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Sample records for apolipoprotein forming soluble

  1. Solubility engineering and crystallization of human apolipoprotein D

    OpenAIRE

    Nasreen, Amber; Vogt, Martin; Kim, Hyun Jin; Eichinger, Andreas; Skerra, Arne

    2006-01-01

    Human apolipoprotein D (ApoD) is a physiologically important member of the lipocalin protein family that was discovered as a peripheral subunit of the high-density lipoprotein (HDL) but is also abundant in other body fluids and organs, including neuronal tissue. Although it has been possible to produce functional ApoD in the periplasm of Escherichia coli and to demonstrate its ligand-binding activity for progesterone and arachidonic acid, the recombinant protein suffers from a pronounced tend...

  2. Solubility engineering and crystallization of human apolipoprotein D

    Science.gov (United States)

    Nasreen, Amber; Vogt, Martin; Kim, Hyun Jin; Eichinger, Andreas; Skerra, Arne

    2006-01-01

    Human apolipoprotein D (ApoD) is a physiologically important member of the lipocalin protein family that was discovered as a peripheral subunit of the high-density lipoprotein (HDL) but is also abundant in other body fluids and organs, including neuronal tissue. Although it has been possible to produce functional ApoD in the periplasm of Escherichia coli and to demonstrate its ligand-binding activity for progesterone and arachidonic acid, the recombinant protein suffers from a pronounced tendency to aggregate and to adsorb to vessel surfaces as well as chromatography matrices, thus hampering further structural investigation. Here, we describe a systematic mutagenesis study directed at presumably exposed hydrophobic side chains of the unglycosylated recombinant protein. As a result, one ApoD mutant with just three new amino acid substitutions—W99H, I118S, and L120S—was identified, which exhibits the following features: (1) improved yield upon periplasmic biosynthesis in E. coli, (2) elution as a monomeric protein from a gel permeation chromatography column, and (3) unchanged binding activity for its physiological ligands. In addition, the engineered ApoD was successfully crystallized (space group I4 with unit cell parameters a = 75.1 Å, b = 75.1 Å, c = 166.0 Å, α = β = γ = 90°), thus demonstrating its conformationally homogeneous behavior and providing a basis for the future X-ray structural analysis of this functionally still puzzling protein. PMID:16322568

  3. Apolipoprotein L-I Promotes Trypanosome Lysis by Forming Pores in Lysosomal Membranes

    Science.gov (United States)

    Pérez-Morga, David; Vanhollebeke, Benoit; Paturiaux-Hanocq, Françoise; Nolan, Derek P.; Lins, Laurence; Homblé, Fabrice; Vanhamme, Luc; Tebabi, Patricia; Pays, Annette; Poelvoorde, Philippe; Jacquet, Alain; Brasseur, Robert; Pays, Etienne

    2005-07-01

    Apolipoprotein L-I is the trypanolytic factor of human serum. Here we show that this protein contains a membrane pore-forming domain functionally similar to that of bacterial colicins, flanked by a membrane-addressing domain. In lipid bilayer membranes, apolipoprotein L-I formed anion channels. In Trypanosoma brucei, apolipoprotein L-I was targeted to the lysosomal membrane and triggered depolarization of this membrane, continuous influx of chloride, and subsequent osmotic swelling of the lysosome until the trypanosome lysed.

  4. Production of a soluble and functional recombinant apolipoproteinD in the Pichia pastoris expression system.

    Science.gov (United States)

    Armanmehr, Shiva; Kalhor, Hamid Reza; Tabarraei, Alijan

    2016-05-01

    ApolipoproteinD (ApoD) is a human glycoprotein from the lipocalin family. ApoD contains a conserved central motif of an 8-stranded antiparallel β-sheet, which forms a beta-barrel that can be used for transport and storage of diverse hydrophobic ligands. Due to hydrophobic nature of ApoD, it has been difficult to generate a recombinant version of this protein. In the present work, we aimed at the production of ApoD in the robust Pichia pastoris expression system. To this end, the ApoD gene sequence was synthesized and subcloned for expression in the yeast host cells. Following integration of the ApoD gene into the yeast genomic region using homologous recombination, the ApoD recombinant protein was induced using methanol, reaching its maximum induction at 96 h. Having purified the ApoD recombinant protein by affinity chromatography, we measured the dissociation constant (KD) using its natural ligands: progesterone and arachidonic acid. Our results provide a viable solution to the production of recombinant ApoD protein in lieu of previous obstacles in generating soluble and functional ApoD protein. PMID:26826316

  5. Influences of apolipoprotein E on soluble and heparin-immobilized hepatic lipase

    Energy Technology Data Exchange (ETDEWEB)

    Landis, B.A.; Rotolo, F.S.; Meyers, W.C.; Clark, A.B.; Quarfordt, S.H.

    1987-06-01

    The effect of human apolipoprotein E (apoE), either alone or in combination with apoC, on the lipolysis of a radiolabeled triglyceride emulsion was studied with hepatic lipase in solution and immobilized on heparin-Sepharose. The soluble hepatic lipase was inhibited, whereas the heparin-immobilized lipase was stimulated by apoE. This stimulation was attenuated by combining apoE with either apoC-II or C-III. The heparin-immobilized lipase demonstrated much less lipolysis of the zwitterionic phosphatidylcholine-stabilized triglyceride emulsion than did the soluble enzyme. This difference was less when the emulsion was stabilized by a nonionic detergent. apoE inhibited lipase activity when assayed under conditions (0.4 M NaCl) of bound enzyme and unbound substrate. Increasing the emulsion apoE content beyond optimum inhibited lipolysis by the immobilized enzyme. Kinetic analysis of phosphatidylcholine-stabilized triglyceride emulsions revealed a significant decrease in immobilized enzyme K/sub m/ and an increase in V/sub max/ when the emulsion was supplemented with apoE. Distributing the immobilized lipase in clustered aggregates produced more lipolysis than when the same enzyme content was uniformly bound.

  6. Influences of apolipoprotein E on soluble and heparin-immobilized hepatic lipase

    International Nuclear Information System (INIS)

    The effect of human apolipoprotein E (apoE), either alone or in combination with apoC, on the lipolysis of a radiolabeled triglyceride emulsion was studied with hepatic lipase in solution and immobilized on heparin-Sepharose. The soluble hepatic lipase was inhibited, whereas the heparin-immobilized lipase was stimulated by apoE. This stimulation was attenuated by combining apoE with either apoC-II or C-III. The heparin-immobilized lipase demonstrated much less lipolysis of the zwitterionic phosphatidylcholine-stabilized triglyceride emulsion than did the soluble enzyme. This difference was less when the emulsion was stabilized by a nonionic detergent. apoE inhibited lipase activity when assayed under conditions (0.4 M NaCl) of bound enzyme and unbound substrate. Increasing the emulsion apoE content beyond optimum inhibited lipolysis by the immobilized enzyme. Kinetic analysis of phosphatidylcholine-stabilized triglyceride emulsions revealed a significant decrease in immobilized enzyme K/sub m/ and an increase in V/sub max/ when the emulsion was supplemented with apoE. Distributing the immobilized lipase in clustered aggregates produced more lipolysis than when the same enzyme content was uniformly bound

  7. Solubility and transferability of several industrial forms of uranium oxides

    International Nuclear Information System (INIS)

    This study was aimed at determining the solubility of two uranium oxides (U3O8 and UO2+Umetal) produced by a new enrichment process using laser technology and at understanding some mechanisms involved in the intracellular particle transformation. The solubility of the two compounds is lower when they have been phagocytised by alveolar macrophages than in a medium without cells. The addition of new macrophages during the culture has permitted the solubility of U3O8 to be tested over 14 days in spite of the toxicity of this compound. The biokinetics of uranium after exposure of rats to UO2+Umetal have confirmed the in vitro results. The electron microscopy study and EELS analysis of alveolar macrophages from rats instilled with both compounds have shown the formation of very thin needles of uranyl phosphate within the lysosomes. (Author)

  8. Effect of HPMC on solubility and dissolution of carbamazepine form III in simulated gastrointestinal fluids

    Directory of Open Access Journals (Sweden)

    Bhise S

    2008-01-01

    Full Text Available The effect of HPMC on solubility and dissolution of carbamazepine form III (CBZ was investigated in 50% w/w of CBZ form III in HPMC solid dispersion and physical mixture. Powdered samples of CBZ form III, physical mixture, and solid dispersion were characterized for thermal behavior (DSC, crystallinity (PXRD, and compatibility (FT-IR. Solubility and dissolution studies were carried out in different simulated gastrointestinal fluids and de-ionized water. Solubility studies in simulated gastric fluid (SGF revealed that acidic pH favors formation of CBZ dihydrate. Triton X 100 in blank fast-state simulated gastric fluid (FaSSGF prevents the formation of CBZ dihydrate in acidic pH. A maximum solubility of 268.77 µg/mL was achieved with fed-state simulated intestinal fluid (FeSSIF. Correlation between solubility and pH could not be established. Both solubility and dissolution studies revealed that HPMC had a profound effect of enhancement of solubility and dissolution of CBZ form III in both physical mixtures and solid dispersions. HPMC prevents the formation of CBZ dihydrate and thereby improves the solubility and dissolution. This was further correlated with results obtained from DSC and XRD. There was no drastic difference in solubility and dissolution of CBZ form III with different media. It was observed that there was no existing relationship between solubility and dissolution of CBZ form III in different media.

  9. Determination and correlation of solubility of spironolactone form II in pure solvents and binary solvent mixtures

    International Nuclear Information System (INIS)

    Highlights: • The solubility data of spironolactone form II in pure solvents and binary solvent mixtures were determined. • The experimental solubility data in pure solvents were correlated by three models. • The experimental solubility data in binary solvent mixtures were correlated by two models. • The dissolution thermodynamic properties of spironolactone form II were obtained. - Abstract: The solubility data of spironolactone form II in six pure solvents and binary solvent mixtures of ethyl acetate and methanol were measured over the temperature range from (278.85 to 317.75) K by using a dynamic method under atmospheric pressure. The results show that the solubility of spironolactone form II in pure solvents increases with increasing temperature while the solubility in binary solvent mixtures increases with the increasing of the fraction of ethyl acetate. This phenomenon is well explained by using relative dielectric constants of the solvents. The solubility data of spironolactone form II in pure solvents were well correlated by the modified Apelblat equation, the Wilson model and the NRTL model while the solubility of spironolactone form II in binary solvent mixtures were correlated by the modified Apelblat equation and the CNIBS/R-K model. Furthermore, the thermodynamic properties of the dissolution process of spironolactone form II were also determined by using the van’t Hoff equation

  10. Apolipoprotein M

    OpenAIRE

    Nilsson-Ehle Peter; Zhang Xiaoying; Luo Guanghua; Xu Ning

    2004-01-01

    Abstract Apolipoprotein M (apoM) is a 26-kDa protein that is mainly associated with high-density lipoprotein (HDL) in human plasma, with a small proportion present in triglyceride-rich lipoproteins (TGRLP) and low-density lipoproteins (LDL). Human apoM gene is located in p21.31 on chromosome 6 (chromosome 17, in mouse). Human apoM cDNA (734 base pairs) encodes 188-amino acid residue-long protein. It belongs to lipocalin protein superfamily. Human tissue expression array study indicates that a...

  11. Apolipoprotein C-II Adopts Distinct Structures in Complex with Micellar and Submicellar Forms of the Amyloid-Inhibiting Lipid-Mimetic Dodecylphosphocholine.

    Science.gov (United States)

    Ryan, Timothy M; Griffin, Michael D W; McGillivray, Duncan J; Knott, Robert B; Wood, Kathleen; Masters, Colin L; Kirby, Nigel; Curtain, Cyril C

    2016-01-01

    The formation of amyloid deposits is a common feature of a broad range of diseases, including atherosclerosis, Alzheimer's disease, and Parkinson's disease. The basis and role of amyloid deposition in the pathogenesis of these diseases is still being defined, however an interesting feature of amyloidogenic proteins is that the majority of the pathologically associated proteins are involved in lipid homeostasis, be it in lipid transport, incorporation into membranes, or the regulation of lipid pathways. Thus, amyloid-forming proteins commonly bind lipids, and lipids are generally involved in the proper folding of these proteins. However, understanding of the basis for these lipid-related aspects of amyloidogenesis is lacking. Thus, we have used the apolipoprotein C-II amyloid model system in conjunction with x-ray and neutron scattering analyses to address this problem. Apolipoprotein C-II is a well-studied model system of systemic amyloid fibril formation, with a clear and well-defined pathway for fibril formation, where the effects of lipid interaction are characterized, particularly for the lipid mimetic dodecylphosphocholine. We show that the micellar state of an inhibitory lipid can have a very significant effect on protein conformation, with micelles stabilizing a particular α-helical structure, whereas submicellar lipids stabilize a very different dimeric, α-helical structure. These results indicate that lipids may have an important role in the development and progression of amyloid-related diseases. PMID:26745412

  12. Biological consequences of exposure to soluble forms of natural uranium

    International Nuclear Information System (INIS)

    Depending on dose, route of administration and chemical form of the administered uranium, exposure to uranium compounds can produce effects in a variety of organs. Of these, the kidney is the most sensitive, and is considered to be a critical target organ for hazard assessment. Although dose-effect relationships differ among species, injury and necrosis of the terminal segments of the renal proximal tubule is characteristic in all mammalian species that have been studied. Glomerular injury has also been reported. The critical occupational health issues is thus, ''To what extent can laboratory animal models be useful for predicting human health hazards to uranium?''. While direct quantitative extrapolations of dose-effect relationships in laboratory animals to humans is not a reality at present, it is possible, nevertheless, to explore in laboratory animal models certain specific questions regarding the biological effects of uranium in kidney that are relevant to hazard assessment. Indeed, a complete understanding of the laboratory animal model is critical for establishing valid extrapolations to humans. Issues relating to mechanisms of renal injury, dose-effect relationships and biological monitoring for uranium-induced nephrotoxicity are considered in this review. (author)

  13. Apolipoprotein M

    Directory of Open Access Journals (Sweden)

    Nilsson-Ehle Peter

    2004-10-01

    Full Text Available Abstract Apolipoprotein M (apoM is a 26-kDa protein that is mainly associated with high-density lipoprotein (HDL in human plasma, with a small proportion present in triglyceride-rich lipoproteins (TGRLP and low-density lipoproteins (LDL. Human apoM gene is located in p21.31 on chromosome 6 (chromosome 17, in mouse. Human apoM cDNA (734 base pairs encodes 188-amino acid residue-long protein. It belongs to lipocalin protein superfamily. Human tissue expression array study indicates that apoM is only expressed in liver and in kidney and small amounts are found in fetal liver and kidney. In situ apoM mRNA hybridization demonstrates that apoM is exclusively expressed in the hepatocytes and in the tubule epithelial cells in kidney. Expression of apoM could be regulated by platelet activating factor (PAF, transforming growth factors (TGF, insulin-like growth factor (IGF and leptin in vivo and/or in vitro. It has been demonstrated that apoM expression is dramatically decreased in apoA-I deficient mouse. Hepatocyte nuclear factor-1α (HNF-1α is an activator of apoM gene promoter. Deficiency of HNF-1α mouse shows lack of apoM expression. Mutations in HNF-1α (MODY3 have reduced serum apoM levels. Expression of apoM is significantly decreased in leptin deficient (ob/ob mouse or leptin receptor deficient (db/db mouse. ApoM concentration in plasma is positively correlated to leptin level in obese subjects. These may suggest that apoM is related to the initiation and progression of MODY3 and/or obesity.

  14. Structure, Solubility and Stability of Orbifloxacin Crystal Forms: Hemihydrate versus Anhydrate.

    Science.gov (United States)

    Santos, Olimpia Maria Martins; Freitas, Jennifer Tavares Jacon; Cazedey, Edith Cristina Laignier; de Araújo, Magali Benjamim; Doriguetto, Antonio Carlos

    2016-01-01

    Orbifloxacin (ORBI) is a widely used antimicrobial drug of the fluoroquinolone class. In the official pharmaceutical compendia the existence of polymorphism in this active pharmaceutical ingredient (API) is reported. No crystal structure has been reported for this API and as described in the literature, its solubility is very controversial. Considering that different solid forms of the same API may have different physicochemical properties, these different solubilities may have resulted from analyses inadvertently carried out on different polymorphs. The solubility is the most critical property because it can affect the bioavailability and may compromise the quality of a drug product. The crystalline structure of ORBI determined by SCXRD is reported here for the first time. The structural analysis reveals that the ORBI molecule is zwitterionic and hemihydrated. ORBI hemihydrated form was characterized by the following techniques: TG/DTA, FTIR-ATR, and PXRD. A second crystalline ORBI form is also reported: the ORBI anhydrous form was obtained by heating the hemihydrate. These ORBI solid forms were isomorphous, since no significant change in unit cell and space group symmetry were observed. The solid-state phase transformation between these forms is discussed and the equilibrium solubility data were examined in order to check the impact of the differences observed in their crystalline structures. PMID:27005603

  15. Structure, Solubility and Stability of Orbifloxacin Crystal Forms: Hemihydrate versus Anhydrate

    Directory of Open Access Journals (Sweden)

    Olimpia Maria Martins Santos

    2016-03-01

    Full Text Available Orbifloxacin (ORBI is a widely used antimicrobial drug of the fluoroquinolone class. In the official pharmaceutical compendia the existence of polymorphism in this active pharmaceutical ingredient (API is reported. No crystal structure has been reported for this API and as described in the literature, its solubility is very controversial. Considering that different solid forms of the same API may have different physicochemical properties, these different solubilities may have resulted from analyses inadvertently carried out on different polymorphs. The solubility is the most critical property because it can affect the bioavailability and may compromise the quality of a drug product. The crystalline structure of ORBI determined by SCXRD is reported here for the first time. The structural analysis reveals that the ORBI molecule is zwitterionic and hemihydrated. ORBI hemihydrated form was characterized by the following techniques: TG/DTA, FTIR-ATR, and PXRD. A second crystalline ORBI form is also reported: the ORBI anhydrous form was obtained by heating the hemihydrate. These ORBI solid forms were isomorphous, since no significant change in unit cell and space group symmetry were observed. The solid-state phase transformation between these forms is discussed and the equilibrium solubility data were examined in order to check the impact of the differences observed in their crystalline structures.

