acids (docosahexaenoic acid) (P<0.05 for each). Overall, this diet transition resulted in blood nutrient profiles that more closely match that of values found in free-ranging giraffe.

  13. Prednisone lowers serum uric acid levels in patients with decompensated heart failure by increasing renal uric acid clearance.

    PubMed

    Liu, Chao; Zhen, Yuzhi; Zhao, Qingzhen; Zhai, Jian-Long; Liu, Kunshen; Zhang, Jian-Xin

    2016-07-01

    Clinical studies have shown that large doses of prednisone could lower serum uric acid (SUA) in patients with decompensated heart failure (HF); however, the optimal dose of prednisone and underlying mechanisms are unknown. Thirty-eight patients with decompensated HF were randomized to receive standard HF care alone (n = 10) or with low-dose (15 mg/day, n = 8), medium-dose (30 mg/day, n = 10), or high-dose prednisone (60 mg/day, n = 10), for 10 days. At the end of the study, only high-dose prednisone significantly reduced SUA, whereas low- and medium-dose prednisone and standard HF care had no effect on SUA. The reduction in SUA in high-dose prednisone groups was associated with a significant increase in renal uric acid clearance. In conclusion, prednisone can reduce SUA levels by increasing renal uric acid clearance in patients with decompensated HF.

  14. Comparison of free fraction serum valproic acid concentrations between inpatients and outpatients.

    PubMed

    Gibbs, Haley G; Zimmerman, David E; Shermock, Kenneth M; Clarke, William; Mirski, Marek A; Lewin, John J

    2015-01-15

    The differences in free fraction serum valproic acid concentrations between inpatients and outpatients were compared, and factors associated with therapeutic discordance were evaluated. This retrospective, single-center, cross-sectional study included patients with both a free and a total valproic acid concentration drawn within 30 minutes of each other between January 7, 2003, and June 1, 2011. Serum valproic acid concentrations were stratified by admission status (inpatient versus outpatient). In the primary analysis, for patients who had multiple paired concentrations drawn, one free valproic acid level and one total valproic acid level (i.e., one pair) were chosen at random for each inpatient. Information regarding patient demographics, laboratory data, and concomitant medication therapy was collected. Single and multivariable logistic regressions were performed to determine the odds of therapeutic discordance. During the study period, inpatient concentrations were measured in 220 patients, and outpatient concentrations were measured in 41 patients. The median total valproic acid concentration in the inpatient group was significantly lower than that in the outpatient group (54 μg/mL versus 83 μg/mL, p < 0.001). The median free fraction of inpatient levels was nearly twice as high as that of outpatient levels (28.8% versus 15.5%, p < 0.001). Levels drawn in inpatients were therapeutically discordant 63% of the time compared to only 19% in outpatients (p < 0.001). Multivariable logistic regression identified low albumin as an independent risk factor for therapeutic discordance. The median free fraction of valproic acid was significantly higher in inpatients than in outpatients. Low albumin concentration was a predictor of discordance between free and total valproic acid concentrations. Copyright © 2015 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

  15. [Study of Reaction Dynamics between Bovine Serum Albumin and Folic Acid by Stopped-Flow/Fluorescence].

    PubMed

    Ye, San-xian; Luo, Yun-jing; Qiao, Shu-liang; Li, Li; Liu, Cai-hong; Shi, Jian-long; An, Xue-jing

    2016-01-01

    As a kind of coenzyme of one-carbon enzymes in vivo, folic acid belongs to B vitamins, which can interact with other vitamins and has great significance for converting among amino acids, dividing growth of cells and protein synthesis reactions. Half-life, concentration and reaction rate constant of drugs are important parameters in pharmacokinetic study. In this paper, by utilizing fluorescence spectrophotometer and stopped-flow spectrum analyzer, reaction kinetic parameters between bovine serum albumin(BSA) and folic acid in a bionic system have been investigated, which provide references for parameters of drug metabolism related to folic acid. By using Stern-Volmer equation dealing with fluorescence quenching experiments data, we concluded that under 25, 30, and 37 degrees C, the static quenching constants of folic acid to intrinsic fluorescence from bovine serum albumin were 2.455 x 10(10), 4.900 x 10(10) and 6.427 x 10(10) L x mol(-1) x s(-1) respectively; The results of kinetic reaction rate have shown that the reaction rate of BSA and folic acid are greater than 100 mol x L(-1) x s(-1) at different temperatures, pH and buffering media, illustrating that the quenching mechanism between BSA and folic acid is to form composite static quenching process. Reaction concentration of bovine serum albumin and its initial concentration were equal to the secondary reaction formula, and the correlation coefficient was 0.998 7, while the half-life (t1/2) was 0.059 s at physiological temperature. With the increase of folic acid concentration, the apparent rate constant of this reaction had a linear increasing trend, the BSA fluorescence quenching rate constant catalyzed by folic acid was 3.174 x 10(5) mol x L(-1) x s(-1). Furthermore, with different buffer, the apparent rate constant and reaction rate constant of BSA interacting with folic acid were detected to explore the influence on the reaction under physiological medium, which is of great significance to determine the

  16. Elucidating the Influence of Gold Nanoparticles on the Binding of Salvianolic Acid B and Rosmarinic Acid to Bovine Serum Albumin

    PubMed Central

    Peng, Xin; Qi, Wei; Huang, Renliang; Su, Rongxin; He, Zhimin

    2015-01-01

    Salvianolic acid B and rosmarinic acid are two main water-soluble active ingredients from Salvia miltiorrhiza with important pharmacological activities and clinical applications. The interactions between salvianolic acid B (or rosmarinic acid) and bovine serum albumin (BSA) in the presence and absence of gold nanoparticles (Au NPs) with three different sizes were investigated by using biophysical methods for the first time. Experimental results proved that two components quenched the fluorescence of BSA mainly through a static mechanism irrespective of the absence or presence of Au NPs. The presence of Au NPs decreased the binding constants of salvianolic acid B with BSA from 27.82% to 10.08%, while Au NPs increased the affinities of rosmarinic acid for BSA from 0.4% to 14.32%. The conformational change of BSA in the presence of Au NPs (caused by a noncompetitive binding between Au NPs and drugs at different albumin sites) induced changeable affinity and binding distance between drugs and BSA compared with no Au NPs. The competitive experiments revealed that the site I (subdomain IIA) of BSA was the primary binding site for salvianolic acid B and rosmarinic acid. Additionally, two compounds may induce conformational and micro-environmental changes of BSA. The results would provide valuable binding information between salvianolic acid B (or rosmarinic acid) and BSA, and also indicated that the Au NPs could alter the interaction mechanism and binding capability of drugs to BSA, which might be beneficial to understanding the pharmacokinetics and biological activities of the two drugs. PMID:25861047

  17. The serum uric acid concentration is not causally linked to diabetic nephropathy in type 1 diabetes.

    PubMed

    Ahola, Aila J; Sandholm, Niina; Forsblom, Carol; Harjutsalo, Valma; Dahlström, Emma; Groop, Per-Henrik

    2017-05-01

    Previous studies have shown a relationship between uric acid concentration and progression of renal disease. Here we studied causality between the serum uric acid concentration and progression of diabetic nephropathy in 3895 individuals with type 1 diabetes in the FinnDiane Study. The renal status was assessed with the urinary albumin excretion rate and estimated glomerular filtration rate (eGFR) at baseline and at the end of the follow-up. Based on previous genomewide association studies on serum uric acid concentration, 23 single nucleotide polymorphisms (SNPs) with good imputation quality were selected for the SNP score. This score was used to assess the causality between serum uric acid and renal complications using a Mendelian randomization approach. At baseline, the serum uric acid concentration was higher with worsening renal status. In multivariable Cox regression analyses, baseline serum uric acid concentration was not independently associated with progression of diabetic nephropathy over a mean follow-up of 7 years. However, over the same period, baseline serum uric acid was independently associated with the decline in eGFR. In the cross-sectional logistic regression analyses, the SNP score was associated with the serum uric acid concentration. Nevertheless, the Mendelian randomization showed no causality between uric acid and diabetic nephropathy, eGFR categories, or eGFR as a continuous variable. Thus, our results suggest that the serum uric acid concentration is not causally related to diabetic nephropathy but is a downstream marker of kidney damage. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  18. Metabolic changes in rat serum after administration of suberoylanilide hydroxamic acid and discriminated by SVM.

    PubMed

    Yu, J; Wu, H; Lin, Z; Su, K; Zhang, J; Sun, F; Wang, X; Wen, C; Cao, H; Hu, L

    2017-01-01

    Suberoylanilide hydroxamic acid (SAHA) exerts marked anticancer effects via promotion of apoptosis, cell cycle arrest, and prevention of oncogene expression. In this study, serum metabolomics and artificial intelligence recognition were used to investigate SAHA toxicity. Forty rats (220 ± 20 g) were randomly divided into control and three SAHA groups (low, medium, and high); the experimental groups were treated with 12.3, 24.5, or 49.0 mg kg(-1) SAHA once a day via intragastric administration. After 7 days, blood samples from the four groups were collected and analyzed by gas chromatography-mass spectrometry, and pathological changes in the liver were examined using microscopy. The results showed that increased levels of urea, oleic acid, and glutaconic acid were the most significant indicators of toxicity. Octadecanoic acid, pentadecanoic acid, glycerol, propanoic acid, and uric acid levels were lower in the high SAHA group. Microscopic observation revealed no obvious damage to the liver. Based on these data, a support vector machine (SVM) discrimination model was established that recognized the metabolic changes in the three SAHA groups and the control group with 100% accuracy. In conclusion, the main toxicity caused by SAHA was due to excessive metabolism of saturated fatty acids, which could be recognized by an SVM model.

  19. Analytic validation of a gas chromatography-mass spectrometry method for quantification of six amino acids in canine serum samples.

    PubMed

    Lopes, Rosana; Grützner, Niels; Berghoff, Nora; Lidbury, Jonathan A; Suchodolski, Jan S; Steiner, Jörg M

    2015-12-01

    To analytically validate a gas concentration of chromatography-mass spectrometry (GC-MS) method for measurement of 6 amino acids in canine serum samples and to assess the stability of each amino acid after sample storage. Surplus serum from 80 canine samples submitted to the Gastrointestinal Laboratory at Texas A&M University and serum samples from 12 healthy dogs. GC-MS was validated to determine precision, reproducibility, limit of detection, and percentage recovery of known added concentrations of 6 amino acids in surplus serum samples. Amino acid concentrations in serum samples from healthy dogs were measured before (baseline) and after storage in various conditions. Intra- and interassay coefficients of variation (10 replicates involving 12 pooled serum samples) were 13.4% and 16.6% for glycine, 9.3% and 12.4% for glutamic acid, 5.1% and 6.3% for methionine, 14.0% and 15.1% for tryptophan, 6.2% and 11.0% for tyrosine, and 7.4% and 12.4% for lysine, respectively. Observed-to-expected concentration ratios in dilutional parallelism tests (6 replicates involving 6 pooled serum samples) were 79.5% to 111.5% for glycine, 80.9% to 123.0% for glutamic acid, 77.8% to 111.0% for methionine, 85.2% to 98.0% for tryptophan, 79.4% to 115.0% for tyrosine, and 79.4% to 110.0% for lysine. No amino acid concentration changed significantly from baseline after serum sample storage at -80°C for ≤ 7 days. GC-MS measurement of concentration of 6 amino acids in canine serum samples yielded precise, accurate, and reproducible results. Sample storage at -80°C for 1 week had no effect on GC-MS results.

  20. Analysis of Serum Concentrations of Tranexamic Acid Given by Alternate Routes in Swine (Sus scrofa) During Controlled Hemorrhage.

    DTIC Science & Technology

    2017-08-17

    additional pages if necessary.) PROTOCOL#: FDG20160013A DATE: 25 July 2017 PROTOCOL TITLE: Analysis of Serum Concentrations of Tranexamic Acid Given...marked decrease and delay to peak concentration . However, all routes achieved a serum adequate concentration as defined by previous studies in humans...used to determine the concentration of TXA in the serum at these time points. Results: There were no significant differences in baseline

  1. [Ascorbic acid consumption and serum levels in smokers and non-smokers adult men in Hermosillo, Sonora, México].

    PubMed

    Méndez, Rosa Olivia; Wyatt, C Jane; Saavedra, Javier; Ornelas, Alicia

    2002-12-01

    Ascorbic acid is one of the important antioxidant nutrients that can aid in the prevention of oxidative cellular damage. Adequate dietary intake is essential as humans can not synthesize this vitamin. It has been reported that smokers require higher dietary intakes to maintain their serum levels. The objective of this study was to determine serum levels of ascorbic acid in young male smokers and non smokers in the city of Hermosillo, Sonora, Mexico. In addition, their dietary intake of ascorbic acid was determined by a 24 h dietary recall. The dietary intake of ascorbic acid in 12 smokers was 64 +/- 11 mg/d and in 13 non smokers it was 70 +/- 12 mg/d. The smokers in this study did not meet the dietary recommendation of 100 mg/d. Serum ascorbic acid values in smokers and non smokers were 24.2 +/- 6.9 mumol/L and 30.9 +/- 3.7 mumol/L respectively. No significant difference was found among the 2 groups. Although the average serum ascorbic acid values fell within the range considered normal, 50% of the smokers had individual values that were below 23 mumol/L, indicating that these subjects have hipovitaminosis. A positive correlation between intake and serum levels was obtained for smokers (r = 0.71; p = 0.03). The results of this study suggest smokers may be at increased risk for chronic diseases due to their low intake and low serum levels of ascorbic acid.

  2. Serum sialic acid in malignant tumors, bacterial infections, and chronic liver diseases.

    PubMed

    Stefenelli, N; Klotz, H; Engel, A; Bauer, P

    1985-01-01

    The total serum sialic acid concentration was determined in 2,264 persons with various malignant tumors, bacterial infections, rheumatic diseases, and chronic liver diseases, and in a control group. The thiobarbiturate method according to Warren was used. The upper limit (95% percentile) in the control group was 2.23 mumol/ml. Higher values were found in the groups with neoplasms (mean: 3.04 mumol/ml), inflammatory diseases (e.g., pneumonia: 3.02 mumol/ml), and active rheumatoid arthritis (3.05 mumol/ml). In the group with malignant diseases, the sialic acid concentration at the time of diagnosis was highest for bronchial carcinoma (3.29 mumol/ml) and lowest for breast cancer (2.58 mumol/ml). In chronic liver diseases the mean sialic acid level was lower than in a heterogeneous group of noninflammatory and nonneoplastic diseases. The estimation of the serum sialic acid concentration could be useful in the detection of tumor burden and metastases, and in the evaluation of the later course and prognosis of malignant neoplasms if bacterial/inflammatory and active rheumatoid processes can be excluded.

  3. Antibody and Viral Nucleic Acid Testing of Serum and Cerebrospinal Fluid for Diagnosis of Eastern Equine Encephalitis.

    PubMed

    Sherwood, James A; Brittain, David C; Howard, John J; Oliver, JoAnne

    2015-08-01

    Eastern equine encephalitis diagnostic serum antibody can appear 6 days after the onset of symptoms, and its numbers can increase 4-fold in 4 days, arguing for early and frequent serum testing. In populations where cerebrospinal fluid viral nucleic acid testing sensitivity and specificity remain undetermined, cerebrospinal antibody testing should also be performed.

  4. Antibody and Viral Nucleic Acid Testing of Serum and Cerebrospinal Fluid for Diagnosis of Eastern Equine Encephalitis

    PubMed Central

    Brittain, David C.; Howard, John J.; Oliver, JoAnne

    2015-01-01

    Eastern equine encephalitis diagnostic serum antibody can appear 6 days after the onset of symptoms, and its numbers can increase 4-fold in 4 days, arguing for early and frequent serum testing. In populations where cerebrospinal fluid viral nucleic acid testing sensitivity and specificity remain undetermined, cerebrospinal antibody testing should also be performed. PMID:26063852

  5. Content of trans fatty acids in human cheek epithelium: comparison with serum and adipose tissue.

    PubMed

    Abraham, Ransi A; Bahl, Vinay K; Parshad, Rajinder; Seenu, V; Roy, Ambuj; Golandaz, Smita; Dorairaj, Prabhakaran; Ramakrishnan, Lakshmy

    2013-01-01

    Studies pertaining to trans fatty acids (TFA), which have been implicated in development of chronic diseases, are more relevant in developing countries where nutrition transition is changing traditional habits and practices. Measuring TFA is an arduous task because of the need for fat biopsies. This study identifies a tissue, which can be easily accessed for analytical measurement of trans fatty acid. In this cross-sectional study, fatty acid in adipose tissue, cheek epithelium, and blood samples were assessed by gas chromatography. Spearman correlation coefficient was computed to study the correlation of fatty acid distribution among the three tissues. The correlation coefficient of total trans fatty acid between cheek epithelium and serum was 0.30 (P < 0.02) and between cheek epithelium and adipose tissue was 0.33 (P < 0.019). This study is the first to report trans fatty acid profile in cheek epithelium giving scope for utilizing the cheek epithelium as a tissue for objective assessment of trans fatty acid intake.

  6. Oral intake and serum levels of ascorbic acid in continuous ambulatory peritoneal dialysis patients.

    PubMed

    Lim, S L; Lee, E J; Myint, C C; Ong, K T; Tay, M E; Yusuf, N; Ong, C N

    2001-01-01

    Oral intake of ascorbic acid is essential for optimum health in human beings. Continuous ambulatory peritoneal dialysis (CAPD) patients have an increased need for ascorbic acid, because of increased loss through dialysate, reduced intake owing to nausea and loss of appetite, and increased oxidative stress. However, optimum intake is still controversial. We studied 50 clinically stable patients to determine the relationship between oral ascorbic acid intake and serum ascorbic acid (SAA) level. Total oral intake ranged from 28 mg daily to 412 mg daily. Only one patient had an oral intake of ascorbic acid below 60 mg per day. The SAA levels ranged from 1 mg/L to 36.17 mg/L. Although a strong correlation existed between intake and SAA (p < 0.001, R2 = 0.47), the variation in SAA at any given intake level was wide. Of the studied patients, 62% had an SAA < 8.7 mg/L, 40% had an SAA < 5.1 mg/L (below the level in a healthy population), and 12% had a level below 2 mg/L (scorbutic). None of the patients demonstrated clinical manifestations of scurvy. Our results show that, in CAPD patients, ascorbic acid deficiency can be reliably detected only with SAA measurements, and oral intake may influence SAA level. To maintain ascorbic acid in the normal range for healthy adults, daily oral intake needs to be increased above the U.S. recommended dietary allowance to 80-140 mg.

  7. Changes in serum vitamin D and PTH values using denosumab with or without bisphosphonate pre-treatment in osteoporotic patients: a short-term study.

    PubMed

    Nakamura, Yukio; Kamimura, Mikio; Ikegami, Shota; Mukaiyama, Keijiro; Uchiyama, Shigeharu; Taguchi, Akira; Kato, Hiroyuki

    2015-12-15

    Denosumab is a fully human monoclonal antibody that inhibits receptor activator of nuclear factor kappa-β ligand (RANKL). Previous reports have shown that denosumab treatment of osteoporotic patients decreases bone resorption and fracture risk, but there have been no clinical studies on changes in bone turnover markers, 1,25(OH)2D3, or parathyroid hormone (PTH) in denosumab therapy with or without bisphosphonate (BP) pre-treatment in Japan. Here, we report such findings in 22 patients (11 in the denosumab alone group and 11 in the BP pre-treated group) with osteoporosis following 4 months of treatment. Bone metabolism had been inhibited by prior BP administration in the BP pre-treated group. The bone resorption markers serum tartrate-resistant acid phosphatase type 5b and urinary type I collagen cross-linked N-telopeptide were significantly decreased from baseline values for the entire study period in both groups. The bone formation marker bone alkaline phosphatase was significantly decreased at 4 months in the denosumab alone group only, and N-terminal propeptide of type 1 procollagen was significantly decreased at 2 and 4 months in the denosumab alone group versus no remarkable change in the BP pre-treated group. In the denosumab alone group, 1,25(OH)2D3 and PTH were significantly increased at 1 week and decreased gradually thereafter, but these did not change notably in the BP pre-treated group. Our results suggest that treatment with denosumab causes a strong inhibitory effect on bone resorption markers and mild inhibitory effect on bone formation markers. 1,25(OH)2D3 and PTH were significantly increased by denosumab but these did not change in the BP pre-treated group. Current Controlled Trials NCT02156960. Registered 31 May 2014.

  8. Effects of domoic acid on serum levels of TSH and thyroid hormones.

    PubMed

    Arufe, M C; Arias, B; Durán, R; Alfonso, M

    1995-08-01

    The actions of Domoic Acid (Dom), a marine toxin, on the levels of serum TSH and thyroid hormones (T4 and T3) has been studied to determine if these actions could be mediated by the serotoninergic system. In all the experiments, adult male Wistar rats were used. The Dom dissolved in saline was administered via i.p. in doses of 0.5 and 1 mg/kg. The T4 and T3 concentrations were determined by enzimoinmunoassay and TSH concentration was determined by radioinmunoassay. The results show that Dom 1 mg/kg increases the serum T4 levels one hour after treatment and decreases these levels 2 and 3 hr after treatment. Dom 0.5 mg/kg decreased the serum T4 levels 2 and 3 hr after treatment. The concentrations of T3 in serum were unchanged by both doses of Dom. The concentration of TSH was increased by Dom. In order to study the possible mediation of the serotoninergic system in the effect of Dom on the hormone levels, PCPA, a tryptophan hydroxylase inhibitor, was administered i.p. 90 min before blood sampling. In this case, with both doses of Dom a decrease in the levels of both hormones occurred with respect to the PCPA group. These results indicate that the serotoninergic system could affect the actions of Dom on TSH and thyroid hormone secretion.

  9. Retrospective exposure assessment of perfluorooctanoic acid serum concentrations at a fluoropolymer manufacturing plant.

    PubMed

    Woskie, Susan R; Gore, Rebecca; Steenland, Kyle

    2012-11-01

    Perfluorooctanoic acid (PFOA) is a suspect human carcinogen, causes neonatal loss, liver enlargement, and a variety of tumors in rodents, and has been associated with increased cholesterol levels in humans. Mortality analyses of worker cohorts have not been conclusive or consistent. As part of a series of epidemiologic studies of workers in a West Virginia plant that manufactures fluoropolymers, estimates of serum PFOA for the worker cohort were developed for the period of 1950-2004. An existing database of 2125 worker biomarker measurements of serum PFOA was used to model retrospective exposures. Historical PFOA serum levels for eight job category/job group combinations were modeled using linear mixed models to account for repeated measures, along with exposure determinants such as cumulative years worked in potentially exposed jobs, the amount of C8 used or emitted by the plant over time, as well as a four-knot restricted cubic spline function to reflect the influence of process changes over calendar time on exposure. The modeled biomarker levels matched well with measured levels, including those collected independently as part of a community study of PFOA levels (Spearman correlations of 0.8 for internal data comparisons and 0.6 for external data comparisons). These annualized PFOA serum estimates will be used in a series of morbidity and mortality studies of this worker cohort.

  10. Webinar Presentation: Suspect Screening of Environmental Organic Acids in Human Serum Using High-resolution Mass Spectrometry (HRMS)

    EPA Pesticide Factsheets

    This presentation, Suspect Screening of Environmental Organic Acids in Human Serum Using High-resolution Mass Spectrometry (HRMS), was given at the NIEHS/EPA Children's Centers 2016 Webinar Series: Exposome held on May 11, 2016.

  11. Vanillic Acid Ameliorates Cationic Bovine Serum Albumin Induced Immune Complex Glomerulonephritis in BALB/c Mice.

    PubMed

    Motiram Kakalij, Rahul; Tejaswini, G; Patil, Madhoosudan A; Dinesh Kumar, B; Diwan, Prakash V

    2016-06-01

    Preclinical Research Vanillic acid (VA) is a dihydroxybenzoic acid derivative widely used as a flavoring agent. It has chemopreventive effects on experimentally-induced carcinogenesis and in ulcerative colitis. The object of the present study was to investigate the effects of VA, alone and in combination with methylprednisolone (MP), on cationic bovine serum albumin (cBSA induced immune-complex glomerulonephritis in female BALB/c mice. Pre-immunization was carried out with cBSA in BALB/c mice and repeated (cBSA, 13 mg/kg, 3 times/week, i.v.) for 6 weeks to induce glomerulonephritis which was confirmed by the presence of severe proteinuria. The effect of VA (50, 100, and 200 mg/kg, p.o.) and its combination with MP (12.5 mg/kg, p.o.) was assessed in the nephrotic disease model. Treatment with VA decreased inflammatory nephrotic injury as evidenced by decreased proteinuria, serum creatinine, blood urea nitrogen, serum IgG1 and TNF-α levels. Co-administration of VA with MP showed an improvement in the immunohistochemistry of glomerular nephrin and podocin. The present results indicate that VA has a nephroprotective effect in the management of autoimmune nephritis. Drug Dev Res 77 : 171-179, 2016.   © 2016 Wiley Periodicals, Inc.

  12. Omega-3 Fatty Acid Supplementation Lowers Serum FSH in Normal Weight But Not Obese Women

    PubMed Central

    Al-Safi, Zain A.; Liu, Huayu; Carlson, Nichole E.; Chosich, Justin; Harris, Mary; Bradford, Andrew P.; Robledo, Celeste; Eckel, Robert H.

    2016-01-01

    Context: Dietary omega-3 fatty acids delay ovarian aging and promote oocyte quality in mice. Objective: To test whether dietary supplementation with omega-3 polyunsaturated fatty acids (PUFA) modulates reproductive hormones in reproductive-age women. Design: Prospective interventional study. Setting: Academic center. Participants: Fifteen obese and 12 normal-weight (NW) eumenorrheic women, ages 28–34 years. Intervention: Two frequent blood-sampling studies were performed before and after 1 month of omega-3 PUFA supplementation with 4 g of eicosapentaenoic acid and docosahexaenoic acid daily. Main Outcome Measures: Serum LH and FSH (basal and after GnRH stimulation). Results: The ratio of omega-6 to omega-3 PUFA was significantly reduced in plasma and red blood cell components for both groups after treatment (both P < .01). Omega-3 PUFA supplementation resulted in reduction of FSH and FSH response to GnRH by 17% on average (P = .06 and P = .03, respectively) in NW but not obese women. Serum levels of IL-1β and TNF-α were reduced after omega-3 PUFA supplementation (−72% for IL-1β; −56% for TNF-α; both, P < .05) in obese but not in NW women. This reduction, however, was not associated with a hormonal change in obese women. Conclusions: Dietary administration with omega-3 PUFA decreased serum FSH levels in NW but not in obese women with normal ovarian reserve. This effect is intriguing and is directionally consistent with murine data whereby higher dietary omega-3 PUFA extends reproductive lifespan. Our results imply that this nutritional intervention should be tested in women with diminished ovarian reserve in an attempt to delay ovarian aging. PMID:26523525

  13. Binding of coumarins to site I of human serum albumin. Effect of the fatty acids.

    PubMed

    Zatón, A M; Ferrer, J M; Ruiz de Gordoa, J C; Marquínez, M A

    1995-07-14

    It is known that binding site I on human serum albumin (HSA) consists of a zone of two overlapping regions: the specific binding region represented by warfarin binding and the specific binding region represented by azapropazone and phenylbutazone binding. In this paper binding parameters to defatted HSA and to HSA with fatty acids (molar ratio of fatty acid/HSA = 4) were compared. High-affinity binding sites for warfarin, 4-chromanol, 4-hydroxycoumarin, coumarin, 3-acetylcoumarin and phenylbutazone (759,549 M-1 > Ka > 67,024 M-1) constitute binding site I on HSA. In this binding area defatted HSA can bind two molecules of warfarin, but the presence of fatty acids diminish the binding capacity of warfarin to HSA (2 > n > 1).

  14. Serum uric acid concentrations and SLC2A9 genetic variation in Hispanic children: the Viva La Familia Study.

    PubMed

    Voruganti, V Saroja; Laston, Sandra; Haack, Karin; Mehta, Nitesh R; Cole, Shelley A; Butte, Nancy F; Comuzzie, Anthony G

    2015-04-01

    Elevated concentrations of serum uric acid are associated with increased risk of gout and renal and cardiovascular diseases. Genetic studies in adults have consistently identified associations of solute carrier family 2, member 9 (SLC2A9), polymorphisms with variation in serum uric acid. However, it is not known whether the association of serum uric acid with SLC2A9 polymorphisms manifests in children. The aim was to investigate whether variation in serum uric acid is under genetic influence and whether the association with SLC2A9 polymorphisms generalizes to Hispanic children of the Viva La Familia Study. We conducted a genomewide association study with 1.1 million genetic markers in 815 children. We found serum uric acid to be significantly heritable [h(2) ± SD = 0.45 ± 0.08, P = 5.8 × 10(-11)] and associated with SLC2A9 variants (P values between 10(-16) and 10(-7)). Several of the significantly associated polymorphisms were previously identified in studies in adults. We also found positive genetic correlations between serum uric acid and BMI z score (ρG = 0.45, P = 0.002), percentage of body fat (ρG = 0.28, P = 0.04), fat mass (ρG = 0.34, P = 0.02), waist circumference (ρG = 0.42, P = 0.003), and waist-to-height ratio (ρG = 0.46, P = 0.001). Our results show that variation in serum uric acid in Hispanic children is under considerable genetic influence and is associated with obesity-related phenotypes. As in adults, genetic variation in SLC2A9 is associated with serum uric acid concentrations, an important biomarker of renal and cardiovascular disease risk, in Hispanic children. © 2015 American Society for Nutrition.