  16. A minichaperone-based fusion system for producing insoluble proteins in soluble stable forms.

    Science.gov (United States)

    Sharapova, Olga A; Yurkova, Maria S; Fedorov, Alexey N

    2016-02-01

    We have developed a fusion system for reliable production of insoluble hydrophobic proteins in soluble stable forms. A carrier is thermophilic minichaperone, GroEL apical domain (GrAD), a 15 kDa monomer able to bind diverse protein substrates. The Met-less variant of GrAD has been made for further convenient use of Met-specific CNBr chemical cleavage, if desired. The Met-less GrAD retained stability and solubility of the original protein. Target polypeptides can be fused to either C-terminus or N-terminus of GrAD. The system has been tested with two unrelated insoluble proteins fused to the C-terminus of GrAD. One of the proteins was also fused to GrAD N-terminus. The fusions formed inclusion bodies at 25°C and above and were partly soluble only at lower expression temperatures. Most importantly, however, after denaturation in urea, all fusions without exception were completely renatured in soluble stable forms that safely survived freezing-thawing as well as lyophilization. All fusions for both tested target proteins retained solubility at high concentrations for days. Functional analysis revealed that a target protein may retain functionality in the fusion. Convenience features include potential thermostability of GrAD fusions, capacity for chemical and enzymatic cleavage of a target and His6 tag for purification. PMID:26612097

  17. Teratogenicity and metabolism of water-soluble forms of vitamin A in the pregnant rat

    International Nuclear Information System (INIS)

    Retinoyl β-glucuronide, unlike retinoic acid, has been shown to be non-teratogenic when administered orally, even in large doses, to pregnant rats. The degree to which water-solubility is associated with low teratogenicity is not known. Other water-soluble forms of vitamin A have now been synthesized in our laboratory and are being evaluated for teratogenicity. New water-soluble forms of vitamin A were administered orally to pregnant Sprague-Dawley rats in a single dose of 0.35 mmole/kg bw on day 8 of gestation. On day 19, the dams were sacrificed and the litters were examined. Control animals received either vehicle only or an equivalent dose of all-trans retinoic acid. Maternal and fetal tissues were taken and analyzed by HPLC for vitamin A metabolites. In another experiment, a large single oral dose of the radiolabelled water-soluble compound was administered on day 10. At either 30 minutes or 1 hour after the dose, dams were sacrificed and the embryos analyzed both for radioactivity and for specific metabolites. In contrast to retinoyl β-glucuronide, retinoyl β-glucose is highly teratogenic under identical conditions. Thus, water-solubility does not seem to be the determining factor in the teratogenicity of retinoic acid conjugates

  18. Identification of apolipoprotein using feature selection technique.

    Science.gov (United States)

    Tang, Hua; Zou, Ping; Zhang, Chunmei; Chen, Rong; Chen, Wei; Lin, Hao

    2016-01-01

    Apolipoprotein is a kind of protein which can transport the lipids through the lymphatic and circulatory systems. The abnormal expression level of apolipoprotein always causes angiocardiopathy. Thus, correct recognition of apolipoprotein from proteomic data is very crucial to the comprehension of cardiovascular system and drug design. This study is to develop a computational model to predict apolipoproteins. In the model, the apolipoproteins and non-apolipoproteins were collected to form benchmark dataset. On the basis of the dataset, we extracted the g-gap dipeptide composition information from residue sequences to formulate protein samples. To exclude redundant information or noise, the analysis of various (ANOVA)-based feature selection technique was proposed to find out the best feature subset. The support vector machine (SVM) was selected as discrimination algorithm. Results show that 96.2% of sensitivity and 99.3% of specificity were achieved in five-fold cross-validation. These findings open new perspectives to improve apolipoproteins prediction by considering the specific dipeptides. We expect that these findings will help to improve drug development in anti-angiocardiopathy disease. PMID:27443605

  19. Determining the solubility and crystal form of clenbuterol in thin films of eudragit NE30D

    OpenAIRE

    Göpferich, Achim; Lee, Geoffrey

    1992-01-01

    The solubility of the drug clenbuterol in thin films of surfactant-free Eudragit NE30D has been measured. Light microscopy and differential scanning calorimetry were supplemented by a technique based on measurement of the rate of drug release from the films. The clenbuterol crystals had the form of a fractal, as could be shown by a computer simulation of diffusion-controlled aggregation.

  20. Aluminosilicate saturation as a solubility control in leaching of nuclear waste-form materials

    International Nuclear Information System (INIS)

    In the slow flow region, material loss rates of nuclear waste form materials are determined by the solubilities and the flow rates. Present studies show that the solubilities of various, widely different waste forms, as well as of minerals, can be correlated with the Al x Si concentration products. This indicates that in these cases the solubilities are controlled by a combined equimolar aluminosilicate species. This observation serves as a basis for a predictive model for the long-term stability of waste forms under slow flow conditions. This model also provides explanations of other experimental findings, such as the increases in solubility upon departure from a neutral pH in the low as well as in the high pH region, the small magnitude of the temperature dependence, and the observation that the release rate of Cs is low relative to that of Na in the slow flow region. The relative concentrations of Si and of Al, respectively, in the leachates are related to the composition of the leach solids and are shown to depend on the immersion time in different ways in the cases of high-silica solids and of high-alumina solids, respectively. In both cases, however, the dependence of the Si:Al ratio on contact time furnishes another strong indication for the formation of a solid surface with comparable contents of Al and of Si, respectively, upon prolonged immersion in water. The results are shown to form the basis for an accurate long-term prediction of material loss rates. 1 figure, 4 tables

  1. Functional expression of soluble forms of human CD38 in Escherichia coli and Pichia pastoris.

    Science.gov (United States)

    Fryxell, K B; O'Donoghue, K; Graeff, R M; Lee, H C; Branton, W D

    1995-06-01

    Cyclic adenosine diphosphate (ADP)-ribose (cADPR), a metabolite of nicotinamide adenine dinucleotide (NAD+), mobilizes calcium from intracellular stores in many cells. The synthesis of cADPR from NAD+ and its subsequent hydrolysis to ADPR is catalyzed by an ADP-ribosyl cyclase and a cADPR hydrolase, respectively. The ADP-ribosyl cyclase cloned from the ovotestis of the marine invertebrate Aplysia californica has amino acid sequence homology to the human lymphocyte surface antigen CD38. CD38 has been shown to catalyze both the formation and the hydrolysis of cADPR. In this study, we produced soluble, enzymatically active CD38 using recombinant expression techniques in bacteria and yeast. We engineered a gene coding for a soluble form of CD38 by excision of the region of the gene coding for the N-terminal amino acids representing the putative membrane spanning sequence and short putative intracellular sequence. For expression in bacteria (Escherichia coli), this construct was cloned into the pFlag-1 plasmid which allows induced, periplasmic expression and relatively simple purification of the soluble CD38. For expression in yeast (Pichia pastoris) the CD38 sequence was further modified to eliminate four putative N-linked glycosylation sites and the resulting construct was expressed as a secreted protein. Both systems produce soluble enzymes of approximately 30 kDa and both recombinant enzymes display similar cyclase and hydrolase activities. PMID:7663169

  2. Activation of human natural killer cells by the soluble form of cellular prion protein

    International Nuclear Information System (INIS)

    Cellular prion protein (PrPC) is widely expressed in various cell types, including cells of the immune system. However, the specific roles of PrPC in the immune system have not been clearly elucidated. In the present study, we investigated the effects of a soluble form of recombinant PrPC protein on human natural killer (NK) cells. Recombinant soluble PrPC protein was generated by fusion of human PrPC with the Fc portion of human IgG1 (PrPC-Fc). PrPC-Fc binds to the surface of human NK cells, particularly to CD56dim NK cells. PrPC-Fc induced the production of cytokines and chemokines and the degranulation of granzyme B from NK cells. In addition, PrPC-Fc facilitated the IL-15-induced proliferation of NK cells. PrPC-Fc induced phosphorylation of ERK-1/2 and JNK in NK cells, and inhibitors of the ERK or the JNK pathways abrogated PrPC-Fc-induced cytokine production in NK cells. In conclusion, the soluble form of recombinant PrPC-Fc protein activates human NK cells via the ERK and JNK signaling pathways. - Highlights: • Recombinant soluble PrPC (PrPC-Fc) was generated by fusion of human PrPC with IgG1 Fc portion. • PrPC-Fc protein induces the production of cytokines and degranulation from human NK cells. • PrPC-Fc protein enhances the IL-15-induced proliferation of human NK cells. • PrPC-Fc protein activates human NK cells via the ERK and JNK signaling pathways

  3. Activation of human natural killer cells by the soluble form of cellular prion protein

    Energy Technology Data Exchange (ETDEWEB)

    Seong, Yeon-Jae [Laboratory of Immunology and Infectious Diseases, Graduate School of Medical Science and Engineering, KAIST, Daejeon (Korea, Republic of); Hafis Clinic, Seoul (Korea, Republic of); Sung, Pil Soo; Jang, Young-Soon; Choi, Young Joon [Laboratory of Immunology and Infectious Diseases, Graduate School of Medical Science and Engineering, KAIST, Daejeon (Korea, Republic of); Park, Bum-Chan [Aging Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon (Korea, Republic of); Park, Su-Hyung [Laboratory of Translational Immunology and Vaccinology, Graduate School of Medical Science and Engineering, KAIST, Daejeon (Korea, Republic of); Park, Young Woo [Aging Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon (Korea, Republic of); Shin, Eui-Cheol, E-mail: ecshin@kaist.ac.kr [Laboratory of Immunology and Infectious Diseases, Graduate School of Medical Science and Engineering, KAIST, Daejeon (Korea, Republic of)

    2015-08-21

    Cellular prion protein (PrP{sup C}) is widely expressed in various cell types, including cells of the immune system. However, the specific roles of PrP{sup C} in the immune system have not been clearly elucidated. In the present study, we investigated the effects of a soluble form of recombinant PrP{sup C} protein on human natural killer (NK) cells. Recombinant soluble PrP{sup C} protein was generated by fusion of human PrP{sup C} with the Fc portion of human IgG{sub 1} (PrP{sup C}-Fc). PrP{sup C}-Fc binds to the surface of human NK cells, particularly to CD56{sup dim} NK cells. PrP{sup C}-Fc induced the production of cytokines and chemokines and the degranulation of granzyme B from NK cells. In addition, PrP{sup C}-Fc facilitated the IL-15-induced proliferation of NK cells. PrP{sup C}-Fc induced phosphorylation of ERK-1/2 and JNK in NK cells, and inhibitors of the ERK or the JNK pathways abrogated PrP{sup C}-Fc-induced cytokine production in NK cells. In conclusion, the soluble form of recombinant PrP{sup C}-Fc protein activates human NK cells via the ERK and JNK signaling pathways. - Highlights: • Recombinant soluble PrP{sup C} (PrP{sup C}-Fc) was generated by fusion of human PrP{sup C} with IgG1 Fc portion. • PrP{sup C}-Fc protein induces the production of cytokines and degranulation from human NK cells. • PrP{sup C}-Fc protein enhances the IL-15-induced proliferation of human NK cells. • PrP{sup C}-Fc protein activates human NK cells via the ERK and JNK signaling pathways.

  4. Soluble Proteins Form Film by the Treatment of Low Temperature Plasma

    Science.gov (United States)

    Ikehara, Sanae; Sakakita, Hajime; Ishikawa, Kenji; Akimoto, Yoshihiro; Nakanishi, Hayao; Shimizu, Nobuyuki; Hori, Masaru; Ikehara, Yuzuru

    2015-09-01

    It has been pointed out that low temperature plasma in atmosphere was feasible to use for hemostasis without heat injury. Indeed, earlier studies demonstrated that low temperature plasma played an important role to stimulate platelets to aggregate and turned on the proteolytic activities of coagulation factors, resulting in the acceleration of the natural blood coagulation process. On the other hands, our developed equips could immediately form clots upon the contact with plasma flair, while the histological appearance was different from natural coagulation. Based on these findings in formed clots, we sought to determine if plasma flair supplied by our devices was capable of forming film using a series of soluble proteins Following plasma treatment, films were formed from bovine serum albumin, and the other plasma proteins at physiological concentration. Analysis of trans-electron microscope demonstrated that plasma treatment generated small protein particles and made them fuse to be larger aggregations The combined results demonstrated that plasma are capable of aggregating soluble proteins and that platelets and coagulation factors are not necessary for plasma induced blood coagulation. Supported in part by Grants-in-Aid for Scientific Research on Priority Area (21590454, 24590498, and 24108006 to Y. I.).

  5. Migration of 239Pu in soluble and insoluble forms in soil

    International Nuclear Information System (INIS)

    A field experiment study was performed at the rural site of South-East Lithuania. The main tasks of the study included an evaluation of the peculiarities of partition of 239Pu in soluble (239Pu(NO3)4, 239PuCl3) and insoluble (239PuO2) forms in soddy and forest soil horizons. The results of durable experiments (418 and 326 days) have shown that from 44.1% to 92.2% of 239Pu of investigated chemical forms were accumulated in the top (0-5 cm) soil layer. Some share (5.7-39.2%) of plutonium from studied chemical forms was found in the 5-20 cm layers of studied soil samples (columns). Obtained distribution of plutonium in soil layers may be attributed to the consideration that the migration rate to the soil depth for plutonium is 0.1-1.0 cm x y-1 but for some part of plutonium 10 times higher migration rate is characteristic as well. Plutonium transfer factor (TF) to the grassland plants was calculated, the values ranged from 10-2 to 10-1. (author)

  6. A soluble form of CTLA-4 is present in serum of pediatric patients with acute lymphoblastic leukaemia

    Directory of Open Access Journals (Sweden)

    R. Simone

    2011-01-01

    Full Text Available CTLA-4 can regulate and maintain self-telerance, providing a negative signal limiting immunoresponses. Acute lymphoblastic leukemia is a clonal disorder of lymphoid progenitors representing the most frequent malignancy of childhood. Here, we show the presence of significantly elevated levels of a soluble form of CTLA-4 in 70% of B-ALL patients. A possible role of this soluble molecule in the pathogenesis of this neoplastic disease can be envisaged.

  7. Vesicle-independent extracellular release of a proinflammatory outer membrane lipoprotein in free-soluble form

    Directory of Open Access Journals (Sweden)

    Oscarsson Jan

    2008-01-01

    Full Text Available Abstract Background Aggregatibacter actinomycetemcomitans is an oral bacterium associated with aggressively progressing periodontitis. Extracellular release of bacterial outer membrane proteins has been suggested to mainly occur via outer membrane vesicles. This study investigated the presence and conservation of peptidoglycan-associated lipoprotein (AaPAL among A. actinomycetemcomitans strains, the immunostimulatory effect of AaPAL, and whether live cells release this structural outer membrane lipoprotein in free-soluble form independent of vesicles. Results The pal locus and its gene product were confirmed in clinical A. actinomycetemcomitans strains by PCR-restriction fragment length polymorphism and immunoblotting. Culturing under different growth conditions revealed no apparent requirement for the AaPAL expression. Inactivation of pal in a wild-type strain (D7S and in its spontaneous laboratory variant (D7SS resulted in pleiotropic cellular effects. In a cell culture insert model (filter pore size 0.02 μm, AaPAL was detected from filtrates when strains D7S and D7SS were incubated in serum or broth in the inserts. Electron microscopy showed that A. actinomycetemcomitans vesicles (0.05–0.2 μm were larger than the filter pores and that there were no vesicles in the filtrates. The filtrates were immunoblot negative for a cytoplasmic marker, cyclic AMP (cAMP receptor protein. An ex vivo model indicated cytokine production from human whole blood stimulated by AaPAL. Conclusion Free-soluble AaPAL can be extracellularly released in a process independent of vesicles.

  8. Studies on the solubilities of precipitates formed by thorium and plutonium with resin degradation products

    International Nuclear Information System (INIS)

    During the anion exchange purification of plutonium white precipitates are often encountered in the initial stages of the elution streams whenever aged and degraded resins are employed. In order to study the solubility behaviour of this precipitate, anion exchange resin, Dowex-1x4 was thermally degraded under simulated conditions. Thorium and plutonium were precipitated with soluble degradation products of the resin and the solubilities of these precipitates were determined at various HNO3 concentrations (author). 3 refs., 1 tab

  9. Pharmacokinetics of salicylic acid following administration of aspirin tablets and three different forms of soluble aspirin in normal subjects.

    Science.gov (United States)

    Gatti, G; Barzaghi, N; Attardo Parrinello, G; Vitiello, B; Perucca, E

    1989-01-01

    The pharmacokinetic profile of an innovative formulation of soluble aspirin (l-ornithine acetylsalicylate, ldB 1003) was compared with that of conventional tablets and two other soluble dosage forms (d, l-lysine acetylsalicylate and a buffered effervescent formulation of acetylsalicylic acid) after administration of single oral doses in six normal volunteers. All soluble forms showed a rapid absorption profile, peak plasma salicylic acid levels being attained after about 30 min on average and without statistically significant differences among the solutions tested. As compared to the soluble formulations, acetylsalicylic acid given as tablets resulted in slower absorption, with peak plasma salicylic acid levels being reached more than 1 h after dosing. Despite these differences in time course of plasma level profiles, the extent of absorption was similar for all formulations. Apart from the potential advantages in terms of improved gastric tolerability, the increased rate of absorption of aspirin solutions is therapeutically useful whenever a rapid onset of action is required. In this respect, the kinetic pattern of the innovative formulation compares favourably with that of other available soluble dosage forms. PMID:2517497

  10. Nasal carcinomas in beagle dogs after inhalatioon of relatively soluble forms of beta-emitting radionuclides

    International Nuclear Information System (INIS)

    Beagle dogs were exposed by inhalation to relatively soluble forms of three beta-emitting radionuclides and are being held for life span observation to evaluate hazards associated with nuclear power production. Dogs were exposed to graded activity levels of 91YCl3, 144CeCl3 or 90SrCl2. With 91YCl3 and 144CeCl3, significant radiation dose was delivered to liver, respiratory tract, and skeleton. With 90SrCl2, the dose was essentially to skeleton. Nasal cavity squamous cell carcinomas have been the most frequent neoplasms in the 91Y and one of the most frequent in the 144Ce study while relatively few have been seen after 90Sr exposure. Also one nasal cavity hemangiosarcoma was seen in the 144Ce study. The 90Sr-exposed dogs have survived longer after exposure and have higher skeletal radiation doses than do the dogs exposed to 91Y or 144Ce. The greater incidence of nasal carcinomas can be explained by the finding of high concentrations of the lanthanides, 91Y and 144Ce, associated with the nasal turbinate epithelium

  11. Combining inkjet printing and amorphous nanonization to prepare personalized dosage forms of poorly-soluble drugs.

    Science.gov (United States)

    Cheow, Wean Sin; Kiew, Tie Yi; Hadinoto, Kunn

    2015-10-01

    Inkjet printing of drug nanosuspension on edible porous substrates was carried out for the first time with the objective of preparing personalized dosage forms of poorly soluble drugs. Amorphous drug-polysaccharide nanoparticle complex (or drug nanoplex in short) was used as the nanosuspension ink, instead of the conventional crystalline nanodrug. The amorphous drug nanoplex exhibited low propensity to Ostwald ripening growth, high colloidal stability, and supersaturation generation capability making it ideal for printing. Nanoplexes of ciprofloxacin - a BCS Class IV compound - prepared by complexation with dextran sulfate were used as the nanosuspension ink at two different sizes (i.e. ≈265nm and 188nm). Inkjet printing was performed on cellulose substrate at 0.25% (w/v) nanosuspension concentration and 5% (w/v) polyethylene glycol. For both nanoplex sizes, the results indicated that the printed dose could be increased by increasing the number of droplets dispensed. However, exact correlations between the achievable dose and the number of droplets dispensed were not evident, which was likely caused by the spatial non-homogeneity in the nanosuspension concentration. Compared to the larger nanoplex, printed nanodrugs of the smaller nanoplex consistently exhibited higher payload with better batch-to-batch reproducibility (nanodrug were successfully established in vitro. PMID:26325060

  12. Summary of Uranium Solubility Studies in Concrete Waste Forms and Vadose Zone Environments

    Energy Technology Data Exchange (ETDEWEB)

    Golovich, Elizabeth C.; Wellman, Dawn M.; Serne, R. Jeffrey; Bovaird, Chase C.

    2011-09-30

    One of the methods being considered for safely disposing of Category 3 low-level radioactive wastes is to encase the waste in concrete. Concrete encasement would contain and isolate the waste packages from the hydrologic environment and act as an intrusion barrier. The current plan for waste isolation consists of stacking low-level waste packages on a trench floor, surrounding the stacks with reinforced steel, and encasing these packages in concrete. These concrete-encased waste stacks are expected to vary in size with maximum dimensions of 6.4 m long, 2.7 m wide, and 4 m high. The waste stacks are expected to have a surrounding minimum thickness of 15 cm of concrete encasement. These concrete-encased waste packages are expected to withstand environmental exposure (solar radiation, temperature variations, and precipitation) until an interim soil cover or permanent closure cover is installed and to remain largely intact thereafter. Any failure of concrete encasement may result in water intrusion and consequent mobilization of radionuclides from the waste packages. This report presents the results of investigations elucidating the uranium mineral phases controlling the long-term fate of uranium within concrete waste forms and the solubility of these phases in concrete pore waters and alkaline, circum-neutral vadose zone environments.

  13. Apical secretion of apolipoproteins from enterocytes

    DEFF Research Database (Denmark)

    Danielsen, E M; Hansen, Gert Helge; Poulsen, Mona Dam

    1993-01-01

    soluble fraction, suggesting a basolateral secretion into the intercellular space, and both this accumulation and the release to the medium was prevented by culture at 20 degrees C. The specific radioactivity of apo A-1 and apo B-48 released to the medium was significantly higher than that of the...... corresponding apolipoproteins remaining associated with the intestinal tissue. Furthermore, during culture periods of up to 5 h, the enterocytes and their tight junctions largely remained intact as evidenced by the inaccessibility of the nonpermeable surface marker Ruthenium red. We therefore propose that...

  14. Soluble forms of extracellular cytokeratin 18 may differentiate simple steatosis from nonalcoholic steatohepatitis

    Institute of Scientific and Technical Information of China (English)

    Yusuf Yilmaz; Macit Gulten; Selim Giray Nak; Enver Dolar; Engin Ulukaya; Semra Akgoz; Murat Keskin; Murat Kiyici; Sibel Aker; Arzu Yilmaztepe; Selim Gurel

    2007-01-01

    AIM: To investigate whether serum levels of two soluble forms of extracellular cytokeratin 18 (M30-antigen and M65-antigen) may differentiate nonalcoholic steatohepatitis (NASH) from simple steatosis in patients with nonalcoholic fatty liver disease (NAFLD).METHODS: A total of 83 patients with suspected NAFLD and 49 healthy volunteers were investigated. Patients with suspected NAFLD were classified according to their liver histology into four groups: definitive NASH (n = 45), borderline NASH (n = 24), simple fatty liver (/7 = 9), and normal tissue (n = 5). Serum levels of caspase-3 generated cytokeratin-18 fragments (M30-antigen) and total cytokeratin-18 (M65-antigen) were determined by ELISA.RESULTS: Levels of M30-antigen and M65-antigen were significantly higher in patients with definitive NASH compared to the other groups. An abnormal value (> 121.60 IU/L) of M30-antigen yielded a 60.0% sensitivity and a 97.4% specificity for the diagnosis of NASH. Sensitivity and specificity of an abnormal M65-antigen level (> 243.82 IU/L) for the diagnosis of NASH were 68.9% and 81.6%, respectively. Among patients with NAFLD, M30-antigen and M65-antigen levels distinguished between advanced fibrosis and early-stage fibrosis with a sensitivity of 64.7% and 70.6%, and a specificity of 77.3% and 71.2%, respectively.CONCLUSION: Serum levels of M30-antigen and M65-antigen may be of clinical usefulness to identify patients with NASH. Further studies are mandatory to better assess the role of these apoptonecrotic biomarkers in NAFLD pathophysiology.

  15. Influence of drug release properties of conventional solid dosage forms on the systemic exposure of highly soluble drugs

    OpenAIRE

    Yu, Lawrence X.; Ellison, Christopher D.; Conner, Dale P.; Lesko, Larry J.; Hussain, Ajaz S.

    2001-01-01

    This study was designed to theoretically investigate the influence of drug release properties, characterized by the disintegration of a solid dosage form and dissolution of drug particles, on the systemic exposure of highly soluble drugs in immediate release products. An absorption model was developed by considering disintegration of a solid dosage form, dissolution of drug particles, gastrointestinal transit flow, and intestinal absorption processes. The absorption model was linked to a conv...

  16. Potential application of surfactant systems in formulation of dosage forms with slightly soluble substances

    Directory of Open Access Journals (Sweden)

    Ibrić Svetlana R.

    2012-01-01

    Full Text Available In order to achieve fast release of ibuprofen, slightly soluble model substance (0.52104 mol/l, surfactant systems for oral use with different PEG-40 hydrogenated castor oil (C/diethylene glycol monoethyl ether (T ratios were investigated. Comparison between dissolution profiles for ibuprofen from formulated systems and from two commercial products, film tablets and soft capsules, is presented in this paper. Photon correlation spectroscopy has shown that after high dilution with water, surfactant systems were able to form micellar solutions. The size of micelles varies from 14.8 ± 0,075 nm to 16.2 ± 0,021 nm with increasing C/T ratio from 1:2 to 2:1. Although with increasing content of PEG-40 hydrogenated castor oil larger micelles have formed, lower values of polydispersity index indicated that more homogeneous distribution of micelles size was gained. Conductometric analysis has demonstrated that system composing of C/T ratio 2:1, has shown most pronounced interaction between droplets, which can be seen as high rise of electrical conductivity with increasing water content (% (wwater/wtotal in the sample. No significant difference in percolation threshold between formulations with different C/T ratios was observed. Different surfactant systems were adsorbed on magnesium aluminometasilicate, as adsorbent with high specific active surface (≈300 m2/g, in order to investigate potential influence of adsorbent on ibuprofen dissolution rate. Formulated systems, with or without adsorbent were filled in hard gelatin capsules. The dissolution profiles of ibuprofen from different formulations were obtained in 30 minutes by dissolution apparatus with rotating baskets and compared with dissolution profiles of ibuprofen from commercial products. For formulations without adsorbent faster release of ibuprofen in first minutes of dissolution test, showed formulations with C/T ratio 2:1 and 1:1. Magnesium aluminometasilicate, as adsorbent with high specific

  17. Characterization of the conglomerate form of acetyl-DL-leucine by thermal analysis and solubility measurements

    Science.gov (United States)

    Estime, N.; Pena, R.; Teychené, S.; Autret, J. M.; Biscans, B.

    2012-03-01

    Starting from a mixture of enantiomers in solution, crystallization can generate different types of crystals. In order to determine which type of crystal is obtained in the case of acetyl leucine, an active pharmaceutical ingredient (API), analytical methods have been used to partially elucidate the binary and ternary phase diagrams of the system composed of the two enantiomers and water. The melting temperature phase diagram of this compound has been obtained by using differential scanning calorimetry (DSC) analyzes. The results show that it is characteristic of a conglomerate. This mode of crystallization has also been confirmed by X-ray powder diffraction analysis. Solubility measurements of enantiomerical mixtures in water enabled the determination of the ternary diagram of solubility. The empiric Meyerhoffer double solubility rule has been modified, due to the characterization of interactions between enantiomers.

  18. a Step Toward Development of Printable Dosage Forms for Poorly Soluble Drugs

    DEFF Research Database (Denmark)

    Raijada, Dhara; Genina, Natalja; Fors, Daniela;

    2013-01-01

    deposition was obtained by PIJ as compared with flexography. More than 90% drug release was achieved within 5 min regardless of printing method used. The solubility of drug in solvents/cosolvents, rheological properties of formulations, properties of substrate, feasibility and accuracy of the printing...

  19. Solubility and some crystallization properties of conglomerate forming chiral drug guaifenesin in water.

    Science.gov (United States)

    Fayzullin, Robert R; Lorenz, Heike; Bredikhina, Zemfira A; Bredikhin, Alexander A; Seidel-Morgenstern, Andreas

    2014-10-01

    The solubility of 3-(2-methoxyphenoxy)-propane-1,2-diol, the well-known chiral drug guaifenesin 1, in water has been investigated by means of polythermal and isothermal approaches. It was found that the solubilities of racemic and enantiomeric diols rac- and (R)-1 depend strongly on temperature. The ternary phase diagram of the guaifenesin enantiomers in water in the temperature range between 10°C and 40°C was constructed. Clear evidence was obtained that rac-1 crystallizes as a stable conglomerate. The Meyerhoffer coefficient for the guaifenesin-water system is more than two and strongly depends on temperature. Neither crystalline hydrates nor polymorphs were detected within the range of conditions covered. Metastable zone width data with regard to primary nucleation were also collected for rac-1 and (R)-1. On the basis of the knowledge acquired, the resolution of racemic guaifenesin by preferential crystallization from solution could be realized successfully. PMID:25091705

  20. Soluble forms of leukocyte differentiation antigens in chronic obstructive pulmonary disease and their relation with pulmonary ventilation disorders

    Directory of Open Access Journals (Sweden)

    Makarova Е.М.

    2015-12-01

    Full Text Available Objective: to study the characteristics of soluble forms of leukocyte membrane molecules and their relationship with disease progression in chronic obstructive pulmonary disease (COPD. Materials and Methods. The study involved 50 patients with COPD. All the patients underwent physical examination, spirometry; serum concentration of antigens sCD54, sCD50, sCD38, sCD25, sCD8, sCD95, sHLA I, sHLA-DR was assessed by ELISA, and the results were compared with serum samples of 30 healthy donors. Results. The level of all soluble forms of membrane molecules of leukocytes decreased in patients with severe COPD. We have found the increased content of the differentiation molecules in patients with moderate COPD, indicating the activation of immune cells during the immune response. Conclusion. There was a correlation between the soluble forms of membrane molecules and impaired pulmonary ventilation, which confirmed the role of immune cells in the pathogenesis of COPD.

  1. Multiple sources of carbonic anhydrase activity in pea thylakoids: soluble and membrane-bound forms.

    Science.gov (United States)

    Rudenko, Natalia N; Ignatova, Lyudmila K; Ivanov, Boris N

    2007-01-01

    Carbonic anhydrase (CA) activity of pea thylakoids, thylakoid membranes enriched with photosystem I (PSI-membranes), or photosystem II (PSII-membranes) as well as both supernatant and pellet after precipitation of thylakoids treated with detergent Triton X-100 were studied. CA activity of thylakoids in the presence of varying concentrations of Triton X-100 had two maxima, at Triton/chlorophyll (triton/Chl) ratios of 0.3 and 1.0. CA activities of PSI-membranes and PSII-membranes had only one maximum each, at Triton/Chl ratio 0.3 or 1.0, respectively. Two CAs with characteristics of the membrane-bound proteins and one CA with characteristics of the soluble proteins were found in the medium after thylakoids were incubated with Triton. One of the first two CAs had mobility in PAAG after native electrophoresis the same as that of CA residing in PSI-membranes, and the other CA had mobility the same as the mobility of CA residing in PSII-membranes, but the latter was different from CA situated in PSII core-complex (Ignatova et al. 2006 Biochemistry (Moscow) 71:525-532). The properties of the "soluble" CA removed from thylakoids were different from the properties of the known soluble CAs of plant cell: apparent molecular mass was about 262 kD and it was three orders more sensitive to the specific CA inhibitor, ethoxyzolamide, than soluble stromal CA. The data are discussed as indicating the presence of, at least, four CAs in pea thylakoids. PMID:17347907

  2. Life-span health effects of relatively soluble forms of internally deposited beta-emitting radionuclides

    International Nuclear Information System (INIS)

    As part of a large research effort to study the lifetime health risks of inhaled radionuclides, Beagle dogs inhaled 90SrCl2 or 144CeCl3 or were injected intravenously with 137CsCl. Because these three compounds were soluble in body fluids, the resulting widely differing patterns of radionuclide distribution and dose reflected tissue affinities of the elements involved. Long-term health effects, predominantly cancers, were seen in the organs receiving the highest doses. Investigations are continuing on the extent to which other less irradiated organs may have also been affected

  3. Lipid peroxides as endogenous oxidants forming 8-oxo-guanosine and lipid-soluble antioxidants as suppressing agents.

    Science.gov (United States)

    Kanazawa, Kazuki; Sakamoto, Miku; Kanazawa, Ko; Ishigaki, Yoriko; Aihara, Yoshiko; Hashimoto, Takashi; Mizuno, Masashi

    2016-07-01

    The oxidation of guanosine to 8-oxo-2'-deoxyguanosine (8-oxo-dG) in DNA is closely associated with induction of various diseases, but the endogenous oxidant species involved remains unclear. Hydrogen peroxides (H2O2) have been considered to be the oxidant, while lipid peroxides are another possible oxidant because generated easily in bio-membranes surrounding DNA. The oxidant potency was compared between lipid peroxides and H2O2. Linoleic acid hydroperoxides (LOOH) formed 8-oxo-dG at a higher level than H2O2 in guanosine or double-stranded DNA. In the presence of a physiological concentration of Fe(2+) to produce hydroxyl radicals, LOOH was also a stronger oxidant. In a lipid micelle, LOOH markedly produced 8-oxo-dG at a concentration one-tenth of that of H2O2. Upon adding to rat hepatic mitochondria, phosphatidylcholine hydroperoxides produced 8-oxo-dG abundantly. Employing HepG2 cells after pretreated with glutathione peroxidase inhibitor, LOOH formed 8-oxo-dG more abundantly than H2O2. Then, antioxidants to suppress the 8-oxo-dG formation were examined, when the nuclei of pre-incubated HepG2 with antioxidants were exposed to LOOH. Water-soluble ascorbic acid, trolox, and N-acetyl cysteine showed no or weak antioxidant potency, while lipid-soluble 2,6-dipalmitoyl ascorbic acid, α-tocopherol, and lipid-soluble phytochemicals exhibited stronger potency. The present study shows preferential formation of 8-oxo-dG upon LOOH and the inhibition by lipid-soluble antioxidants. PMID:27499574

  4. Control of Reactivity by the Use of Absorption Elements in Soluble Form in Power- Reactor Moderators

    International Nuclear Information System (INIS)

    The paper indicates the advantages of a uniform distribution of the absorption element in the core of a power reactor and briefly describes possible uses of soluble compounds of nuclear poisons for reactivity compensation purposes. The various qualities required of an element which is to serve as a soluble poison in the moderator call for a detailed examination of its physical and chemical properties. In the end only a very limited choice is left between boric acid, cadmium sulphate, lithium sulphate and gadolinium sulphate. The evolution of the concentration of nuclear poisons in a reactor moderator is quantitatively studied in order to find out the relative effectiveness of consumption by neutron reaction and chemical purification. The power of the reactor will affect the choice of poisoning procedure. A comparison is made with poisoning by the xenon effect. The paper describes tbe use of a purification circuit with ion-exchange resins to obtain a suitable anti-reactivity evolution programme for the nuclear poison in solution in the heavy water in a power reactor. The effect of the nuclear poison in solution in the heavy water on the velocity of its radiolysis are examined. The economic aspects of reactivity control by homogeneous poisoning of the moderator are discussed. (author)

  5. Use of New Water Soluble Surface Film—Forming Material to Reduce Ammonia Loss from Water Solution

    Institute of Scientific and Technical Information of China (English)

    YINBIN; SHENRENFANG; 等

    1996-01-01

    A new water soluble surface film-forming material was developed and its effect on reducing ammonia volatilization from an alkaline solution was investigated in laboratory,Results showed that the new film formed by the material was not only more effective in reducing ammonia loss than any other films tested but also much cheaper.The optimum amount of addition of the new film-forming material was about 10times the theoretical amount to form a monomolecular film.Under the experimental conditions,the new film could effectively depress the ammonia volatilization for at least 6 days.The cumulative ammonia loss rates for different films were fitted to a simple logistic equation ,and some important parameters such as the cumulative loss,and the maximum and average volatilization rates were calculated.The effect of different films could be,therefore,compared quantitatively,indicating the new film was most effective in depressing ammonia volatilization.