  15. Serum uric acid concentrations and SLC2A9 genetic variation in Hispanic children: the Viva La Familia Study1234

    PubMed Central

    Voruganti, V Saroja; Laston, Sandra; Haack, Karin; Mehta, Nitesh R; Cole, Shelley A; Butte, Nancy F; Comuzzie, Anthony G

    2015-01-01

    Background: Elevated concentrations of serum uric acid are associated with increased risk of gout and renal and cardiovascular diseases. Genetic studies in adults have consistently identified associations of solute carrier family 2, member 9 (SLC2A9), polymorphisms with variation in serum uric acid. However, it is not known whether the association of serum uric acid with SLC2A9 polymorphisms manifests in children. Objective: The aim was to investigate whether variation in serum uric acid is under genetic influence and whether the association with SLC2A9 polymorphisms generalizes to Hispanic children of the Viva La Familia Study. Design: We conducted a genomewide association study with 1.1 million genetic markers in 815 children. Results: We found serum uric acid to be significantly heritable [h2 ± SD = 0.45 ± 0.08, P = 5.8 × 10−11] and associated with SLC2A9 variants (P values between 10−16 and 10−7). Several of the significantly associated polymorphisms were previously identified in studies in adults. We also found positive genetic correlations between serum uric acid and BMI z score (ρG = 0.45, P = 0.002), percentage of body fat (ρG = 0.28, P = 0.04), fat mass (ρG = 0.34, P = 0.02), waist circumference (ρG = 0.42, P = 0.003), and waist-to-height ratio (ρG = 0.46, P = 0.001). Conclusions: Our results show that variation in serum uric acid in Hispanic children is under considerable genetic influence and is associated with obesity-related phenotypes. As in adults, genetic variation in SLC2A9 is associated with serum uric acid concentrations, an important biomarker of renal and cardiovascular disease risk, in Hispanic children. PMID:25833971

  16. Predictors of osteoclast activity in patients with sickle cell disease.

    PubMed

    Nouraie, Mehdi; Cheng, Kevin; Niu, Xiaomei; Moore-King, Evadne; Fadojutimi-Akinsi, Margaret F; Minniti, Caterina P; Sable, Craig; Rana, Sohail; Dham, Niti; Campbell, Andrew; Ensing, Gregory; Kato, Gregory J; Gladwin, Mark T; Castro, Oswaldo L; Gordeuk, Victor R

    2011-08-01

    Bone changes are common in sickle cell disease, but the pathogenesis is not fully understood. Tartrate-resistant acid phosphatase (TRACP) type 5b is produced by bone-resorbing osteoclasts. In other forms of hemolytic anemia, increased iron stores are associated with osteoporosis. We hypothesized that transfusional iron overload would be associated with increased osteoclast activity in patients with sickle cell disease. We examined tartrate-resistant acid phosphatase 5b concentrations in patients with sickle cell disease and normal controls of similar age and sex distribution at steady state. Serum tartrate-resistant acid phosphatase 5b concentration was measured using an immunocapture enzyme assay and plasma concentrations of other cytokines were assayed using the Bio-Plex suspension array system. Tricuspid regurgitation velocity, an indirect measure of systolic pulmonary artery pressure, was determined by echocardiography. Tartrate-resistant acid phosphatase 5b concentrations were higher in 58 adults with sickle cell disease than in 22 controls (medians of 4.4 versus 2.4 U/L, respectively; P=0.0001). Among the patients with sickle cell disease, tartrate-resistant acid phosphatase 5b independently correlated with blood urea nitrogen (standardized beta=0.40, P=0.003), interleukin-8 (standardized beta=0.30, P=0.020), and chemokine C-C motif ligand 5 (standardized beta=-0.28, P=0.031) concentrations, but not with serum ferritin concentration. Frequent blood transfusions (>10 units in life time) were not associated with higher tartrate-resistant acid phosphatase 5b levels in multivariate analysis. There were strong correlations among tartrate-resistant acid phosphatase 5b, alkaline phosphatase and tricuspid regurgitation velocity (r>0.35, P<0.001). Patients with sickle cell disease have increased osteoclast activity as reflected by serum tartrate-resistant acid phosphatase 5b concentrations. Our results may support a potential role of inflammation rather than increased

  17. Predictors of osteoclast activity in patients with sickle cell disease

    PubMed Central

    Nouraie, Mehdi; Cheng, Kevin; Niu, Xiaomei; Moore-King, Evadne; Fadojutimi-Akinsi, Margaret F.; Minniti, Caterina P.; Sable, Craig; Rana, Sohail; Dham, Niti; Campbell, Andrew; Ensing, Gregory; Kato, Gregory J.; Gladwin, Mark T.; Castro, Oswaldo L.; Gordeuk, Victor R.

    2011-01-01

    Background Bone changes are common in sickle cell disease, but the pathogenesis is not fully understood. Tartrate-resistant acid phosphatase (TRACP) type 5b is produced by bone-resorbing osteoclasts. In other forms of hemolytic anemia, increased iron stores are associated with osteoporosis. We hypothesized that transfusional iron overload would be associated with increased osteoclast activity in patients with sickle cell disease. Design and Methods We examined tartrate-resistant acid phosphatase 5b concentrations in patients with sickle cell disease and normal controls of similar age and sex distribution at steady state. Serum tartrate-resistant acid phosphatase 5b concentration was measured using an immunocapture enzyme assay and plasma concentrations of other cytokines were assayed using the Bio-Plex suspension array system. Tricuspid regurgitation velocity, an indirect measure of systolic pulmonary artery pressure, was determined by echocardiography. Results Tartrate-resistant acid phosphatase 5b concentrations were higher in 58 adults with sickle cell disease than in 22 controls (medians of 4.4 versus 2.4 U/L, respectively; P=0.0001). Among the patients with sickle cell disease, tartrate-resistant acid phosphatase 5b independently correlated with blood urea nitrogen (standardized beta=0.40, P=0.003), interleukin-8 (standardized beta=0.30, P=0.020), and chemokine C-C motif ligand 5 (standardized beta=−0.28, P=0.031) concentrations, but not with serum ferritin concentration. Frequent blood transfusions (>10 units in life time) were not associated with higher tartrate-resistant acid phosphatase 5b levels in multivariate analysis. There were strong correlations among tartrate-resistant acid phosphatase 5b, alkaline phosphatase and tricuspid regurgitation velocity (r>0.35, P<0.001). Conclusions Patients with sickle cell disease have increased osteoclast activity as reflected by serum tartrate-resistant acid phosphatase 5b concentrations. Our results may support a

  18. Zoledronic Acid Preserves Bone Structure and Increases Survival but Does Not Limit Tumour Incidence in a Prostate Cancer Bone Metastasis Model

    PubMed Central

    Hung, Tzong-Tyng; Chan, Jeffrey; Russell, Pamela J.; Power, Carl A.

    2011-01-01

    Background The bisphosphonate, zoledronic acid (ZOL), can inhibit osteoclasts leading to decreased osteoclastogenesis and osteoclast activity in bone. Here, we used a mixed osteolytic/osteoblastic murine model of bone-metastatic prostate cancer, RM1(BM), to determine how inhibiting osteolysis with ZOL affects the ability of these cells to establish metastases in bone, the integrity of the tumour-bearing bones and the survival of the tumour-bearing mice. Methods The model involves intracardiac injection for arterial dissemination of the RM1(BM) cells in C57BL/6 mice. ZOL treatment was given via subcutaneous injections on days 0, 4, 8 and 12, at 20 and 100 µg/kg doses. Bone integrity was assessed by micro-computed tomography and histology with comparison to untreated mice. The osteoclast and osteoblast activity was determined by measuring serum tartrate-resistant acid phosphatase 5b (TRAP 5b) and osteocalcin, respectively. Mice were euthanased according to predetermined criteria and survival was assessed using Kaplan Meier plots. Findings Micro-CT and histological analysis showed that treatment of mice with ZOL from the day of intracardiac injection of RM1(BM) cells inhibited tumour-induced bone lysis, maintained bone volume and reduced the calcification of tumour-induced endochondral osteoid material. ZOL treatment also led to a decreased serum osteocalcin and TRAP 5b levels. Additionally, treated mice showed increased survival compared to vehicle treated controls. However, ZOL treatment did not inhibit the cells ability to metastasise to bone as the number of bone-metastases was similar in both treated and untreated mice. Conclusions ZOL treatment provided significant benefits for maintaining the integrity of tumour-bearing bones and increased the survival of tumour bearing mice, though it did not prevent establishment of bone-metastases in this model. From the mechanistic view, these observations confirm that tumour-induced bone lysis is not a requirement for

  19. Serum concentration of eicosapentaenoic acid is associated with cognitive function in patients with coronary artery disease.

    PubMed

    Yagi, Shusuke; Hara, Tomoya; Ueno, Rie; Aihara, Ken-ichi; Fukuda, Daiju; Takashima, Akira; Hotchi, Junko; Ise, Takayuki; Yamaguchi, Koji; Tobiume, Takeshi; Iwase, Takashi; Yamada, Hirotsugu; Soeki, Takeshi; Wakatsuki, Tetsuzo; Shimabukuro, Michio; Akaike, Masashi; Sata, Masataka

    2014-12-04

    Recent studies have shown that intake of n-3 polyunsaturated fatty acids (PUFAs) is associated with reduced risk of cognitive impairment and coronary artery disease (CAD); however, it is currently unknown whether reduced serum n-3 PUFA is associated with cognitive impairment in patients with CAD. We retrospectively evaluated cognitive function with the mini-mental state examination (MMSE), serum levels of PUFAs (including eicosapentaenoic acid [EPA], docosahexaenoic acid [DHA], dihomogammalinolenic acid [DGLA], and arachidonic acid [AA]), cardiovascular risk factors (hypertension, dyslipidemia, diabetes mellitus, cerebrovascular disease, and history of current/previous smoking), and parameters of cardiac function (left ventricular ejection fraction and brain natriuretic peptide levels) in 146 Japanese CAD patients. The associations between the MMSE scores and the other parameters were evaluated. Pearson correlation analysis showed that EPA (R = 0.25, P <0.01), EPA/AA ratio (R = 0.22, P = 0.01), and left ventricular ejection fraction (R = 0.15, P = 0.04) were positively associated with MMSE score, and that age (R = -0.20, P <0.01) and brain natriuretic peptide levels (R = -0.28, P <0.01) were inversely associated with MMSE score. Multiple regression analysis showed that age (P <0.05) was negatively associated with MMSE score, while EPA (P <0.01) and EPA/AA ratio (P <0.05) were positively associated with MMSE score; however, sex; body mass index; left ventricular ejection fraction; levels of DHA, AA, and DGLA; DHA/AA ratio; brain natriuretic peptide; and presence of hypertension, dyslipidemia, diabetes mellitus, cerebrovascular disease, and history of current/previous smoking were statistically excluded. Serum EPA concentration is associated with cognitive function in patients with CAD, suggesting that a low serum EPA level is a risk factor for cognitive impairment independent of cardiac function, including left ventricular ejection fraction. This correlation

  20. The Prevalence of Nonalcoholic Fatty Liver Disease and Relationship with Serum Uric Acid Level in Uyghur Population

    PubMed Central

    Cai, Wen; Song, Jiang-mei; Zhang, Bei; Sun, Yu-ping; Yao, Hua; Zhang, Yue-xin

    2014-01-01

    Objective. To investigate the prevalence of nonalcoholic fatty liver disease (NAFLD) and the association of serum uric acid level with NAFLD in Uygur people, Xinjiang. Methods. A total of 2241 Uyghur persons (1214 males and 1027 females) were interviewed for physical checkups from 2011 to 2012. The clinical data of questionnaire survey, body mass index (BMI), abdominal circumference, blood pressure, blood sugar, blood lipid, and serum uric acid level were collected for analysis. Results. The prevalence rates of NAFLD determined by abdominal ultrasound examination and hyperuricemia were 43.9% and 8.4%, respectively. The persons with NAFLD had significantly higher serum uric acid levels than those without NAFLD (320 ± 88 versus 254 ± 80 μmol/L; P < 0.001). The prevalence rate of NAFLD was significantly higher in subjects with hyperuricemia than that in those without hyperuricemia (78.19% versus 40.83%; P < 0.001), and the prevalence rate increased with progressively higher serum uric acid levels (P < 0.001). Multiple regression analysis showed that hyperuricemia was associated with an increased risk of NAFLD (odds ratio (OR): 2.628, 95% confidence interval (CI): 1.608–4.294, and P < 0.001). Conclusion. Serum uric acid level was significantly associated with NAFLD, and the prevalence rate of NAFLD increased with progressively higher serum uric acid levels. PMID:24516367

  1. Higher Serum Uric Acid May Contribute to Cerebral Infarction in Patients with Type 2 Diabetes Mellitus: a Meta-Analysis.

    PubMed

    Du, Lei; Ma, Jianhua; Zhang, Xiaoning

    2017-01-01

    Higher levels of serum uric acid tend to increase the diabetes-related complications. We performed a meta-analysis to investigate whether the higher serum uric acid levels were associated with cerebral infarction in type 2 diabetes patients. We searched for relevant studies in the PubMed, Embase, China National Knowledge Infrastructure, China BioMedicine, and VIP database until August 2015. All observational studies comparing serum uric acid levels in type 2 diabetic patients with and without cerebral infarction were included. We calculated the ratio of means (RoM) of serum uric acid by mean cerebral infarction/mean diabetic control from the individual studies and then pooled RoM and its 95 % confidence intervals (CI). A total of 23 eligible studies were identified. Pooled estimates indicated that type 2 diabetes patients with cerebral infarction were associated with 29 % (RoM 1.29; 95 % CI 1.26-1.31) higher serum uric acid levels than those without cerebral infarction in a random effect model. Subgroup analyses based on gender indicated that RoM was 1.23 (95 % CI 1.09-1.38) for men and 1.12 (95 % CI 0.98-1.27) for women. This meta-analysis suggests that higher serum uric acid levels may contribute to cerebral infarction in patients with type 2 diabetes.

  2. Serum folic acid levels are associated with the presence and severity of liver steatosis in Chinese adults.

    PubMed

    Xia, Ming-Feng; Bian, Hua; Zhu, Xiao-Peng; Yan, Hong-Mei; Chang, Xin-Xia; Zhang, Lin-Shan; Lin, Huan-Dong; Hu, Xi-Qi; Gao, Xin

    2017-06-28

    Non-alcoholic fatty liver disease (NAFLD) is a common and strong risk factor for cardiovascular disease and hepatocellular carcinoma. The rapid acceleration of the increase in NAFLD prevalence has exceeded the trends observed for obesity, and has been driven by multiple factors. The aim of this study was to investigate the correlation between the serum levels of folic acid, the endogenous source of methyl groups for DNA methylation, and NAFLD in Chinese adults. The correlations between the serum folic acid levels and NAFLD were investigated in two independent cohorts of 70 subjects who underwent a liver biopsy and 130 subjects with varying liver fat contents, as measured using proton magnetic resonance spectroscopy ((1)H-MRS). Independent correlations between serum folic acid levels and liver steatosis grades were detected using a multivariate ordinal regression analysis. The diagnostic performances of serum folic acid levels alone and in combination with existing NAFLD prediction scores were compared with those of traditional NAFLD prediction parameters using receiver operating characteristic (ROC) curve analyses. Serum folic acid concentrations were inversely correlated with liver histological steatosis grades (ρ = -0.371, P < 0.001) and the (1)H-MRS-measured liver fat content (r = -0.199, P = 0.038). According to the multivariate ordinal regression analysis, serum folic acid levels were inversely correlated with liver steatosis grades (OR 0.739 [0.594-0.918], P = 0.006) independent of age, gender, BMI, components of metabolic syndrome and the serum TC, LDL-c and HOMA-IR levels. The AUROC of serum folic acid for the diagnosis of NAFLD was 0.75 (0.65-0.83), and the addition of serum folic acid to NAFLD prediction scores significantly improved the diagnostic prediction of NAFLD (AUROC = 0.88 [0.81-0.94]). Low serum folic acid levels were identified as an independent risk factor for NAFLD in the Chinese population. The addition of the serum folic acid

  3. Effect of dietary supplementation of organic acids on performance, intestinal histomorphology, and serum biochemistry of broiler chicken.

    PubMed

    Adil, Sheikh; Banday, Tufail; Bhat, Gulam Ahmad; Mir, Masood Saleem; Rehman, Manzoor

    2010-01-01

    The aim of the study was to determine the effect of dietary supplementation of organic acids on the performance, intestinal histomorphology, and blood biochemistry of broiler chicken. The birds in the control (T(1)) group were fed the basal diet whereas in other treatment groups basal diet was supplemented with 2% butyric acid (T(2)), 3% butyric acid (T(4)), 2% fumaric acid (T(4)), 3% fumaric acid (T(5)), 2% lactic acid (T(6)), and 3% lactic acid (T(7)). Broiler chicken fed diets supplemented with organic acids had significantly (P < .05) improved body weight gains and feed conversion ratio. No effect (P < .05) on cumulative feed consumption was observed. The addition of organic increased villus height in the small intestines but the differences were not significant (P < .05) in case of the ileum. Serum calcium and phosphorus concentrations were increased (P < .05) but no effect (P < .05) on the concentration of serum glucose and cholesterol, serum glutamic pyruvic transaminase (SGPT), and serum glutamic oxaloacetate transaminase (SGOT) was observed. The results indicated that the organic acid supplementation, irrespective of type and level of acid used, had a beneficial effect on the performance of broiler chicken.

  4. CYP2E1-dependent elevation of serum cholesterol, triglycerides, and hepatic bile acids by isoniazid

    SciTech Connect

    Cheng, Jie; Krausz, Kristopher W.; Li, Feng; Ma, Xiaochao; Gonzalez, Frank J.

    2013-01-15

    Isoniazid is the first-line medication in the prevention and treatment of tuberculosis. Isoniazid is known to have a biphasic effect on the inhibition–induction of CYP2E1 and is also considered to be involved in isoniazid-induced hepatotoxicity. However, the full extent and mechanism of involvement of CYP2E1 in isoniazid-induced hepatotoxicity remain to be thoroughly investigated. In the current study, isoniazid was administered to wild-type and Cyp2e1-null mice to investigate the potential toxicity of isoniazid in vivo. The results revealed that isoniazid caused no hepatotoxicity in wild-type and Cyp2e1-null mice, but produced elevated serum cholesterol and triglycerides, and hepatic bile acids in wild-type mice, as well as decreased abundance of free fatty acids in wild-type mice and not in Cyp2e1-null mice. Metabolomic analysis demonstrated that production of isoniazid metabolites was elevated in wild-type mice along with a higher abundance of bile acids, bile acid metabolites, carnitine and carnitine derivatives; these were not observed in Cyp2e1-null mice. In addition, the enzymes responsible for bile acid synthesis were decreased and proteins involved in bile acid transport were significantly increased in wild-type mice. Lastly, treatment of targeted isoniazid metabolites to wild-type mice led to similar changes in cholesterol, triglycerides and free fatty acids. These findings suggest that while CYP2E1 is not involved in isoniazid-induced hepatotoxicity, while an isoniazid metabolite might play a role in isoniazid-induced cholestasis through enhancement of bile acid accumulation and mitochondria β-oxidation. -- Highlights: ► Isoniazid metabolites were elevated only in wild-type mice. ► Isoniazid caused no hepatotoxicity in wild-type and Cyp2e1-null mice. ► Isoniazid elevated serum cholesterol and triglycerides, and hepatic bile acids. ► Bile acid transporters were significantly decreased in isoniazid-treated mice.

  5. Detection of folic acid protein in human serum using reduced graphene oxide electrodes modified by folic-acid.

    PubMed

    He, Lijie; Wang, Qian; Mandler, Daniel; Li, Musen; Boukherroub, Rabah; Szunerits, Sabine

    2016-01-15

    The detection of disease markers is considered an important step for early diagnosis of cancer. We design in this work a novel electrochemical sensing platform for the sensitive and selective detection of folic acid protein (FP). The platform is fabricated by electrophoretic deposition (EPD) of reduced graphene oxide (rGO) onto a gold electrode and post-functionalization of rGO with folic acid. Upon FP binding, a significant current decrease can be measured using differential pulse voltammetry (DPV). Using this scheme, a detection limit of 1pM is achieved. Importantly, the method also allows the detection of FP in serum being thus an appealing approach for the sensitive detection of biomarkers in clinical samples.

  6. Spectroscopic analyses and studies on respective interaction of cyanuric acid and uric acid with bovine serum albumin and melamine

    NASA Astrophysics Data System (ADS)

    Chen, Dandan; Wu, Qiong; Wang, Jun; Wang, Qi; Qiao, Heng

    2015-01-01

    In this work, the fluorescence quenching was used to study the interaction of cyanuric acid (CYA) and uric acid (UA) with bovine serum albumin (BSA) at two different temperatures (283 K and 310 K). The bimolecular quenching constant (Kq), apparent quenching constant (Ksv), effective binding constant (KA) and corresponding dissociation constant (KD), binding site number (n) and binding distance (r) were calculated by adopting Stern-Volmer, Lineweaver-Burk, Double logarithm and overlap integral equations. The results show that CYA and UA are both able to obviously bind to BSA, but the binding strength order is BSA + CYA < BSA + UA. And then, the interactions of CYA and UA with melamine (MEL) under the same conditions were also studied by using similar methods. The results indicates that both CYA and UA can bind together closely with melamine (MEL). It is wished that these research results would facilitate the understanding the formation of kidney stones and gout in the body after ingesting excess MEL.

  7. Fatty acid-binding site environments of serum vitamin D-binding protein and albumin are different

    PubMed Central

    Swamy, Narasimha; Ray, Rahul

    2008-01-01

    Vitamin D-binding protein (DBP) and albumin (ALB) are abundant serum proteins and both possess high-affinity binding for saturated and unsaturated fatty acids. However, certain differences exist. We surmised that in cases where serum albumin level is low, DBP presumably can act as a transporter of fatty acids. To explore this possibility we synthesized several alkylating derivatives of 14C-palmitic acid to probe the fatty acid binding pockets of DBP and ALB. We observed that N-ethyl-5-phenylisooxazolium-3′-sulfonate-ester (WRK ester) of 14C-palmitic acid specifically labeled DBP; but p-nitrophenyl- and N-hydroxysuccinimidyl-esters failed to do so. However, p-nitrophenyl ester of 14C-palmitic acid specifically labeled bovine ALB, indicating that the micro-environment of the fatty acid-binding domains of DBP and ALB may be different; and DBP may not replace ALB as a transporter of fatty acids. PMID:18374965

  8. Estimated Net Endogenous Acid Production and Serum Bicarbonate in African Americans with Chronic Kidney Disease

    PubMed Central

    Appel, Lawrence J.; Astor, Brad C.; Miller, Edgar R.; Beddhu, Srinivasan; Woodward, Mark; Parekh, Rulan S.; Anderson, Cheryl A.M.

    2011-01-01

    Summary Background and objectives Metabolic acidosis may contribute to morbidity and disease progression in patients with chronic kidney disease (CKD). The ratio of dietary protein, the major source of nonvolatile acid, to dietary potassium, which is naturally bound to alkali precursors, can be used to estimate net endogenous acid production (NEAP). We tested the association between estimated NEAP and serum bicarbonate in patients with CKD. Design, setting, participants, & measurements NEAP was estimated among 462 African American adults with hypertensive CKD using published equations: NEAP (mEq/d) = −10.2 + 54.5 (protein [g/d]/potassium [mEq/d]). Dietary protein and potassium intake were estimated from 24-hour urinary excretion of urea nitrogen and potassium, respectively. All of the eligible measurements during follow-up were modeled using generalized linear regression clustered by participant and adjusted for demographics, 24-hour urinary sodium, kidney function, and selected medications. Results Higher NEAP was associated with lower serum bicarbonate in a graded fashion (P trend < 0.001). Serum bicarbonate was 1.27 mEq/L lower among those in the highest compared with the lowest quartile of NEAP (P < 0.001). There was a greater difference in serum bicarbonate between the highest and lowest quartiles of NEAP among patients with stage 4/5 CKD (−2.43 mEq/L, P < 0.001) compared with those with stage 2/3 disease (−0.77 mEq/L, P = 0.01; P-interaction = 0.02). Conclusions Reducing NEAP, through reduction of dietary protein and increased intake of fruits and vegetables, may prevent metabolic acidosis in patients with CKD. PMID:21700817

  9. Estimated net endogenous acid production and serum bicarbonate in African Americans with chronic kidney disease.

    PubMed

    Scialla, Julia J; Appel, Lawrence J; Astor, Brad C; Miller, Edgar R; Beddhu, Srinivasan; Woodward, Mark; Parekh, Rulan S; Anderson, Cheryl A M

    2011-07-01

    Metabolic acidosis may contribute to morbidity and disease progression in patients with chronic kidney disease (CKD). The ratio of dietary protein, the major source of nonvolatile acid, to dietary potassium, which is naturally bound to alkali precursors, can be used to estimate net endogenous acid production (NEAP). We tested the association between estimated NEAP and serum bicarbonate in patients with CKD. NEAP was estimated among 462 African American adults with hypertensive CKD using published equations: NEAP (mEq/d) = -10.2 + 54.5 (protein [g/d]/potassium [mEq/d]). Dietary protein and potassium intake were estimated from 24-hour urinary excretion of urea nitrogen and potassium, respectively. All of the eligible measurements during follow-up were modeled using generalized linear regression clustered by participant and adjusted for demographics, 24-hour urinary sodium, kidney function, and selected medications. Higher NEAP was associated with lower serum bicarbonate in a graded fashion (P trend < 0.001). Serum bicarbonate was 1.27 mEq/L lower among those in the highest compared with the lowest quartile of NEAP (P < 0.001). There was a greater difference in serum bicarbonate between the highest and lowest quartiles of NEAP among patients with stage 4/5 CKD (-2.43 mEq/L, P < 0.001) compared with those with stage 2/3 disease (-0.77 mEq/L, P = 0.01; P-interaction = 0.02). Reducing NEAP, through reduction of dietary protein and increased intake of fruits and vegetables, may prevent metabolic acidosis in patients with CKD.

  10. Analysis of lysergic acid amide in human serum and urine after ingestion of Argyreia nervosa seeds.

    PubMed

    Paulke, Alexander; Kremer, Christian; Wunder, Cora; Toennes, Stefan W

    2012-08-01

    The ergot alkaloid lysergic acid amide (LSA) is a secondary plant constituent in a number of plants, but it is mainly present in considerable amounts in Convolvulaceae, like Argyreia nervosa. Due to its close structural similarity to lysergic acid diethylamide, LSA is considered as psychedelic and therefore promoted as so-called "legal high" in various internet forums. During a human behavioral study with orally administered seeds of A. nervosa, blood and urine samples were obtained. The present study describes the validation of a sensitive and robust high performance liquid chromatography method with fluorescence detection, which was applied to the study samples. The limit of detection (LOD) and lower limit of quantification in human serum were 0.05 and 0.17 ng/mL, respectively, and in urine, the LOD was 0.15 ng/mL. Intra- and interday precision and accuracy were below 15 % relative standard deviation with a bias better than ±15 %. No conversion of LSA to its epimer iso-LSA was noted during analyses. The LSA concentrations in the authentic human serum samples were in the range of 0.66 to 3.15 ng/mL approximately 2 h after ingestion. In urine, LSA could be found 1-24 h after ingestion; after 48 h, no LSA could be detected. The LSA epimer iso-LSA was also detected in serum and urine in varying ratios. In conclusion, LSA serum levels in the low nanogram per milliliter range correlated with severe vegetative adverse effects (nausea, weakness, fatigue, tremor, blood pressure elevation) and a psychosis-like state, which led to study termination.

  11. Interaction between serum uric acid and triglycerides in relation to blood pressure.

    PubMed

    Teng, F; Zhu, R; Zou, C; Xue, Y; Yang, M; Song, H; Liang, J

    2011-11-01

    The aim of this study was to examine the independent relationship between serum uric acid (SUA) and blood pressure, and to assess their joint effects on obesity, fasting glucose and lipids. The study samples were from a community-based health examination survey in Xuzhou, Jiangsu province of China (2009). Blood pressure, body mass index, fasting glucose, lipids and SUA were measured. After excluding individuals with fasting glucose greater than 7 mmol l(-1), a total of 8415 subjects with biomarkers available were included in the present study. Blood pressure increased with elevated SUA levels, after adjusting for age and sex. Further adjustment for fasting glucose, lipids and alcohol consumption did not change the increasing trend. The associations between uric acid and hypertension were most evident in those with highest quintiles of high-density lipoprotein cholesterol (HDL-C). In addition, the associations were significant in both men and women, and we found significant interactions between uric acid status and age on hypertension. When the joint effects were examined, we found an additive effect of triglycerides and uric acid levels on diastolic blood pressure (DBP). There was significant association between SUA and hypertension, independent of other metabolic risk factors. HDL-C levels may modify the associations between uric acid and hypertension. The effects of triglycerides and uric acid levels on DBP were additive.

  12. Serum levels of glial fibrillary acidic protein and Nogo-A in children with autism spectrum disorders.

    PubMed

    Cetin, Ihsan; Tezdig, Ihsan; Tarakcioglu, Mahmut Cem; Kadak, Muhammed Tayyib; Demirel, Omer Faruk; Ozer, Omer Faruk

    2016-11-01

    Improved biomarkers would facilitate the diagnosis and treatment of autism spectrum disorders (ASD). Our objective was to examine the levels of Nogo-A and glial fibrillary acidic protein (GFAP) in children with ASD. Serum concentrations of GFAP and Nogo-A were determined by enzyme-linked immunosorbent assay. In this preliminary study, we found that serum Nogo-A was not found significantly different between groups, while serum levels of GFAP were significantly lower in ASD than controls. It will be of great interest to determine other potential causes of elevated serum levels of GFAP, and whether this elevation has any phenotypic effect.

  13. Serum uric acid levels and freezing of gait in Parkinson's disease.

    PubMed

    Ou, Ruwei; Cao, Bei; Wei, Qianqian; Hou, Yanbing; Xu, Yaqian; Song, Wei; Zhao, Bi; Shang, Huifang

    2017-03-01

    Uric acid (UA) is a natural antioxidant and iron scavenger in the human body, which has been hypothesized to exert an anti-oxidative effect in Parkinson's disease (PD). This study aimed to investigate the relationship between serum UA levels and freezing of gait (FOG) in PD. A total of 321 Chinese PD patients with fasting serum UA evaluated were included in the cross-sectional study. Demographics, clinical features, and therapeutic regimen were collected. The Unified PD Rating Scale (UPDRS) III and Hoehn and Yahr (H and Y) stage were used to evaluate the severity of disease, and the Frontal Assessment Battery (FAB) and Montreal Cognitive Assessment (MoCA) scales were used to assess the cognitive function. Patients with FOG showed lower proportion of male, longer disease duration, lower body mass index, lower concentrations of serum UA, higher total levodopa equivalent daily dosage, higher UPDRS III score, greater median H and Y stage, lower scores of FAB and MoCA, and higher frequencies of motor fluctuation, dyskinesia, falls, and festination compared to patients without FOG (P < 0.05). The binary logistic regression model indicated that high UPDRS III score (OR = 1.049, P < 0.001), fluctuation (OR = 2.677, P = 0.035), dyskinesia (OR = 6.294, P = 0.003), festination (OR = 3.948, P < 0.001), falls (OR = 7.528, P < 0.001), and low serum UA levels (OR = 0.990, P < 0.001) were associated with FOG. Our study suggests that low serum UA concentration is associated with the occurrence of FOG in PD.

  14. Dose-response effects of oral guanidinoacetic acid on serum creatine, homocysteine and B vitamins levels.

    PubMed

    Ostojic, Sergej M; Stojanovic, Marko; Drid, Patrik; Hoffman, Jay R

    2014-12-01

    Guanidinoacetic acid (GAA) is an intermediate in the biosynthesis of creatine (Cr), yet its use in human nutrition is limited due to a lack of a clear understanding of its' dose-response effect. Thus, the purpose of this study was to investigate the effect of three different dosages of GAA (1.2, 2.4 and 4.8 g/day) administered for 6 weeks on serum and urinary variables related to GAA metabolism. Forty-eight healthy volunteers participated in the randomized, placebo-controlled, double-blind, repeated-measure study. At baseline, after 1, 2, 4 and 6 weeks, participants provided both fasting blood samples and 24-h urine. GAA intervention significantly increased serum and urinary GAA, Cr and creatinine as compared to placebo (P < 0.05). Differences were found for serum GAA and Cr responses between the three GAA dosages, with high-dose GAA resulting in a greater increase (P < 0.05) in the plasma concentration of both variables as compared to other GAA dosages. In GAA groups, fasting plasma total homocysteine (T-Hcy) increased by 3.5 μmol/L on average at post-administration, yet no dose-response differences were found between trials. Serum B vitamins were not affected by either placebo or GAA intervention (P > 0.05). Results indicate that low-to-high dosages of exogenous GAA can increase serum concentrations of Cr and T-Hcy while not depleting the B vitamins pool available for remethylation of homocysteine. ClinicalTrials.gov, identification number NCT01133899.

  15. GC-FID determination and pharmacokinetic studies of oleanolic acid in human serum.

    PubMed

    Rada, Mirela; Castellano, José María; Perona, Javier S; Guinda, Ángeles

    2015-11-01

    Analytical interest of OA determination in human serum has increased owing to the increasing interest in pharmaceutical research by pharmaceutical properties. A simple, specific, precise and accurate GC method with flame ionization detector (FID) developed and validated for the determination of oleanolic acid (OA) in human serum (HS). To an aliquot of HS, internal standard was added and a combination of liquid-liquid extraction with a mixture of diethyl ether-isopropyl alcohol, filtration and consecutive GC resulted in separation and quantification of OA. The organic phase was analyzed using a GC system equipped with a 30 × 0.25 mm i.d. Rtx-65TG capillary column and FID detection. Total chromatographic time was 10 min and no interfering peaks from endogenous components in blank serum were observed. The OA/internal standard peak area ratio was linearly fitted to the OA concentration (r = 0.992) over the range 10-1500 ng/mL. The mean serum extraction recovery of OA was 96.7 ± 1.0% and the lower limit of quantification based on 5 mL of serum was 10.7 ng/mL. The intra-day coefficient of variation ranged from 1.3 to 3.6% and inter-day varied from 1.4 to 4.5%. The developed method was used to study the pharmacokinetics of OA after oral administration in humans. The assay was simple, sensitive, precise and accurate for the use in the study of the mechanisms of absorption and distribution of OA in humans. Copyright © 2015 John Wiley & Sons, Ltd.

  16. Lower Serum Bilirubin and Uric Acid Concentrations in Patients with Parkinson's Disease in China.

    PubMed

    Qin, Xiao-Ling; Zhang, Qing-Shan; Sun, Li; Hao, Meng-Wei; Hu, Zhao-Ting

    2015-05-01

    The objective of the study is to investigate the correlation between bilirubin and uric acid (UA) concentrations and symptoms of Parkinson's disease (PD) in Chinese population. A total of 425 PD patients and 460 controls were included in the current study. Patients were diagnosed by a neurologist and assessed using the Hoehn & Yahr (H&Y) scale. Venous blood samples were collected, and bilirubin and UA concentrations were analyzed. Compared to controls, indirect bilirubin (IBIL) and UA concentrations were lower in PD patients (P IBIL = 0.015, P UA = 0.000). Serum IBIL in different age subgroups and H&Y stage subgroups were also lower compared to the control group (P IBIL = 0.000, P UA = 0.000) but were not significantly different among these subgroups. Females in the control group had significantly lower serum IBIL and UA concentrations than males (P IBIL = 0.000, P UA = 0.000) and the PD group (P IBIL = 0.027, P UA = 0.000). In early PD (patients with <2-year medical history and no treatment), serum IBIL and UA concentrations were also lower than the controls (P IBIL = 0.013, P UA = 0.000). Although IBIL concentration was positively correlated with UA concentration in controls (R IBIL = 0.229, P IBIL = 0.004), this positive association was not observed in the PD group (R IBIL = -0.032, P IBIL = 0.724). Decreased levels of serum IBIL and UA were observed in PD patients. It is possible that individuals with decreased serum bilirubin and UA concentrations lack the endogenous defense system to prevent peroxynitrite and other free radicals from damaging and destroying dopaminergic cells in the substantia nigra. Our results provide a basis for further investigation into the role of bilirubin in PD.

  17. Lowered omega3 polyunsaturated fatty acids in serum phospholipids and cholesteryl esters of depressed patients.

    PubMed

    Maes, M; Christophe, A; Delanghe, J; Altamura, C; Neels, H; Meltzer, H Y

    1999-03-22

    Depression is associated with a lowered degree of esterification of serum cholesterol, an increased C20:4omega6/C20:5omega3 ratio and decreases in omega3 fractions in fatty acids (FAs) or in the red blood cell membrane. The aims of the present study were to examine: (i) serum phospholipid and cholesteryl ester compositions of individual saturated fatty acids (SFAs), monounsaturated FAs (MUFAs) and polyunsaturated FAs (PUFAs) in major depressed patients vs. healthy volunteers; (ii) the relationships between the above FAs and lowered serum zinc (Zn), a marker of the inflammatory response in depression; and (iii) the effects of subchronic treatment with antidepressants on FAs in depression. The composition of the FAs was determined by means of thin layer chromatography in conjunction with gas chromatography. Lipid concentrations were assayed by enzymatic colorimetric methods. The oxidative potential index (OPI) of FAs was computed in 34 major depressed inpatients and 14 normal volunteers. Major depression was associated with: increased MUFA and C22:5omega3 proportions and increased C20:4omega6/C20:5omega3 and C22:5omega6/C22:6omega3 ratios; lower C22:4omega6, C20:5omega3 and C22:5omega3 fractions in phospholipids; lower C18:3omega3, C20:5omega3 and total (sigma)omega3 FAs, and higher C20:4omega6/C20:5omega3 and sigmaomega6/sigmaomega3 ratios in cholesteryl esters; lower serum concentrations of phospholipids and cholesteryl esters; and a decreased OPI. In depression, there were significant and positive correlations between serum Zn and C20:5omega3 and C22:6omega3 fractions in phospholipids; and significant inverse correlations between serum Zn and the sigmaomega6/sigmaomega3, C20:4omega6/C20:5omega3, and C22:5omega6/C22:6omega3 ratios in phospholipids. There was no significant effect of antidepressive treatment on any of the FAs. The results show that, in major depression, there is a deficiency of omega3 PUFAs and a compensatory increase in MUFAs and C22:5omega6 in

  18. Serum Uric Acid Levels and Cerebral Microbleeds in Patients with Acute Ischemic Stroke

    PubMed Central

    Ryu, Wi-Sun; Kim, Chi Kyung; Kim, Beom Joon; Lee, Seung-Hoon

    2013-01-01

    Unlike experimental studies indicating a neuroprotective property of uric acid, clinical studies have shown that elevated levels of uric acid are associated with a risk of ischemic stroke. However, the association of uric acid with cerebral hemorrhage has seldom been tested. We aimed to elucidate the association between uric acid and cerebral microbleeds (CMBs), a hemorrhage-prone cerebral microangiopathy. Seven hundred twenty-four patients with ischemic stroke who were consecutively admitted to our hospital were included in this study. We collected demographic, clinical, and laboratory data, including uric acid level, and examined the presence of CMBs using T2*-weighted gradient-echo MRI. We used logistic regression analysis to examine an independent association between uric acid and CMBs. Two-hundred twenty-six patients had CMBs (31.2%). After adjusting for possible confounders, elevated uric acid was independently associated with the presence of CMBs (the highest quartile vs. lowest quartile, adjusted odd ratio [OR], 1.98; 95% confidence interval [CI], 1.16–3.39). This association retained in patients with deep or infratentorial CMBs (with or without lobar CMBs) but not among those with lobar CMBs. In addition, this association was robust among patients with hypertension (the highest quartile vs. lowest quartile, adjusted OR, 2.74; 95% CI, 1.43–5.24). In contrast, we did not find the association in patients without hypertension. We demonstrated that serum uric acid is independently associated with the presence of CMBs. In particular, the relation between uric acid and CMBs was robust in hypertensive patients. PMID:23372838

  19. Study of Serum Uric Acid Levels in Myocardial Infarction and Its Association With Killip Class.

    PubMed

    Mehrpooya, Maryam; Larti, Farnoosh; Nozari, Younes; Sattarzadeh-Badkoobeh, Roya; Zand Parsa, Amir Farhang; Zebardast, Jayran; Tavoosi, Anahita; Shahbazi, Fatemeh

    2017-02-01

    The present study aimed to compare the serum level of uric acid in patients with and without heart failure and also to determine the association between uric acid level and clinical status by Killip class in patients with STEMI. This case-control study was conducted on 50 consecutives as control group and 50 patients with acute heart failure, (20 patients had acute STEMI), who documented by both clinical conditions and echocardiography assessment. The mean plasma level of uric acid in the case group was 7.6±1.6 milligrams/deciliter (mg/dL) and in the control group was 4.5±1.5 respectively (P<0.001). These values in patients with STEMI was about 9.2±0.86, but in patients with acute heart failure in absence of STEMI was 6.5±1.04 (P<0.001). Moreover, there was significant difference among the level of uric acid and Killip classes (P<0.001). Also there was significant difference for uric acid level between HFrEF (HF with reduced EF) and severe LV systolic dysfunction (0.049). In STEMI patients with culprit LAD, mean uric acid was significantly higher than cases with culprit LCX [(9.7±0.98 versus 8.6±0.52 respectively) P=0.012]. Regarding  treatment plan in patients with STEMI, mean level of uric acid in those considered for CABG was significantly higher than who were considered for PCI, 9.9±0.82 versus 8.9±0.76 respectively, P=0.029. In STEMI patients with higher killip class, higher level of uric acid was seen. Also, the severity of LV systolic dysfunction was associated with higher level of uric acid.

  20. Comparison of the binding affinity of chlorogenic acid with two serum albumins.

    PubMed

    Wang, Yanli; Zhang, Tong; Xu, Jia; Du, Weihong

    2011-01-01

    Chlorogenic acid (CA) is a well-known ester of caffeic acid present in some food. It is also an active component in traditional Chinese medicines which are used to treat various diseases, but the molecular basis of CA is not clear. In the present work, the proton selective relaxation rate and the affinity index were used to investigate the interaction of CA with human serum albumin and bovine serum albumin under the same buffer conditions. The results indicated that the binding affinity of chlorogenic acid to BSA was stronger than that to HSA. The binding site of the ligand-protein complex was elucidated by molecular docking, and the specific interaction was observed from those hydrogen bonds formed by the ligand and active residues. Using a combination of TR-NOE detection, the optimal ligand conformation was illustrated. Further conformational analysis of the complex revealed that the ability of hydrogen bond formation by polar side chain residues in the binding site of BSA might contribute to the greater binding affinity. The results provide a better understanding of CA binding and should contribute towards the design of modifications of CA for therapeutic purposes. Copyright © 2010 Elsevier B.V. All rights reserved.

  1. Improvement in skin wrinkles using a preparation containing human growth factors and hyaluronic acid serum.

    PubMed

    Lee, Do Hyun; Oh, In Young; Koo, Kyo Tan; Suk, Jang Mi; Jung, Sang Wook; Park, Jin Oh; Kim, Beom Joon; Choi, Yoo Mi

    2015-02-01

    Skin aging is accompanied by wrinkle formation. At some sites, such as the periorbital skin, this is a relatively early phenomenon. We evaluated the anti-wrinkle effect of a preparation containing human growth factor and hyaluronic acid serum on periorbital wrinkles (crow's feet). In total, 23 Korean women (age range: 39-59 years), who were not pregnant, nursing, or undergoing any concurrent therapy, were enrolled in this study. All the patients completed an 8-week trial of twice-daily application of human growth factor and hyaluronic acid serum on the entire face. Efficacy was based on a global photodamage score, photographs, and image analysis using replicas and visiometer analysis every 4 weeks. The standard wrinkle and roughness parameters used in assessing skin by visiometer were calculated and statistically analyzed. Periorbital wrinkles were significantly improved after treatment, with improvements noted both by physician's assessment and visiometer analysis. Topical application of human growth factor and hyaluronic acid was beneficial in reducing periorbital wrinkles.

  2. [The effect of ibuprofen and acetylsalicylic acid on cognitive impairment, total antioxidant power and isoprostane serum].

    PubMed

    Ibáñez-Hernández, Marcia Gabriela; Macías-Islas, Miguel Angel; Zavalza-Gómez, Ana Bertha; Pacheco-Moisés, Fermín Paul; Ortiz, Genaro Gabriel

    2008-01-01

    There are controversial studies on the prevention of Alzheimer's disease with nonsteroidal antiinflammatory drugs (NSAIDs). The objective of this study was to evaluate the effect of ibuprofen and acetylsalicylic acid on cognitive impairment, serum total antioxidant power (TAP) and isoprostane (8-iso-PGF2alpha). From April 2004 to February 2006, a Folstein mini-mental state (MMSE), Syndrome Kurtz Test (SKT) and a geriatric depression scale (Yasevage) were applied to eighteen, 55-56 years old eligible women. All women (n= 18) with normal cognitive state were randomized to ibuprofen 400 mg per day (n= 9) and acetylsalicylic acid 500 mg per day (n= 9) for one year. Serum TAP and 8-iso-PGF2alpha were performed at baseline, after six months and one year of treatment. After one year of treatment with acetylsalicylic acid five women (55.6%) raised their score 4 points in MMSE compared with 3 points increased (33.3%) showed by the ibuprofen group. TAP increased (p=0.01) and 8-iso-PGF2alpha reduced (p=0.01) in both groups compared with baseline. Both drugs improved the cognitive state andoxidative status of our population.

  3. Normal level of sepsis-associated phenylcarboxylic acids in human serum.

    PubMed

    Beloborodova, N V; Moroz, V V; Osipov, A A; Bedova, A Yu; Olenin, A Yu; Getsina, M L; Karpova, O V; Olenina, E G

    2015-03-01

    Previous studies showed that large amounts of phenylcarboxylic acids (PhCAs) are accumulated in a septic patient's blood due to increased endogenous and microbial phenylalanine and tyrosine biotransformation. Frequently, biochemical aromatic amino acid transformation into PhCAs is considered functionally insignificant for people without monogenetic hereditary diseases. The blood of healthy people contains the same PhCAs that are typical for septic patients as shown in this paper. The overall serum PhCAs level was 6 µM on average as measured by gas chromatography with flame ionization detection. This level is a stable biochemical parameter indicating the normal metabolism of aromatic amino acids. The concentrations of PhCAs in the metabolic profile of healthy people are distributed as follows: phenylacetic ≈ p-hydroxyphenyllactic > p-hydroxyphenylacetic > phenyllactic ≈ phenylpropionic > benzoic. We conclude that maintaining of stable PhCAs level in the serum is provided as the result of integration of human endogenous metabolic pathways and microbiota.

  4. Serum uric acid levels in patients with Parkinson’s disease: A meta-analysis

    PubMed Central

    Wen, Min; Zhou, Bo; Chen, Yun-Hua; Ma, Zhao-Lei; Gou, Yun; Zhang, Chun-Lin; Yu, Wen-Feng; Jiao, Ling

    2017-01-01

    Background Lower serum uric acid (UA) levels have been reported as a risk factor in Parkinson’s disease (PD). However, the results have been inconsistent so far. Objectives The aim of the present study was to clarify the potential relationship of uric acid with PD. Methods Comprehensive electronic search in pubmed, web of science, and the Cochrane Library database to find original articles about the association between PD and serum uric acid levels published before Dec 2015. Literature quality assessment was performed with the Newcastle-Ottawa Scale. Random-effects model was used to estimate the standardized mean differences (SMDs) with 95% confidence intervals (CIs). Heterogeneity across studies was assessed using I2 and H2 statistics. Sensitivity analyses to assess the influence of individual studies on the pooled estimate. Publication bias was investigated using funnel plots and Egger’s regression test. Analyses were performed by using Review Manager 5.3 and Stata 11.0. Results Thirteen studies with a total of 4646 participants (2379 PD patients and 2267 controls) were included in this meta-analysis. The current results showed that the serum UA levels in PD patients were significantly lower compared to sex and age-matched healthy controls (SMD: -0.49, 95% CI: [-0.67, -0.30], Z = 5.20, P < 0.001) and these results showed no geographic regional (Asia: SMD = −0.65, 95% CI [−0.84, −0.46], Z = 6.75, p <0.001; Non-Asia: SMD = −0.25, 95% CI [−0.43, −0.07], Z = 2.70, p = 0.007) and sex differences (women: SMD = −0.53, 95% CI [−0.70, −0.35], z = 5.98, p <0.001; men: SMD = −0.66, 95% CI [−0.87, −0.44], z = 6.03, p <0.001). Serum UA levels in middle-late stage PD patients with higher H&Y scales were significantly lower than early stage PD patients with lower H&Y scales (SMD = 0.63, 95% CI [0.36,0.89], z = 4.64, p <0.001). Conclusions Our study showed that the serum UA levels are significantly lower in PD and the level is further decreased as the

  5. Effect of dietary fatty acids on serum parameters, fatty acid compositions, and liver histology in Shaoxing laying ducks*

    PubMed Central

    Liu, Wei-meng; Lai, Shu-jing; Lu, Li-zhi; Shi, Fang-xiong; Zhang, Jing; Liu, Yu; Yu, Bo; Tao, Zheng-rong; Shen, Jun-da; Li, Guo-qin; Wang, De-qian; Li, Jin-jun; Tian, Yong

    2011-01-01

    The effects of different fatty acid (FA) contents in diet on serum parameters, FA compositions of eggs and meat, and liver morphological changes were studied in Shaoxing laying ducks. A total of 264 ducks at 17 weeks were fed a control diet or a diet containing 30 g/kg fish oil (FO), 25 g/kg sunflower oil (SO), or 30 g/kg palm oil with 20 g/kg beef tallow (PBO). Malondialdehyde (MDA) content in the liver and the serum of ducks fed the PBO diet was significantly (P<0.05) higher than that of ducks fed the other diets. Triglyceride (TG) and total cholesterol (TC) levels were significantly lower (P<0.05) in ducks fed the FO diet. Serum TC also was lower in ducks fed the SO diet. Superoxide dismutase (SOD) activity was also affected by diets. The contents of polyunsaturated FAs (PUFAs) in eggs and meat were significantly higher (P<0.001) in ducks fed the FO and SO diets than in ducks fed the control diet. The level of C22:6 (n-3) FA in ducks fed the FO diet was significantly higher than that in ducks fed the other diets. However, the conversion efficiency of the longer-chain C20:5 (n-3) FA was higher than that of C22:6 (n-3). Ducks fed the PBO diet exhibited lipid droplet accumulation in the liver. These results demonstrate that a diet enriched with different FAs has strong effects on serum lipid levels and the deposition of PUFAs into tissue lipids. PMID:21887849

  6. Folic acid therapy reduces serum uric acid in hypertensive patients: a substudy of the China Stroke Primary Prevention Trial (CSPPT).

    PubMed

    Qin, Xianhui; Li, Youbao; He, Mingli; Tang, Genfu; Yin, Delu; Liang, Min; Wang, Binyan; Nie, Jing; Huo, Yong; Xu, Xin; Hou, Fan Fan

    2017-04-01

    Background: The effect of folic acid supplementation on uric acid (UA) concentrations is still inconclusive.Objective: We aimed to test the efficacy of folic acid therapy in reducing serum UA in hypertensive patients.Design: A total of 15,364 hypertensive patients were randomly assigned to a double-blind daily treatment with a single tablet that contained 10 mg enalapril and 0.8 mg folic acid (n = 7685) or 10 mg enalapril alone (n = 7679). The main outcome was the change in serum UA, which was defined as UA at the exit visit minus that at baseline. Secondary outcomes were as follows: 1) controlled hyperuricemia (UA concentration <357 μmol/L after treatment) and 2) new-onset hyperuricemia in participants with normal UA concentrations (<357 μmol/L).Results: After a median of 4.4 y of treatment, the mean ± SD UA concentration increased by 34.7 ± 72.5 μmol/L in the enalapril-alone group and by 30.7 ± 71.8 μmol/L in the enalapril-folic acid group, which resulted in a mean group difference of -4.0 μmol/L (95% CI: -6.5, -1.6 μmol/L; P = 0.001). Furthermore, compared with enalapril alone, enalapril-folic acid treatment showed an increase in controlled hyperuricemia (30.3% compared with 25.6%; OR: 1.31; 95% CI: 1.01, 1.70) and a decrease in new-onset hyperuricemia (15.0% compared with 16.3%; OR: 0.89; 95% CI: 0.79, 0.99). A greater beneficial effect was observed in subjects with hyperuricemia (P-interaction = 0.07) or higher concentrations of total homocysteine (tHcy) (P-interaction = 0.02) at baseline. Furthermore, there was a significant inverse relation (P < 0.001) between the reduction of tHcy and the change in UA concentrations.Conclusions: Enalapril-folic acid therapy, compared with enalapril alone, can significantly reduce the magnitude of the increase of UA concentrations in hypertensive adults. This trial was registered at clinicaltrials.gov as NCT00794885. © 2017 American Society for Nutrition.

  7. Inverse association between serum phospholipid oleic acid and insulin resistance in subjects with primary dyslipidaemia.

    PubMed

    Sala-Vila, A; Cofán, M; Mateo-Gallego, R; Cenarro, A; Civeira, F; Ortega, E; Ros, E

    2011-10-01

    Data on intake of oleic acid (OA) and insulin resistance (IR) are inconsistent. We investigated whether OA in serum phosphatidylcholine relates to surrogate measures of IR in dyslipidaemic subjects from a Mediterranean population. Cross-sectional study of 361 non-diabetic subjects (205 men, 156 women; mean age 44 and 46 y, respectively; BMI 25.7 kg/m(2)). IR was diagnosed by BMI and HOMA values using published criteria validated against the euglycemic clamp. Alternatively, IR was defined by the 75th percentile of HOMA-IR of our study population. The fatty acid composition of serum phosphatidylcholine was determined by gas-chromatography. The mean (±SD) proportion of OA was 11.7 ± 2.0%. Ninety-two subjects (25.5%) had IR. By adjusted logistic regression, including the proportions of other fatty acids known to relate to IR, the odds ratios (OR) (95% confidence intervals) for IR were 0.75 (0.62-0.92) for 1% increase in OA and 0.84 (0.71-0.99) for 1% increase in linoleic acid. Other fatty acids were unrelated to IR. When using the alternate definition of IR, OA remained a significant predictor (0.80 [0.65-0.99]). Higher phospholipid proportions of OA relate to less IR, suggesting an added benefit of increasing olive oil intake within the Mediterranean diet. Copyright © 2011 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  8. Increased hepatocellular carcinoma risk in chronic hepatitis B patients with persistently elevated serum total bile acid: a retrospective cohort study

    PubMed Central

    Wang, Haoliang; Shang, Xiaoyun; Wan, Xing; Xiang, Xiaomei; Mao, Qing; Deng, Guohong; Wu, Yuzhang

    2016-01-01

    To investigate the association between long-term changes of serum total bile acid and hepatocellular carcinoma in chronic hepatitis B patients, we did a retrospective cohort study of 2262 chronic hepatitis B patients with regular antiviral treatment using data from the Hepatitis Biobank at Southwest Hospital Program from 2004 to 2014. Patients in the study were classified into 3 groups according to persistence of elevated serum total bile acid during follow-up: none-low, medium, and high persistence of elevated serum total bile acid. The association between persistence of elevated serum total bile acid and hepatocellular carcinoma was estimated using Cox proportional hazard models and Kaplan-Meier analysis including information about patients’ demographic and clinical characteristics. There were 62 hepatocellular carcinoma cases during a total follow-up of 14756.5 person-years in the retrospective study. Compared to patients with none-low persistence of elevated total bile acid, the multivariate adjusted hazard ratios (95% confidence interval) were 2.37 (1.16–4.84), and 2.57 (1.28–5.16) for patients with medium, and high persistence of elevated total bile acid. Our findings identified persistence of elevated serum total bile acid as an independent risk factor of hepatocellular carcinoma in chronic hepatitis B patients. PMID:27905528

  9. CYP2E1-dependent elevation of serum cholesterol, triglycerides, and hepatic bile acids by isoniazid.

    PubMed

    Cheng, Jie; Krausz, Kristopher W; Li, Feng; Ma, Xiaochao; Gonzalez, Frank J

    2013-01-15

    Isoniazid is the first-line medication in the prevention and treatment of tuberculosis. Isoniazid is known to have a biphasic effect on the inhibition-induction of CYP2E1 and is also considered to be involved in isoniazid-induced hepatotoxicity. However, the full extent and mechanism of involvement of CYP2E1 in isoniazid-induced hepatotoxicity remain to be thoroughly investigated. In the current study, isoniazid was administered to wild-type and Cyp2e1-null mice to investigate the potential toxicity of isoniazid in vivo. The results revealed that isoniazid caused no hepatotoxicity in wild-type and Cyp2e1-null mice, but produced elevated serum cholesterol and triglycerides, and hepatic bile acids in wild-type mice, as well as decreased abundance of free fatty acids in wild-type mice and not in Cyp2e1-null mice. Metabolomic analysis demonstrated that production of isoniazid metabolites was elevated in wild-type mice along with a higher abundance of bile acids, bile acid metabolites, carnitine and carnitine derivatives; these were not observed in Cyp2e1-null mice. In addition, the enzymes responsible for bile acid synthesis were decreased and proteins involved in bile acid transport were significantly increased in wild-type mice. Lastly, treatment of targeted isoniazid metabolites to wild-type mice led to similar changes in cholesterol, triglycerides and free fatty acids. These findings suggest that while CYP2E1 is not involved in isoniazid-induced hepatotoxicity, while an isoniazid metabolite might play a role in isoniazid-induced cholestasis through enhancement of bile acid accumulation and mitochondria β-oxidation. Published by Elsevier Inc.