  6. Hydrogen Production by a Hyperthermophilic Membrane-Bound Hydrogenase in Soluble Nanolipoprotein Particles

    Energy Technology Data Exchange (ETDEWEB)

    Baker, S E; Hopkins, R C; Blanchette, C; Walsworth, V; Sumbad, R; Fischer, N; Kuhn, E; Coleman, M; Chromy, B; Letant, S; Hoeprich, P; Adams, M W; Henderson, P T

    2008-10-22

    Hydrogenases constitute a promising class of enzymes for ex vivo hydrogen production. Implementation of such applications is currently hindered by oxygen sensitivity and, in the case of membrane-bound hydrogenases (MBH), poor water solubility. Nanolipoprotein particles (NLPs), formed from apolipoproteins and phospholipids, offer a novel means to incorporate MBH into in a well-defined water-soluble matrix that maintains the enzymatic activity and is amenable to incorporation into more complex architectures. We report the synthesis, hydrogen-evolving activity and physical characterization of the first MBH-NLP assembly. This may ultimately lead to the development of biomimetic hydrogen production devices.

  7. Separation of water-soluble metabolites of benzo[a]pyrene formed by cultured human colon

    DEFF Research Database (Denmark)

    1979-01-01

    A method has been developed to separate conjugated metabolites of benzo[a]pyrene into three major fractions: sulfate esters, glucuronides and glutathione conjugates. In cultured human colon, formation of sulfate esters and glutathione conjugates is the major conjugation pathway, while formation of...... glucuronides accounts for only 6 per cent of the water-soluble metabolites. Hydrolysis of the sulfate esters with arylsulfatase and the glucuronides with β-glucuronidase released metabolites of benzo[a]pyrene that were extractable with organic solvent. Separation of these metabolites by high-pressure liquid...... chromatography indicated that trans-4,5-dihydro-4,5-dihydroxybenzo[a]pyrene,7,8,9, 10-tetrahydro-7,8,9, 10-tetrahydroxybenzo[a]pyrene and trans-9, 10-dihydro-9, 10-dihydroxybenzo[a]pyrene were the major substrates for UDP-glucuronic acid transferase, while trans-7,8-dihydro-7,8-dihydroxybenzo[a]pyrene and 9...

  8. A soluble form of Siglec-9 provides an antitumor benefit against mammary tumor cells expressing MUC1 in transgenic mice

    Energy Technology Data Exchange (ETDEWEB)

    Tomioka, Yukiko, E-mail: ytomi@muses.tottori-u.ac.jp [Division of Disease Model Innovation, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815 (Japan); Avian Zoonosis Research Center, Faculty of Agriculture, Tottori University, Tottori 680-8553 (Japan); Morimatsu, Masami, E-mail: mmorimat@vetmed.hokudai.ac.jp [Division of Disease Model Innovation, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815 (Japan); Laboratory of Laboratory Animal Science and Medicine, Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818 (Japan); Nishijima, Ken-ichi, E-mail: nishijma@nubio.nagoya-u.ac.jp [Department of Biotechnology, Graduate School of Engineering, Nagoya University, Nagoya 464-8603 (Japan); Usui, Tatsufumi, E-mail: usutatsu@muses.tottori-u.ac.jp [Avian Zoonosis Research Center, Faculty of Agriculture, Tottori University, Tottori 680-8553 (Japan); Yamamoto, Sayo, E-mail: ysayo@anim.med.kyushu-u.ac.jp [Center of Biomedical Research, Research Center for Human Disease Modeling, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582 (Japan); Suyama, Haruka, E-mail: sharuka@anim.med.kyushu-u.ac.jp [Center of Biomedical Research, Research Center for Human Disease Modeling, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582 (Japan); Ozaki, Kinuyo, E-mail: k-ozaki@anim.med.kyushu-u.ac.jp [Center of Biomedical Research, Research Center for Human Disease Modeling, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582 (Japan); Ito, Toshihiro, E-mail: toshiito@muses.tottori-u.ac.jp [Avian Zoonosis Research Center, Faculty of Agriculture, Tottori University, Tottori 680-8553 (Japan); and others

    2014-07-18

    Highlights: • Tumor-associated antigen MUC1 binds to Siglec-9. • Soluble Siglec-9 reduced proliferation of MUC1-positive tumor in transgenic mice. • Soluble Siglec-9 and MUC1 on tumor cells were colocalized in transgenic mice. • MUC1 expression on tumor cells were reduced in soluble Siglec-9 transgenic mice. - Abstract: Tumor-associated MUC1 binds to Siglec-9, which is expected to mediate tumor cell growth and negative immunomodulation. We hypothesized that a soluble form of Siglec-9 (sSiglec-9) competitively inhibits a binding of MUC1 to its receptor molecules like human Siglec-9, leading to provide antitumor benefit against MUC1-expressing tumor, and generated transgenic mouse lines expressing sSiglec-9 (sSiglec-9 Tg). When mammary tumor cells expressing MUC1 were intraperitoneally transplanted into sSiglec-9 Tg, tumor proliferation was slower with the lower histological malignancy as compared with non-transgenic mice. The sSiglec-9 was detected in the ascites caused by the tumor in the sSiglec-9 Tg, and sSiglec-9 and MUC1 were often colocalized on surfaces of the tumor cells. PCNA immunohistochemistry also revealed the reduced proliferation of the tumor cells in sSiglec-9 Tg. In sSiglec-9 Tg with remarkable suppression of tumor proliferation, MUC1 expressions were tend to be reduced. In the ascites of sSiglec-9 Tg bearing the tumor, T cells were uniformly infiltrated, whereas aggregations of degenerative T cells were often observed in the non-transgenic mice. These results suggest that sSiglec-9 has an antitumor benefit against MUC1-expressing tumor in the transgenic mice, which may avoid the negative immunomodulation and/or suppress tumor-associated MUC1 downstream signal transduction, and subsequent tumor proliferation.

  9. A soluble form of Siglec-9 provides an antitumor benefit against mammary tumor cells expressing MUC1 in transgenic mice

    International Nuclear Information System (INIS)

    Highlights: • Tumor-associated antigen MUC1 binds to Siglec-9. • Soluble Siglec-9 reduced proliferation of MUC1-positive tumor in transgenic mice. • Soluble Siglec-9 and MUC1 on tumor cells were colocalized in transgenic mice. • MUC1 expression on tumor cells were reduced in soluble Siglec-9 transgenic mice. - Abstract: Tumor-associated MUC1 binds to Siglec-9, which is expected to mediate tumor cell growth and negative immunomodulation. We hypothesized that a soluble form of Siglec-9 (sSiglec-9) competitively inhibits a binding of MUC1 to its receptor molecules like human Siglec-9, leading to provide antitumor benefit against MUC1-expressing tumor, and generated transgenic mouse lines expressing sSiglec-9 (sSiglec-9 Tg). When mammary tumor cells expressing MUC1 were intraperitoneally transplanted into sSiglec-9 Tg, tumor proliferation was slower with the lower histological malignancy as compared with non-transgenic mice. The sSiglec-9 was detected in the ascites caused by the tumor in the sSiglec-9 Tg, and sSiglec-9 and MUC1 were often colocalized on surfaces of the tumor cells. PCNA immunohistochemistry also revealed the reduced proliferation of the tumor cells in sSiglec-9 Tg. In sSiglec-9 Tg with remarkable suppression of tumor proliferation, MUC1 expressions were tend to be reduced. In the ascites of sSiglec-9 Tg bearing the tumor, T cells were uniformly infiltrated, whereas aggregations of degenerative T cells were often observed in the non-transgenic mice. These results suggest that sSiglec-9 has an antitumor benefit against MUC1-expressing tumor in the transgenic mice, which may avoid the negative immunomodulation and/or suppress tumor-associated MUC1 downstream signal transduction, and subsequent tumor proliferation

  10. Production and Characterization of a Soluble, Active Form of Tva, the Subgroup A Avian Sarcoma and Leukosis Virus Receptor

    OpenAIRE

    Balliet, John W; Berson, Joanne; D’Cruz, Celina M.; Huang, Julie; Crane, Joanne; Gilbert, Joanna M.; Bates, Paul

    1999-01-01

    The receptor for the subgroup A avian sarcoma and leukosis viruses [ASLV(A)] is the cellular glycoprotein Tva. A soluble form of Tva, sTva, was produced and purified with a baculovirus expression system. Using this system, 7 to 10 mg of purified sTva per liter of cultured Sf9 cells was obtained. Characterization of the carbohydrate modification of sTva revealed that the three N glycosylation sites in sTva were differentially utilized; however, the O glycosylation common to Tva produced in mam...

  11. The solubility of the tetragonal form of hen egg white lysozyme from pH 4.0 to 5.4

    Science.gov (United States)

    Cacioppo, Elizabeth; Pusey, Marc L.

    1991-01-01

    Hen egg white lysozyme solubilities in the presence of the tetragonal crystal form have been determined. Conditions investigated cover the pH range 4.0 to 5.4, varying from 2.0 to 7.0 percent NaCl concentrations and from 4 to 25 C. In all instances, the solubilities were found to increase with temperature and decrease with increasing salt concentration. The effects of pH were more complex, showing a decreasing solubility with increasing pH at low salt concentration and an increasing solubility with increasing pH at high salt concentration.

  12. Phosphorus solubility in an acid forest soil as influenced by form of applied phosphorus and liming

    Energy Technology Data Exchange (ETDEWEB)

    Fransson, Ann-Mari; Bergkvist, Bo; Tyler, Germund [Lund Univ. (Sweden). Dept. of Ecology

    1999-07-01

    Sedimentary phosphorus, superphosphate, and wood-ash, as well as either sedimentary phosphorus. superphosphate or ash combined with lime, were distributed in selected plots in an 80-yr-old Norway spruce forest [Picea abies (L.) Karst]. After 2 yrs, the sedimentary phosphorus had increased the oxalate/oxalic acid-extractable P in the O-horizon, and the superphosphate had increased the oxalate/oxalic acid-extractable P in the E-horizon. At first, the percolation water from the superphosphate treatment showed high P concentrations. It soon returned to control levels, however. The percolation water from the sedimentary phosphorus treatment gradually showed increased phosphate concentrations. The wood-ash increased neither the amount of extractable P nor the P concentration in the percolation water. The oxalate/oxalic acid-extractable P from the sedimentary P treatment was reduced by liming. The P concentration in the percolation water also tended to be reduced. This was perhaps due to formation of Ca phosphates in the vicinity of the lime particles. In addition, if the solubility rate was similar to the uptake rate, it could account for the decreased P concentration.

  13. Production and characterization of a soluble, active form of Tva, the subgroup A avian sarcoma and leukosis virus receptor.

    Science.gov (United States)

    Balliet, J W; Berson, J; D'Cruz, C M; Huang, J; Crane, J; Gilbert, J M; Bates, P

    1999-04-01

    The receptor for the subgroup A avian sarcoma and leukosis viruses [ASLV(A)] is the cellular glycoprotein Tva. A soluble form of Tva, sTva, was produced and purified with a baculovirus expression system. Using this system, 7 to 10 mg of purified sTva per liter of cultured Sf9 cells was obtained. Characterization of the carbohydrate modification of sTva revealed that the three N glycosylation sites in sTva were differentially utilized; however, the O glycosylation common to Tva produced in mammalian and avian cells was not observed. Purified sTva demonstrates significant biological activity, specifically blocking infection of avian cells by ASLV(A) with a 90% inhibitory concentration of approximately 25 pM. A quantitative enzyme-linked immunosorbent assay, developed to assess the binding of sTva to ASLV envelope glycoprotein, demonstrates that sTva has a high affinity for EnvA, with an apparent dissociation constant of approximately 0.3 nM. Once they are bound, a very stable complex is formed between EnvA and sTva, with an estimated complex half-life of 6 h. The soluble receptor protein described here represents a valuable tool for analysis of the receptor-envelope glycoprotein interaction and for structural analysis of Tva. PMID:10074155

  14. Enhanced resistance to herpes simplex virus type 1 infection in transgenic mice expressing a soluble form of herpesvirus entry mediator

    International Nuclear Information System (INIS)

    Herpesvirus entry mediator (HVEM) is a member of the tumor necrosis factor (TNF) receptor family used as a cellular receptor by virion glycoprotein D (gD) of herpes simplex virus (HSV). Both human and mouse forms of HVEM can mediate entry of HSV-1 but have no entry activity for pseudorabies virus (PRV). To assess the antiviral potential of HVEM in vivo, three transgenic mouse lines expressing a soluble form of HVEM (HVEMIg) consisting of an extracellular domain of murine HVEM and the Fc portion of human IgG1 were generated. All of the transgenic mouse lines showed marked resistance to HSV-1 infection when the mice were challenged intraperitoneally with HSV-1, but not to PRV infection. The present results demonstrate that HVEMIg is able to exert a significant antiviral effect against HSV-1 infection in vivo

  15. The amorphous solid dispersion of the poorly soluble ABT-102 forms nano/microparticulate structures in aqueous medium: impact on solubility

    Directory of Open Access Journals (Sweden)

    Frank KJ

    2012-11-01

    Full Text Available Kerstin J Frank,1,3 Ulrich Westedt,2 Karin M Rosenblatt,2 Peter Hölig,2 Jörg Rosenberg,2 Markus Mägerlein,2 Gert Fricker,3 Martin Brandl11Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Odense, Denmark; 2Abbott GmbH and Co. KG, Ludwigshafen, Germany; 3Department of Pharmaceutical Technology, University of Heidelberg, Heidelberg, GermanyAbstract: Amorphous solid dispersions (ASDs are a promising formulation approach for poorly soluble active pharmaceutical ingredients (APIs, because they ideally enhance both dissolution rate and solubility. However, the mechanism behind this is not understood in detail. In the present study, we investigated the supramolecular and the nano/microparticulate structures that emerge spontaneously upon dispersion of an ASD in aqueous medium and elucidated their influence on solubility. The ASD, prepared by hot melt extrusion, contained the poorly soluble ABT-102 (solubility in buffer, 0.05 µg/mL, a hydrophilic polymer, and three surfactants. The apparent solubility of ABT-102 from the ASD-formulation was enhanced up to 200 times in comparison to crystalline ABT-102. At the same time, the molecular solubility, as assessed by inverse equilibrium dialysis, was enhanced two times. Asymmetrical flow field-flow fractionation in combination with a multiangle light-scattering detector, an ultraviolet detector, and a refractometer enabled us to separate and identify the various supramolecular assemblies that were present in the aqueous dispersions of the API-free ASD (placebo and of binary/ternary blends of the ingredients. Thus, the supramolecular assemblies with a molar mass between 20,000 and 90,000 could be assigned to the polyvinylpyrrolidone/vinyl acetate 64, while two other kinds of assemblies were assigned to different surfactant assemblies (micelles. The amount of ABT-102 remaining associated with each of the assemblies upon fractionation was quantified offline with high

  16. Structure-function analysis of soluble forms of herpes simplex virus glycoprotein D.

    OpenAIRE

    Nicola, A V; Willis, S. H.; Naidoo, N N; Eisenberg, R J; Cohen, G H

    1996-01-01

    Glycoprotein D (gD) of herpes simplex virus (HSV) is essential for virus entry. Truncated forms of gD lacking the transmembrane and cytoplasmic tail regions have been shown to bind to cells and block plaque formation. Using complementation analysis and a panel of gD mutants, we previously identified four regions of gD (regions I to IV) which are important for virus entry. Here, we used baculovirus vectors to overexpress truncated forms of wild-type gD from HSV type 1 (HSV-1) [gD-1(306t)] and ...

  17. Trigger factor: a soluble protein that folds pro-OmpA into a membrane-assembly-competent form

    International Nuclear Information System (INIS)

    Pro-OmpA that is synthesized in vitro can assemble into bacterial inner membrane vesicles in the presence of ATP and NADH. The authors have purified pro-OmpA to determine which additional soluble proteins are necessary for its membrane assembly. [35S]Pro-OmpA was bound to Sepharose-linked antibody to OmpA, then eluted with 8 M urea and chromatographed on an anion-exchange resin in 8 M urea. This pro-OmpA is purified 2000-fold and is radiochemically pure. After dialysis, it is soluble but incompetent for membrane assembly. Addition of an Escherichia coli cytoplasmic fraction (S100) to the assembly reaction does not allow translocation. However, when S100 is added to pro-OmpA prior to dialysis, full assembly competence is restored, suggesting that a soluble factor, termed trigger factor, triggers the folding of pro-OmpA into an assembly-competent form as the urea is removed. They noted that, prior to the last purification step, the immunoaffinity-purified pro-OmpA was partially competent for membrane assembly without addition of trigger factor. To test whether trigger factor had bound to the antibody column by means of its association with pro-OmpA, the crude pro-OmpA was acid-denatured prior to immunoadsorption. In this experiment, the trigger factor did not bind to the anti-OmpA column, and S100 was required for renaturation of this [35S]pro-OmpA. As suggested by this experiment, the crude [35S]pro-OmpA was in complex with other proteins. Sedimentation velocity studies showed that the trigger factor has an apparent molecular weight of ≅ 60,000. They propose that it is required for translocation-competent folding of pro-OmpA and other precursor proteins

  18. [Isolation and catalytic properties of the soluble monomeric form of inorganic pyrophosphatase from baker's yeast].