  10. Amino Acid Profiles of Serum and Urine in Search for Prostate Cancer Biomarkers: a Pilot Study.

    PubMed

    Dereziński, Paweł; Klupczynska, Agnieszka; Sawicki, Wojciech; Pałka, Jerzy A; Kokot, Zenon J

    2017-01-01

    There is a great interest in searching for diagnostic biomarkers in prostate cancer patients. The aim of the pilot study was to evaluate free amino acid profiles in their serum and urine. The presented paper shows the first comprehensive analysis of a wide panel of amino acids in two different physiological fluids obtained from the same groups of prostate cancer patients (n = 49) and healthy men (n = 40). The potential of free amino acids, both proteinogenic and non-proteinogenic, as prostate cancer biomarkers and their utility in classification of study participants have been assessed. Several metabolites, which deserve special attention in the further metabolomic investigations on searching for prostate cancer markers, were indicated. Moreover, free amino acid profiles enabled to classify samples to one of the studied groups with high sensitivity and specificity. The presented research provides a strong evidence that ethanolamine, arginine and branched-chain amino acids metabolic pathways can be a valuable source of markers for prostate cancer. The altered concentrations of the above-mentioned metabolites suggest their role in pathogenesis of prostate cancer and they should be further evaluated as clinically useful markers of prostate cancer.

  11. Fluorescence study on site-specific binding of perfluoroalkyl acids to human serum albumin.

    PubMed

    Chen, Yan-Min; Guo, Liang-Hong

    2009-03-01

    Binding of five perfluoroalkyl acids with human serum albumin (HSA) was investigated by site-specific fluorescence. Intrinsic fluorescence of tryptophan-214 in HSA was monitored upon addition of the chemicals. Although perfluorobutyl acid (PFBA) and perfluorobutane sulfonate (PFBS) did not cause fluorescence change, perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), and perfluorododecanoic acid (PFDoA) induced fluorescence quenching, from which binding constant of 2.7 x 10(5) M(-1) for PFOA and 2.2 x 10(4) M(-1) for PFOS was calculated. Two fluorescent probes, dansylamide (DA) and dansyl-L: -proline (DP), were employed in fluorescence displacement measurements to study the interaction at two Sudlow's binding sites. At Site I, both PFBA and PFBS displaced DA with binding constants of 1.0 x 10(6) M(-1) and 2.2 x 10(6) M(-1). At Site II, PFBS and PFDoA displaced DP with binding constants of 6.5 x 10(6) M(-1) and 1.2 x 10(6) M(-1), whereas PFBA did not bind. The data were compared with fatty acids to evaluate the potential toxicological effect of these environmental chemicals.

  12. Amino Acid Profiles of Serum and Urine in Search for Prostate Cancer Biomarkers: a Pilot Study

    PubMed Central

    Dereziński, Paweł; Klupczynska, Agnieszka; Sawicki, Wojciech; Pałka, Jerzy A.; Kokot, Zenon J.

    2017-01-01

    There is a great interest in searching for diagnostic biomarkers in prostate cancer patients. The aim of the pilot study was to evaluate free amino acid profiles in their serum and urine. The presented paper shows the first comprehensive analysis of a wide panel of amino acids in two different physiological fluids obtained from the same groups of prostate cancer patients (n = 49) and healthy men (n = 40). The potential of free amino acids, both proteinogenic and non-proteinogenic, as prostate cancer biomarkers and their utility in classification of study participants have been assessed. Several metabolites, which deserve special attention in the further metabolomic investigations on searching for prostate cancer markers, were indicated. Moreover, free amino acid profiles enabled to classify samples to one of the studied groups with high sensitivity and specificity. The presented research provides a strong evidence that ethanolamine, arginine and branched-chain amino acids metabolic pathways can be a valuable source of markers for prostate cancer. The altered concentrations of the above-mentioned metabolites suggest their role in pathogenesis of prostate cancer and they should be further evaluated as clinically useful markers of prostate cancer. PMID:28138303

  13. A Prospective Study on Serum Methylmalonic Acid and Homocysteine in Pregnant Women.

    PubMed

    Choi, Rihwa; Choi, Sunkyu; Lim, Yaeji; Cho, Yoon Young; Kim, Hye Jeong; Kim, Sun Wook; Chung, Jae Hoon; Oh, Soo-Young; Lee, Soo-Youn

    2016-12-08

    This study aimed to investigate serum methylmalonic acid (MMA) and homocysteine levels and to assess their effects on pregnancy and neonatal outcomes. Serum MMA and homocysteine levels in 278 pregnant Korean women, determined by liquid chromatography-tandem mass spectrometry in each trimester, were compared with those of previous studies in other ethnic groups. We investigated the association between MMA and homocysteine status with pregnancy and neonatal events: gestational diabetes, preeclampsia, gestational age at delivery, preterm birth, small for gestational age, neonatal birth weight, and congenital abnormalities. The median (range) MMA level was 0.142 (0.063-0.446) µmol/L and homocysteine level was 10.6 (4.4-38.0) µmol/L in pregnant women. MMA levels were significantly higher in the third trimester than during other trimesters (p < 0.05), while homocysteine levels were not. No significant association was observed between MMA or homocysteine levels and any of the maternal or neonatal outcomes examined. Future studies are needed to assess the associations among maternal serum concentrations of MMA and homocysteine, and maternal and neonatal outcomes.

  14. Urinary D-glucaric acid and serum hepatic enzyme levels in chronic alcoholics.

    PubMed

    Tutor, J C; Alvarez-Prechous, A; Bernabeu, F; Pardiñas, M C; Paz, J M; Lareu, V

    1988-06-01

    Urinary D-glucaric acid (DGA) and the activities of gamma-glutamyl transferase (GGT) and other hepatic enzymes in serum were determined in 33 noncirrhotic male alcoholics who had continued to consume alcohol until at least 24 h prior to the taking of samples. DGA excretion was significantly greater in them than in a group of 30 healthy controls (p less than 0.001), exceeding the upper reference level in 38% of the alcoholic cases (as compared with 88% for GGT). In the alcoholic patients, there was highly significant correlation between urinary DGA and serum GGT (r = 0.613, p less than 0.001), suggesting that in both cases the increased levels are due to enzyme induction. None of the biochemical variables studied were significantly correlated with estimated daily alcohol consumption. Urinary DGA levels fell off rapidly with abstinence, and in 31 alcoholic patients who had consumed no alcohol for 5 days, there was no statistically significant correlation between DGA excretion and serum GGT (r = 0.158, p congruent to 0.4).

  15. Fructose Intake, Serum Uric Acid, and Cardiometabolic Disorders: A Critical Review

    PubMed Central

    Caliceti, Cristiana; Calabria, Donato; Roda, Aldo; Cicero, Arrigo F. G.

    2017-01-01

    There is a direct relationship between fructose intake and serum levels of uric acid (UA), which is the final product of purine metabolism. Recent preclinical and clinical evidence suggests that chronic hyperuricemia is an independent risk factor for hypertension, metabolic syndrome, and cardiovascular disease. It is probably also an independent risk factor for chronic kidney disease, Type 2 diabetes, and cognitive decline. These relationships have been observed for high serum UA levels (>5.5 mg/dL in women and >6 mg/dL in men), but also for normal to high serum UA levels (5–6 mg/dL). In this regard, blood UA levels are much higher in industrialized countries than in the rest of the world. Xanthine-oxidase inhibitors can reduce UA and seem to minimize its negative effects on vascular health. Other dietary and pathophysiological factors are also related to UA production. However, the role of fructose-derived UA in the pathogenesis of cardiometabolic disorders has not yet been fully clarified. Here, we critically review recent research on the biochemistry of UA production, the relationship between fructose intake and UA production, and how this relationship is linked to cardiometabolic disorders. PMID:28420204

  16. A Prospective Study on Serum Methylmalonic Acid and Homocysteine in Pregnant Women

    PubMed Central

    Choi, Rihwa; Choi, Sunkyu; Lim, Yaeji; Cho, Yoon Young; Kim, Hye Jeong; Kim, Sun Wook; Chung, Jae Hoon; Oh, Soo-young; Lee, Soo-Youn

    2016-01-01

    This study aimed to investigate serum methylmalonic acid (MMA) and homocysteine levels and to assess their effects on pregnancy and neonatal outcomes. Serum MMA and homocysteine levels in 278 pregnant Korean women, determined by liquid chromatography–tandem mass spectrometry in each trimester, were compared with those of previous studies in other ethnic groups. We investigated the association between MMA and homocysteine status with pregnancy and neonatal events: gestational diabetes, preeclampsia, gestational age at delivery, preterm birth, small for gestational age, neonatal birth weight, and congenital abnormalities. The median (range) MMA level was 0.142 (0.063–0.446) µmol/L and homocysteine level was 10.6 (4.4–38.0) µmol/L in pregnant women. MMA levels were significantly higher in the third trimester than during other trimesters (p < 0.05), while homocysteine levels were not. No significant association was observed between MMA or homocysteine levels and any of the maternal or neonatal outcomes examined. Future studies are needed to assess the associations among maternal serum concentrations of MMA and homocysteine, and maternal and neonatal outcomes. PMID:27941633

  17. Elevated Serum Uric Acid Levels Are Related to Cognitive Deterioration in an Elderly Japanese Population

    PubMed Central

    Suzuki, Kazushi; Koide, Daisuke; Fujii, Kurumi; Yamazaki, Tsutomu; Tsuji, Shoji; Iwata, Atsushi

    2016-01-01

    Aims The association between serum uric acid (UA) levels and cognitive function is controversial since UA can be a risk factor for cerebral ischemia as well as acting as a neuroprotective antioxidant. Methods We conducted a cross-sectional analysis of 228 elderly participants and examined neuropsychological test results, clinical data as well as brain magnetic resonance imaging data. Patients Overall, 64 participants were diagnosed with cognitive deterioration. To control for the effect of sex differences, 2 independent sets of single-variable and multivariate logistic regression analyses were performed with quartiles divided into non-sex-specific and sex-specific cutoff values for UA. Results In non-sex-specific quartiles, the participants in the highest quartiles of UA levels were found to be at a significantly higher risk of cognitive deterioration than those in the lowest quartiles. In sex-specific quartiles, the highest quartile showed an increased risk of cognitive deterioration, and a greater than fourfold increase in the risk in the highest quartiles was confirmed using multivariate regression models. However, no significant association was observed between serum UA levels and the presence of white matter lesions. Conclusions Elevated serum UA levels were independently associated with cognitive deterioration. UA might have unknown adverse effects on cognitive function, other than causing vascular pathology. PMID:28203247

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

    PubMed Central

    Lombardi, Rosa; Pisano, Giuseppina; Fargion, Silvia

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD), tightly linked to the metabolic syndrome (MS), has emerged as a leading cause of chronic liver disease worldwide. Since it is potentially progressive towards non-alcoholic steatohepatitis (NASH) and hepatic fibrosis, up to cirrhosis and its associated complications, the need for predictive factors of NAFLD and of its advanced forms is mandatory. Despite the current “gold standard” for the assessment of liver damage in NAFLD being liver biopsy, in recent years, several non-invasive tools have been designed as alternatives to histology, of which fibroscan seems the most promising. Among the different serum markers considered, serum uric acid (SUA) and ferritin have emerged as possible predictors of severity of liver damage in NAFLD. In fact, as widely described in this review, they share common pathogenetic pathways and are both associated with hepatic steatosis and MS, thus suggesting a likely synergistic action. Nevertheless, the power of these serum markers seems to be too low if considered alone, suggesting that they should be included in a wider perspective together with other metabolic and biochemical parameters in order to predict liver damage. PMID:27077854

  19. Total and lipid-bound serum sialic acid as markers for carcinoma of the uterine cervix.

    PubMed

    Vivas, I; Spagnuolo, L; Palacios, P

    1992-08-01

    Concentrations of total sialic acid (TSA) and lipid-bound sialic acid (LSA) were determined in serum samples from 88 patients with squamous cell carcinoma of the cervix, 26 normal subjects, and 44 patients with benign uterine or ovarian disease. TSA concentrations in patients with cervical cancer were found to correlate with advanced-stage disease. LSA concentrations were only increased in stage IV of the disease. Sensitivity of the test for stage IB was zero for TSA and 27% for LSA. The specificity of both markers was about 80% due to a low incidence of false-positive values in the pathologic control group. Measurements of TSA or LSA appear to be of no value for the early detection of cervical cancer or to complement the clinical staging of this tumor.

  20. Schistosomiasis mansoni: ultrasound-evaluated hepatic fibrosis and serum concentrations of hyaluronic acid.

    PubMed

    Silva, C C; Domingues, A L; Lopes, E P; Morais, C N; Santos, R B; Luna, C F; Nader, H B; Martins, J R

    2011-04-01

    Schistosomiasis mansoni is a fibrogenic liver disease that constitutes a major health problem in north-eastern Brazil. Although one common manifestation of the disease, periportal fibrosis (PPF), can be assessed by ultrasonography by well-trained physicians, the necessary equipment and personnel are not always readily available. Serum markers, including hyaluronic acid (HA), have been used as alternative means of measuring fibrosis. Recently serum concentrations of HA have been evaluated in 77 Brazilians (61 cases of schistosomiasis mansoni and 16 healthy controls) and compared against the ultrasound-evaluated PPF in the same subjects. The HA was measured using a non-competitive fluorescence-based assay, while the PPF was explored using a portable ultrasound scanner (SSD-500; Aloka, Tokyo) and graded, as patterns A-F, according to the World Health Organization's 'Niamey protocol'. In general, the serum concentrations of HA were found to be positively correlated with the severity of the PPF. The mean concentration of HA in the sera of the 16 controls was significantly lower than that recorded in the schistosomiasis cases who showed PPF of patterns D or E (P<0·001 for each). The cases who showed pattern-C PPF also had significantly less HA in their sera than the cases with PPF of patterns D or E (P<0·001 for each), and the cases with pattern-D fibrosis had significantly lower HA concentrations in their sera than the cases with PPF of pattern E (P<0·001). In an analysis based on a receiver-operating-characteristic (ROC) curve, an HA concentration of 20·2 μg/litre of serum was identified as a threshold that could be used to distinguish moderate cases of PPF (i.e. patterns C or D) from the more advanced cases (i.e. patterns E or F), with a sensitivity of 60% and specificity of 65%. In conclusion, it appears that serum concentrations of hyaluronic acid could be used as markers for periportal fibrosis in patients with schistosomiasis mansoni.

  1. Association of Serum Uric Acid Concentration with Diabetic Retinopathy and Albuminuria in Taiwanese Patients with Type 2 Diabetes Mellitus.

    PubMed

    Liang, Ching-Chao; Lin, Pi-Chen; Lee, Mei-Yueh; Chen, Szu-Chia; Shin, Shyi-Jang; Hsiao, Pi-Jung; Lin, Kun-Der; Hsu, Wei-Hao

    2016-08-02

    Patients with type 2 diabetes mellitus (DM) may experience chronic microvascular complications such as diabetic retinopathy (DR) and diabetic nephropathy (DN) during their lifetime. In clinical studies, serum uric acid concentration has been found to be associated with DR and DN. The goal of this study was to evaluate the relationship between the increases in serum uric acid level and the severity of DR and albuminuria in Taiwanese patients with type 2 DM. We recorded serum uric acid concentration, the severity of DR, and the severity of albuminuria by calculating urinary albumin-to-creatinine ratio (UACR) in 385 patients with type 2 DM. In multivariate logistic regression analysis, a high uric acid concentration was a risk factor for albuminuria (odds ratio (OR), 1.227; 95% confidence interval (CI) = 1.015-1.482; p = 0.034) and DR (OR, 1.264; 95% CI = 1.084-1.473; p = 0.003). We also demonstrated that there was a higher concentration of serum uric acid in the patients with more severe albuminuria and DR. In conclusion, an increased serum uric acid level was significantly correlated with the severity of albuminuria and DR in Taiwanese patients with type 2 DM.

  2. Interaction of chlorogenic acids and quinides from coffee with human serum albumin.

    PubMed

    Sinisi, Valentina; Forzato, Cristina; Cefarin, Nicola; Navarini, Luciano; Berti, Federico

    2015-02-01

    Chlorogenic acids and their derivatives are abundant in coffee and their composition changes between coffee species. Human serum albumin (HSA) interacts with this family of compounds with high affinity. We have studied by fluorescence spectroscopy the specific binding of HSA with eight compounds that belong to the coffee polyphenols family, four acids (caffeic acid, ferulic acid, 5-O-caffeoyl quinic acid, and 3,4-dimethoxycinnamic acid) and four lactones (3,4-O-dicaffeoyl-1,5-γ-quinide, 3-O-[3,4-(dimethoxy)cinnamoyl]-1,5-γ-quinide, 3,4-O-bis[3,4-(dimethoxy)cinnamoyl]-1,5-γ-quinide, and 1,3,4-O-tris[3,4-(dimethoxy)cinnamoyl]-1,5-γ-quinide), finding dissociation constants of the albumin-chlorogenic acids and albumin-quinides complexes in the micromolar range, between 2 and 30μM. Such values are comparable with those of the most powerful binders of albumin, and more favourable than the values obtained for the majority of drugs. Interestingly in the case of 3,4-O-dicaffeoyl-1,5-γ-quinide, we have observed the entrance of two ligand molecules in the same binding site, leading up to a first dissociation constant even in the hundred nanomolar range, which is to our knowledge the highest affinity ever observed for HSA and its ligands. The displacement of warfarin, a reference drug binding to HSA, by the quinide has also been demonstrated. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Serum Phospholipid Fatty Acids and Prostate Cancer Risk: Results From the Prostate Cancer Prevention Trial

    PubMed Central

    Brasky, Theodore M.; Till, Cathee; White, Emily; Neuhouser, Marian L.; Song, Xiaoling; Goodman, Phyllis; Thompson, Ian M.; King, Irena B.; Albanes, Demetrius; Kristal, Alan R.

    2011-01-01

    Inflammation may be involved in prostate cancer development and progression. This study examined the associations between inflammation-related phospholipid fatty acids and the 7-year-period prevalence of prostate cancer in a nested case-control analysis of participants, aged 55–84 years, in the Prostate Cancer Prevention Trial during 1994–2003. Cases (n = 1,658) were frequency matched to controls (n = 1,803) on age, treatment, and prostate cancer family history. Phospholipid fatty acids were extracted from serum, and concentrations of ω-3, ω-6, and trans-fatty acids (TFAs) were expressed as proportions of the total. Logistic regression models estimated odds ratios and 95% confidence intervals of associations of fatty acids with prostate cancer by grade. No fatty acids were associated with low-grade prostate cancer risk. Docosahexaenoic acid was positively associated with high-grade disease (quartile 4 vs. 1: odds ratio (OR) = 2.50, 95% confidence interval (CI): 1.34, 4.65); TFA 18:1 and TFA 18:2 were linearly and inversely associated with risk of high-grade prostate cancer (quartile 4 vs. 1: TFA 18:1, OR = 0.55, 95% CI: 0.30, 0.98; TFA 18:2, OR = 0.48, 95% CI: 0.27, 0.84). The study findings are contrary to those expected from the pro- and antiinflammatory effects of these fatty acids and suggest a greater complexity of effects of these nutrients with regard to prostate cancer risk. PMID:21518693

  4. Thermodynamic Study of the Interaction of Bovine Serum Albumin and Amino Acids with Cellulose Nanocrystals.

    PubMed

    Lombardo, Salvatore; Eyley, Samuel; Schütz, Christina; van Gorp, Hans; Rosenfeldt, Sabine; Van den Mooter, Guy; Thielemans, Wim

    2017-06-06

    The interaction of bovine serum albumin (BSA) with sulfated, carboxylated, and pyridinium-grafted cellulose nanocrystals (CNCs) was studied as a function of the degree of substitution by determining the adsorption isotherm and by directly measuring the thermodynamics of interaction. The adsorption of BSA onto positively charged pyridinium-grafted cellulose nanocrystals followed Langmuirian adsorption with the maximum amount of adsorbed protein increasing linearly with increasing degree of substitution. The binding mechanism between the positively charged pyridinum-grafted cellulose nanocrystals and BSA was found to be endothermic and based on charge neutralization. A positive entropy of adsorption associated with an increase of the degree of disorder upon addition of BSA compensated for the unfavorable endothermic enthalpy and enabled formation of pyridinium-g-CNC-BSA complexes. The endothermic enthalpy of adsorption was further found to decrease as a function of increasing degree of substitution. Negatively charged cellulose nanocrystals bearing sulfate and/or carboxylic functionalities were found to not interact significantly with the BSA protein. To investigate in more detail the role of single amino acids in the adsorption of proteins onto cellulose nanocrystals, we also studied the interaction of different types of amino acids with CNCs, i.e., charged (lysine, aspartic acid), aromatic (tryptophan, tyrosine), and polar (serine) amino acids. We found that none of the single amino acids bound with CNCs irrespective of surface charge and that therefore the binding of proteins with CNCs appears to require larger amino acid sequences that induce a greater entropic contribution to stabilize binding. Single amino acids are thus not adsorbed onto cellulose nanocrystals.

  5. Long-term effect of early postnatal overnutrition on insulin resistance and serum fatty acid profiles in male rats.

    PubMed

    Bei, Fei; Jia, Jia; Jia, Yi-Qun; Sun, Jian-Hua; Liang, Fei; Yu, Zhong-Yi; Cai, Wei

    2015-08-26

    Increasing evidence suggests that overnutrition during the early postnatal period, a critical window of development, increases the risk of adult-onset obesity and insulin resistance. In this study, we investigated the impact of overnutrition during the suckling period on body weight, serum biochemistry and serum fatty acid metabolomics in male rats. Rats raised in small litters (SL, 3 pups/dam) and normal litters (NL, 10 pups/dam) were used to model early postnatal overnutrition and control, respectively. Serum glucose, triglyceride, high-density lipoprotein-cholesterol, free fatty acid, insulin and leptin concentrations were assayed using standard biochemical techniques. Serum fatty acids were identified and quantified using a gas chromatography-mass spectrometry-based metabolomic approach. mRNA and protein levels of key components of the insulin receptor signaling pathway were measured in epididymal fat and gastrocnemius muscle by quantitative PCR and western blotting. SL rats were 37.3 % and 15.1 % heavier than NL rats at weaning and 16-weeks-old, respectively. They had increased visceral fat mass, adult-onset insulin resistance and glucose intolerance as well as elevated serum levels of free fatty acids and triglycerides. All detectable fatty acids were elevated in the serum of SL pups at weaning compared to NL controls, and significant increases in the levels of four fatty acids (palmitic acid, palmitoleic acid, oleic acid and arachidonic acid) persisted into adulthood. Moreover, a significantly positive correlation was identified between an insulin resistance index (HOMA-IR) and concentrations of myristic, palmitic, palmitoleic and oleic acid in serum at postnatal 16 weeks. Early postnatal overnutrition also resulted in a significant downregulation of insulin receptor substrate-1 (Irs-1), protein kinase B (Akt2) and glucose transporter 4 (Glut4) at the protein level in epididymal fat of SL rats at 16 weeks, accompanied by decreased mRNA levels for Irs-1 and

  6. Low serum levels of uric acid and albumin in patients with Guillain–Barre syndrome

    PubMed Central

    Su, Zhongqian; Chen, Zhibo; Xiang, Yian; Wang, Bingjie; Huang, Yuanyuan; Yang, Dehao; Li, Xiang; Weng, Yiyun; Lin, XianFeng; Chen, Guoqian; Liu, Wenyue; Zhao, Chenchen; Wang, Qingqing; Li, Shanshan; Chen, Ying; Chen, Ying; Quan, Weiwei; Tong, Qiuling; Wu, Shengjie; Huang, Shihao; Mei, Peina; Li, Zhengzheng; Li, Jia; Hou, Shengtao; Zhang, Xu

    2017-01-01

    Abstract Free radical toxicity due to poorly maintained cellular redox levels is crucial events that have been associated with the pathogenesis of Guillain–Barre syndrome (GBS) patients. Uric acid (UA) and albumin correlate with oxidative stress in some degree. We aimed to evaluate the relationship between GBS and serum levels of UA and albumin in the present study. The serum levels of UA and albumin were determined in 203 individuals including 88 patients with GBS and 153 healthy controls (HC). We found that serum levels of UA and albumin in patients with GBS were significantly lower than those in HC group. Besides, similar phenomenon was observed when the male and female subgroups were estimated, respectively. Additionally, we found that there is no statistic difference among subgroups of GBS regarding UA and albumin. The univariate analysis revealed that both the high UA and high albumin were protective factors for patients with GBS (odds ratio [OR] 0.140; 95% confidence interval [CI]: 0.074–0.264; P < .001 and OR 0.016; 95% CI: 0.006–0.038; P < .001, respectively). It was further confirmed by the multivariable logistic regression analysis after adjusting for other potential confounding factors (OR 0.168; 95% CI: 0.055–0.514; P = .002 and OR 0.027; 95% CI: 0.011–0.071; P < .001, respectively). In conclusion, we found that patients with GBS had significantly low serum UA and albumin levels. Moreover, we demonstrated that both the high UA and high albumin were protective factors for patients with GBS. PMID:28403109

  7. Total serum bile acid as a potential marker for the diagnosis of cholangiocarcinoma without jaundice.

    PubMed

    Sombattheera, Sutthikan; Proungvitaya, Tanakorn; Limpaiboon, Temduang; Wongkham, Sopit; Wongkham, Chaisiri; Luvira, Vor; Proungvitaya, Siriporn

    2015-01-01

    Diagnosis of cholangiocarcinoma (CCA) is difficult when patients do not show jaundice. The aim of this study was to examine the feasibility of using the total serum bile acid (TSBA) level as an aid for the diagnosis of CCA in patients without jaundice. For this purpose, TSBA of the following groups were measured using a Beckman Synchron CX4 clinical chemistry analyzer: 60 cases of CCA with total serum bilirubin ≤2 mg/dL (low total bilirubin group, LTB); 32 cases of CCA with total serum bilirubin >2 mg/dL (high total bilirubin group, HTB); and 115 healthy controls. Liver function parameters such as serum cholesterol, albumin, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) were also examined. The results showed that the TSBA of both LTB and HTB groups of the CCA patients were significantly higher than that of the healthy controls. Also, significant correlation was observed between TSBA and total bilirubin levels in the HTB group of CCA patients. However, no such correlation was seen in the LTB group. The cut-off value of TSBA was determined for the LTB group of CCA patients using the receiver operating characteristic curve analysis, and it was 6.05 μmol/L with the sensitivity and specificity of 46.7% and 84.4%, respectively. In addition, the ALP level was correlated well with the TSBA level and ALP in HTB group was significantly higher than that of LTB group. Moreover, the combination of high TSBA and high ALP levels gave higher specificity up to 97.4%. TSBA might be useful for the diagnosis of CCA patients without jaundice.