    Science.gov (United States)

    Kasho, V N; Bakuleva, N P; Baĭkov, A A; Avaeva, S M

    1982-06-01

    Data from sedimentation analysis suggest that modification of about 40% of free amino groups of inorganic pyrophosphatase by maleic anhydride, pH 10.5, results in a loss of the enzyme ability to form dimers at neutral values of pH. The specific activity of monomeric pyrophosphatase is 50-80% of that of the dimeric form. The monomer has a pH optimum of about 7, requires metal ions for activation of both enzyme and substrate and is capable of exergonic synthesis of PPi in the active center. The enzyme binding to PPi is strongly stabilized by fluoride. The experimental data indicate that the individual subunit of inorganic pyrophosphatase possesses all the main catalytic properties of native dimeric molecule. PMID:6126223

  19. Serum albumin forms a lactoferrin-like soluble iron-binding complex in presence of hydrogen carbonate ions.

    Science.gov (United States)

    Ueno, Hiroshi M; Urazono, Hiroshi; Kobayashi, Toshiya

    2014-02-15

    The iron-lactoferrin complex is a common food ingredient because of its iron-solubilizing capability in the presence of hydrogen carbonate ions. However, it is unclear whether the formation of a stable iron-binding complex is limited to lactoferrin. In this study, we investigated the effects of bovine serum albumin (BSA) on iron solubility and iron-catalyzed lipid oxidation in the presence of hydrogen carbonate ions. BSA could solubilize >100-fold molar equivalents of iron at neutral pH, exceeding the specific metal-binding property of BSA. This iron-solubilizing capability of BSA was impaired by thermally denaturing BSA at ≥ 70 °C for 10 min at pH 8.5. The resulting iron-BSA complex inhibited iron-catalyzed oxidation of soybean oil in a water-in-oil emulsion measured using the Rancimat test. Our study is the first to show that BSA, like lactoferrin, forms a soluble iron-binding complex in the presence of hydrogen carbonate ions. PMID:24128453

  20. Development of a new generation of waste form for entrapment and immobilization of highly volatile and soluble radionuclides.

    Energy Technology Data Exchange (ETDEWEB)

    Rodriguez, Mark Andrew; Bencoe, Denise Nora; Brinker, C. Jeffrey; Murphy, Andrew Wilson; Holt, Kathleen Caroline; Turnham, Rigney; Kruichak, Jessica Nicole; Tellez, Hernesto; Miller, Andy; Xiong, Yongliang; Pohl, Phillip Isabio; Ockwig, Nathan W.; Wang, Yifeng; Gao, Huizhen

    2010-09-01

    The United States is now re-assessing its nuclear waste disposal policy and re-evaluating the option of moving away from the current once-through open fuel cycle to a closed fuel cycle. In a closed fuel cycle, used fuels will be reprocessed and useful components such as uranium or transuranics will be recovered for reuse. During this process, a variety of waste streams will be generated. Immobilizing these waste streams into appropriate waste forms for either interim storage or long-term disposal is technically challenging. Highly volatile or soluble radionuclides such as iodine ({sup 129}I) and technetium ({sup 99}Tc) are particularly problematic, because both have long half-lives and can exist as gaseous or anionic species that are highly soluble and poorly sorbed by natural materials. Under the support of Sandia National Laboratories (SNL) Laboratory-Directed Research & Development (LDRD), we have developed a suite of inorganic nanocomposite materials (SNL-NCP) that can effectively entrap various radionuclides, especially for {sup 129}I and {sup 99}Tc. In particular, these materials have high sorption capabilities for iodine gas. After the sorption of radionuclides, these materials can be directly converted into nanostructured waste forms. This new generation of waste forms incorporates radionuclides as nano-scale inclusions in a host matrix and thus effectively relaxes the constraint of crystal structure on waste loadings. Therefore, the new waste forms have an unprecedented flexibility to accommodate a wide range of radionuclides with high waste loadings and low leaching rates. Specifically, we have developed a general route for synthesizing nanoporous metal oxides from inexpensive inorganic precursors. More than 300 materials have been synthesized and characterized with x-ray diffraction (XRD), BET surface area measurements, and transmission electron microscope (TEM). The sorption capabilities of the synthesized materials have been quantified by using stable

  1. Dielectrophoretic manipulation and solubility of protein nanofibrils formed from crude crystallins

    DEFF Research Database (Denmark)

    Domigan, Laura; Andersen, Karsten B.; Sasso, Luigi; Dimaki, Maria; Svendsen, Winnie E.; Gerrard, Juliet A.; Castillo, Jaime

    2013-01-01

    Protein nanofibrils and nanotubes are now widely accepted as having potential for use in the field of bionanotechnology. For this to be a feasible alternative to existing technologies, there is a need for a commercially viable source. Previous work has identified amyloid fibrils formed from crude...... crystallin proteins as such a source, since these fibrils can be produced in large quantities at a low cost. Applications include use of fibrils as templates for the formation of nanowires or as biosensing scaffolds. There remains a number of practical considerations, such as stability and the ability to...... microelectrodes using dielectrophoresis, which enabled the recording of I–V curves for small numbers of fibrils. This investigation showed the fibrils to have low conductivity, with current values in the range of 10−10 A recorded. This low conductivity could be increased through modification, or alternately, the...

  2. Apolipoproteins, lipids and risk of cancer.

    Science.gov (United States)

    Borgquist, Signe; Butt, Talha; Almgren, Peter; Shiffman, Dov; Stocks, Tanja; Orho-Melander, Marju; Manjer, Jonas; Melander, Olle

    2016-06-01

    The epidemiological evidence for an obesity-cancer association is solid, whereas the association between obesity-associated lipoprotein levels and cancer is less evident. We investigated circulating levels of Apolipoprotein A1 (ApoA1), Apolipoprotein B (ApoB), LDL-cholesterol (LDL-C) and HDL-cholesterol (HDL-C) and association to risk of overall cancer and common cancer forms. The Malmö Diet and Cancer Study, a population-based prospective cohort study, enrolled 17,035 women and 11,063 men (1991-1996). Incident cancer cases were ascertained by record linkage with the Swedish Cancer Registry until end of follow-up, January 1, 2012. Baseline serum levels of ApoA1 and ApoB were analyzed for the entire cohort and HDL-C and LDL-C levels in 5,281 participants. Hazard ratios, with 95% confidence interval, were calculated using Cox's proportional hazards analysis. In the entire cohort, none of the exposures were related to overall cancer risk (HRadj ApoA1 = 0.98, 95%CI: 0.95,1.01; HRadj ApoB = 1.01, 95%CI: 0.98-1.04). Among men, ApoB was positively associated with cancer risk (HRadj ApoB = 1.06, 95%CI: 1.01,1.10). Female breast cancer risk was inversely associated with ApoB (HRadj = 0.92, 95%CI: 0.86,0.99). Among both genders, ApoA1 was inversely associated with lung cancer risk (HRadj = 0.88, 95%CI: 0.80,0.97), whereas high ApoB increased lung cancer risk (HRadj = 1.08, 95%CI: 0.99,1.18). Colorectal cancer risk was increased with high ApoB (HRadj = 1.08, 95%CI: 1.01,1.16) among both genders. Apolipoprotein levels were not associated with prostate cancer incidence. Circulating levels of apolipoproteins are associated with overall cancer risk in men and across both genders with breast, lung and colorectal cancer risk. Validation of these findings may facilitate future primary prevention strategies for cancer. PMID:26804063

  3. Characterization of a soluble, catalytically active form of Escherichia coli leader peptidase: requirement of detergent or phospholipid for optimal activity.

    Science.gov (United States)

    Tschantz, W R; Paetzel, M; Cao, G; Suciu, D; Inouye, M; Dalbey, R E

    1995-03-28

    Leader peptidase is a novel serine protease in Escherichia coli, which functions to cleave leader sequences from exported proteins. Its catalytic domain extends into the periplasmic space and is anchored to the membrane by two transmembrane segments located at the N-terminal end of the protein. At present, there is no information on the structure of the catalytic domain. Here, we report on the properties of a soluble form of leader peptidase (delta 2-75), and we compare its properties to those of the wild-type enzyme. We find that the truncated leader peptidase has a kcat of 3.0 S-1 and a Km of 32 microM with a pro-OmpA nuclease A substrate. In contrast to the wild-type enzyme (pI of 6.8), delta 2-75 is water-soluble and has an acidic isoelectric point of 5.6. We also show with delta 2-75 that the replacement of serine 90 and lysine 145 with alanine residues results in a 500-fold reduction in activity, providing further evidence that leader peptidase employs a catalytic serine/lysine dyad. Finally, we find that the catalysis of delta 2-75 is accelerated by the presence of the detergent Triton X-100, regardless if the substrate is pro-OmpA nuclease A or a peptide substrate. Triton X-100 is required for optimal activity of delta 2-75 at a level far below the critical micelle concentration. Moreover, we find that E. coli phospholipids stimulate the activity of delta 2-75, suggesting that phospholipids may play an important physiological role in the catalytic mechanism of leader peptidase. PMID:7696258

  4. Production of a highly active, soluble form of the cytochrome P450 reductase (CPR A) from Candida tropicalis

    Science.gov (United States)

    Donnelly, Mark

    2006-08-01

    The present invention provides soluble cytochrome p450 reductase (CPR) proteins from Candida sp. having an altered N-terminal region which results in reduced hydrophobicity of the N-terminal region. Also provided are host cells comprising the subject soluble CPR proteins. In addition, the present invention provides nucleotide and corresponding amino acid sequences for soluble CPR proteins and vectors comprising the nucleotide sequences. Methods for producing a soluble CPR, for increasing production of a dicarboxylic acid, and for detecting a cytochrome P450 are also provided.

  5. Kan apolipoprotein-nivåer målt fra opptinte blodprøver etter 12-14 års nedfrysing brukes for epidemiologiske formål? En pilotanalyse av HUNT 2-data

    Directory of Open Access Journals (Sweden)

    Ingar Holme

    2011-03-01

    Full Text Available I Norge er det lagret store mengder nedfrosne blodprøver fra helseundersøkelser av ulike slag. Stabilitet av målinger av apolipoproteiner fra langtids nedfrosne blodprøver er lite dokumentert. Ny forståelse av lipoproteinenes fysiologi og betydning for utvikling av ateromatose reiser spørsmålet om andre lipoproteinkomponenter enn total (TC, LDL (LDL-C og HDL-kolesterol (HDL-C bør vurderes som risikomarkører. Ikke minst gjelder dette apolipoproteinene og balansen mellom apolipoprotein B (apoB og apolipoprotein A-1 (apoA-1. Nedfrosne blodprøver kunne kanskje anvendes til å analysere sammenheng mellom nivåer på apolipoproteiner og utvikling av kardiovaskulære hendelser, hvis det ikke har skjedd vesentlige konsentrasjonsforandringer under lagring. For å undersøke dette ble det foretatt en pilotstudie av blodprøver fra 300 personer i HUNT 2. For disse hadde en ferske blodprøver, og i 2009 opptinte blodprøvemålinger av lipoproteiner samt apoB og apo A-1. Disse har bare vært lagret ved –40 ºC. Resultatene viste at TC var øket med 0,3 mmol/L fra fersk til smeltet tilstand til tross for at HDL-C var blitt redusert med 0,25 mmol/L. Korrelasjonene mellom ferske og opptinte prøver var høye (0,93-0,99. Variasjonskoeffisientene var derimot høye (5,8-13,7% og endringene var nivåavhengige. Nivåene på apolipoproteinene var klart høyere, mens apoB/apoA-1 ratio samsvarte mer med andre studierapporter. Korrelasjonene mellom apo-og lipoproteiner var på et nivå man gjenfinner i andre studier. Resultatene må tolkes som bare indikative på at apolipoproteiner, og da spesielt ratio apoB/apoA-1, kan brukes i HUNT 2 til prognostiske studier av kardiovaskulære hendelser og død. Hoveddelen av HUNT 2 biobank har imidlertid ligget i ro i –80 ºC og lipoproteiner endres neppe ved denne temperatur. Prognostiske studier med apolipoproteiner som prediktorer burde derfor med rimelig sikkerhet kunne utføres i HUNT 2. Endelig bevis for dette

  6. Distribution and Solubility of Radionuclides and Neutron Absorbers in Waste Forms for Disposition of Plutonium Ash and Scraps, Excess Plutonium, and Miscellaneous Spent Nuclear Fuels

    International Nuclear Information System (INIS)

    The initial goal of this project was to investigate the solubility of radionuclides in glass and other potential waste forms for the purpose of increasing the waste loading in glass and ceramic waste forms. About one year into the project, the project decided to focus on two potential waste forms - glass at PNNL and initiate ceramics at the Australian Nuclear Science and Technology Organisation (ANSTO)

  7. Active and water-soluble form of lipidated Wnt protein is maintained by a serum glycoprotein afamin/α-albumin.

    Science.gov (United States)

    Mihara, Emiko; Hirai, Hidenori; Yamamoto, Hideki; Tamura-Kawakami, Keiko; Matano, Mami; Kikuchi, Akira; Sato, Toshiro; Takagi, Junichi

    2016-01-01

    Wnt plays important role during development and in various diseases. Because Wnts are lipidated and highly hydrophobic, they can only be purified in the presence of detergents, limiting their use in various in vitro and in vivo assays. We purified N-terminally tagged recombinant Wnt3a secreted from cells and accidentally discovered that Wnt3a co-purified with a glycoprotein afamin derived from the bovine serum included in the media. Wnt3a forms a 1:1 complex with afamin, which remains soluble in aqueous buffer after isolation, and can induce signaling in various cellular systems including the intestical stem cell growth assay. By co-expressing with afamin, biologically active afamin-Wnt complex can be easily obtained in large quantity. As afamin can also solubilize Wnt5a, Wnt3, and many more Wnt subtypes, afamin complexation will open a way to put various Wnt ligands and their signaling mechanisms under a thorough biochemical scrutiny that had been difficult for years. PMID:26902720

  8. Formulation, development and evaluation of patient friendly dosage forms of metformin, Part-III: Soluble effervescent tablets

    Directory of Open Access Journals (Sweden)

    Mohapatra Ashutosh

    2008-01-01

    Full Text Available Metformin hydrochloride is an orally administered antihyperglycemic agent, used in the management of non-insulin-dependant (type-2 diabetes mellitus. Difficulty in swallowing (dysphagia is common among all age groups, especially in elderly and pediatrics. Unfortunately, a high percentage of patients suffering from type-2 diabetes are elderly people showing dysphagia. The above problem becomes even more severe due to high dose (500-1000 mg and need for daily intake of metformin. Thus, the above titled work was undertaken to provide patient friendly dosage form. Not only metformin is poorly compressible (Carr′s index 37, but effervescent ingredients are also poorly compressible so, method of wet granulation was used for preparation of tablets using absolute alcohol as binder. Metformin effervescent tablets were prepared using citric acid (CA, tartaric acid (TA, and treated sodium bicarbonate (heating at 120°C for 30 min, glycine, talc, sucralose, and mango flavor. Controlled heating of sodium bicarbonate formed a sheath or desiccant skin of sodium carbonate on bicarbonate nucleus leading to surface passivation which prevents onset effervescent reaction in presence of moisture leading to stability. Of all combinations, CA and TA in the molar ratio 1:2 was found to be most stable as higher amount of least hygroscopic TA protects hygroscopic CA from the attack of moisture. Also, it was found that using treated sodium bicarbonate in stoichiometric ratio gave substantially stable effervescent tablets on short term stability study (room temperature and humidity and 75% relative humidity (RH and room temperature as sodium carbonate preferentially absorbs moisture. All the ingredients selected were water soluble.

  9. Apolipoprotein E genotype in schizophrenia

    Energy Technology Data Exchange (ETDEWEB)

    Joober, R.; Lal, S.; Bloom, D.; Benkelfat, C. [McGill Research Centre for Schizophrenia, Douglas Hospital, Montreal (Canada)] [and others

    1996-04-09

    We investigated the association between schizophrenia and the allelic polymorphism in the apolipoprotein E (Apo E) gene in 51 schizophrenic patients and 35 controls. The Apo E4 allele was equally represented in the schizophrenic group (16%) and the control group (20%) suggesting no association between schizophrenia and the Apo E4 allele. The apolipoprotein E (Apo E) is a polymorphic (E2, E3, and E4) lipoprotein involved in the transmembrane transport of cholesterol and is thought to play an important role in neuronal growth and in the central nervous system response to injury, particularly in the hippocampal region. Recent findings strongly suggest that the Apo E4 allele is associated with cognitive deficits in normal and pathological aging, e.g., Alzheimer`s disease. 5 refs., 1 tab.

  10. Apolipoprotein E and familial longevity

    DEFF Research Database (Denmark)

    Schupf, Nicole; Barral, Sandra; Perls, Thomas;

    2013-01-01

    Exceptional longevity is associated with substantial heritability. The ε4 allele in apolipoprotein E and the linked G allele in rs2075650 of TOMM40 have been associated with increased mortality and the ε2 allele with decreased mortality, although inconsistently. Offspring from long-lived families...... findings support the hypothesis that both reduction in the frequency of the ε4 allele and increase in the frequency of the ε2 allele contribute to longevity....