  8. Kynurenic acid, an aryl hydrocarbon receptor ligand, is elevated in serum of Zucker fatty rats

    PubMed Central

    Oxenkrug, G; Cornicelli, J; van der Hart, M; Roeser, J; Summergrad, P

    2016-01-01

    Obesity is an increasingly urgent global problem and the molecular mechanisms of obesity are not fully understood. Dysregulation of the tryptophan (Trp) – kynurenine (Kyn) metabolic pathway (TKP) have been suggested as a mechanism of obesity and described in obese humans and in animal models of obesity. However, to the best of our knowledge, TKP metabolism has not been studied in leptin-receptor-deficient Zucker fatty rats (ZFR) (fa/fa), the best-known and most widely used rat model of obesity. We were interested to determine if there are any deviations of TKP in ZFR. Concentrations of major TKP metabolites were evaluated (HPLC- MS method) in serum of ZFR (fa/fa) and age-matched lean rats (FA/-). Concentrations of kynurenic acid (KYNA) were 50% higher in ZFR than in lean rats (p<0.004, Mann-Whitney two-tailed test). Anthranilic acid (AA) concentrations, while elevated by 33%, did not reach statistical significance (p<0.04, one-tailed test). Elevated KYNA serum concentrations might contribute to development of obesity via KYNA-induced activation of aryl hydrocarbon receptor. Present results warrant further studies of KYNA and AA in ZFR and other animal models of obesity. PMID:27738521

  9. Perfluoroalkyl Acids in Maternal Serum and Indices of Fetal Growth: The Aarhus Birth Cohort.

    PubMed

    Bach, Cathrine Carlsen; Bech, Bodil Hammer; Nohr, Ellen Aagaard; Olsen, Jørn; Matthiesen, Niels Bjerregård; Bonefeld-Jørgensen, Eva Cecilie; Bossi, Rossana; Henriksen, Tine Brink

    2016-06-01

    Previous studies indicated an association between intrauterine exposure to perfluorooctane sulfonate (PFOS) or perfluorooctanoate (PFOA) and lower birth weight. However, these perfluoroalkyl acids (PFAAs) have to some extent been substituted by other compounds on which little is known. We investigated the association between specific PFAAs and birth weight, birth length, and head circumference at birth. We studied 1,507 mothers and their children from the Aarhus Birth Cohort (2008-2013). Nulliparous women were included during pregnancy, and serum levels of 16 PFAAs were measured between 9 and 20 completed gestational weeks (96% within 13 weeks). For compounds with quantifiable values in > 50% of samples (7 compounds), we report the associations with birth weight, birth length, and head circumference at birth determined by multivariable linear regression. Estimated mean birth weights were lower among women with serum perfluorohexane sulfonate, perfluoroheptane sulfonate, and PFOS concentrations above the lowest exposure quartile, but we found no consistent monotonic dose-response patterns. These associations were stronger when the population was restricted to term births (n = 1,426). For PFOS, the birth weight estimates for the highest versus lowest quartile were -50 g (95% CI: -123, 23 g) in all births and -62 g (95% CI: -126, 3 g) in term births. For the other PFAAs, the direction of the associations was inconsistent, and no overall association with birth weight was apparent. No PFAAs were associated with birth length or head circumference at birth. Overall, we did not find strong or consistent associations between PFAAs and birth weight or other indices of fetal growth, though estimated mean birth weights were lower among those with exposures above the lowest quartile for some compounds. Bach CC, Bech BH, Nohr EA, Olsen J, Matthiesen NB, Bonefeld-Jørgensen EC, Bossi R, Henriksen TB. 2016. Perfluoroalkyl acids in maternal serum and indices of fetal growth: the

  10. Salicylic acid in the serum of subjects not taking aspirin. Comparison of salicylic acid concentrations in the serum of vegetarians, non-vegetarians, and patients taking low dose aspirin

    PubMed Central

    Blacklock, C; Lawrence, J; Wiles, D; Malcolm, E; Gibson, I; Kelly, C; Paterson, J

    2001-01-01

    Aims—To determine serum salicylic acid concentrations in non-vegetarians and vegetarians not taking salicylate drugs, and to compare these concentrations with those found in patients taking aspirin, 75 mg daily. Methods—Serum samples were obtained from vegetarians (n = 37) and non-vegetarians (n = 39) not taking salicylate drugs. Non-vegetarians and vegetarians were recruited from the community and from a Buddhist monastery, respectively, in Dumfries and Galloway, Scotland. Patients (n = 14) taking aspirin (75 mg daily) were recruited from the Dumfries diabetic clinic. Serum salicylic acid concentrations were determined using a high performance liquid chromatography method with electrochemical detection. Results—Salicylic acid was detected in every serum sample analysed. Higher serum concentrations of salicylic acid were found in vegetarians than non-vegetarians: median concentrations of 0.11 (range, 0.04–2.47) µmol/litre and 0.07 (range, 0.02–0.20) µmol/litre, respectively; the median of the difference was 0.05 µmol/litre (95% confidence interval for difference, 0.03 to 0.08; p < 0.0001). The median serum concentration of salicylic acid in patients taking aspirin (75 mg daily) was 10.03 (range, 0.23–25.40) µmol/litre, which was significantly higher than that found in non-vegetarians and vegetarians. There was overlap in serum salicylic acid concentrations between the vegetarians and patients taking aspirin. Conclusions—Salicylic acid, a non-steroidal anti-inflammatory drug, is present in fruits and vegetables and is found in higher concentrations in vegetarians than non-vegetarians. This suggests that a diet rich in fruits and vegetables contributes to the presence of salicylic acid in vivo. There is overlap between the serum concentrations of salicylic acid in vegetarians and patients taking aspirin, 75 mg daily. These findings may explain, in part, the health promoting effects of dietary fruits and vegetables. Key Words: salicylic acid

  11. Serum homocysteine and folate concentrations among a US cohort of adolescents before and after folic acid fortification

    PubMed Central

    Enquobahrie, Daniel A.; Feldman, Henry A.; Hoelscher, Deanna H.; Steffen, Lyn M.; Webber, Larry S.; Zive, Michelle M.; Rimm, Eric B.; Stampfer, Meir J.; Osganian, Stavroula K.

    2013-01-01

    Objective We assessed serum homocysteine (tHcy) and folate concentrations pre- and post-folic acid fortification among US adolescents, and associations with demographic, behavioral, and physiologic factors. Design Observational study conducted among participants of a randomized trial. Setting The Child and Adolescent Trial for Cardiovascular Health (CATCH) study. Subjects Adolescents (N=2,445) in grades 8 (pre-folic acid fortification, mean age 14 y) and 12 (post-folic acid fortification). Results Average serum concentrations of tHcy, folate and vitamin B6 increased by 17%, 16% and 14%, respectively, while serum concentrations of vitamin B12 decreased by 11% post-fortification. Folic acid fortification provided, on average, an additional 118µg/day of folate intake. Male sex and white race were associated with significantly greater increases in tHcy concentration, while increases in BMI and serum folate concentration were associated with significant decreases in tHcys concentration. Female sex, non-smoking, use of multivitamins, and higher dietary intake of folate were associated with significantly greater increases in serum folate concentrations. From grade 8 to grade 12, the upward age trend in serum tHcy concentration was uninterrupted in its course (p-value>0.50); whereas, serum folic acid concentration showed a downward trend that incurred a discrete jump upward (17% higher; p-value <0.0001) with fortification. These trends differed significantly for males vs. females (p<0.001 for interaction). Conclusion Fortification had a significant impact on improving folate status but not serum tHcy concentrations among US adolescents. PMID:22974678

  12. Mechanistic Studies on the Photoallergy Mediated by Fenofibric Acid: Photoreactivity with Serum Albumins.

    PubMed

    Vayá, Ignacio; Andreu, Inmaculada; Monje, Vicente T; Jiménez, M Consuelo; Miranda, Miguel A

    2016-01-19

    The photoreactivity of fenofibric acid (FA) in the presence of human and bovine serum albumins (HSA and BSA, respectively) has been investigated by steady-state irradiation, fluorescence, and laser flash photolysis (LFP). Spectroscopic measurements allowed for the determination of a 1:1 stoichiometry for the FA/SA complexes and pointed to a moderate binding of FA to the proteins; by contrast, the FA photoproducts were complexed more efficiently with SAs. Covalent photobinding to the protein, which is directly related to the photoallergic properties of the drug, was detected after long irradiation times and was found to be significantly higher in the case of BSA. Intermolecular FA-amino acid and FA-albumin irradiations resulted in the formation of photoproducts arising from coupling between both moieties, as indicated by mass spectrometric analysis. Mechanistic studies using model drug-amino acid linked systems indicated that the key photochemical step involved in photoallergy is formal hydrogen atom transfer from an amino acid residue to the excited benzophenone chromophore of FA or (more likely) its photoproducts. This results in the formation of caged radical pairs followed by C-C coupling to give covalent photoaducts.

  13. Spectroscopic investigation of the interaction between human serum albumin and three organic acids

    NASA Astrophysics Data System (ADS)

    Liu, Yuan; Xie, Meng-Xia; Jiang, Min; Wang, Ying-Dian

    2005-07-01

    The interactions of human serum albumin (HSA) with sinapic acid (SA), gallic acid (GA) and shikimic acid (SI) were investigated by fluorescence and Fourier transformed infrared spectrometry. Fluorescence results showed that one molecule of protein combined with one molecule of GA at the molar ratio of drug to HSA ranging from 0.1 to 30, and their binding constant ( KA) is 1.1 × 10 4 M -1. While one HSA molecule combined with one or two molecule of SA at the molar ratio of drug to HSA ranging from 0.1 to 4.26 or 4.26 to 30, and their binding affinities ( KA) are 1.92 × 10 3 M -1 and 6.87 × 10 8 M -1, respectively. There is no specific interaction between HSA and SI. Combining the curve-fitting results of infrared amide I and amide III bands, the alterations of protein secondary structures induced by drugs were estimated. The drug-protein combination brought gradual reductions of the protein α-helix structure with increasing the concentrations of SA and GA, but SI did not change the protein secondary structure. From the fluorescence and FT-IR results, the binding mode was discussed in relation to the structures of the organic acids.

  14. Coffee, tea, and caffeine consumption and serum uric acid level: the third national health and nutrition examination survey.

    PubMed

    Choi, Hyon K; Curhan, Gary

    2007-06-15

    Coffee is one of the most widely consumed beverages in the world and may affect serum uric acid levels and risk of gout via various mechanisms. Our objective was to evaluate the relationship between coffee, tea, and caffeine intake and serum uric acid level in a nationally representative sample of men and women. Using data from 14,758 participants ages >/=20 years in the Third National Health and Nutrition Examination Survey (1988-1994), we examined the relationship between coffee, tea, and caffeine intake and serum uric acid level using linear regression. Additionally, we examined the relationship with hyperuricemia (serum uric acid >7.0 mg/dl among men and >5.7 mg/dl among women) using logistic regression. Intake was assessed by a food frequency questionnaire. Serum uric acid level decreased with increasing coffee intake. After adjusting for age and sex, serum uric acid level associated with coffee intake of 4 to 5 and >/=6 cups daily was lower than that associated with no intake by 0.26 mg/dl (95% confidence interval [95% CI] 0.11, 0.41) and 0.43 mg/dl (95% CI 0.23, 0.65; P for trend < 0.001), respectively. After adjusting for other covariates, the differences remained significant (P for trend < 0.001). Similarly, there was a modest inverse association between decaffeinated coffee intake and serum uric acid levels (multivariate P for trend 0.035). Total caffeine from coffee and other beverages and tea intake were not associated with serum uric acid levels (multivariate P for trend 0.15). The multivariate odds ratio for hyperuricemia in individuals with coffee intake >/=6 cups daily compared with those with no coffee use was 0.57 (95% CI 0.35, 0.94; P for trend 0.001). These findings from a nationally representative sample of US adults suggest that coffee consumption is associated with lower serum uric acid level and hyperuricemia frequency, but tea consumption is not. The inverse association with coffee appears to be via components of coffee other than caffeine.

  15. Relationship Between Serum Uric Acid and Bone Mineral Density in the General Population and in Rats with Experimental Hyperuricemia

    PubMed Central

    Zhang, Dihua; Bobulescu, I. Alexandru; Maalouf, Naim M.; Adams-Huet, Beverley; Poindexter, John; Park, Sun; Wei, Fuxin; Chen, Christopher; Moe, Orson W.; Sakhaee, Khashayar

    2015-01-01

    Higher serum uric acid concentrations have been associated with higher bone mineral density in observational studies of older men and peri- or postmenopausal women, prompting speculation of a potential protective effect of uric acid on bone. Whether this relationship is present in the general population has not been examined and there is no data to support causality. We conducted a cross-sectional analysis of a probability sample of the US population. Demographic data, dietary intake, lifestyle risk factors and physical activity assessment data, serum biochemistry including serum uric acid, and bone mineral density were obtained from 6,759 National Health and Nutrition Examination Survey (NHANES; 2005-2010) participants over 30 years of age. In unadjusted analyses, higher serum uric acid levels were associated with higher bone mineral density at the femoral neck, total hip and lumbar spine in men, pre-menopausal women, and post-menopausal women not treated with estrogen. However, these associations were no longer statistically significant after adjustment for potential confounders, including age, body mass index, black race, alcohol consumption, estimated glomerular filtration rate (eGFR), serum alkaline phosphatase, and C-reactive protein (CRP). This is in contradistinction to some prevailing conclusions in the literature. To further examine the causal effect of higher serum uric acid on skeletal health, including biomechanical properties that are not measurable in humans, we used an established rat model of inducible mild hyperuricemia. There were no differences in bone mineral density, volume density, and biomechanical properties between hyperuricemic rats and normouricemic control animals. Taken together, our data do not support the hypothesis that higher serum uric acid has protective effects on bone health. This article is protected by copyright. All rights reserved PMID:25491196

  16. Correlation between plasma ammonia level and serum trough concentration of free valproic acid in patients with epilepsy.

    PubMed

    Itoh, Hiroki; Suzuki, Yosuke; Fujisaki, Kanako; Sato, Yuhki; Takeyama, Masaharu

    2012-01-01

    Therapeutic drug monitoring of valproic acid (VPA) is essential to prevent toxicity, but the correlation between plasma ammonia level and serum VPA concentration remains unclear. We examined the correlation of plasma ammonia level with VPA dose and serum trough concentrations of total and free VPA in Japanese patients with epilepsy. Thirty-eight data sets from 19 Japanese patients with epilepsy were analyzed. The relations of VPA dose and serum total and free VPA concentrations with plasma ammonia level, and the breakpoints of VPA parameters predicting hyperammonemia (plasma ammonia higher than 60 µmol/L) were analyzed. A significant positive correlation was observed between plasma ammonia level and VPA dose (r(s)=0.56, p=0.00062), serum trough total VPA concentration (r(s)=0.55, p=0.00086) and serum trough free VPA concentration (r(s)=0.58, p=0.00041). The breakpoints predicting hyperammonemia were VPA dose of 30.4 mg/kg, serum trough total VPA concentration of 90.9 µg/mL, and serum trough free VPA concentration of 8.65 µg/mL, with impurity reductions at 1.35, 1.35 and 2.02, respectively. These findings suggest that serum trough concentration of free VPA is the most reliable predictor for hyperammonemia, and that the risk of developing hyperammonemia may increase in patients with serum trough free VPA concentrations higher than 8.65 µg/mL.

  17. Serum choline plasmalogens, particularly those with oleic acid in sn-2, are associated with proatherogenic state[S

    PubMed Central

    Nishimukai, Megumi; Maeba, Ryouta; Yamazaki, Yuya; Nezu, Toru; Sakurai, Toshihiro; Takahashi, Yuji; Hui, Shu-Ping; Chiba, Hitoshi; Okazaki, Tomoki; Hara, Hiroshi

    2014-01-01

    Serum plasmalogens (Pls) (1-O-alk-1’-enyl-2-acyl glycerophospholipids) are of particular interest for studies on metabolic disorders associated with oxidative stress and chronic inflammation. Serum levels of Pls are known to correlate positively with HDL-cholesterol (HDL-C); however, few studies have examined serum Pls molecular species in association with pathophysiological conditions and their clinical significance. To clarify these, we determined serum levels of individual ether glycerophospholipids in Japanese asymptomatic cohorts (n = 428; 362 male and 66 female subjects) by LC/MS/MS, and examined their correlations with clinical parameters. We found that the proportion of choline Pls (PlsCho) among total serum phospholipids was significantly lower in the male group over 40 years old and was associated with multiple risk parameters more strongly than HDL-C. The abundance of serum PlsCho with oleic acid (18:1) in sn-2 exhibited the strongest positive correlation with serum concentrations of adiponectin and HDL-C, while being inversely associated with waist circumference and the serum levels of TG and small dense LDL-cholesterol. The characterization of serum ether glycerophospholipids verified the specificity of PlsCho, particularly the ones with 18:1 in sn-2, as a sensitive biomarker for the atherogenic state. PMID:24616482

  18. Prediction of bone mass in renal hyperparathyroidism by newly developed bone metabolic markers: evaluation of serum levels of carboxy-terminal pyridinoline cross-linked telopeptide of type I collagen and carboxy-terminal propeptide of type I procollagen.

    PubMed

    Katagiri, M; Fukunaga, M; Ohtawa, T; Harada, T

    1996-09-01

    Serum levels of the carboxy-terminal pyridinoline cross-linked telopeptide of type I collagen (ICTP) and the carboxy-terminal propeptide of type I procollagen (PICP) were measured in 95 patients with renal hyperparathyroidism who had undergone a total parathyroidectomy and autotransplantation of a small portion of the resected gland. The results were compared with the serum levels of other bone metabolic markers and bone mineral densities in the distal radius (R-BMD) and lumbar vertebrae (L-BMD), which were measured by dual energy x-ray absorptiometry and converted to the percentage of the mean value of sex- and age-matched healthy controls. The preoperative mean values of ICTP and PICP were 142.4 ng/ml and 187.8 ng/ml, respectively. Although the serum levels of PICP levels exceeded the normal range in 42.1% of the patients, those of ICTP exceeded it in all of them. The serum levels of ICTP correlated positively not only with those of tartrate-resistant acid phosphatase (TRACP), total alkaline phosphatase (ALP), and osteocalcin but also negatively with the values of %R-BMD and %L-BMD and seemed to manifest specifically the disturbance of bone metabolism. On the other hand, the serum levels of PICP correlated with those of ALP and TRACP but not with values of %BMDs. After surgery, the serum levels of ICTP decreased gradually, but those of PICP increased immediately up to peak values at 7 days and then decreased gradually after 14 days, reaching the normal range at 3 months. These changes in the bone metabolic markers seemed to reflect the change in bone metabolism that was converting from bone resorption to bone formation. The percent change in the PICP/ICTP ratio at 7 days correlated significantly with the percent change in R-BMD at 12 months, and it was suggested that postoperative bone gain might be predicted using a combination of postoperative changes in PICP and ICTP.

  19. High-fat diet alters serum fatty acid profiles in obesity prone rats: implications for in-vitro studies

    PubMed Central

    Liu, Tzu-Wen; Heden, Timothy D.; Morris, E. Matthew; Fritsche, Kevin L.; Vieira-Potter, Victoria J.; Thyfault, John P.

    2015-01-01

    High-fat diets (HFD) are commonly used in rodents to induce obesity, increase serum fatty acids, and induce lipotoxicity in various organs. In-vitro studies commonly utilize individual free fatty acids (FFA) to study lipid exposure in an effort to model what is occurring in-vivo, however, these approaches are not physiological as tissues are exposed to multiple fatty acids in-vivo. Here we characterize circulating lipids in obese-prone rats fed a HFD in both fasted and fed states with the goal of developing physiologically relevant fatty acid mixtures for subsequent in-vitro studies. Rats were fed a HFD (60% kcal fat) or a control diet (10% kcal fat) for 3 weeks; liver tissue, and both portal and systemic blood was collected. Fatty acid profiles and absolute concentrations of triglycerides (TAG) and FFA in the serum and TAG, diacylglycerol (DAG), and phospholipids (PL) in the liver were measured. Surprisingly, both systemic and portal serum TAG were ~40% lower in HFD-fed compared to controls. Overall, compared to the control diet, HFD feeding consistently induced an increase in the proportion of circulating polyunsaturated fatty acids (PUFA) with a concomitant decline in monounsaturated fatty acids (MUFA), and saturated fatty acids (SFA) in both serum TAG and FFA. The elevations of PUFA were mostly attributed to increases in n-6 PUFA, linoleic acid and arachidonic acid. In conclusion, fatty acid mixtures enriched with linoleic and arachidonic acid in addition to SFA and MUFA should be utilized for in-vitro studies attempting to model lipid exposures that occur during in-vivo HFD condition. PMID:26318121

  20. High serum palmitic acid is associated with low antiviral effects of interferon-based therapy for hepatitis C virus.

    PubMed

    Miyake, Teruki; Hiasa, Yoichi; Hirooka, Masashi; Tokumoto, Yoshio; Watanabe, Takao; Furukawa, Shinya; Ueda, Teruhisa; Yamamoto, Shin; Kumagi, Teru; Miyaoka, Hiroaki; Abe, Masanori; Matsuura, Bunzo; Onji, Morikazu

    2012-11-01

    Hepatitis C virus (HCV) infection alters fatty acid synthesis and metabolism in association with HCV replication. The present study examined the effect of serum fatty acid composition on interferon (IFN)-based therapy. Fifty-five patients with HCV were enrolled and received IFN-based therapy. Patient characteristics, laboratory data (including fatty acids), and viral factors that could be associated with the anti-HCV effects of IFN-based therapy were evaluated. The effects of individual fatty acids on viral replication and IFN-based therapy were also examined in an in-vitro system. Multivariate logistic regression analysis showed that the level of serum palmitic acid before treatment and HCV genotype were significant predictors for rapid virological response (RVR), early virological response (EVR), and sustained virological response (SVR). High levels of palmitic acid inhibited the anti-HCV effects of IFN-based therapy. HCV replication assays confirmed the inhibitory effects of palmitic acid on anti-HCV therapy. The concentration of serum palmitic acid is an independent predictive factor for RVR, EVR, and SVR in IFN-based antiviral therapy. These results suggest that the effect of IFN-based antiviral therapy in patients with HCV infection might be enhanced by treatment that modulates palmitic acid levels.

  1. Quantitative measurement of serum hyaluronic acid molecular weight in rheumatoid arthritis patients and the role of hyaluronidase.

    PubMed

    Sasaki, Yoshiko; Uzuki, Miwa; Nohmi, Kenji; Kitagawa, Hironoshin; Kamataki, Akihisa; Komagamine, Masataka; Murakami, Kenya; Sawai, Takashi

    2011-10-01

    Hyaluronic acid (HA) is a glycosaminoglycan and is essential for protecting the cartilage surface by its physical property. It is known that serum HA concentration in rheumatoid arthritis (RA) patients is higher than in healthy volunteer. However, molecular weight (MW) of serum HA in RA patients is not clear, since it needs a large sample volume to assay serum HA MW. The aim of this study is to establish the method for measuring serum HA MW in small sample sizes and to assess the association between serum HA MW and hyaluronidase (HAase) activity. MW of serum HA in RA patients was measured using high-performance liquid chromatography and HA-binding protein. Additionally, the correlation between serum HA and HAase activity was examined using zymographic measurements. Serum HA MW peaked at 1-2 × 10(5) Da in all cases. However, in certain cases two peaks were observed, one each at low (1-2 × 10(5) Da) and high (8-14 × 10(5) Da) MW. HAase activity was lower in cases exhibiting this two-peaked serum HA MW pattern than in those cases with only a single peak. The novel method developed for this study permits accurate measurement of serum HA MW. The correlation observed between serum HA MW and HAase activity suggests that serum HA MW may reflect the condition of subjects' joints. © 2011 The Authors. International Journal of Rheumatic Diseases © 2011 Asia Pacific League of Associations for Rheumatology and Blackwell Publishing Asia Pty Ltd.

  2. Lipid Profiles and trans Fatty Acids in Serum Phospholipids of Semi-nomadic Fulani in Northern Nigeria

    PubMed Central

    Glew, Robert H.; Chuang, Lu-Te; Berry, Tammy; Okolie, Henry; Crossey, Michael J.

    2010-01-01

    The Fulani are semi-nomadic pastoralists of West Africa whose diet, culture, and economy are centred on cattle. Previous studies have shown that the Fulani of northern Nigeria derive 50% of their total calories from fat and 30% of their calories from milk, cheese, yogurt, and butter oil that contain significant amounts of trans fatty acids (TFAs), primarily vaccenic acid, which raise total serum cholesterol and low-density lipoprotein-cholesterol (LDL-C), and lower high-density lipoprotein-cholesterol (HDL-C). The study was conducted to know how the consumption of relatively large amounts of dairy products by adult Fulani affected the TFA content of their serum phospholipids. Blood samples were collected from 22 male and 29 female Fulani, aged 35–60 years, who were living in rural areas of Gombe state in northeastern Nigeria. The total serum phospholipid fraction was isolated, and its fatty acid composition was determined. Surprisingly, vaccenic acid was not detected, and three other TFAs—18:1-t6, 18:1-t9, and 18:2-t9, t12—together accounted for only 0.16% of the total fatty acid. The mean serum total cholesterol, LDL-C, and triglyceride concentrations of the subjects were within the normal range for populations in developed countries; however, at 32 mg/dL, the mean serum HDL-C concentration of the Fulani males was slightly below the lower limit of the reference range. No correlations were observed between the total TFA percentage or that of the three individual TFAs and any of the parameters of the serum lipid profile. These findings indicate that, with respect to TFAs at least, the fatty acid pattern of the serum phospholipids of Fulani pastoralists does not reflect the high TFA content of their traditional diet. Despite the consumption of rumenic acid-rich dairy products, for unknown reasons, the semi-nomadic Fulani manage to maintain a low level of TFAs in their blood and a relatively healthful serum lipid profile. While the mechanism that accounts for

  3. Lipid profiles and trans fatty acids in serum phospholipids of semi-nomadic Fulani in northern Nigeria.

    PubMed

    Glew, Robert H; Chuang, Lu-Te; Berry, Tammy; Okolie, Henry; Crossey, Michael J; VanderJagt, Dorothy J

    2010-04-01

    The Fulani are semi-nomadic pastoralists of West Africa whose diet, culture, and economy are centred on cattle. Previous studies have shown that the Fulani of northern Nigeria derive 50% of their total calories from fat and 30% of their calories from milk, cheese, yogurt, and butter oil that contain significant amounts of trans fatty acids (TFAs), primarily vaccenic acid, which raise total serum cholesterol and low-density lipoproteincholesterol (LDL-C), and lower high-density lipoprotein-cholesterol (HDL-C). The study was conducted to know how the consumption of relatively large amounts of dairy products by adult Fulani affected the TFA content of their serum phospholipids. Blood samples were collected from 22 male and 29 female Fulani, aged 35-60 years, who were living in rural areas of Gombe state in northeastern Nigeria. The total serum phospholipid fraction was isolated, and its fatty acid composition was determined. Surprisingly, vaccenic acid was not detected, and three other TFAs--18:1-t6, 18:1-t9, and 18:2-t9,t12--together accounted for only 0.16% of the total fatty acid. The mean serum total cholesterol, LDL-C, and triglyceride concentrations of the subjects were within the normal range for populations in developed countries; however, at 32 mg/dL, the mean serum HDL-C concentration of the Fulani males was slightly below the lower limit of the reference range. No correlations were observed between the total TFA percentage or that of the three individual TFAs and any of the parameters of the serum lipid profile. These findings indicate that, with respect to TFAs at least, the fatty acid pattern of the serum phospholipids of Fulani pastoralists does not reflect the high TFA content of their traditional diet. Despite the consumption of rumenic acid-rich dairy products, for unknown reasons, the semi-nomadic Fulani manage to maintain a low level of TFAs in their blood and a relatively healthful serum lipid profile. While the mechanism that accounts for this

  4. Prenatal exposures to perfluoroalkyl acids and serum lipids at ages 7 and 15 in females.

    PubMed

    Maisonet, Mildred; Näyhä, Simo; Lawlor, Debbie A; Marcus, Michele

    2015-09-01

    In some cross-sectional epidemiologic studies the shape of the association between serum concentrations of perfluoroalkyl acids (PFAAs) and lipids suggests departures from linearity. We used statistical approaches allowing for non-linearity to determine associations of prenatal exposures of perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) with lipid concentrations. PFAAs were measured in serum from pregnant women collected in 1991-1992 at enrollment in the Avon Longitudinal Study of Parents and Children and lipids in serum from their daughters at ages 7 (n=111) and 15 (n=88). The associations of PFAAs with lipids were first explored by cubic splines, followed by piecewise linear regressions by tertiles to obtain regression coefficients (β) and their 95% confidence limits (95% CL) (in mg/dL per 1ng/mL). At age 7, total cholesterol was positively associated with prenatal PFOA concentrations in the lower tertile (β=15.01; 95% CL=2.34, 27.69) but not with PFOA concentrations in the middle (β=-3.63; 95% CL=-17.43, 10.16) and upper (β=-1.58; 95% CL=-4.58, 1.42) tertiles. At age 15, a similar pattern was noted as well. Positive associations between LDL-C and prenatal PFOA concentration in the lower tertile were observed in daughters at ages 7 (β=14.91; 95% CL=3.53, 28.12) and 15 (β=13.93; 95% CL=0.60, 27.26). LDL-C was not associated with PFOA concentrations in the middle or upper tertile at any age. Neither HDL-C nor triglycerides was associated with prenatal PFOA exposure. Non-linear patterns of association of total cholesterol and LDL-C with prenatal PFOS were less consistently noted. Exposure to low levels of PFOA during prenatal development may alter lipid metabolism later in life. Given the small sample size further replication of the association in large independent cohorts is important. Copyright © 2015. Published by Elsevier Ltd.