  11. A soluble form of the macrophage-related mannose receptor (MR/CD206) is present in human serum and elevated in critical illness

    DEFF Research Database (Denmark)

    Rødgaard-Hansen, Sidsel; Rafique, Aisha; Christensen, Peter A;

    2014-01-01

    Background: This study tests the hypothesis that the mannose receptor (MR/CD206), which is expressed primarily by macrophages and dendritic cells, can be found in a soluble form (sMR, sMR) in human serum. Furthermore, we wished to establish and validate an enzyme-linked immunosorbent assay (ELISA...

  12. CYTOPLASMIC HIGH-LEVEL EXPRESSION OF A SOLUBLE, ENZYMATICALLY ACTIVE FORM OF THE ESCHERICHIA-COLI PENICILLIN-BINDING PROTEIN-5 AND PURIFICATION BY DYE CHROMATOGRAPHY

    NARCIS (Netherlands)

    VANDERLINDEN, MPG; MOTTL, H; KECK, W

    1992-01-01

    High-level expression of a soluble form of pencillin-binding protein 5 (PBP5), called PBP5s, and translocation across the cytoplasmic membrane results in lysis of Escherichia coli cells. The detrimental effect of increased amounts of this D,D-carboxypeptidase on the stability of the murein polymer c

  13. Contribution to the study of external contamination by radioactive products: skin contamination by radioactive cobalt in soluble form and decontamination

    International Nuclear Information System (INIS)

    The aim of this work was to characterize the behavior of the radioactive cobalt isotopes, which are present in reactor coolant systems of a pressurized water reactor (PWR), in the case of occupational skin exposure, and to study different therapies. Our experimental approach stems from standardized methods in skin pharmacology. In a first step, a physico-chemical study of a primary coolant water was carried out to characterize the soluble fraction of radio-cobalt and its skin affinity. The second step consisted in quantifying the diffusion through the skin, in vivo and in vitro in rats, and in vitro in human. Parallel experiments were carried out to study biokinetics of cobalt in rats, after intravenous, intramuscular and subcutaneous injection. Whatever the route of administration, cobalt diffuses easily in the organism. On the contrary, its skin absorption is very limited. In a fourth step, the influence of the skin injuries on absorption was estimated in vivo on rat skin. Several skin models were developed to standardize different injuries: excoriation, heat burns (convection, conduction) and chemical burns (acid or alkaline). Biokinetics study over 24 hours and histological study have shown a relation between skin absorption and stratum corneum alteration. In the latest step of this work, we compared the efficacy of various decontaminating agents administered under different galenic forms. Per (3, 6- anhydro, 2-O-carboxy-methyl)-α-cyclo-dextrin exhibited a significant efficacy for cobalt decontamination of skin. This macromolecule was tested in aqueous solution, in agarose gel and loaded on 'functionalized' fibers intended for development of new decontaminating tissues. (author)

  14. Studies on Conversion of K in Potash Feldspar into Water-soluble Form%提高钾长石转化的实验室研究

    Institute of Scientific and Technical Information of China (English)

    李华; 范秀山; 王光龙; 刘大壮

    2001-01-01

    The studies for raising potash feldspar utilization ratio by physical, biological and chemical methods are carried out in laboratory and the results are presented. It is shown that calcinatory and biological methods have positive effects on conversion of K in potash feldspar into water-soluble form, but the conversion is low; chemical method can change most of insoluble potassium into available form, and might be significant in industry to some extent.``

  15. High levels of the soluble form of CD30 molecule in rheumatoid arthritis (RA) are expression of CD30+ T cell involvement in the inflamed joints.

    Science.gov (United States)

    Gerli, R; Muscat, C; Bistoni, O; Falini, B; Tomassini, C; Agea, E; Tognellini, R; Biagini, P; Bertotto, A

    1995-12-01

    The CD30 is a surface molecule expressed by Th2-type lymphokine-producing T cells upon activation. CD30-expressing activated T cells release a soluble form of the molecule, which can be detectable both in vitro and in vivo. In the present study, high levels of soluble CD30 were found in peripheral blood and synovial fluid from patients with RA. However, CD30+ CD3+ cells, either CD4+ or CD8+, were significantly present in synovial fluid, but not in peripheral blood, of RA patients. Serum values of soluble CD30 were higher in active than inactive RA patients and directly correlated with rheumatoid factor serum titres. These data strongly support an involvement of CD30+ T cells in the immune processes of rheumatoid synovitis, and may suggest a relationship between Th2-type cytokine-secreting T cells and the pathological response in RA. PMID:8536371

  16. Beryllium metal solubility in the lung, comparison of metal and hot pressed forms by in vivo and in vitro dissolution bioassays

    International Nuclear Information System (INIS)

    The solubility of two industrial forms of beryllium, i.e. particles of metal powder and particles of hot-pressed beryllium, was investigated using in vivo and in vitro models. In the in vivo model, baboons and rats were used and were injected via the trachea with amounts of beryllium equivalent to 100,500 and 1000 fold the maximum permissible concentration (MPC). In vivo experiments showed that in both species the daily beryllium solubility rates were about 5 x 10-6 for metal particles and that in rats the daily beryllium solubility rate was about 5 x 10-5 for the hot-pressed particles. With regard to results for the in vitro models, the outcome of the acellular dissolution test using a serum simulant was not consistent with the in vivo results, though a cellular model using cultured macrophages showed the same trends in the dissolution rates for the two forms of beryllium as those observed in vivo. This result suggests that a cellular rather than an acellular dissolution model would be better at predicting solubility of beryllium compounds in the lungs. (author)

  17. Role of apolipoprotein E in febrile convulsion.

    Science.gov (United States)

    Giray, Ozlem; Ulgenalp, Ayfer; Bora, Elçin; Uran, Nedret; Yilmaz, Ebru; Unalp, Aycan; Erçal, Derya

    2008-10-01

    Apolipoprotein E is consistently associated with the progression of some common human neurodegenerative diseases, e.g., epilepsy. We hypothesized that genetic variations in the apolipoprotein E gene have implications for susceptibility to, and prognoses in, febrile convulsion, which plays an apparent role in the development of epilepsy. We used the polymerase chain reaction and restriction enzyme digestion to characterize variations of the apolipoprotein E gene. Sixty-nine patients with febrile convulsion (simple/complex) and a corresponding cohort of healthy patients (n = 75) were used. There was no significant difference in genotypic distribution and allelic frequencies of the apolipoprotein E gene between the febrile convulsion and control groups. Comparing subpopulations of the febrile convulsion group (patients with simple and complex febrile convulsion), we noted that no patients with the epsilon3/epsilon4 genotype had complex febrile convulsions. The apolipoprotein E epsilon3/epsilon4 genotype was more frequently seen in the simple febrile than in the complicated febrile convulsion group (9 versus 0 patients, respectively). The data indicate an association with the epsilon3/epsilon4 genotype of the apolipoprotein E gene with a milder phenotype. Although apolipoprotein E4 is not a vulnerability factor regarding febrile convulsions, it seems effective in regard to prognoses. PMID:18805361

  18. Effect of statins on the serum soluble form of receptor for advanced glycation end-products and its association with coronary atherosclerosis in patients with angina pectoris

    OpenAIRE

    Tsuyoshi Nozue; Sho-ichi Yamagishi; Masayoshi Takeuchi; Tsutomu Hirano; Shingo Yamamoto; Shinichi Tohyama; Kazuki Fukui; Shigeo Umezawa; Yuko Onishi; Tomoyuki Kunishima; Kiyoshi Hibi; Mitsuyasu Terashima; Ichiro Michishita

    2014-01-01

    Background: Advanced glycation end-products (AGEs) and their receptor (RAGE) play an important role in the pathogenesis of diabetic vascular complications. Recently, soluble form of RAGE (sRAGE) has been identified in mice and humans. Statins have been reported to increase serum sRAGE levels. However, whether modulation of circulating sRAGE levels has a beneficial effect on the progression of atherosclerosis is unknown. Methods: We reviewed 91 patients who had undergone percutaneous corona...

  19. D25V apolipoprotein C-III variant causes dominant hereditary systemic amyloidosis and confers cardiovascular protective lipoprotein profile

    Science.gov (United States)

    Valleix, Sophie; Verona, Guglielmo; Jourde-Chiche, Noémie; Nédelec, Brigitte; Mangione, P. Patrizia; Bridoux, Frank; Mangé, Alain; Dogan, Ahmet; Goujon, Jean-Michel; Lhomme, Marie; Dauteuille, Carolane; Chabert, Michèle; Porcari, Riccardo; Waudby, Christopher A.; Relini, Annalisa; Talmud, Philippa J.; Kovrov, Oleg; Olivecrona, Gunilla; Stoppini, Monica; Christodoulou, John; Hawkins, Philip N.; Grateau, Gilles; Delpech, Marc; Kontush, Anatol; Gillmore, Julian D.; Kalopissis, Athina D.; Bellotti, Vittorio

    2016-01-01

    Apolipoprotein C-III deficiency provides cardiovascular protection, but apolipoprotein C-III is not known to be associated with human amyloidosis. Here we report a form of amyloidosis characterized by renal insufficiency caused by a new apolipoprotein C-III variant, D25V. Despite their uremic state, the D25V-carriers exhibit low triglyceride (TG) and apolipoprotein C-III levels, and low very-low-density lipoprotein (VLDL)/high high-density lipoprotein (HDL) profile. Amyloid fibrils comprise the D25V-variant only, showing that wild-type apolipoprotein C-III does not contribute to amyloid deposition in vivo. The mutation profoundly impacts helical structure stability of D25V-variant, which is remarkably fibrillogenic under physiological conditions in vitro producing typical amyloid fibrils in its lipid-free form. D25V apolipoprotein C-III is a new human amyloidogenic protein and the first conferring cardioprotection even in the unfavourable context of renal failure, extending the evidence for an important cardiovascular protective role of apolipoprotein C-III deficiency. Thus, fibrate therapy, which reduces hepatic APOC3 transcription, may delay amyloid deposition in affected patients. PMID:26790392

  20. D25V apolipoprotein C-III variant causes dominant hereditary systemic amyloidosis and confers cardiovascular protective lipoprotein profile.

    Science.gov (United States)

    Valleix, Sophie; Verona, Guglielmo; Jourde-Chiche, Noémie; Nédelec, Brigitte; Mangione, P Patrizia; Bridoux, Frank; Mangé, Alain; Dogan, Ahmet; Goujon, Jean-Michel; Lhomme, Marie; Dauteuille, Carolane; Chabert, Michèle; Porcari, Riccardo; Waudby, Christopher A; Relini, Annalisa; Talmud, Philippa J; Kovrov, Oleg; Olivecrona, Gunilla; Stoppini, Monica; Christodoulou, John; Hawkins, Philip N; Grateau, Gilles; Delpech, Marc; Kontush, Anatol; Gillmore, Julian D; Kalopissis, Athina D; Bellotti, Vittorio

    2016-01-01

    Apolipoprotein C-III deficiency provides cardiovascular protection, but apolipoprotein C-III is not known to be associated with human amyloidosis. Here we report a form of amyloidosis characterized by renal insufficiency caused by a new apolipoprotein C-III variant, D25V. Despite their uremic state, the D25V-carriers exhibit low triglyceride (TG) and apolipoprotein C-III levels, and low very-low-density lipoprotein (VLDL)/high high-density lipoprotein (HDL) profile. Amyloid fibrils comprise the D25V-variant only, showing that wild-type apolipoprotein C-III does not contribute to amyloid deposition in vivo. The mutation profoundly impacts helical structure stability of D25V-variant, which is remarkably fibrillogenic under physiological conditions in vitro producing typical amyloid fibrils in its lipid-free form. D25V apolipoprotein C-III is a new human amyloidogenic protein and the first conferring cardioprotection even in the unfavourable context of renal failure, extending the evidence for an important cardiovascular protective role of apolipoprotein C-III deficiency. Thus, fibrate therapy, which reduces hepatic APOC3 transcription, may delay amyloid deposition in affected patients. PMID:26790392

  1. Intracellular and extracellular processing of human apolipoprotein A-I: secreted apolipoprotein A-I isoprotein 2 is a propeptide.

    OpenAIRE

    Zannis, V I; Karathanasis, S K; Keutmann, H. T.; Goldberger, G; Breslow, J L

    1983-01-01

    We have recently proposed that the major secreted isoprotein form of human apolipoprotein A-I (designated apo A-I2) is modified extracellularly to become the predominant apo A-I form seen in plasma (designated apo A-I4). In the current report we demonstrate that the primary translation product of human apo A-I (designated apo A-I2p) has a 24-amino-acid NH2-terminal extension with a sequence of Met-Lys-Ala-Ala-Val-Leu-Thr-Leu-Ala-Val-Leu-Phe- Leu-Thr-Gly-Ser-Gln-Ala-Arg-His-Phe-Trp-Gln-Gln. Th...

  2. The chaperone DnaK controls the fractioning of functional protein between soluble and insoluble cell fractions in inclusion body-forming cells

    Directory of Open Access Journals (Sweden)

    Ventura Salvador

    2006-08-01

    Full Text Available Abstract Background The molecular mechanics of inclusion body formation is still far from being completely understood, specially regarding the occurrence of properly folded, protein species that exhibit natural biological activities. We have here comparatively explored thermally promoted, in vivo protein aggregation and the formation of bacterial inclusion bodies, from both structural and functional sides. Also, the status of the soluble and insoluble protein versions in both aggregation systems have been examined as well as the role of the main molecular chaperones GroEL and DnaK in the conformational quality of the target polypeptide. Results While thermal denaturation results in the formation of heterogeneous aggregates that are rather stable in composition, protein deposition as inclusion bodies renders homogenous but strongly evolving structures, which are progressively enriched in the main protein species while gaining native-like structure. Although both type of aggregates display common features, inclusion body formation but not thermal-induced aggregation involves deposition of functional polypeptides that confer biological activity to such particles, at expenses of the average conformational quality of the protein population remaining in the soluble cell fraction. In absence of DnaK, however, the activity and conformational nativeness of inclusion body proteins are dramatically impaired while the soluble protein version gains specific activity. Conclusion The chaperone DnaK controls the fractioning of active protein between soluble and insoluble cell fractions in inclusion body-forming cells but not during thermally-driven protein aggregation. This cell protein, probably through diverse activities, is responsible for the occurrence and enrichment in inclusion bodies of native-like, functional polypeptides, that are much less represented in other kind of protein aggregates.

  3. Comparison of Carbohydrate Compositions of Total Apolipoproteins in Lipoproteins

    OpenAIRE

    Güldür, Tayfun; OZAN, Sema; İLERİ, Tülay

    1998-01-01

    Terminal carbohydrate moieties of apolipoproteins of lipoproteins in human and goat serum were ascertained and compared. Apolipoproteins of b+pre-b (apolipoprotein B containing lipoproteins) and a lipoproteins separated by phosphotungstic acid/MgCl2 precipitation method were applied to SDS-PAGE and blotted onto nitrocellulose membrane. Digoxigenin labelled lectins, each of which recognizes a specific sugar sequence, were incubated with apolipoproteins immobilized on a western blot membrane to...

  4. Membrane curvature induction and tubulation are common features of synucleins and apolipoproteins

    DEFF Research Database (Denmark)

    Varkey, Jobin; Isas, Jose Mario; Mizuno, Naoko;

    2010-01-01

    Synucleins and apolipoproteins have been implicated in a number of membrane and lipid trafficking events. Lipid interaction for both types of proteins is mediated by 11 amino acid repeats that form amphipathic helices. This similarity suggests that synucleins and apolipoproteins might have...... amphipathic helices alone. Moreover, we frequently observed that a-synuclein caused membrane structures that had the appearance of nascent budding vesicles. The ability to function as a minimal machinery for vesicle budding agrees well with recent findings that a-synuclein plays a role in vesicle trafficking...

  5. The 26S Proteasome Degrades the Soluble but Not the Fibrillar Form of the Yeast Prion Ure2p In Vitro.

    Directory of Open Access Journals (Sweden)

    Kai Wang

    Full Text Available Yeast prions are self-perpetuating protein aggregates that cause heritable and transmissible phenotypic traits. Among these, [PSI+] and [URE3] stand out as the most studied yeast prions, and result from the self-assembly of the translation terminator Sup35p and the nitrogen catabolism regulator Ure2p, respectively, into insoluble fibrillar aggregates. Protein quality control systems are well known to govern the formation, propagation and transmission of these prions. However, little is known about the implication of the cellular proteolytic machineries in their turnover. We previously showed that the 26S proteasome degrades both the soluble and fibrillar forms of Sup35p and affects [PSI+] propagation. Here, we show that soluble native Ure2p is degraded by the proteasome in an ubiquitin-independent manner. Proteasomal degradation of Ure2p yields amyloidogenic N-terminal peptides and a C-terminal resistant fragment. In contrast to Sup35p, fibrillar Ure2p resists proteasomal degradation. Thus, structural variability within prions may dictate their ability to be degraded by the cellular proteolytic systems.

  6. New head process for non-HEU 99Mo production based on the oxidation of irradiated UO2-pellets forming soluble U3O8

    Directory of Open Access Journals (Sweden)

    Beyer Gerd Juergen

    2016-01-01

    Full Text Available All fission-based 99Mo producers worldwide are required to convert their 99Mo production processes from using highly enriched uranium to low-enriched uranium. At a recent IAEA meeting in Vienna, problems related to bottlenecks and target modification and optimization of low-enriched uranium-based 99Mo production processes were discussed. Ceramic UO2-pellets (as used in fuel were excluded from the discussion with the argument that this material cannot be dissolved under practically applicable conditions. In this paper, we suggest transforming the non-soluble ceramic UO2 fuel-pellets into the U3O8 form by simple oxidation and the use of the soluble U-oxide modification as the starting material for the 99Mo production processes. Due to the absence of Al, larger target quantities could be processed and the waste volume could still be kept small. The approach is known and proven in nuclear technology. In principle, this new head process can be connected to any of the presently used 99Mo production procedures.

  7. Pancreatic beta cells express two autoantigenic forms of glutamic acid decarboxylase, a 65-kDa hydrophilic form and a 64-kDa amphiphilic form which can be both membrane-bound and soluble

    DEFF Research Database (Denmark)

    Christgau, S; Schierbeck, H; Aanstoot, H J;

    1991-01-01

    The 64-kDa pancreatic beta-cell autoantigen, which is a target of autoantibodies associated with early as well as progressive stages of beta-cell destruction, resulting in insulin-dependent diabetes (IDDM) in humans, has been identified as the gamma-aminobutyric acid-synthesizing enzyme glutamic...... compartment and hydrophobicity. A major portion of GAD64 is hydrophobic and firmly membrane-anchored and can only be released from membrane fractions by detergent. A second portion is hydrophobic but soluble or of a low membrane avidity, and a third minor portion is soluble and hydrophilic. All the GAD64...

  8. Influence of the concentration of water-soluble polyelectrolytes on the kinetics of flocculation of kaolin suspension and strength of formed floccules

    Directory of Open Access Journals (Sweden)

    R. Taubaeva

    2013-05-01

    Full Text Available The influence of the concentration and the charge of water-soluble (WS polyelectrolytes on the kinetics aggregation of particles kaolin was investigated. It is shown that with the alternation of slow and fast mixing result to the formation of large and strong flocs. The rate of aggregation and size of particles formed flocs increases with the concentration of the reagent and the charge density of the polyelectrolyte. It was found that at low concentrations (10-5~2,5·10-3% polyelectrolytes (cationic - Zetag 89, Zetag 92, anionic - Magnafloc 155, Magnafloc 156 flocculants flocculation of  kaolin suspensions increases and the higher concentrations of flocculants (more on 2,5·10-3% - suspension of kaolin is stabilized.

  9. Apolipoprotein M - a new biomarker in sepsis

    DEFF Research Database (Denmark)

    Christoffersen, Christina; Nielsen, Lars Bo

    2012-01-01

    Care Kumaraswamy and colleagues have investigated whether plasma apolipoprotein M (apoM) is affected during different grades of sepsis, septic shock and systemic inflammatory response syndrome. Interestingly, plasma apoM was significantly decreased in all groups of patients with a relationship to...

  10. A Comparative Evaluation of Mono-, Di- and Triglyceride of Medium Chain Fatty Acids by Lipid/Surfactant/Water Phase Diagram, Solubility Determination and Dispersion Testing for Application in Pharmaceutical Dosage Form Development

    OpenAIRE

    Hetal N. Prajapati; Dalrymple, Damon M.; Abu T. M. Serajuddin

    2011-01-01

    ABSTRACT Purpose To compare physiochemical properties of mono-, di- and triglycerides of medium chain fatty acids for development of oral pharmaceutical dosage forms of poorly water-soluble drugs using phase diagrams, drug solubility, and drug dispersion experiments. Methods Phase diagrams were prepared using a monoglyceride (glycerol monocaprylocaprate: Capmul MCM® EP), a diglyceride (glycerol dicaprylate) and two triglycerides (glycerol tricaprylate: Captex 8000®; caprylic/capric triglyceri...

  11. Apolipoprotein E Related Co-Morbidities and Alzheimer's Disease.

    Science.gov (United States)

    Singhrao, Sim K; Harding, Alice; Chukkapalli, Sasanka; Olsen, Ingar; Kesavalu, Lakshmyya; Crean, StJohn

    2016-01-01

    The primary goal of advancement in clinical services is to provide a health care system that enhances an individual's quality of life. Incidence of diabetes mellitus, cardiovascular disease, and associated dementia coupled with the advancing age of the population, have led to an increase in the worldwide challenge to the healthcare system. In order to overcome these challenges, prior knowledge of common, reliable risk factors and their effectors is essential. Oral health constitutes one such relatively unexplored but indispensable risk factor for aforementioned co-morbidities, in the form of poor oral hygiene and tooth loss during aging. Behavioral traits such as low education, smoking, poor diet, neglect of oral health, lack of exercise, and hypertension are few of the risk factors that are shared commonly among these conditions. In addition, common genetic susceptibility traits such as the apolipoprotein E gene, together with an individual's lifestyle can also influence the development of co-morbidities such as periodontitis, atherosclerosis/stroke, diabetes, and Alzheimer's disease. This review specifically addresses the susceptibility of apolipoprotein E gene allele 4 as the plausible commonality for the etiology of co-morbidities that eventually result from periodontal diseases and ultimately progress to dementia. PMID:26923007

  12. Localization and environment of tryptophans in soluble and membrane-bound states of a pore-forming toxin from Staphylococcus aureus.

    Science.gov (United States)

    Raja, S M; Rawat, S S; Chattopadhyay, A; Lala, A K

    1999-01-01

    The location and environment of tryptophans in the soluble and membrane-bound forms of Staphylococcus aureus alpha-toxin were monitored using intrinsic tryptophan fluorescence. Fluorescence quenching of the toxin monomer in solution indicated varying degrees of tryptophan burial within the protein interior. N-Bromosuccinimide readily abolished 80% of the fluorescence in solution. The residual fluorescence of the modified toxin showed a blue-shifted emission maximum, a longer fluorescence lifetime as compared to the unmodified and membrane-bound alpha-toxin, and a 5- to 6-nm red edge excitation shift, all indicating a restricted tryptophan environment and deeply buried tryptophans. In the membrane-bound form, the fluorescence of alpha-toxin was quenched by iodide, indicating a conformational change leading to exposure of some tryptophans. A shorter average lifetime of tryptophans in the membrane-bound alpha-toxin as compared to the native toxin supported the conclusions based on iodide quenching of the membrane-bound toxin. Fluorescence quenching of membrane-bound alpha-toxin using brominated and spin-labeled fatty acids showed no quenching of fluorescence using brominated lipids. However, significant quenching was observed using 5- and 12-doxyl stearic acids. An average depth calculation using the parallax method indicated that the doxyl-quenchable tryptophans are located at an average depth of 10 A from the center of the bilayer close to the membrane interface. This was found to be in striking agreement with the recently described structure of the membrane-bound form of alpha-toxin. PMID:10049328

  13. Apolipoprotein E Polymorphism in Tuberculosis Patients

    Science.gov (United States)

    Naserpour Farivar, Taghi; Sharifi Moud, Batool; Sargazi, Mansur; Moeenrezakhanlou, Alireza

    In this study, we aimed to determine the significance of association between Tuberculosis and apolipoprotein E polymorphism. The apolipoprotein E genotypes were assayed in 250 tuberculosis patients by polymerase chain reaction followed by enzymatic digestion with Hha I. The results were compared with the results of the same experiments on 250 sex and age matched control peoples. Present results showed that in studied populations, prevalence of E4 genotype was lower in controls than in patients (8 v. 13.2%; OR = 1.75, pStatistically significant difference was found between patients and controls with respect to ɛ2 allele frequencies, while ɛ2 allele frequency was found to be much less prevalent in controls (6%) than in patients (35.8%; OR = 8.72, p<0.05). Also, our study revealed that there is an association between apolipoprotein E genotypes and amplitude to tuberculosis in studied populations. However, large population-based studies are needed to understand the exact role played by the locus in causing the condition.

  14. Metabolism and Modification of Apolipoprotein B-Containing Lipoproteins Involved in Dyslipidemia and Atherosclerosis.

    Science.gov (United States)

    Morita, Shin-ya

    2016-01-01

    Increased levels of apolipoprotein B (apoB)-containing lipoproteins, such as low density lipoproteins (LDL) and chylomicron remnants, are associated with the development of atherosclerosis. Chylomicrons containing apoB-48 are secreted from the intestine during the postprandial state, whereas very low density lipoproteins (VLDL) containing apoB-100 are constitutively formed in the liver. Chylomicron remnants and VLDL remnants are produced by the lipoprotein lipase-mediated lipolysis of triglycerides, which is activated by apolipoprotein C-II bound on the particle surfaces. The hepatic uptake of these remnants is facilitated by apolipoprotein E (apoE), but is inhibited by apolipoproteins C-I, C-II and C-III. In the plasma, VLDL remnants are further converted into LDL by the hydrolysis of triglycerides. ApoB-100 is responsible for the hepatic uptake of LDL. LDL receptor, LDL receptor-related protein and heparan sulfate proteoglycans are involved in the hepatic clearance of lipoproteins containing apoB-100 and/or apoE. The subendothelial retention and modification of apoB-containing lipoproteins are crucial events in the initiation of atherosclerosis. In the subendothelium, the uptake of modified lipoproteins by macrophages leads to the formation of foam cells storing excess amounts of cholesteryl esters and subsequently to apoptosis. This review describes the current knowledge about the metabolism and modification of apoB-containing lipoproteins involved in dyslipidemia and atherogenesis. In particular, I focus on the effects of apolipoproteins, lipid composition and particle size on lipoprotein metabolism and on the roles of cholesterol, sphingomyelinase and apoB denaturation in macrophage foam cell formation and apoptosis. A detailed understanding of these mechanisms will help to develop new therapeutic strategies. PMID:26725424

  15. Plutonium solubilities

    International Nuclear Information System (INIS)

    Thermochemical data has been selected for plutonium oxide, hydroxide, carbonate and phosphate equilibria. Equilibrium constants have been evaluated in the temperature range 0 to 300 degrees C at a pressure of 1 bar to T≤100 degrees C and at the steam saturated pressure at higher temperatures. Measured solubilities of plutonium that are reported in the literature for laboratory experiments have been collected. Solubility data on oxides, hydroxides, carbonates and phosphates have been selected. No solubility data were found at temperatures higher than 60 degrees C. The literature solubility data have been compared with plutonium solubilities calculated with the EQ3/6 geochemical modelling programs, using the selected thermodynamic data for plutonium. (authors)

  16. Soluble recombinant influenza vaccines.

    OpenAIRE

    Fiers, W; Neirynck, S; Deroo, T; Saelens, X; Jou, W M

    2001-01-01

    Soluble, recombinant forms of influenza A virus haemagglutinin and neuraminidase have been produced in cells of lower eukaryotes, and shown in a mouse model to induce complete protective immunity against a lethal virus challenge. Soluble neuraminidase, produced in a baculovirus system, consisted of tetramers, dimers and monomers. Only the tetramers were enzymatically active. The immunogenicity decreased very considerably in the order tetra > di > mono. Therefore, we fused the head part of the...

  17. Generation of a soluble recombinant trimeric form of bovine CD40L and its potential use as a vaccine adjuvant in cows.

    Science.gov (United States)

    Pujol, Julien; Bouillenne, Fabrice; Farnir, Frédéric; Dufrasne, Isabelle; Mainil, Jacques; Galleni, Moreno; Lekeux, Pierre; Bureau, Fabrice; Fiévez, Laurence

    2015-11-15

    Vaccination is the most cost-effective way to control infectious diseases in cattle. However, many infectious diseases leading to severe economical losses worldwide still remain for which a really effective and safe vaccine is not available. These diseases are most often due to intracellular pathogens such as bacteria or viruses, which are, by their localization, protected from antibiotics and/or CD4(+) T cell-dependent humoral responses. We therefore postulated that strategies leading to induction of not only CD4(+) T cell responses but also CD8(+) cytotoxic T lymphocyte (CTL) responses against infected cells should be privileged in the development of new vaccines against problematic intracellular pathogens in bovines. CD40 signaling in antigen-presenting cells may lead to the induction of robust CD4-independent CTL responses and several studies, especially in mice, have used CD40 stimulation to promote CD8(+) T cell-mediated immunity. For example, we have recently shown that immunization of mice with heat-killed Staphylococcus aureus (HKSA) and agonistic anti-CD40 monoclonal antibodies elicits strong CTL responses capable of protecting mice from subsequent staphylococcal mastitis. Unfortunately, there is at present no tool available to efficiently stimulate CD40 in cattle. In this study, we therefore first produced a soluble recombinant trimeric form of the natural bovine CD40 ligand (sboCD40LT). We then observed that sboCD40LT was able to potently stimulate bovine cells in vitro. Finally, we provide evidence that immunization of cows with sboCD40LT combined with HKSA was able to significantly increase the number of both HKSA-specific CD4(+) and CD8(+) T cells in the draining lymph nodes. In conclusion, we suggest that this new molecular tool could help in the development of vaccine strategies against bovine diseases caused by intracellular pathogens. PMID:26553560

  18. Apolipoprotein E mimetic peptide protects against diffuse brain injur y

    Institute of Scientific and Technical Information of China (English)

    Yaning Zhao; Jianmin Li; Qiqun Tang; Junling Gao; Changxiang Chen; Liwei Jing; Pan Zhang; Shuxing Li

    2014-01-01

    Apolipoprotein E plays a crucial role in inhibiting chronic neurodegenerative processes. Howev-er, its impact on neurological function following diffuse brain injury is still unclear. This study was designed to evaluate the therapeutic effects and mechanisms of action of apolipoprotein E mimetic peptide on diffuse brain injury. Apolipoprotein E mimetic peptide was administered into the caudal vein of rats with diffuse brain injury before and after injury. We found that apo-lipoprotein E mimetic peptide signiifcantly decreased the number of apoptotic neurons, reduced extracellular signal-regulated kinase1/2 phosphorylation, down-regulated Bax and cytochrome c expression, decreased malondialdehyde content, and increased superoxide dismutase activity in a dose-dependent manner. These experimental ifndings demonstrate that apolipoprotein E mimetic peptide improves learning and memory function and protects against diffuse brain injury-induced apoptosis by inhibiting the extracellular signal-regulated kinase1/2-Bax mito-chondrial apoptotic pathway.

  19. Cloning and characterization of an apolipoprotein C2 promoter in the mouse central nervous system

    Institute of Scientific and Technical Information of China (English)

    Zhaoyang Li; Bing Du; Shengyang Li; Xiangchuan Lv; Shenglai Zhou; Yang Yu; Wei Wang; Zhihong Zheng

    2013-01-01

    Apolipoprotein C2 is an important member of the apolipoprotein C family, and is a potent activator of lipoprotein lipase. In the central nervous system, apolipoprotein C2 plays an important role in the catabolism of triglyceride-rich lipoproteins. Studies into the exact regulatory mechanism of mouse apolipoprotein C2 expression have not been reported. In this study, seven luciferase expression vectors, which contained potential mouse apolipoprotein C2 gene promoters, were constructed and co-transfected with pRL-TK into HEK293T cells to investigate apolipoprotein C2 promoter activity. Luciferase assays indicated that the apolipoprotein C2 promoter region was mainly located in the +104 bp to +470 bp region. The activity of the different lengths of apolipoprotein C2 promoter region varied. This staggered negative-positive-negative arrangement indicates the complex regulation of apolipoprotein C2 expression and provides important clues for elucidating the regulatory mechanism of apolipoprotein C2 gene transcription.

  20. Multiplex bead-based immunoassay for the free soluble forms of the HLA-G receptors, ILT2 and ILT4

    DEFF Research Database (Denmark)

    Wu, Ching-Lien; Svendsen, Signe Goul; Riviere, Adrien; Desgrandchamps, François; Carosella, Edgardo D; LeMaoult, Joël

    2016-01-01

    Human leukocyte antigen (HLA)-G is an immune-inhibitory molecule that exerts its function via interaction with two main inhibitory receptors: ILT2 and ILT4. This interaction is considered to be an immune checkpoint. HLA-G can be found as a soluble molecule, but it is not known if its receptors ca...

  1. Soluble form of membrane attack complex independently predicts mortality and cardiovascular events in patients with ST-elevation myocardial infarction treated with primary percutaneous coronary intervention

    DEFF Research Database (Denmark)

    Lindberg, Søren; Pedersen, Sune H; Mogelvang, Rasmus;

    2012-01-01

    The complement system is an important mediator of inflammation, which plays a pivotal role in atherosclerosis and acute myocardial infarction (AMI). Animal studies suggest that activation of the complement cascade resulting in the formation of soluble membrane attack complex (sMAC), contributes to...

  2. Fed-batch production of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in soluble form in Escherichia coli and its purification and characterization.