  5. Prolactin messenger ribonucleic acid concentrations throughout the ovine estrous cycle: Assessment relative to prolactin serum and pituitary amounts

    SciTech Connect

    Landefeld, T.; Roulia, V.; Bagnell, T.; Ballard, T.; Levitan, I. )

    1991-01-01

    Prolactin (PRL) mRNA concentrations were assessed by nucleic acid hybridization assays in pituitaries of ewes representing the defined stages of the ovine estrous cycle. Concomitantly, pituitary and serum PRL concentrations were measured in these ewes using radioimmunoassays. It was observed that PRL serum, pituitary and mRNA concentrations tended to increase near the time of the gonadotropin preovulatory surge, particularly between 24 hrs before behavioral estrus to 5 hours after estrus. However, the changes in PRL mRNA, serum and pituitary concentrations were shown not to be statistically significant. These data suggest that PRL production during the sheep estrous cycle is maintained without dramatic changes in synthesis or secretion.

  6. Association between serum phospholipid fatty acid levels and adiposity in Mexican women[S

    PubMed Central

    Aglago, Elom K.; Biessy, Carine; Torres-Mejía, Gabriela; Angeles-Llerenas, Angélica; Gunter, Marc J.; Romieu, Isabelle; Chajès, Veronique

    2017-01-01

    Fatty acids (FAs) have been postulated to impact adiposity, but few epidemiological studies addressing this hypothesis have been conducted. This study investigated the association between serum phospholipid FAs (S-PLFAs) and indicators of obesity. BMI and waist-to-hip ratio (WHR) were collected from 372 healthy Mexican women included as controls in a case-control study. S-PLFA percentages were determined through gas chromatography. Desaturation indices, SCD-16, SCD-18, FA desaturase (FADS)1, and FADS2, biomarkers of endogenous metabolism, were proxied respectively as 16:1n-7/16:0, 18:1n-9/18:0, 20:4n-6/20:3n-6, and 22:6n-3/20:5n-3. Multiple linear regressions adjusted for relevant confounders and corrected for multiple testing were conducted to determine the association between S-PLFA, desaturation indices, and indicators of adiposity. SCD-16 (β = 0.034, P = 0.001, q = 0.014), palmitoleic acid (β = 0.031, P = 0.001, q = 0.014), and dihomo-γ-linolenic acid (β = 0.043, P = 0.000, q = 0.0002) were positively associated with BMI. Total n-6 PUFAs (β = 1.497, P = 0.047, q = 0.22) and the ratio of n-6/n-3 PUFAs (β = 0.034, P = 0.040, q = 0.19) were positively associated with WHR, while odd-chain FAs (pentadecanoic and heptadecanoic acid) showed negative associations with all the adiposity indicators. In conclusion, increased endogenous synthesis of palmitoleic acid and a high n-6/n-3 ratio are associated with increased adiposity, while odd-chain FAs are associated with decreased adiposity. Further studies are needed to determine the potential causality behind these associations. PMID:28465289

  7. Serum uric acid levels contribute to new renal damage in systemic lupus erythematosus patients.

    PubMed

    Reátegui-Sokolova, C; Ugarte-Gil, Manuel F; Gamboa-Cárdenas, Rocío V; Zevallos, Francisco; Cucho-Venegas, Jorge M; Alfaro-Lozano, José L; Medina, Mariela; Rodriguez-Bellido, Zoila; Pastor-Asurza, Cesar A; Alarcón, Graciela S; Perich-Campos, Risto A

    2017-04-01

    This study aims to determine whether uric acid levels contribute to new renal damage in systemic lupus erythematosus (SLE) patients. This prospective study was conducted in consecutive patients seen since 2012. Patients had a baseline visit and follow-up visits every 6 months. Patients with ≥2 visits were included; those with end-stage renal disease (regardless of dialysis or transplantation) were excluded. Renal damage was ascertained using the SLICC/ACR damage index (SDI). Univariable and multivariable Cox-regression models were performed to determine the risk of new renal damage. Uric acid was included as a continuous and dichotomous (per receiving operating characteristic curve) variable. Multivariable models were adjusted for age at diagnosis, disease duration, socioeconomic status, SLEDAI, SDI, serum creatinine, baseline use of prednisone, antimalarials, and immunosuppressive drugs. One hundred and eighty-six patients were evaluated; their mean (SD) age at diagnosis was 36.8 (13.7) years; nearly all patients were mestizo. Disease duration was 7.7 (6.8) years. Follow-up time was 2.3 (1.1) years. The SLEDAI was 5.2 (4.3) and the SDI 0.8 (1.1). Uric acid levels were 4.5 (1.3) mg/dl. During follow-up, 16 (8.6%) patients developed at least one new point in the renal domain of the SDI. In multivariable analyses, uric acid levels (continuous and dichotomous) at baseline predicted the development of new renal damage (HR 3.21 (1.39-7.42), p 0.006; HR 18.28 (2.80-119.48), p 0.002; respectively). Higher uric acid levels contribute to the development of new renal damage in SLE patients independent of other well-known risk factors for such occurrence.

  8. Profiling serum bile acid glucuronides in humans: gender divergences, genetic determinants and response to fenofibrate

    PubMed Central

    Trottier, Jocelyn; Perreault, Martin; Rudkowska, Iwona; Levy, Cynthia; Dallaire-Theroux, Amélie; Verreault, Mélanie; Caron, Patrick; Staels, Bart; Vohl, Marie-Claude; Straka, Robert J.; Barbier, Olivier

    2014-01-01

    Glucuronidation, catalyzed by UDP-glucuronosyltransferase (UGT) enzymes detoxifies cholestatic bile acids (BAs). We aimed at i) characterizing the circulating BA-glucuronide (-G) pool composition in humans, ii) evaluating how sex and UGT polymorphisms influence this composition, and iii) analyzing the effects of lipid-lowering drug fenofibrate on the circulating BA-G profile in 300 volunteers and 5 cholestatic patients. Eleven BA-Gs were determined in pre- and post-fenofibrate samples. Men exhibited higher BA-G concentrations, and various genotype/BA-G associations were discovered in relevant UGT genes. The chenodeoxycholic acid-3G concentration was associated with the UGT2B7 802C>T polymorphism. Glucuronidation assays confirmed the predominant role of UGT2B7 and UGT1A4 in CDCA-3G formation. Fenofibrate exposure increased the serum levels of 5 BA-G species, including CDCA-3G, and up-regulated expression of UGT1A4, but not UGT2B7, in hepatic cells. This study demonstrates that fenofibrate stimulates BA glucuronidation in humans, and thus reduces bile acid toxicity in the liver. PMID:23756370

  9. Separation of tissue and serum acid phosphatase isoenzymes by ion-exchange column chromatography.

    PubMed

    Mercer, D W

    1977-01-01

    I describe a simple, rapid ion-exchange column-chromatographic technique for separating the acid phosphatase (EC 3.1.3.2) isoenzymes in human serum and tissue. Extracts of platelets, spleen, liver, erythrocytes, and prostate were used to determine optimum conditions for separating these isoenzymes. Samples layered on mini-colunms of DEAE-Sephadex A-50 were eluted stepwise with sodium chloride (100, 200, and 300 mmol/liter, buffered with tris (hydroxymethyl)aminomethane). Activity in column effluents was measured with p-nitrophenol phosphate as substrate, and their isoenzyme content was assessed by electrophoresis on polyacrylamide gel. Comparision of activity patterns so derived for various tissues revealed prostatic tissue to be a rich source of acid phosphatase isoenzyme 2 activity. Evaluation of sera from six patients with prostatic cancer revealed isoenzyme patterns with prominent amount of isoenzyme 2 (3.8 to 27.6 U/liter). sera from 10 healthy laboratory technicians contained isoenzyme 2 in the range of 0.3-0.5 U/liter. Samples from two patients with abnormally high activity owing to nonprostatic conditions (Gaucher's disease and carcinoma of lung) exhibited less than 2 U of isoenzyme 2 per liter and acid phosphatase isoenzymes 3-5 that were 50- to 100-fold the normal range. Quantification of isoenzyme 2 by DEAE-Sephadex column chromatography as described appears to provide a more sensitive and specific approach to diagnosis of prostatic cancer.

  10. Serum uric acid concentration and metabolic syndrome among elderly Koreans: The Korean Urban Rural Elderly (KURE) study.

    PubMed

    Choi, Hansol; Kim, Hyeon Chang; Song, Bo Mi; Park, Ji Hye; Lee, Ju-Mi; Yoon, Da-Lim; Yoon, Young Mi; Rhee, Yumie; Youm, Yousik; Kim, Chang Oh

    2016-01-01

    Epidemiologic studies have demonstrated that elevated serum uric acid concentration is an independent risk factor for metabolic syndrome. However, few studies have focused on elderly populations. Thus, we investigated the association of serum uric acid concentration with metabolic syndrome in community-dwelling elderly Koreans. This cross-sectional analysis included 2940 participants (986 men and 1954 women) aged 65 years or older who participated in a baseline health assessment for the Korean Urban Rural Elderly cohort study from 2012 to 2014. Serum uric acid concentration was analyzed using both continuous and dichotomous variables. Hyperuricemia was defined as a uric acid concentration ≥7.0 mg/dL in men and ≥6.0 mg/dL in women. Metabolic syndrome was defined according to the 2009 harmonizing definition. Multiple logistic regression models were used to investigate independent association between serum uric acid and metabolic syndrome, after adjusting for age, body mass index, LDL cholesterol, glycated hemoglobin, blood urea nitrogen, estimated glomerular filtration rate health behaviors, and medications. Prevalence of metabolic syndrome and its components increased significantly according to uric acid concentration in both sexes. The adjusted odds ratios for having metabolic syndrome per 1.0mg/dL higher uric acid concentration were 1.16 (95% CI: 1.03-1.31) in men and 1.27 (95% CI: 1.13-1.42) in women. Hyperuricemia was also associated with metabolic syndrome, with adjusted odds ratios of 1.71 (95% CI: 1.11-2.63) in men and 1.55 (95% CI: 1.05-2.29) in women. Elevated serum uric acid concentration was independently associated with an increased prevalence of metabolic syndrome in community-dwelling elderly Koreans. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  11. The Relationship between Serum Oxalic Acid, Central Hemodynamic Parameters and Colonization by Oxalobacter formigenes in Hemodialysis Patients.

    PubMed

    Gulhan, Baris; Turkmen, Kultigin; Aydin, Merve; Gunay, Murat; Cıkman, Aytekin; Kara, Murat

    2015-06-01

    Elevated pulse wave velocity (PWV) and central aortic blood pressures are independent predictors of increased cardiovascular morbidity and mortality in hemodialysis (HD) patients. Oxalic acid is a uremic retention molecule that is extensively studied in the pathogenesis of calcium oxalate stones. Oxalobacter formigenes, a member of the colon microbiota, has important roles in oxalate homeostasis. Data regarding the colonization by and the exact role of O. formigenes in the pathogenesis of oxalic acid metabolism in HD patients are scant. Hence, we aimed to determine the relationship between fecal O. formigenes colonization, serum oxalic acid and hemodynamic parameters in HD patients with regard to the colo-reno-cardiac axis. Fifty HD patients were enrolled in this study. PWV and central aortic systolic (cASBP) and diastolic blood pressures (cADBP) were measured with a Mobil-O-Graph (I.E.M. GmbH, Stolberg, Germany). Serum oxalic acid levels were assessed by ELISA, and fecal O. formigenes DNA levels were isolated and measured by real-time PCR. Isolation of fecal O. formigenes was found in only 2 HD patients. One of them had 113,609 copies/ml, the other one had 1,056 copies/ml. Serum oxalic acid levels were found to be positively correlated with PWV (r = 0.29, p = 0.03), cASBP (r = 0.33, p = 0.001) and cADBP (r = 0.42, p = 0.002) and negatively correlated with LDL (r = -0.30, p = 0.03). In multivariate linear regression analysis, PWV was independently predicted by oxalic acid, glucose and triglyceride. This is the first study that demonstrates the absence of O. formigenes as well as a relation between serum oxalic acid and cASBP, cADBP and PWV in HD patients. Replacement of O. formigenes with pre- and probiotics might decrease serum oxalic acid levels and improve cardiovascular outcomes in HD patients.

  12. Spectroscopic analyses and studies on respective interaction of cyanuric acid and uric acid with bovine serum albumin and melamine.

    PubMed

    Chen, Dandan; Wu, Qiong; Wang, Jun; Wang, Qi; Qiao, Heng

    2015-01-25

    In this work, the fluorescence quenching was used to study the interaction of cyanuric acid (CYA) and uric acid (UA) with bovine serum albumin (BSA) at two different temperatures (283 K and 310 K). The bimolecular quenching constant (Kq), apparent quenching constant (Ksv), effective binding constant (KA) and corresponding dissociation constant (KD), binding site number (n) and binding distance (r) were calculated by adopting Stern-Volmer, Lineweaver-Burk, Double logarithm and overlap integral equations. The results show that CYA and UA are both able to obviously bind to BSA, but the binding strength order is BSA+CYA

  13. Serum uric acid to creatinine ratio: A predictor of incident chronic kidney disease in type 2 diabetes mellitus patients with preserved kidney function.

    PubMed

    Gu, Liubao; Huang, Liji; Wu, Haidi; Lou, Qinglin; Bian, Rongwen

    2017-05-01

    Serum uric acid has shown to be a predictor of renal disease progression in most but not all studies. This study aims to test whether renal function-normalized serum uric acid is superior to serum uric acid as the predictor of incident chronic kidney disease in type 2 diabetes mellitus patients. In this study, 1339 type 2 diabetes mellitus patients with estimated glomerular filtration rate ⩾60 mL/min/1.73 m(2) and normouricemia were included. Renal function-normalized serum uric acid was calculated using serum uric acid/creatinine. Cox regression analysis was used to estimate the association between serum uric acid, renal function-normalized serum uric acid and incident chronic kidney disease. In total, 74 (5.53%) patients developed to chronic kidney disease 3 or greater during a median follow-up of 4 years, with older ages, longer diabetes duration and lower estimated glomerular filtration rate at baseline. The decline rate of estimated glomerular filtration rate was positively correlated with serum uric acid/creatinine ( r = 0.219, p < 0.001), but not serum uric acid ( r = 0.005, p = 0.858). Moreover, multivariate analysis revealed that serum uric acid was not an independent risk factor for incident chronic kidney disease ( p = 0.055), whereas serum uric acid to creatinine ratio was significantly associated with incident chronic kidney disease independently of potential confounders including baseline estimated glomerular filtration rate. serum uric acid to creatinine ratio might be a better predictor of incident chronic kidney disease in type 2 diabetes mellitus patients.

  14. Effect of substratum, serum and linoleic acid on the lipid synthesis of isolated alveolar type II cells

    SciTech Connect

    Cott, G.R.; Edeen, K.E.; Hale, S.G.; Mason, R.J.

    1986-03-05

    The authors examined the effect of cellular substratum (plastic or amnionic basement membrane (ABM)) and serum additive (fetal bovine (FBS), pork, horse, rat or human) on phospholipid synthesis in alveolar type II cells. The cells were isolated from adult rats, cultured for 48 hours under the various substratum and serum conditions, and then incubated for an additional 2 hours with (1-/sup 14/C) acetate. ABM consistently caused a significant increase in the percent of radiolabel incorporated into phosphatidylcholine (PC) and/or phosphatidylglycerol (PG). Serum also had a significant effect with the highest values of PC and saturated PC being obtained with rat serum and the highest PG values with horse serum. The fatty acid composition of the sera used varied according to species with the largest variations in percent linoleic acid. Supplementing media with linoleic acid resulted in a marked increase in saturated PC values and a fall in PG values. Therefore, they conclude that: 1) ABM improves differentiated function, 2) FBS supplementation may not be optimal, and 3) the different effects of linoleic acid supplementation on PC, saturated PC, and PG values suggests an independent regulation of synthesis for these lipid species in vitro.

  15. Essential Amino Acids in the Gluten-Free Diet and Serum in Relation to Depression in Patients with Celiac Disease

    PubMed Central

    van Hees, Nathalie J. M.; Giltay, Erik J.; Tielemans, Susanne M. A. J.; Geleijnse, Johanna M.; Puvill, Thomas; Janssen, Nadine; van der Does, Willem

    2015-01-01

    Introduction Celiac disease (CD) is associated with an increased risk of major depressive disorder, possibly due to deficiencies in micronutrients in the gluten-free diet. We aimed to investigate whether essential amino acids (i.e., the precursors of serotonin, dopamine and other neurotransmitters) are depleted in the diet and serum of CD patients with major depressive disorder. Methods In a cross-sectional study we assessed dietary intake of amino acids and serum levels of amino acids, in 77 CD patients on a gluten-free diet and in 33 healthy controls. Major depressive disorder was assessed with structured interviews (using the Mini International Neuropsychiatric Interview Plus). Dietary intake was assessed using a 203-item food frequency questionnaire. Results Participants had a mean age of 55 years and 74% were women. The intake of vegetable protein was significantly lower in CD patients than in healthy controls (mean difference of 7.8 g/d; 95% CI: 4.7–10.8), as were serum concentrations of tyrosine, phenylalanine and tryptophan (all p < 0.005). However, within the CD patient group, the presence of major depressive disorder (n = 42) was not associated with intake or serum levels of essential amino acids. Conclusions Patients with CD on a long-term gluten-free diet, with good adherence, consume significantly less vegetable protein than controls, and their serum levels of several essential amino acids were also lower. Despite its potential adverse effect, intake and serum levels of essential amino acids were not related to major depression. PMID:25884227

  16. [Association between urinary polycyclic aromatic hydrocarbon metabolites and elevated serum uric acid levels in coke oven workers].

    PubMed

    Deng, Siyun; Deng, Qifei; Hu, Die; Li, Jun; Zhu, Xiaoyan; Guo, Huan; Wu, Tangchun

    2014-06-01

    To analyze the relationship between metabolites of polycyclic aromatic hydrocarbons (PAHs) and serum uric acid levels in coke oven workers and to provide new clues to the pathogenic mechanism of PAHs. A total of 1302 coke oven workers were divided into four groups, namely control group and low-, intermediate-, and high-dose exposure groups. The concentrations of ambient PAHs at each workplace were determined by high-performance liquid chromatography. The detailed information on the occupational history and health of workers was collected by questionnaire survey and physical examination, and so were their blood and urine samples. Serum uric acid and creatinine levels were measured using a Hitachi 7020 automatic biochemical analyzer. Ten urinary PAH metabolites were detected by gas chromatography-mass spectrometry. Serum uric acid levels were the highest in the high-dose exposure group, followed by the intermediate- and low-dose exposure groups, and were the lowest in the control group. There were significant correlations between serum uric acid levels and the quartiles of 1-hydroxynaphthalene and 1-hydroxyphenanthrene (P < 0.05). After adjustment for PAH metabolite-related relationship, only urinary 1-hydroxyphenanthrene was significantly correlated with serum uric acid levels (P = 0.001). After adjustment for confounding factors and using the 1st quartile of 1-hydroxyphenanthrene as a reference, the odds ratio for hyperuricemia in subjects with the 2nd, 3rd, and 4th quartiles of 1-hydroxyphenanthrene were 1.55, 1.57, and 2.35, respectively. Urinary 1-hydroxyphenanthrene is associated with a dose-response increase in serum uric acid levels in coke oven workers, and exposure to phenanthrene in PAHs may be a risk factor for hyperuricemia.

  17. Reference Intervals for Preprandial and Postprandial Serum Bile Acid in Adult Rhesus Macaques (Macaca mulatta)

    PubMed Central

    Lemoy, Marie-Josee MF; Westworth, Diccon R; Ardeshir, Amir; Tarara, Ross P

    2013-01-01

    The purpose of this study was to determine the 12-h fasting preprandial and 2-h postprandial serum bile acid concentration (SBAC) reference intervals for healthy, adult rhesus macaques (Macaca mulatta). We hypothesized that the mean 2-h postprandial SBAC would be significantly higher than the mean preprandial SBAC. We included 40 (24 male, 16 female) macaques after confirming that their health records, physical examinations, CBC, serum chemistry panels, and urinalyses were all within normal limits. In addition, hepatitis A titers were determined, an ultrasound examination of the liver was performed, and two 16-gauge ultrasound guided percutaneous liver biopsies were collected and submitted for histopathology. Macaques were confirmed healthy according to hepatitis A screens and sonographic and histologic evaluation of hepatic tissue. Within 2 wk of the screening procedures, preprandial and postprandial SBACs were measured. Preprandial SBAC (mean ± 1 SD) was 11.1 ± 1.9 µmol/L and postprandial SBAC was 19.7 ± 8.0 µmol/L, which was significantly higher than the preprandial value. Sex and hepatitis titers did not significantly influence preprandial and postprandial SBAC. The current study indicates that the SBAC reference values for rhesus macaques are higher than those reported for humans and companion animals. PMID:23849441

  18. Blood acid-base and serum electrolyte values in red deer (Cervus elaphus).

    PubMed Central

    Bouda, J; Dávalos-Flores, J L; Núñez-Ochoa, L; Paasch-Martínez, L; Quiroz-Rocha, G F

    2000-01-01

    Acid-base, serum electrolyte, plasma protein, and packed cell volume (PCV) values were determined in venous blood samples from 30 red deer (Cervus elaphus) of both sexes showing no clinical signs of disease. The animals were 5 months of age and kept on pasture in the Valley of Mexico, at an altitude of 2450 m. Blood samples were collected without sedation. Mean blood values were: pH 7.411 +/- 0.041, pCO2 37.7 +/- 4.4 mmHg, base excess 0.7 +/- 3.2 mmol/L, actual bicarbonate 24.3 +/- 3.1 mmol/L, total CO2 25.3 +/- 3.2 mmol/L and anion gap 23.5 +/- 5.5 mmol/L. Mean serum electrolyte levels were: Na+ 142.3 +/- 2.5 mmol/L, Cl- 100.5 +/- 2.3 mmol/L, and K+ 7.03 +/- 1.03 mmol/L. Plasma protein and PCV values were 60.0 +/- 6.6 g/L and 0.47 +/- 0.05 L/L, respectively. Blood values determined in this study can be considered reference data for health control and disease diagnosis. PMID:11041499

  19. Effects on Serum Fractalkine by Diet and Omega-3 Fatty Acid Intervention: Relation to Clinical Outcome

    PubMed Central

    Seljeflot, Ingebjørg; Fagerland, Morten Wang; Njerve, Ida Unhammer; Arnesen, Harald; Solheim, Svein

    2015-01-01

    Introduction. Fractalkine is a chemokine associated with atherosclerosis. Increased serum levels have been reported in unstable coronary artery disease (CAD) and to predict mortality in heart failure. Mediterranean-like diet and omega-3 fatty acids (n3-PUFA) have documented cardioprotective and anti-inflammatory effects. We have investigated the effect of Mediterranean-like dietary counseling and n-3 PUFA on serum fractalkine in an elderly population and its ability to predict cardiovascular disease (CVD). Materials and Methods. 563 men (age 64–75 yrs) at high risk of CAD were randomized into a 2 × 2 factorial designed trial for 3-year dietary counseling and/or n-3 PUFA supplementation (2.4 g/d). Circulating levels of fractalkine were measured at baseline and at end of study. Clinical events were recorded after 3 years. Results. Fractalkine levels were significantly reduced in all groups from baseline to 3 years (P < 0.001, all), but without between-group differences in changes. Fractalkine levels at baseline were not predictive for CVD events (n = 68) or total mortality. Lower fractalkine levels were observed in smokers (P = 0.019). Conclusions. Reduced levels of fractalkine from baseline to 3 years were observed, however, without any influence of Mediterranean-like diet or n-3 PUFA supplementation. Fractalkine levels at baseline were not predictive for later CVD events. PMID:25733777

  20. Binding of ring-substituted indole-3-acetic acids to human serum albumin.

    PubMed

    Soskić, Milan; Magnus, Volker

    2007-07-01

    The plant hormone, indole-3-acetic acid (IAA), and its ring-substituted derivatives have recently attracted attention as promising pro-drugs in cancer therapy. Here we present relative binding constants to human serum albumin for IAA and 34 of its derivatives, as obtained using the immobilized protein bound to a support suitable for high-performance liquid chromatography. We also report their octanol-water partition coefficients (logK(ow)) computed from retention data on a C(18) coated silica gel column. A four-parameter QSPR (quantitative structure-property relationships) model, based on physico-chemical properties, is put forward, which accounts for more than 96% of the variations in the binding affinities of these compounds. The model confirms the importance of lipophilicity as a global parameter governing interaction with serum albumin, but also assigns significant roles to parameters specifically related to the molecular topology of ring-substituted IAAs. Bulky substituents at ring-position 6 increase affinity, those at position 2 obstruct binding, while no steric effects were noted at other ring-positions. Electron-withdrawing substituents at position 5 enhance binding, but have no obvious effect at other ring positions.

  1. Changes in the serum composition of free-fatty acids during an intravenous glucose tolerance test.

    PubMed

    Soriguer, Federico; García-Serrano, Sara; García-Almeida, Jose M; Garrido-Sánchez, Lourdes; García-Arnés, Juan; Tinahones, Francisco J; Cardona, Isabel; Rivas-Marín, Jose; Gallego-Perales, Jose L; García-Fuentes, Eduardo

    2009-01-01

    Recent studies suggest that measuring the free-fatty acids (FFA) during an intravenous glucose tolerance test (IVGTT) may provide information about the metabolic associations between serum FFA and carbohydrate and insulin metabolism. We evaluated the FFA profile during an IVGTT and determined whether this test changes the composition and concentration of FFA. An IVGTT was given to 38 severely obese persons before and 7 months after undergoing bariatric surgery and also to 12 healthy, nonobese persons. The concentration and composition of the FFA were studied at different times during the test. The concentration of FFA fell significantly faster during the IVGTT in the controls and in the severely obese persons with normal-fasting glucose (NFG) than in the severely obese persons with impaired-fasting glucose (IFG) or type 2 diabetes mellitus (T2DM) (P < 0.05). Significant differences were found in the time to minimum serum concentrations of FFA (control = NFG < IFG < T2DM) (P < 0.001). These variables improved after bariatric surgery in the three groups. The percentage of monounsaturated and n-6 polyunsaturated FFA in the control subjects and in the obese persons, both before and after surgery, decreased significantly during the IVGTT. In conclusion, during an IVGTT, severely obese persons with IFG or T2DM experienced a lower fall in the FFA than the severely obese persons with NFG and the controls, becoming normal after bariatric surgery.

  2. An impact of the diet on serum fatty acid and lipid profiles in Polish vegetarian children and children with allergy.

    PubMed

    Gorczyca, D; Paściak, M; Szponar, B; Gamian, A; Jankowski, A

    2011-02-01

    Vegetarian diet has become an increasing trend in western world and in Poland. The frequency of allergies is growing, and the effectiveness of vegetarian diet in allergic diseases is a concern for research. We aimed to study an effect of vegetarian diet on lipid profile in serum in a group of Polish children in Poland and to investigate lipid parameters in healthy vegetarian children and in omnivorous children with diagnosed atopic disease. Serum lipid profiles (triglycerides, total cholesterol, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, fatty acids) were assessed in groups of children: healthy vegetarians (n=24) and children with diagnosed atopic diseases (n=16), with control group of healthy omnivores (n=18). Diet classification was assessed by a questionnaire. No differences were observed in serum triglycerides, LDL cholesterol and saturated and monounsaturated fatty acids level in all groups. In the group of Polish vegetarian children, we recorded high consumption of vegetable oils rich in monounsaturated fatty acid, and sunflower oil containing linoleic acid. This observation was associated with higher content of linoleic acid in serum in this group. Among polyunsaturated n-6 fatty acids, linoleic acid revealed significantly (P<0.05) lower levels in allergy vs vegetarian groups. In case of eicosapentaenoic acid (n-3 fatty acid), the allergy group showed higher levels of this compound in comparison to vegetarians. Significantly higher concentration of linoleic acid in vegetarian children in comparison to allergy group indicated possible alternative path of lipid metabolism in studied groups, and in consequence, some elements of vegetarian diet may promote protection against allergy.

  3. Association between serum free fatty acid levels and nonalcoholic fatty liver disease: a cross-sectional study

    PubMed Central

    Zhang, Juanwen; Zhao, Ying; Xu, Chengfu; Hong, Yani; Lu, Huanle; Wu, Jianping; Chen, Yu

    2014-01-01

    High serum free fatty acid (FFA) levels are associated with metabolic syndrome (MS). This study aimed to assess the association of fasting serum FFAs with nonalcoholic fatty liver disease (NAFLD) in a Chinese population. A total of 840 subjects fulfilled the diagnostic criteria of NAFLD and 331 healthy control participants were enrolled in this cross-sectional study. Fasting serum FFA levels and other clinical and laboratory parameters were measured. NAFLD patients had significantly higher serum FFA levels than controls (P < 0.001). Serum FFA levels were significantly and positively correlated with parameters of MS, inflammation indexes, and markers of hepatocellular damage. Elevated serum FFA levels were found in NAFLD subjects with individual components of MS (obesity, hypertriglyceridaemia, and hyperglycaemia). Stepwise regression showed that serum FFA levels were an independent factor predicting advanced fibrosis (FIB-4 ≥ 1.3) in NAFLD patients. Serum FFA levels correlated with NAFLD and could be used as an indicator for predicting advanced fibrosis in NAFLD patients. PMID:25060337

  4. Self-assembling of poly(aspartic acid) with bovine serum albumin in aqueous solutions.

    PubMed

    Nita, L E; Chiriac, A P; Bercea, M; Asandulesa, M; Wolf, Bernhard A

    2017-02-01

    Macromolecular co-assemblies built up in aqueous solutions, by using a linear polypeptide, poly(aspartic acid) (PAS), and a globular protein, bovine serum albumin (BSA), have been studied. The main interest was to identify the optimum conditions for an interpenetrated complex formation in order to design materials suitable for biomedical applications, such as drug delivery systems. BSA surface possesses several amino- and carboxylic groups available for covalent modification, and/or bioactive substances attachment. In the present study, mixtures between PAS and BSA were investigated at 37°C in dilute aqueous solution by viscometry, dynamic light scattering and zeta potential determination, as well as in solid state by AFM microscopy and dielectric spectroscopy. The experimental data have shown that the interpolymer complex formation occurs for a PAS/BSA molar ratio around 0.541.

  5. Interaction of bovine serum albumin protein with self assembled monolayer of mercaptoundecanoic acid

    NASA Astrophysics Data System (ADS)

    Poonia, Monika; Agarwal, Hitesh; Manjuladevi, V.; Gupta, R. K.

    2016-05-01

    Detection of proteins and other biomolecules in liquid phase is the essence for the design of a biosensor. The sensitivity of a sensor can be enhanced by the appropriate functionalization of the sensing area so as to establish the molecular specific interaction. In the present work, we have studied the interaction of bovine serum albumin (BSA) protein with a chemically functionalized surface using a quartz crystal microbalance (QCM). The gold-coated quartz crystals (AT-cut/5 MHz) were functionalized by forming self-assembled monolayer (SAM) of 11-Mercaptoundecanoic acid (MUA). The adsorption characteristics of BSA onto SAM of MUA on quartz crystal are reported. BSA showed the highest affinity for SAM of MUA as compared to pure gold surface. The SAM of MUA provides carboxylated surface which enhances not only the adsorption of the BSA protein but also a very stable BSA-MUA complex in the liquid phase.

  6. Spectroscopic studies on the interaction between 3,4,5-trimethoxybenzoic acid and bovine serum albumin

    NASA Astrophysics Data System (ADS)

    Hu, Yan-Jun; Yu, Hua-Guang; Dong, Jia-Xin; Yang, Xi; Liu, Yi

    2006-11-01

    The interaction between 3,4,5-trimethoxybenzoic acid (TMBA) and bovine serum albumin (BSA) was studied by fluorescence and UV-vis absorption spectroscopy. In the mechanism discussion, it was proved that the fluorescence quenching of BSA by TMBA is a result of the formation of TMBA-BSA complex. Quenching constants were determined using the Stern-Volmer equation to provide a measure of the binding affinity between TMBA and BSA. The thermodynamic parameters Δ H, Δ G, Δ S at different temperatures were calculated, and electrostatic interactions play an important role to stabilize the complex. The distance r between donor (BSA) and acceptor (TMBA) was obtained according to fluorescence resonance energy transfer (FRET).

  7. Serum Trans Fatty Acids Are Not Associated with Weight Gain or Linear Growth in School-Age Children123

    PubMed Central

    Baylin, Ana; Perng, Wei; Mora-Plazas, Mercedes; Marin, Constanza; Villamor, Eduardo

    2015-01-01

    Background: Animal and human adult studies indicate that long-term intake of trans fatty acids (TFAs) may be associated with weight gain. High intake of fast foods and snacks, which are rich in TFAs, is linked to overweight status among school-age children. However, the specific effects of TFAs in this population are unknown. Objective: We examined whether serum TFAs, used as biomarkers of intake, are associated with faster weight gain and linear growth during school years. Methods: We quantified TFAs by GLC in serum samples of 668 children aged 5–12 y at the time of recruitment into an ongoing cohort study performed in Bogota (Colombia) since 2006. Serum proportions of trans palmitoleic acid (16:1t), trans oleic acid (18:1t), trans linoleic acid (18:2t), and total TFAs were used as biomarkers of intake. Anthropometric characteristics were measured periodically for a median of 30 mo. Body mass index-for-age z scores (BAZs) and height-for-age z scores (HAZs) were calculated with the use of the WHO reference. We estimated mean changes in BAZs and HAZs over follow-up according to quartiles of each TFA at baseline by using mixed-effects regression models with restricted cubic splines. Results: Proportions of trans palmitoleic acid, trans oleic acid, trans linoleic acid, and total TFAs (mean ± SD, % of total serum FAs), were 0.22 ± 0.06, 0.91 ± 0.37, 0.96 ± 0.27, and 2.10 ± 0.59, respectively. Serum TFAs were not associated with changes in BAZs and HAZs after adjusting for sex, baseline age, and socioeconomic status. In a subgroup analysis by sex, serum trans palmitoleic acid was positively associated with the estimated change in HAZs from ages 6 to 14 y in boys (with use of the first quartile as the reference, differences in HAZs for trans palmitoleic acid quartiles were 0.73, 0.53, and 0.70, P-trend = 0.03). Conclusions: Proportions of serum TFAs, used as biomarkers of TFA intake, were not associated with weight gain in children aged 6–14 y in low- and middle

  8. Serum uric acid level as a determinant of the metabolic syndrome: A case control study.

    PubMed

    Khichar, Satyendra; Choudhary, Shyama; Singh, Veer Bahadur; Tater, Priyanka; Arvinda, R V; Ujjawal, Vivek

    To determine whether elevations of uric acid levels are associated with the cluster of disorders described in metabolic syndrome and to evaluate whether hyperuricemia may be considered a component of this syndrome. One year case-control study was conducted in Bikaner, Rajasthan, India from January to December 2013. The study population consisted of 200 subjects, 100 with metabolic syndrome (case) and 100 without metabolic syndrome (control) aged between 18 and 80 years, attending OPD at PBM Hospital were studied. Controls were age and sex matched to the cases. Blood tests and all physical variables were examined using standard methods. Subjects were divided into 6 groups according to their possession of 0, 1, 2, 3, 4 or 5 components of the metabolic syndrome. Statistical analysis was done using ANOVA, linear regression analysis and multivariate linear regression model. Mean serum UA level was significantly associated with all components of metabolic syndrome (p<0.001) and had strong positive correlation (r=+0.66 to +0.77, p<0.0001) with all of them except serum HDL with which it showed strong negative correlation(r=-0.71, p<0.0001). It increased as the number of metabolic factors increased showing a highly significant trend (p<0.0001). On multivariate regression analysis UA contributed to 66.84% variance of metabolic syndrome. The current multivariate regression analysis clearly infers that uric acid can be considered as a marker and potential modifier of metabolic syndrome. Copyright © 2016 Diabetes India. Published by Elsevier Ltd. All rights reserved.

  9. Fatty acid and prostaglandin metabolism in children with diabetes mellitus. II. The effect of evening primrose oil supplementation on serum fatty acid and plasma prostaglandin levels.

    PubMed

    Arisaka, M; Arisaka, O; Yamashiro, Y

    1991-07-01

    Our previous study demonstrated that levels of dihomo-gamma-linolenic acid (DGLA) and arachidonic acid in serum total lipids decreased in association with increased plasma levels of prostaglandins E2 (PGE2) and F2 alpha (PGF2 alpha) in patients with insulin-dependent diabetes mellitus. In this study, 11 children with insulin-dependent diabetes mellitus completed a double-blind, placebo-controlled study to assess the effect of dietary supplementation with gamma-linolenic acid (GLA) on serum essential fatty acid and plasma PGE2 and PGF2 alpha levels. GLA was given as the seed oil from the evening primrose (EPO) and all patients received either EPO capsules (containing 45 mg of GLA and 360 mg of linoleic acid) or indistinguishable placebo capsules for 8 months. Initially patients took 2 capsules daily for 4 months then 4 capsules daily for a further 4 months. All patients were assessed at the start of the study, after 4 months and at the end of the study, by measuring serum essential fatty acid and plasma PGE2 and PGF2 alpha levels. After administration of 4 capsules daily the DGLA levels increased and PGE2 levels decreased significantly (p less than 0.01) in the EPO compared with the placebo group. Neither fatty acid nor PGE2 and PGF2 alpha levels were altered by administration of 2 EPO capsules daily. This suggests that the altered essential fatty acid and PG metabolism in diabetes may be reversed by direct GLA supplementation.

  10. Serum homocysteine and folate concentrations among a US cohort of adolescents before and after folic acid fortification.

    PubMed

    Enquobahrie, Daniel A; Feldman, Henry A; Hoelscher, Deanna H; Steffen, Lyn M; Webber, Larry S; Zive, Michelle M; Rimm, Eric B; Stampfer, Meir J; Osganian, Stavroula K

    2012-10-01

    We assessed serum homocysteine (tHcy) and folate concentrations among US adolescents before and after fortification of cereal-grain products with folic acid, and associations with demographic, behavioural and physiological factors. Observational study conducted among participants of a randomized trial. The Child and Adolescent Trial for Cardiovascular Health (CATCH) study. Adolescents (n 2445) in grades 8 (pre-fortification, mean age 14 years) and 12 (post-fortification, mean age 18 years). Average serum concentrations of tHcy, folate and vitamin B6 increased by 17 %, 16 % and 14 %, respectively, while serum concentrations of vitamin B12 decreased by 11 % post-fortification. Folic acid fortification provided, on average, an additional intake of 118 μg folate/d. Male sex (P < 0.0001) and white race (P = 0.0008) were associated with significantly greater increases in tHcy concentration, while increases in BMI (P = 0.006) and serum folate concentration (P < 0.0001) were associated with significant decreases in tHcy concentration. Female sex (P < 0.0001), non-smoking (P < 0.0001), use of multivitamins (P < 0.0001) and higher dietary intake of folate (P = 0.001) were associated with significantly greater increases in serum folate concentrations. From grade 8 to grade 12, the upward age trend in serum tHcy concentration was uninterrupted in its course (P > 0.50); whereas serum folic acid concentration showed a downward trend that incurred a discrete jump upward (17 % higher; P < 0.0001) with fortification. These trends differed significantly for males v. females (P < 0.001 for interaction). Fortification had a significant impact on improving folate status but not serum tHcy concentrations among US adolescents.

  11. Serum saturated fatty acid decreases plasma adiponectin and increases leptin throughout pregnancy independently of BMI.

    PubMed

    Lepsch, Jaqueline; Farias, Dayana Rodrigues; Vaz, Juliana Dos Santos; de Jesus Pereira Pinto, Thatiana; da Silva Lima, Natália; Freitas Vilela, Ana Amélia; Cunha, Marcelo; Factor-Litvak, Pam; Kac, Gilberto

    2016-01-01

    The aim of this study was to investigate whether serum concentrations of total saturated fatty acids (SFAs), polyunsaturated fatty acids (PUFAs), and their fractions are associated with plasma adiponectin and leptin concentrations throughout pregnancy. A prospective cohort of 201 pregnant women was followed from gestational weeks 5 to 13, 20 to 26, and 30 to 36. Blood samples were collected at the three visits after 12 h of fasting. Fatty acid concentrations were determined using fast gas-liquid chromatography. Plasma adiponectin (μg/mL) and leptin (ng/dL) concentrations were evaluated using enzyme-linked immunosorbent assay kits. Statistical analyses included median adipokine concentrations according to the tertiles of fatty acid distribution and multiple linear mixed-effect models adjusted for body mass index, gestational age, total energy intake, alcohol consumption, and smoking. Women classified in the third SFA concentration tertile had lower median values of adiponectin compared with those in the first tertile ([first trimester: first tertile = 5.36; third tertile = 5.00]; [second trimester: first tertile = 6.39; third tertile = 4.47]; [third trimester: first tertile = 6.46; third tertile = 4.60]). Similar trends were observed for the 14:0, 16:0 and 18:0 fractions. In the multiple longitudinal models, total SFA (β = -41.039; P = 0.008) and 16:0 were negatively associated with plasma adiponectin (16:0, β = -0.511; P = 0.001). Total PUFA ω-6 (β = 28.961; P = 0.002) and 18:2 ω-6 (β = 0.259, P = 0.006) were positively associated with the adiponectin. Total SFA (β = 0.110, P = 0.007), 14:0 (β = 0.072, P = 0.011), and 20:3 ω-6 (β = 0.039; P = 0.035) were positively associated with plasma leptin. Total serum SFA and the 16:0 fraction were negatively associated with plasma adiponectin and positively associated with leptin concentrations. Total ω-6 PUFA was positively associated only with plasma adiponectin

  12. High incidence of hypocalcemia and serum creatinine increase in patients with bone metastases treated with zoledronic acid.

    PubMed

    Zuradelli, Monica; Masci, Giovanna; Biancofiore, Giuseppe; Gullo, Giuseppe; Scorsetti, Marta; Navarria, Pierina; Tancioni, Flavio; Berlusconi, Marco; Giordano, Laura; Santoro, Armando

    2009-05-01

    Zoledronic acid belongs to the new generation of bisphosphonates with demonstrated clinical benefit for the treatment of bone metastases from different kinds of neoplasms. Hypocalcemia and serum creatinine elevation are expected adverse events during this therapy. The monitoring of serum calcium and creatinine is therefore recommended. The primary aim of this study was to establish the actual incidence of hypocalcemia and serum creatinine elevation during treatment with zoledronic acid. Skeletal-related events and side effects were also assessed. Serum creatinine and calcium levels were evaluated in 240 consecutive patients (83 males, 157 females; mean age, 62 years) with metastatic bone lesions from different solid tumors treated with zoledronic acid. Overall, 93 of 240 patients (38.8%) developed hypocalcemia, which was grade (G)1 in 45 patients (48.4%), G2 in 37 patients (39.8%), G3 in 10 patients (10.8%), and G4 in one patient (1.1%). The median time to occurrence of hypocalcemia (any grade) was 2.3 months after the beginning of the treatment (range, 0-34.9 months). Increased serum creatinine was observed in 33 of 240 patients (13.7%), of whom 19 had G1 (57.6%), 11 had G2 (33.3%), and three had G3 (9.1%). The median time to serum creatinine increase (for any grade) was 4.7 months (range, 0-29.2 months). Our analysis shows a high incidence of hypocalcemia and increased serum creatinine level during treatment with zoledronic acid. These results strongly support the need for accurate monitoring of plasma calcium and creatinine levels.

  13. Effect of almond consumption on the serum fatty acid profile: a dose-response study.

    PubMed

    Nishi, Stephanie; Kendall, Cyril W C; Gascoyne, Ana-Maria; Bazinet, Richard P; Bashyam, Balachandran; Lapsley, Karen G; Augustin, Livia S A; Sievenpiper, John L; Jenkins, David J A

    2014-10-14

    Consumption of almonds has been shown to be associated with a decreased risk of CHD, which may be related to their fatty acid (FA) composition. However, the effect of almond consumption on the serum FA composition is not known. Therefore, in the present study, we investigated whether almond consumption would alter the serum FA profile and risk of CHD, as calculated using Framingham's 10-year risk score, in a dose-dependent manner in hyperlipidaemic individuals when compared with a higher-carbohydrate control group using dietary interventions incorporating almonds. A total of twenty-seven hyperlipidaemic individuals consumed three isoenergetic (mean 1770 kJ/d) supplements during three 1-month dietary phases: (1) full-dose almonds (50-100 g/d); (2) half-dose almonds with half-dose muffins; (3) full-dose muffins. Fasting blood samples were obtained at weeks 0 and 4 for the determination of FA concentrations. Almond intake (g/d) was found to be inversely associated with the estimated Framingham 10-year CHD risk score (P= 0·026). In both the half-dose and full-dose almond groups, the proportions of oleic acid (OA) and MUFA in the TAG fraction (half-almond: OA P= 0·003; MUFA P= 0·004; full-almond: OA P< 0·001; MUFA P< 0·001) and in the NEFA fraction (half-almond: OA P= 0·01; MUFA P= 0·04; full-almond: OA P= 0·12; MUFA P= 0·06) increased. The estimated Framingham 10-year CHD risk score was inversely associated with the percentage change of OA (P= 0·011) and MUFA (P= 0·016) content in the TAG fraction. The proportions of MUFA in the TAG and NEFA fractions were positively associated with changes in HDL-cholesterol concentrations. Similarly, the estimated Framingham 10-year CHD risk score was inversely associated with the percentage change of OA (P= 0·069) and MUFA content in the NEFA fraction (P= 0·009). In conclusion, the results of the present study indicate that almond consumption increases OA and MUFA content in serum TAG and NEFA fractions

  14. Perfluoroalkyl Acids in Maternal Serum and Indices of Fetal Growth: The Aarhus Birth Cohort

    PubMed Central

    Bach, Cathrine Carlsen; Bech, Bodil Hammer; Nohr, Ellen Aagaard; Olsen, Jørn; Matthiesen, Niels Bjerregård; Bonefeld-Jørgensen, Eva Cecilie; Bossi, Rossana; Henriksen, Tine Brink

    2015-01-01

    Background: Previous studies indicated an association between intrauterine exposure to perfluorooctane sulfonate (PFOS) or perfluorooctanoate (PFOA) and lower birth weight. However, these perfluoroalkyl acids (PFAAs) have to some extent been substituted by other compounds on which little is known. Objectives: We investigated the association between specific PFAAs and birth weight, birth length, and head circumference at birth. Methods: We studied 1,507 mothers and their children from the Aarhus Birth Cohort (2008–2013). Nulliparous women were included during pregnancy, and serum levels of 16 PFAAs were measured between 9 and 20 completed gestational weeks (96% within 13 weeks). For compounds with quantifiable values in > 50% of samples (7 compounds), we report the associations with birth weight, birth length, and head circumference at birth determined by multivariable linear regression. Results: Estimated mean birth weights were lower among women with serum perfluorohexane sulfonate, perfluoroheptane sulfonate, and PFOS concentrations above the lowest exposure quartile, but we found no consistent monotonic dose–response patterns. These associations were stronger when the population was restricted to term births (n = 1,426). For PFOS, the birth weight estimates for the highest versus lowest quartile were –50 g (95% CI: –123, 23 g) in all births and –62 g (95% CI: –126, 3 g) in term births. For the other PFAAs, the direction of the associations was inconsistent, and no overall association with birth weight was apparent. No PFAAs were associated with birth length or head circumference at birth. Conclusions: Overall, we did not find strong or consistent associations between PFAAs and birth weight or other indices of fetal growth, though estimated mean birth weights were lower among those with exposures above the lowest quartile for some compounds. Citation: Bach CC, Bech BH, Nohr EA, Olsen J, Matthiesen NB, Bonefeld-Jørgensen EC, Bossi R, Henriksen TB

  15. Correlation of retinal nerve fibre layer and macular thickness with serum uric acid among type 2 diabetes mellitus.

    PubMed

    Vinuthinee-Naidu, Munisamy-Naidu; Zunaina, Embong; Azreen-Redzal, Anuar; Nyi-Nyi, Naing

    2017-06-14

    Uric acid is a final breakdown product of purine catabolism in humans. It's a potent antioxidant and can also act as a pro-oxidant that induces oxidative stress on the vascular endothelial cells, thus mediating progression of diabetic related diseases. Various epidemiological and experimental evidence suggest that uric acid has a role in the etiology of type 2 diabetes mellitus. We conducted a cross-sectional study to evaluate the correlation of retinal nerve fibre layer (RNFL) and macular thickness with serum uric acid in type 2 diabetic patients. A cross-sectional study was conducted in the Eye Clinic, Hospital Universiti Sains Malaysia, Kelantan between the period of August 2013 till July 2015 involving type 2 diabetes mellitus patients with no diabetic retinopathy and with non-proliferative diabetic retinopathy (NPDR). An evaluation for RNFL and macular thickness was measured using Spectralis Heidelberg optical coherence tomography. Six ml of venous blood was taken for the measurement of serum uric acid and glycosylated haemoglobin (HbA1C). A total of 180 diabetic patients were recruited (90 patients with no diabetic retinopathy and 90 patients with NPDR) into the study. The mean level of serum uric acid for both the groups was within normal range and there was no significance difference between the two groups. Based on gender, both male and female gender showed significantly higher level of mean serum uric acid in no diabetic retinopathy group (p = 0.004 respectively). The mean serum uric acid was significantly higher in patient with HbA1C < 6.5% (p < 0.031). Patients with NPDR have thicker RNFL and macular thickness compared to patients with no diabetic retinopathy. However, only the RNFL thickness of the temporal quadrant and the macular thickness of the superior outer, inferior outer and temporal outer subfields were statistically significant (p = 0.038, p = 0.004, 0.033 and <0.001 respectively). There was poor correlation between RNFL and macular

  16. Unmasking Heavily O-Glycosylated Serum Proteins Using Perchloric Acid: Identification of Serum Proteoglycan 4 and Protease C1 Inhibitor as Molecular Indicators for Screening of Breast Cancer

    PubMed Central

    Lee, Cheng-Siang; Taib, Nur Aishah Mohd; Ashrafzadeh, Ali; Fadzli, Farhana; Harun, Faizah; Rahmat, Kartini; Hoong, See Mee; Abdul-Rahman, Puteri Shafinaz; Hashim, Onn Haji

    2016-01-01

    Heavily glycosylated mucin glycopeptides such as CA 27.29 and CA 15–3 are currently being used as biomarkers for detection and monitoring of breast cancer. However, they are not well detected at the early stages of the cancer. In the present study, perchloric acid (PCA) was used to enhance detection of mucin-type O-glycosylated proteins in the serum in an attempt to identify new biomarkers for early stage breast cancer. Sensitivity and specificity of an earlier developed sandwich enzyme-linked lectin assay were significantly improved with the use of serum PCA isolates. When a pilot case-control study was performed using the serum PCA isolates of normal participants (n = 105) and patients with stage 0 (n = 31) and stage I (n = 48) breast cancer, higher levels of total O-glycosylated proteins in sera of both groups of early stage breast cancer patients compared to the normal control women were demonstrated. Further analysis by gel-based proteomics detected significant inverse altered abundance of proteoglycan 4 and plasma protease C1 inhibitor in both the early stages of breast cancer patients compared to the controls. Our data suggests that the ratio of serum proteoglycan 4 to protease C1 inhibitor may be used for screening of early breast cancer although this requires further validation in clinically representative populations. PMID:26890881

  17. Serum concentrations of perfluorinated alkyl acids and their associations with diet and personal characteristics among Swedish adults.

    PubMed

    Bjermo, Helena; Darnerud, Per Ola; Pearson, Monika; Barbieri, Heléne Enghardt; Lindroos, Anna Karin; Nälsén, Cecilia; Lindh, Christian H; Jönsson, Bo A G; Glynn, Anders

    2013-12-01

    In this study, food is suggested as a major source of human exposure to perfluorinated alkyl acids (PFAA). We investigated relations between serum levels of PFAA in adults and diet/lifestyle factors nationwide in Sweden. In 2010-2011, adults (18-80 years, N = 270) recorded their diet for 4 days and answered a food frequency questionnaire. PFAA were measured in blood serum as well as v-3 fatty acids in plasma phospholipids as a biomarker for fish consumption. Higher levels of PFAA were associated with male sex, increased age, and higher education. Women reporting full breastfeeding for ≥12 months had 32-44% lower levels of perfluorooctane sulfonate, perfluorooctanoic acid, and perfluorohexane sulfonate than women who never nursed their infants full-time. Serum perfluorooctane sulfonate, perfluorononanoic acid, perfluorodecanoic acid, and perfluoroundecanoic acid were positively related to n-3 fatty acids in plasma (partial r = 0.19-0.34, p ≤ 0.05). The relatively strong correlations between biomarkers of fish consumption and certain PFAA suggest that PFAA exposure should be taken into account in health risk and benefit assessment of fish consumption. Breastfeeding appears to be a major source of elimination of certain PFAA among women, and consequently PFAA exposure of nursed infants could be significant. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. [The amino acid composition of blood serum of harp seal pups in the period of adaptation to captivity].

    PubMed

    Erokhina, I A

    1998-01-01

    It is cited results of investigation of amino acid composition of blood serum of harp seal pups in the first days after catch adaptation in conditions of oceanarium. It is shown that changes of amino acid composition are most expressed in the first ten-day period of observation and manifest itself by increase of free amino acid concentration at the expense of their endogenous entrance in blood. At the same time it was detected amino acid imbalance which is conditioned by stress of animals. Results of investigation witness intensification of protein catabolism under conditions of stress. Because of it it is necessary to correlate protein metabolism for prophylaxis of hypotrophy seal pups.

  19. New amperometric biosensors based on diamond paste for the assay of L- and D-pipecolic acids in serum samples.

    PubMed

    Stefan, Raluca-Ioana; Nejem, R'afat Mahmoud; van Staden, Jacobus F; Aboul-Enein, Hassan Y

    2004-05-01

    Monocrystalline natural diamond, L-amino acid oxidase (L-AAOD), D-amino acid oxidase (D-AAOD), and paraffin oil were used for the design of the modified diamond paste. The technique used for the direct voltammetric assay was differential pulse voltammetry (DPV) with applied potential pulse amplitude of 25 mV vs. Ag/AgCl. Using the new amperometric biosensors L-pipecolic acid (L-PA) and D-pipecolic acid (D-PA) were determined reliably from serum samples at 700 and 200 mV vs. Ag/AgCl, respectively, with low limits of detection.

  20. Elevated serum alpha-linolenic acid levels are associated with decreased chance of pregnancy after in vitro fertilization

    PubMed Central

    Jungheim, Emily S.; Macones, George A.; Odem, Randall R.; Patterson, Bruce W.; Moley, Kelle H.

    2011-01-01

    Study Objective To analyze relationships between serum free fatty acid (FFA) concentrations and pregnancy. Design Prospective cohort Setting University hospital Patients 91 women undergoing in vitro fertilization (IVF) Interventions Serum was analyzed for total and specific serum FFAs including myristic, palmitic, stearic, oleic, linoleic and α-linolenic acids. Main outcome measures Univariate analyses were used to identify specific FFAs and other factors associated with pregnancy after IVF. Logistic regression was performed modeling relationships between identified factors and chance of pregnancy. Results In unadjusted analyses, women with elevated serum α-linolenic (ALA) levels (highest quartile) demonstrated a decreased chance of pregnancy compared to women with the lowest levels (OR:0.24, 95% CI:0.052–0.792, p=0.022). No associations between other FFAs and pregnancy were identified. In a multivariable regression model, associations between elevated serum ALA levels and decreased chance of pregnancy remained after adjusting for patient age, body mass index, and history of endometriosis or previous live birth (adjusted OR:0.139, 95% CI:0.028–0.686, p=0.015). Conclusions Elevated serum ALA levels are associated with decreased chance of pregnancy in women undergoing IVF. Further work is needed to determine if ALA is involved in early reproductive processes and if the relationship between ALA and pregnancy is associated with excess ALA intake, impaired ALA metabolism or both. PMID:21840520

  1. Rapid determination of domoic acid in serum and urine by liquid chromatography-electrospray tandem mass spectrometry.

    PubMed

    Tor, Elizabeth R; Puschner, Birgit; Whitehead, William E

    2003-03-26

    A rapid, selective, and sensitive LC-MS/MS method was developed for the quantitative determination of domoic acid in serum and urine samples. Samples were prepared for analysis using an Oasis HLB SPE column. Determination was by a reversed phase HPLC using a mixture of methanol, acetonitrile, and water containing 1% acetic acid and an electrospray ionization (ESI) ion-trap mass spectrometer (Finnigan LCQ). The method was validated by analyzing five replicates each of negative control bovine serum or urine fortified with domoic acid at the 0.005 microg/g method detection limit (MDL) and at the 0.05 microg/g level. Recoveries ranged from 90 to 95% for fortifications at the MDL and from 92 to 98% for fortifications 10 times higher than the MDL. The diagnostic utility of the method was tested by analyzing samples from live animals showing clinical signs suggestive of domoic acid poisoning submitted to the veterinary toxicology laboratory.

  2. Profiling serum bile acid glucuronides in humans: gender divergences, genetic determinants, and response to fenofibrate.

    PubMed

    Trottier, J; Perreault, M; Rudkowska, I; Levy, C; Dallaire-Theroux, A; Verreault, M; Caron, P; Staels, B; Vohl, M-C; Straka, R J; Barbier, O

    2013-10-01

    Glucuronidation, catalyzed by uridine 5'-diphospho-glucuronosyltransferase (UGT) enzymes, detoxifies cholestatic bile acids (BAs). We aimed to (i) characterize the circulating BA-glucuronide (BA-G) pool composition in humans, (ii) determine how sex and UGT polymorphisms influence this composition, and (iii) analyze the effects of the lipid-lowering drug fenofibrate on the circulating BA-G profile in 300 volunteers and 5 cholestatic patients. Eleven BA-Gs were determined in pre- and postfenofibrate samples. Men exhibited higher BA-G concentrations, and various genotype/BA-G associations were discovered in relevant UGT genes. The chenodeoxycholic acid-3G (CDCA-3G) concentration was associated with the UGT2B7 802C>T polymorphism. Glucuronidation assays confirmed the predominant role of UGT2B7 and UGT1A4 in CDCA-3G formation. Fenofibrate exposure increased the serum levels of five BA-G species, including CDCA-3G, and upregulated expression of UGT1A4, but not UGT2B7, in hepatic cells. This study demonstrated that fenofibrate stimulates BA glucuronidation in humans and thus reduces BA toxicity in the liver.

  3. Evaluation of serum sialic acid, heat stable alkaline phosphatase and fucose as markers of breast carcinoma.

    PubMed

    Patel, P S; Baxi, B R; Adhvaryu, S G; Balar, D B

    1990-01-01

    Serum levels of total sialic acid (TSA), lipid bound sialic acid (LSA), heat stable alkaline phosphatase (HSAP) and fucose were measured in 39 patients with breast carcinoma, 14 patients with benign breast diseases and 35 healthy female individuals. Elevated levels of the four biomarkers in breast carcinoma were significant when compared with controls (p less than 0.001). Fucose levels were most sensitive (71.8%), while TSA levels were most specific (64.3%) for breast carcinoma. Sensitivity and specificity were 100% when combinations of LSA with fucose and TSA with HSAP were studied respectively. LSA was significantly elevated in infiltrating duct carcinoma patients compared with lobular carcinoma (p less than 0.001). TSA, HSAP and fucose also had lower mean values in lobular carcinoma as compared to infiltrating duct carcinoma. Increase in the levels of LSA and HSAP after surgical removal of the tumor in breast carcinoma occurred prior to the clinical evidence of the recurrence. The results indicate that the combination of the markers studied might be useful in breast cancer diagnosis and treatment monitoring.

  4. Glycomic analysis of sialic acid linkages in glycans derived from blood serum glycoproteins.

    PubMed

    Alley, William R; Novotny, Milos V

    2010-06-04

    A number of alterations to the normal glycomic profile have been previously described for a number of diseases and disorders, thus underscoring the medical importance of studying the glycans associated with proteins present in biological samples. An important alteration in cancer progression is an increased level of alpha2,6-sialylation, which aids in increasing the metastatic potential of tumor cells. Here we report a glycomic method that selectively amidates alpha2,6-linked sialic acids, while those that are alpha2,3-linked undergo spontaneous lactonization. Following subsequent permethylation, MALDI-TOF MS analysis revealed that many sialylated glycans present on glycoproteins found in blood serum featured increased levels of alpha2,6-sialylation in breast cancer samples. On the basis of the altered ratios of alpha2,3-linked to alpha2,6-linked sialic acids, many of these glycans became diagnostically relevant when they did not act as such indicators when based on traditional glycomic profiling alone.

  5. Alterations of primary fatty acid amides in serum of patients with severe mental illness.

    PubMed

    Schwarz, Emanuel; Whitfield, Phil; Nahnsen, Sven; Wang, Lan; Major, Hilary; Leweke, F Markus; Koethe, Dagmar; Lio, Pietro; Bahn, Sabine

    2011-01-01

    Cannabis consumption is a well known risk factor for the onset of schizophrenia and evidence accumulates that the endocannabinoid system may play a central role in the disease etiology. Using a clinical bioinformatics approach, we have previously found primary fatty acid amides, which are linked to the endocannabinoid system, to be elevated in drug naive schizophrenia and affective disorder. Here, we provide a detailed description of these findings and expand the investigation by analyzing serum from 74 patients after short term treatment with antipsychotic medication using a liquid chromatography-mass spectrometry (LC-MS) metabolomics approach. We show that primary fatty acid amide (pFAA) levels normalize after treatment with typical but not after treatment with atypical antipsychotic medication. Also, the comparison of pFAA levels in schizophrenia patients to those of sleep deprived healthy volunteers suggests that pFAA abnormalities were not related to changes in the sleep architecture of patients with mental illness. Our findings support the involvement of the endocannabinoid system in the pathology of schizophrenia.

  6. An electrochemical clamp assay for direct, rapid analysis of circulating nucleic acids in serum

    NASA Astrophysics Data System (ADS)

    Das, Jagotamoy; Ivanov, Ivaylo; Montermini, Laura; Rak, Janusz; Sargent, Edward H.; Kelley, Shana O.

    2015-07-01

    The analysis of cell-free nucleic acids (cfNAs), which are present at significant levels in the blood of cancer patients, can reveal the mutational spectrum of a tumour without the need for invasive sampling of the tissue. However, this requires differentiation between the nucleic acids that originate from healthy cells and the mutated sequences shed by tumour cells. Here we report an electrochemical clamp assay that directly detects mutated sequences in patient serum. This is the first successful detection of cfNAs without the need for enzymatic amplification, a step that normally requires extensive sample processing and is prone to interference. The new chip-based assay reads out the presence of mutations within 15 minutes using a collection of oligonucleotides that sequester closely related sequences in solution, and thus allow only the mutated sequence to bind to a chip-based sensor. We demonstrate excellent levels of sensitivity and specificity and show that the clamp assay accurately detects mutated sequences in a collection of samples taken from lung cancer and melanoma patients.

  7. Circulating nucleic acids in plasma and serum (CNAPS): applications in oncology

    PubMed Central

    González-Masiá, José A; García-Olmo, Damián; García-Olmo, Dolores C

    2013-01-01

    The presence of small amounts of circulating nucleic acids in plasma and serum (CNAPS) is not a new finding. The verification that such amounts are significantly increased in cancer patients, and that CNAPS might carry a variety of genetic and epigenetic alterations related to cancer development and progression, has aroused great interest in the scientific community in the last decades. Such alterations potentially reflect changes that occur during carcinogenesis, and include DNA mutations, loss of heterozygosity, viral genomic integration, disruption of microRNA, hypermethylation of tumor suppressor genes, and changes in the mitochondrial DNA. These findings have led to many efforts toward the implementation of new clinical biomarkers based on CNAPS analysis. In the present article, we review the main findings related to the utility of CNAPS analysis for early diagnosis, prognosis, and monitoring of cancer, most of which appear promising. However, due to the lack of harmonization of laboratory techniques, the heterogeneity of disease progression, and the small number of recruited patients in most of those studies, there has been a poor translation of basic research into clinical practice. In addition, many aspects remain unknown, such as the release mechanisms of cell-free nucleic acids, their biological function, and the way by which they circulate in the bloodstream. It is therefore expected that in the coming years, an improved understanding of the relationship between CNAPS and the molecular biology of cancer will lead to better diagnosis, management, and treatment. PMID:23874104

  8. Serum Amino Acid Profiles in Childhood Predict Triglyceride Level in Adulthood: A 7-Year Longitudinal Study in Girls.

    PubMed

    Wiklund, Petri; Zhang, Xiaobo; Tan, Xiao; Keinänen-Kiukaanniemi, Sirkka; Alen, Markku; Cheng, Sulin

    2016-05-01

    Branched-chain and aromatic amino acids are associated with high risk of developing dyslipidemia and type II diabetes in adults. This study aimed to examine whether serum amino acid profiles associate with triglyceride concentrations during pubertal growth and predict hypertriglyceridemia in early adulthood. This was a 7.5-year longitudinal study. The study was conducted at the Health Science Laboratory, University of Jyväskylä. A total of 396 nondiabetic Finnish girls aged 11.2 ± 0.8 years at the baseline participated in the study. Body composition was assessed by dual-energy x-ray absorptiometry; serum concentrations of glucose, insulin, and triglyceride by enzymatic photometric methods; and amino acids by nuclear magnetic resonance spectroscopy. Serum leucine and isoleucine correlated significantly with future triglyceride, independent of baseline triglyceride level (P < .05 for all). In early adulthood (at the age of 18 years), these amino acids were significantly associated with hypertriglyceridemia, whereas fat mass and homeostasis model assessment of insulin resistance were not. Leucine was the strongest determinant discriminating subjects with hypertriglyceridemia from those with normal triglyceride level (area under the curve, 0.822; 95% confidence interval, 0.740-0.903; P = .000001). Serum leucine and isoleucine were associated with future serum triglyceride levels in girls during pubertal growth and predicted hypertriglyceridemia in early adulthood. Therefore, these amino acid indices may serve as biomarkers to identify individuals at high risk for developing hypertriglyceridemia and cardiovascular disease later in life. Further studies are needed to elucidate the role these amino acids play in the lipid metabolism.

  9. Serum Uric Acid Level Predicts Progression of IgA Nephropathy in Females but Not in Males

    PubMed Central

    Shoji, Tatsuya; Shinzawa, Maki; Hasuike, Yukiko; Nagatoya, Katsuyuki; Yamauchi, Atsushi; Hayashi, Terumasa; Kuragano, Takayuki; Moriyama, Toshiki; Isaka, Yoshitaka; Nakanishi, Takeshi

    2016-01-01

    Background Immunoglobulin A nephropathy (IgAN) is one of most common forms of glomerulonephritis. At this point, the clinical impact of hyperuricemia on IgAN is not clear. The aim of the present study was to explore the clinical impact of hyperuricemia on the progression of IgAN. Study Design Multicenter retrospective cohort study. Setting & Participants 935 IgAN patients who were diagnosed by kidney biopsy at Osaka University Hospital, Osaka General Hospital, and Osaka Rosai Hospital. were included in this study. Predictor Uric acid levels at renal biopsy. Outcomes The outcome of interest was the time from the kidney biopsy to the time when a 50% increase in the baseline serum creatinine level was observed, which was defined as "progression". Measurements The baseline characteristics according to the kidney biopsy at the time of diagnosis were collected from the medical records, and included age, gender, body mass index, hypertension, diabetes (use of antidiabetic drugs), serum levels of creatinine, urinary protein, smoking status, RAAS blockers and steroid therapy. Results An elevated serum uric acid level was an independent risk factor for progression in female patients (per 1.0 mg/dL, multivariate-adjusted incident rate ratio 1.33 [95% confidence interval 1.07, 1.64], P = 0.008) but not in male patients (1.02 [0.81, 1.29], P = 0.855). To control a confounding effect of renal function on an association between serum uric acid level and progression in female patients, age- and serum creatinine-matched and propensity score-matched analyses were performed, and these results also supported the effect by uric acid on kidney disease progression independent of basal kidney function. Limitations A cohort analyzed retorospectively. Conclusions This study revealed that an elevated uric acid level was an independent risk factor for ESKD in female IgAN patients. Therefore, uric acid might be a treatable target in female IgAN patients. PMID:27560997

  10. Benefits of Omega-3 Fatty Acids Supplementation on Serum Paraoxonase 1 Activity and Lipids Ratios in Polycystic Ovary Syndrome

    PubMed Central

    Mohammadi, Elahe; Rafraf, Maryam

    2012-01-01

    Background: Polycystic ovary syndrome (PCOS) is a common endocrine disorder associated with increased risk of cardiovascular disease. The purpose of this study was to investigate the ef¬fects of omega-3 fatty acids on serum paraoxonase 1 activity and lipids ratios in polycystic ovary syndrome. Methods: This double-blind randomized controlled clinical trial was conducted on 64 PCOS pa¬tients with 20-35 years old. Thirty two of the subjects had taken 4 g/day omega -3 fatty acids and 32 patients were given placebo for 8 weeks. Fasting blood samples, anthropometric measure¬ments and dietary intakes were collected at the beginning and the end of the study. Serum total cholesterol, triglyceride, and HDL-C were measured using the enzymatic methods. LDL-C con¬centration was calculated by the Friedewald formula and arylesterase activity of serum PON1 was measured. Data were analyzed using SPSS software. Results: Omega-3 fatty acids significantly decreased TC/HDL-C and LDL-C/HDL-C ratios (P = 0.009 for both) and significantly increased serum PON1 activity (P = 0.048) compared with placebo. Changes in TG/HDL-C ratio were not statistically significant in omega-3 fatty acids group at the end of the study in comparison to placebo group. Reduction in TC/HDL-C, LDL-C/HDL-C and TG/HDL-C ratios and increase in serum PON1 activity were also significant in omega-3 fatty acids group at the end of the study compared with baseline values (P <0.001, P < 0.001, P = 0.004, and P = 0.001, respectively). Conclusion: Omega-3 fatty acids may decrease the risk for cardiovascular disease through the improvement in paraxonase-1 activity and reduction in some lipids ratio in PCOS women. PMID:24688934

  11. Serum sialic acid and prostate-specific antigen in differential diagnosis of benign prostate hyperplasia and prostate cancer.

    PubMed

    Romppanen, Jarkko; Haapalainen, Terhi; Punnonen, Kari; Penttilä, Ilkka

    2002-01-01

    In order to improve the diagnostic accuracy of the serum total and free prostate-specific antigen (PSA) in differential diagnosis between benign prostate hyperplasia (BPH) and prostate cancer, the serum total sialic acid (TSA) was measured and logistic regression (LR) models were built. Significantly higher serum PSA (p<0.001) concentrations were observed in patients with prostate cancer compared to control subjects, but no statistically significant differences were found in serum TSA concentrations between these groups. Serum PSA reliably discriminated patients with prostate cancer from control subjects, the area under the ROC curve (AUC) being 0.991 (0.010). When serum PSA was in the gray zone, from 4 to 10 microg/l, the diagnostic accuracy of PSA in discriminating patients with prostate cancer from BPH patients was very poor, AUC being 0.563 (0.132). However, using the same set of patients the LR model combining serum PSA, free to total PSA ratio and TSA values, as well as digital rectal examination results, had good diagnostic accuracy in discriminating the prostate cancer patients from patients with BPH, the area under the ROC curve being 0.895 (0.054). The present data suggest that the logistic regression model combining laboratory measurements and results of the clinical examination may be a useful adjunct in the differential diagnosis of benign and malignant prostate disease.

  12. Rapid quantification of conjugated and unconjugated bile acids and C27 precursors in dried blood spots and small volumes of serum[S

    PubMed Central

    Janzen, N.; Sander, S.; Terhardt, M.; Das, A. M.; Sass, J. O.; Kraetzner, R.; Rosewich, H.; Peter, M.; Sander, J.

    2010-01-01

    The aim of the study was to develop a method for fast and reliable diagnosis of peroxisomal diseases and to facilitate differential diagnosis of cholestatic hepatopathy. For the quantification of bile acids and their conjugates as well as C27 precursors di- and trihydroxycholestanoic acid (DHCA, THCA), in small pediatric blood samples we combined HPLC separation on a reverse-phase C18 column with ESI-MS/MS analysis in the negative ion mode. Analysis was done with good precision (CV 3,7%–11.1%) and sufficient sensitivity (LOQ: 11–91 nmol/L) without derivatization. Complete analysis of 17 free and conjugated bile acids from dried blood spots and 10 µL serum samples, respectively, was performed within 12 min. Measurement of conjugated primary bile acids plus DHCA and THCA as well as ursodeoxycholic acid was done in 4.5 min. In blood spots of healthy newborns, conjugated primary bile acids were found in the range of 0.01 to 2.01 µmol/L. Concentrations of C27 precursors were below the detection limit in normal controls. DHCA and THCA were specifically elevated in cases of peroxysomal defects and one Zellweger patient. PMID:20093478

  13. SGLT2 inhibitor lowers serum uric acid through alteration of uric acid transport activity in renal tubule by increased glycosuria.

    PubMed

    Chino, Yukihiro; Samukawa, Yoshishige; Sakai, Soichi; Nakai, Yasuhiro; Yamaguchi, Jun-ichi; Nakanishi, Takeo; Tamai, Ikumi

    2014-10-01

    Sodium glucose cotransporter 2 (SGLT2) inhibitors have been reported to lower the serum uric acid (SUA) level. To elucidate the mechanism responsible for this reduction, SUA and the urinary excretion rate of uric acid (UE(UA)) were analysed after the oral administration of luseogliflozin, a SGLT2 inhibitor, to healthy subjects. After dosing, SUA decreased, and a negative correlation was observed between the SUA level and the UE(UA), suggesting that SUA decreased as a result of the increase in the UE(UA). The increase in UE(UA) was correlated with an increase in urinary D-glucose excretion, but not with the plasma luseogliflozin concentration. Additionally, in vitro transport experiments showed that luseogliflozin had no direct effect on the transporters involved in renal UA reabsorption. To explain that the increase in UE(UA) is likely due to glycosuria, the study focused on the facilitative glucose transporter 9 isoform 2 (GLUT9ΔN, SLC2A9b), which is expressed at the apical membrane of the kidney tubular cells and transports both UA and D-glucose. It was observed that the efflux of [(14) C]UA in Xenopus oocytes expressing the GLUT9 isoform 2 was trans-stimulated by 10 mm D-glucose, a high concentration of glucose that existed under SGLT2 inhibition. On the other hand, the uptake of [(14) C]UA by oocytes was cis-inhibited by 100 mm D-glucose, a concentration assumed to exist in collecting ducts. In conclusion, it was demonstrated that the UE(UA) could potentially be increased by luseogliflozin-induced glycosuria, with alterations of UA transport activity because of urinary glucose.

  14. SGLT2 inhibitor lowers serum uric acid through alteration of uric acid transport activity in renal tubule by increased glycosuria

    PubMed Central

    Chino, Yukihiro; Samukawa, Yoshishige; Sakai, Soichi; Nakai, Yasuhiro; Yamaguchi, Jun-ichi; Nakanishi, Takeo; Tamai, Ikumi

    2014-01-01

    Sodium glucose cotransporter 2 (SGLT2) inhibitors have been reported to lower the serum uric acid (SUA) level. To elucidate the mechanism responsible for this reduction, SUA and the urinary excretion rate of uric acid (UEUA) were analysed after the oral administration of luseogliflozin, a SGLT2 inhibitor, to healthy subjects. After dosing, SUA decreased, and a negative correlation was observed between the SUA level and the UEUA, suggesting that SUA decreased as a result of the increase in the UEUA. The increase in UEUA was correlated with an increase in urinary d-glucose excretion, but not with the plasma luseogliflozin concentration. Additionally, in vitro transport experiments showed that luseogliflozin had no direct effect on the transporters involved in renal UA reabsorption. To explain that the increase in UEUA is likely due to glycosuria, the study focused on the facilitative glucose transporter 9 isoform 2 (GLUT9ΔN, SLC2A9b), which is expressed at the apical membrane of the kidney tubular cells and transports both UA and d-glucose. It was observed that the efflux of [14C]UA in Xenopus oocytes expressing the GLUT9 isoform 2 was trans-stimulated by 10 mm d-glucose, a high concentration of glucose that existed under SGLT2 inhibition. On the other hand, the uptake of [14C]UA by oocytes was cis-inhibited by 100 mm d-glucose, a concentration assumed to exist in collecting ducts. In conclusion, it was demonstrated that the UEUA could potentially be increased by luseogliflozin-induced glycosuria, with alterations of UA transport activity because of urinary glucose. PMID:25044127

  15. Optimization of pH values to formulate the bireagent kit for serum uric acid assay.

    PubMed

    Huang, Ya; Chen, Yuanxiang; Yang, Xiaolan; Zhao, Hua; Hu, Xiaolei; Pu, Jun; Liao, Juan; Long, Gaobo; Liao, Fei

    2015-01-01

    A new formulation of the bireagent kit for serum uric acid assay was developed based on the effects of pH on enzyme stability. At 4 °C, half-lives of uricases from Bacillus fastidious and Arthrobacter globiforms were longer than 15 months at pH 9.2, but became shorter at pH below 8.0; half-lives of ascorbate oxidase and peroxidase were comparable at pH 6.5 and 7.0, but became much shorter at pH higher than 7.4. In the new formulation of the bireagent kit, Reagent A contained peroxidase, 4-aminoantipyrine, and ascorbate oxidase in 50 mM phosphate buffer at pH 6.5; Reagent B contained B. fastidious or A. globiforms uricase in 50 mM sodium borate buffer at pH 9.2; Reagents A and B were mixed at 4:1 to produce a final pH from 7.2 to 7.6 for developing a stable color. The new bireagent kit consumed smaller quantities of three enzymes for the same shelf life. With the new bireagent kit, there were linear responses of absorbance at 546 nm to uric acid up to 34 mM in reaction mixtures and a good correlation of uric acid levels in clinical sera with those by a commercial kit, but stronger resistance to ascorbate. Therefore, the new formulation was advantageous. © 2014 International Union of Biochemistry and Molecular Biology, Inc.

  16. Dietary induced serum phenolic acids promote bone growth via p38 MAPK / Beta-Catenin Canonical Wnt signaling

    USDA-ARS?s Scientific Manuscript database

    Diet and nutritional status are critical factors that influences bone development. In this report, we demonstrate that a mixture of phenolic acids found in the serum of young rats fed blueberries (BB), significantly stimulated osteoblast differentiation, resulting in significantly increased bone mas...

  17. Binding of diazepam, salicylic acid and digitoxin to albumin isolated from fetal and adult serum.

    PubMed

    Viani, A; Cappiello, M; Pacifici, G M

    1991-01-01

    Albumin was isolated from pooled fetal serum obtained at normal delivery at term and from pooled adult plasma. Albumin isolation was carried out by means of PEG precipitation followed by ion exchange chromatography on DEAE-Sephadex A 50 and then on SP-Sephadex C 50. The binding of diazepam (1 microM), salicylic acid (2 mM) and digitoxin (6 nM) to albumin (40 g/l) was measured by equilibrium dialysis at 37 degrees C. The unbound fraction (mean +/- SD) for fetal and adult albumin of diazepam was 1.86 +/- 0.24 and 1.82 +/- 0.15% (NS), that of digitoxin was 3.18 +/- 0.27 and 3.36 +/- 0.04% (NS) and that of salicylic acid was 11.65 +/- 0.99 and 9.47 +/- 0.75% (p less than 0.05), respectively. With both fetal and adult albumin, a single class of binding sites was observed for diazepam and digitoxin, whereas two classes of binding sites were observed for salicylic acid. The number of binding sites (n, moles of drug per mole of albumin) for fetal and adult albumin was 0.83 and 1.02 for diazepam and 0.014 and 0.018 for digitoxin, respectively. For salicylic acid, n was 1.45 (fetal albumin) and 1.55 (adult albumin) for the higher affinity site, and 3.06 (fetal albumin) and 3.27 (adult albumin) for the lower affinity site. The association constant (Ka, M-1) for diazepam was 1.36 x 10(5) (fetal albumin) and 1.00 x 10(5) (adult albumin) and that for digitoxin was 4.12 x 10(6) (fetal albumin) and 2.7 x 10(6) (adult albumin). For salicylic acid, Ka was 38.4 x 10(3) (fetal albumin) and 35.8 x 10(3) (adult albumin) for the higher affinity site, and 2.7 x 10(3) (fetal albumin) and 4.3 x 10(3) (adult albumin) for the lower affinity site. This work shows that fetal and adult albumin have similar binding properties and corroborates our previous findings with furosemide.

  18. The predictive value of mean serum uric acid levels for developing prediabetes.

    PubMed

    Zhang, Qing; Bao, Xue; Meng, Ge; Liu, Li; Wu, Hongmei; Du, Huanmin; Shi, Hongbin; Xia, Yang; Guo, Xiaoyan; Liu, Xing; Li, Chunlei; Su, Qian; Gu, Yeqing; Fang, Liyun; Yu, Fei; Yang, Huijun; Yu, Bin; Sun, Shaomei; Wang, Xing; Zhou, Ming; Jia, Qiyu; Zhao, Honglin; Huang, Guowei; Song, Kun; Niu, Kaijun

    2016-08-01

    We aimed to assess the predictive value of mean serum uric acid (SUA) levels for incident prediabetes. Normoglycemic adults (n=39,353) were followed for a median of 3.0years. Prediabetes is defined as impaired fasting glucose (IFG), impaired glucose tolerance (IGT), or impaired HbA1c (IA1c), based on the American Diabetes Association criteria. Serum SUA levels were measured annually. Four diagnostic strategies were used to detect prediabetes in four separate analyses (Analysis 1: IFG. Analysis 2: IFG+IGT. Analysis 3: IFG+IA1c. Analysis 4: IFG+IGT+IA1c). Cox proportional hazards regression models were used to assess the relationship between SUA quintiles and prediabetes. C-statistic was additionally used in the final analysis to assess the accuracy of predictions based upon baseline SUA and mean SUA, respectively. After adjustment for potential confounders, the hazard ratios (95% confidence interval) of prediabetes for the highest versus lowest quintile of mean SUA were 1.22 (1.10, 1.36) in analysis 1; 1.59 (1.23, 2.05) in analysis 2; 1.62 (1.34, 1.95) in analysis 3 and 1.67 (1.31, 2.13) in analysis 4. In contrast, for baseline SUA, significance was only reached in analyses 3 and 4. Moreover, compared with baseline SUA, mean SUA value was associated with a significant increase in the C-statistic (P<0.001). Mean SUA value was strongly and positively related to prediabetes risk, and showed better predictive ability for prediabetes than baseline SUA. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  19. Cytidine-5'-monophosphate-N-acetylneuraminic acid. Asialoglycoprotein sialic acid transferase activity in liver and serum of patients with juvenile hepatic cirrhosis and alpha-1-antitrypsin deficiency.

    PubMed

    Kuhlenschmidt, M S; Peters, S P; Pinkard, O D; Glew, R H; Sharp, H

    1976-04-08

    The molecular basis for the accumulation of a substance which displays the immunological reactivity of alpha-1-antitrypsin within vesicles of liver parenchymal cells of individuals with hepatic cirrhosis and serum alpha-1-antitrypsin deficiency remains unclear. We recently reported that serum from a patient with alpha-1-antitrypsin deficiency and hepatic cirrhosis was substantially deficient in sialyltransferease (EC 2.4.99.1) an enzyme which transfers sialic acid from cytidine 5'-monophosphate-N-acetylneuraminic acid to a variety of asialoglycoprotein acceptors. In the present report we have extended these studies to include serum from five additional patients with alpha-1-antitrypsin deficiency and juvenile hepatic cirrhosis as well as a liver specimen obtained at autopsy of one of these patients. We find the sialytransferase activity in serum from six patients with alpha-1-antitrypsin deficiency and hepatic cirrhosis to be 50% of healthy pediatric control values and 30% of pediatric patients with liver disease. However, serum from family members homozygous for alpha-1-antitrypsin deficiency but without hepatic cirrhosis, and serum from patients with a variety of other kinds of liver disease, failed to exhibit the marked sialytransferase deficiency. Similar assays carried out on a homogenate of a liver sample from one patient with alpha-1-antitrypsin deficiency and hepatic cirrhosis indicated that the deficiency of sialyltransferase activity was not demonstrable in liver. Furthermore, a comparative kinetic analysis of serum and liver sialytransferase in normal and afflicted individuals failed to detect differences in substrate affinities which might account for a decrease in functional sialyltransferase capacity in individuals with alpha-1-antitrypsin deficiency and hepatic cirrhosis. These observations suggest that the serum sialyltransferase deficiency in such patients probably arises after chronic and extensive liver disease involving hepatic accumulation of

  20. [Correlation between serum levels of bile acids in pregnant women with intrahepatic cholestasis of pregnancy and condition of their newborns].

    PubMed

    Kowalski, Artur; Janosz-Gałdyś, Iwona; Olejek, Anita; Bodzek, Piotr

    2014-02-01

    The aim of the study was to determine a relation between the level of total serum bile acids in pregnant women and the condition of their newborns on the basis of select parameters of acid-base balance in the cord blood. The study group consisted of 64 pregnant women with Intrahepatic Cholestasis of Pregnancy and 78 healthy pregnant women constituted the control group. Colorimetric enzymatic measurements of serum total bile acids were performed in both groups. In the mild cholestasis group, mean concentration of bile acids amounted to 20.6 +/- 1.0 micromol/l and was statistically significantly lower as compared to women with severe cholestasis (58.9 +/- 9.5 micromol/l). In the control group, mean concentration of bile acids was 4.1 +/- 0.3 micromol/l and was statistically significantly lower as compared to groups with cholestasis. Caesarean section was performed in 60.9% of women with cholestasis as compared to 19.2% of controls. Also, neonatal condition in the first minute of life was worse in the group with cholestasis as compared to the infants in the control group. The body weight of newborns of mothers with cholestasis was statistically significantly lower than in infants born to controls. Lowered neonatal pH (below 7.20) was noted in 2.6% of the newborns from the control group and was statistically significantly less frequent as compared to infants from the group with cholestasis. Periodic measurements of total bile acid concentrations in serum of pregnant women with cholestasis is of high value in establishing the diagnosis and determining severity of the disease in the mother as well as potential hazard for the fetus. Simultaneous monitoring of the changes total bile acids concentrations in the blood serum and the well-being allows to reduce the rates of neonatal distresses after birth and cesarean sections.