    Science.gov (United States)

    Li, Ping; Gu, Qing; Wu, Xuechang

    2016-10-01

    Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anticancer agent. The aim of this study is to produce large quantities of highly pure and bioactive recombinant human TRAIL. Here, TRAIL was expressed in soluble form by pH-stat fed-batch cultivation and purified using a rapid and simple two-step chromatographic procedure. To improve the soluble yield, expression of TRAIL in Escherichia coli was induced with low IPTG concentration (0.1 mM) at low temperature (28 °C) supplemented with ZnSO4 (0.5 mM), using glycerol as carbon source. Under the optimized conditions, 4.14 ± 0.19 g/L of TRAIL in soluble form was achieved at 19 h without pure oxygen. To purify the recombinant TRAIL, we developed an efficient two-step chromatographic procedure including affinity chromatography and cation-exchange chromatography, especially improved the cation-exchange chromatography using a combination of pH and NaCl gradients strategy. Consequently, 4313.5 mg of target protein with high purity (98.1%) was obtained from 2.3 L of cell broth. Our results also showed that the purified TRAIL was with ordered secondary and tertiary structures, in homogeneous form and with strong cytotoxicity. PMID:27335160

  3. Solubility limits of radionuclides in interstitial water. Americium in cement. Task 3. Characterization of radioactive waste forms. A series of final reports (1985-89). No 34

    International Nuclear Information System (INIS)

    The migration of actinides inside cement (or concrete) is very slow, even when the material is saturated with water: precipitation of actinide hydroxide explains this retention phenomenon. The aim of this work is to measure Am solubility in aqueous solutions equilibrated with CPA55 cement to: (i) compare it with thermodynamic predictions; and (ii) correlate it to (future) migration measurements of Am through cement discs. 12 figs.; 8 tabs.; 3 refs

  4. Distribution and solubility of radionuclides and neutron absorbers in waste forms for disposition of plutonium ash and scraps, excess plutonium, and miscellaneous spent nuclear fuels. 1998 annual progress report

    International Nuclear Information System (INIS)

    'The objective of this research is to gain a fundamental understanding of the distributions and the solubility limits for actinides Pu and U and rare earth neutron absorbers such as Gd and Hf in waste forms. This will be accomplished by systematically studying the local structural environments of these constituents in representative waste forms such as glass, ceramics, and vitreous ceramics. Basic knowledge of these issues will provide a technical and scientific basis that can be used by the US Department of Energy (DOE), Environment Management (EM) Program in developing, evaluating, and selecting waste forms for the safe disposal of Pu, spent nuclear fuel, and other transuranic wastes. The work presented here is a summary of the research activity from November 1997 to May 1998. The elucidation of the correlations between the local structural environments of actinides and rare earth neutron absorbers in waste forms as functions of waste form compositions, and waste form processing conditions will also advance basic material science. The work presented here is a summary of the research activity from November 1997 to May 1998. Currently being studied is the effect of the Pu oxidation state on its solubility in borosilicate-based glasses. When glasses are melted in ambient atmosphere, Pu(IV) has been shown to be the dominant oxidation state as determined by ultraviolet-visible-near infrared spectroscopy (UV-VIS-NIR) and x-ray absorption fine structure (XAFS) techniques. However, no literature data are available for glasses containing Pu predominantly as Pu(III) nor the solubility for Pu(III) in the glass. The results of the study demonstrate that in borosilicate glass, Pu(III) is significantly more soluble than Pu(IV). Using x-ray diffraction analysis the solubility of Pu(III) as oxide was determined to be at least 25 mass% in the reduced glass, while it was no greater than 10 mass% in the same glass under oxidizing conditions (glass melting temperature was 1,400 C

  5. Independent effects of apolipoprotein AV and apolipoprotein CIII on plasma triglyceride concentrations

    Energy Technology Data Exchange (ETDEWEB)

    Baroukh, Nadine N.; Bauge, Eric; Akiyama, Jennifer; Chang, Jessie; Fruchart, Jean-Charles; Rubin, Edward M.; Fruchart, Jamila; Pennacchio, Len A.

    2003-08-15

    Both the apolipoprotein A5 and C3 genes have repeatedly been shown to play an important role in determining plasma triglyceride concentrations in humans and mice. In mice, transgenic and knockout experiments indicate that plasma triglyceride levels are negatively and positively correlated with APOA5 and APOC3 expression, respectively. In humans, common polymorphisms in both genes have also been associated with plasma triglyceride concentrations. The evolutionary relationship among these two apolipoprotein genes and their close proximity on human chromosome 11q23 have largely precluded the determination of their relative contribution to altered Both the apolipoprotein A5 and C3 genes have repeatedly been shown to play an important role in determining plasma triglyceride concentrations in humans and mice. In mice, transgenic and knockout experiments indicate that plasma triglyceride levels are negatively and positively correlated with APOA5 and APOC3 expression, respectively. In humans, common polymorphisms in both genes have also been associated with plasma triglyceride concentrations. The evolutionary relationship among these two apolipoprotein genes and their close proximity on human chromosome 11q23 have largely precluded the determination of their relative contribution to altered triglycerides. To overcome these confounding factors and address their relationship, we generated independent lines of mice that either over-expressed (''double transgenic'') or completely lacked (''double knockout'') both apolipoprotein genes. We report that both ''double transgenic'' and ''double knockout'' mice display intermedia tetriglyceride concentrations compared to over-expression or deletion of either gene alone. Furthermore, we find that human ApoAV plasma protein levels in the ''double transgenic'' mice are approximately 500-fold lower than human ApoCIII levels, supporting Apo

  6. Apolipoprotein M promotes mobilization of cellular cholesterol in vivo

    DEFF Research Database (Denmark)

    Elsøe, Sara; Christoffersen, Christina; Luchoomun, Jayraz;

    2013-01-01

    The HDL associated apolipoprotein M (apoM) protects against experimental atherosclerosis but the mechanism is unknown. ApoM increases prebeta-HDL formation. We explored whether plasma apoM affects mobilization of cholesterol from peripheral cells in mice.......The HDL associated apolipoprotein M (apoM) protects against experimental atherosclerosis but the mechanism is unknown. ApoM increases prebeta-HDL formation. We explored whether plasma apoM affects mobilization of cholesterol from peripheral cells in mice....

  7. Resolving the Relationship between Apolipoprotein E and Depression

    OpenAIRE

    Slifer, Michael A; Martin, Eden R.; Gilbert, John R.; Haines, Jonathan L.; Pericak-Vance, Margaret A.

    2009-01-01

    Several studies have reported an association between the ApolipoproteinE-ε4 (APOE4) allele and depression among elders. However others have failed to find an association. Since APOE4 is a well recognized risk factor for Alzheimer dementia, cognitive status may represent an important confounder between APOE4 and depression. In this investigation, we examined the relationship between the ApolipoproteinE-ε4 allele and depression among elders accounting for cognitive status.

  8. Apolipoprotein E-mimetics inhibit neurodegeneration and restore cognitive functions in a transgenic Drosophila model of Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Svetlana Sarantseva

    Full Text Available BACKGROUND: Mutations of the amyloid precursor protein gene (APP are found in familial forms of Alzheimer's disease (AD and some lead to the elevated production of amyloid-beta-protein (Abeta. While Abeta has been implicated in the causation of AD, the exact role played by Abeta and its APP precursor are still unclear. PRINCIPAL FINDINGS: In our study, Drosophila melanogaster transgenics were established as a model to analyze AD-like pathology caused by APP overexpression. We demonstrated that age related changes in the levels and pattern of synaptic proteins accompanied progressive neurodegeneration and impairment of cognitive functions in APP transgenic flies, but that these changes may be independent from the generation of Abeta. Using novel peptide mimetics of Apolipoprotein-E, COG112 or COG133 proved to be neuroprotective and significantly improved the learning and memory of APP transgenic flies. CONCLUSIONS: The development of neurodegeneration and cognitive deficits was corrected by injections of COG112 or COG133, novel mimetics of apolipoprotein-E (apoE with neuroprotective activities.

  9. The solution structure of the soluble form of the lipid-modified azurin from Neisseria gonorrhoeae, the electron donor of cytochrome c peroxidase.

    Science.gov (United States)

    Nóbrega, Cláudia S; Saraiva, Ivo H; Carreira, Cíntia; Devreese, Bart; Matzapetakis, Manolis; Pauleta, Sofia R

    2016-02-01

    Neisseria gonorrhoeae colonizes the genitourinary track, and in these environments, especially in the female host, the bacteria are subjected to low levels of oxygen, and reactive oxygen and nitrosyl species. Here, the biochemical characterization of N. gonorrhoeae Laz is presented, as well as, the solution structure of its soluble domain determined by NMR. N. gonorrhoeae Laz is a type 1 copper protein of the azurin-family based on its spectroscopic properties and structure, with a redox potential of 277±5 mV, at pH7.0, that behaves as a monomer in solution. The globular Laz soluble domain adopts the Greek-key motif, with the copper center located at one end of the β-barrel coordinated by Gly48, His49, Cys113, His118 and Met122, in a distorted trigonal geometry. The edge of the His118 imidazole ring is water exposed, in a surface that is proposed to be involved in the interaction with its redox partners. The heterologously expressed Laz was shown to be a competent electron donor to N. gonorrhoeae cytochrome c peroxidase. This is an evidence for its involvement in the mechanism of protection against hydrogen peroxide generated by neighboring lactobacilli in the host environment. PMID:26589091

  10. Contribution to the study of external contamination by radioactive products: skin contamination by radioactive cobalt in soluble form and decontamination; Contribution a l'etude de la contamination externe par des produits radioactifs: contamination cutanee par les cobalts radioactifs sous forme soluble et decontamination

    Energy Technology Data Exchange (ETDEWEB)

    Tymen, H.

    2002-12-15

    The aim of this work was to characterize the behavior of the radioactive cobalt isotopes, which are present in reactor coolant systems of a pressurized water reactor (PWR), in the case of occupational skin exposure, and to study different therapies. Our experimental approach stems from standardized methods in skin pharmacology. In a first step, a physico-chemical study of a primary coolant water was carried out to characterize the soluble fraction of radio-cobalt and its skin affinity. The second step consisted in quantifying the diffusion through the skin, in vivo and in vitro in rats, and in vitro in human. Parallel experiments were carried out to study biokinetics of cobalt in rats, after intravenous, intramuscular and subcutaneous injection. Whatever the route of administration, cobalt diffuses easily in the organism. On the contrary, its skin absorption is very limited. In a fourth step, the influence of the skin injuries on absorption was estimated in vivo on rat skin. Several skin models were developed to standardize different injuries: excoriation, heat burns (convection, conduction) and chemical burns (acid or alkaline). Biokinetics study over 24 hours and histological study have shown a relation between skin absorption and stratum corneum alteration. In the latest step of this work, we compared the efficacy of various decontaminating agents administered under different galenic forms. Per (3, 6- anhydro, 2-O-carboxy-methyl)-{alpha}-cyclo-dextrin exhibited a significant efficacy for cobalt decontamination of skin. This macromolecule was tested in aqueous solution, in agarose gel and loaded on 'functionalized' fibers intended for development of new decontaminating tissues. (author)

  11. Soluble vs. insoluble fiber

    Science.gov (United States)

    Insoluble vs. soluble fiber; Fiber - soluble vs. insoluble ... There are two different types of fiber -- soluble and insoluble. Both are important for health, digestion, and preventing diseases. Soluble fiber attracts water and turns to gel during digestion. ...

  12. Toward a Molecular Understanding of Protein Solubility: Increased Negative Surface Charge Correlates with Increased Solubility

    OpenAIRE

    Kramer, Ryan M.; Shende, Varad R.; Motl, Nicole; Pace, C. Nick; Scholtz, J. Martin

    2012-01-01

    Protein solubility is a problem for many protein chemists, including structural biologists and developers of protein pharmaceuticals. Knowledge about how intrinsic factors influence solubility is limited due to the difficulty of obtaining quantitative solubility measurements. Solubility measurements in buffer alone are difficult to reproduce, because gels or supersaturated solutions often form, making it impossible to determine solubility values for many proteins. Protein precipitants can be ...

  13. Role of Apolipoprotein E in Anxiety

    Directory of Open Access Journals (Sweden)

    Jacob Raber

    2007-07-01

    Full Text Available Anxiety is most common among Alzheimer's disease (AD patients with an age at onset under age 65. Apolipoprotein E4 (apoE4 is a risk factor for developing AD at an earlier age and might contribute to this effect. In mice, apoE plays a role in the regulation of anxiety, which might involve histamine receptor-mediated signaling and steroidogenesis in the adrenal gland. In addition, human apoE isoforms have differential effects on anxiety in adult mice lacking apoE and probable AD patients. Compared to wild-type mice, mice lacking apoE and apoE4 mice showed pathological alterations in the central nucleus of the amygdala, which is involved in regulation of anxiety. ApoE4, but not mice lacking apoE, or apoE3 mice showed impaired dexamethasone suppression of plasma corticosterone. Understanding how apoE modulates measures of anxiety might help the developments of therapeutic targets to reduce or even prevent measures of anxiety in health and in dementing illnesses.

  14. Mutations increasing exposure of a receptor binding site epitope in the soluble and oligomeric forms of the caprine arthritis-encephalitis lentivirus envelope glycoprotein.

    Science.gov (United States)

    Hötzel, Isidro; Cheevers, William P

    2005-09-01

    The caprine arthritis-encephalitis (CAEV) and ovine maedi-visna (MVV) viruses are resistant to antibody neutralization, a feature shared with all other lentiviruses. Whether the CAEV gp135 receptor binding site(s) (RBS) in the functional surface envelope glycoprotein (Env) is protected from antibody binding, allowing the virus to resist neutralization, is not known. Two CAEV gp135 regions were identified by extrapolating a gp135 structural model that could affect binding of antibodies to the RBS: the V1 region and a short sequence analogous in position to the human immunodeficiency virus type 1 gp120 loop B postulated to be located between two major domains of CAEV gp135. Mutation of isoleucine-166 to alanine in the putative loop B of gp135 increased the affinity of soluble gp135 for the CAEV receptor(s) and goat monoclonal antibody (Mab) F7-299 which recognizes an epitope overlapping the gp135 RBS. The I166A mutation also stabilized or exposed the F7-299 epitope in anionic detergent buffers, indicating that the I166A mutation induces conformational changes and stabilizes the RBS of soluble gp135 and enhances Mab F7-299 binding. In contrast, the affinity of a V1 deletion mutant of gp135 for the receptor and Mab F7-299 and its structural stability did not differ from that of the wild-type gp135. However, both the I166A mutation and the V1 deletion of gp135 increased cell-to-cell fusion activity and binding of Mab F7-299 to the oligomeric Env. Therefore, the CAEV gp135 RBS is protected from antibody binding by mechanisms both dependent and independent of Env oligomerization which are disrupted by the V1 deletion and the I166A mutation, respectively. In addition, we found a correlation between side-chain beta-branching at amino acid position 166 and binding of Mab F7-299 to oligomeric Env and cell-to-cell fusion, suggesting local secondary structure constraints in the region around isoleucine-166 as one determinant of gp135 RBS exposure and antibody binding. PMID

  15. Mutations increasing exposure of a receptor binding site epitope in the soluble and oligomeric forms of the caprine arthritis-encephalitis lentivirus envelope glycoprotein

    International Nuclear Information System (INIS)

    The caprine arthritis-encephalitis (CAEV) and ovine maedi-visna (MVV) viruses are resistant to antibody neutralization, a feature shared with all other lentiviruses. Whether the CAEV gp135 receptor binding site(s) (RBS) in the functional surface envelope glycoprotein (Env) is protected from antibody binding, allowing the virus to resist neutralization, is not known. Two CAEV gp135 regions were identified by extrapolating a gp135 structural model that could affect binding of antibodies to the RBS: the V1 region and a short sequence analogous in position to the human immunodeficiency virus type 1 gp120 loop B postulated to be located between two major domains of CAEV gp135. Mutation of isoleucine-166 to alanine in the putative loop B of gp135 increased the affinity of soluble gp135 for the CAEV receptor(s) and goat monoclonal antibody (Mab) F7-299 which recognizes an epitope overlapping the gp135 RBS. The I166A mutation also stabilized or exposed the F7-299 epitope in anionic detergent buffers, indicating that the I166A mutation induces conformational changes and stabilizes the RBS of soluble gp135 and enhances Mab F7-299 binding. In contrast, the affinity of a V1 deletion mutant of gp135 for the receptor and Mab F7-299 and its structural stability did not differ from that of the wild-type gp135. However, both the I166A mutation and the V1 deletion of gp135 increased cell-to-cell fusion activity and binding of Mab F7-299 to the oligomeric Env. Therefore, the CAEV gp135 RBS is protected from antibody binding by mechanisms both dependent and independent of Env oligomerization which are disrupted by the V1 deletion and the I166A mutation, respectively. In addition, we found a correlation between side-chain β-branching at amino acid position 166 and binding of Mab F7-299 to oligomeric Env and cell-to-cell fusion, suggesting local secondary structure constraints in the region around isoleucine-166 as one determinant of gp135 RBS exposure and antibody binding

  16. Uranyl Oxalate Solubility

    International Nuclear Information System (INIS)

    The solubility of uranyl oxalate was determined at ambient temperature by precipitation in oxalic-nitric solutions, using an initial uranyl concentration of 0.1 mol/L. Oxalic concentration varied from 0.075 to 0.3 mol/L while nitric concentration ranged between 0.75 and 3 mol/L. Dissolution tests, using complementary oxalic-nitric media, were carried out for 550 hours in order to study the kinetic to reach thermodynamic equilibrium. Similar solubility values were reached by dissolution and precipitation. Using the results, it was possible to draw the solubility surface versus oxalic and nitric concentrations and to determine both the apparent solubility constant of UO2C2O4, 3H2O (Ks) and the apparent formation constant of the first uranyl-oxalate complex UO2C2O4 (log β1), for ionic strengths varying between 1 and 3 mol/L. Ks and log β1 values were found to vary from 1.9 10-8 to 9.2 10-9 and from 5.95 to 6.06, respectively, when ionic strength varied from 1 to 3 mol/L. A second model may fit our data obtained at an ionic strength of 3 mol/L suggesting as reported by Moskvin et al. (1959) that no complexes are formed for [H+] at 3 M. The Ks value would then be 1.3 10-8. (authors)

  17. DMPD: Regulation of endogenous apolipoprotein E secretion by macrophages. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18388328 Regulation of endogenous apolipoprotein E secretion by macrophages. Kockx ...svg) (.html) (.csml) Show Regulation of endogenous apolipoprotein E secretion by macrophages. PubmedID 18388...328 Title Regulation of endogenous apolipoprotein E secretion by macrophages. Aut

  18. Increased Expression of Ganglioside GM1 in Peripheral CD4+ T Cells Correlates Soluble Form of CD30 in Systemic Lupus Erythematosus Patients

    Directory of Open Access Journals (Sweden)

    Lingli Dong

    2010-01-01

    Full Text Available Gangliosides GM1 is a good marker of membrane microdomains (lipid rafts with important function in cellular activation processes. In this study we found that GM1 expression on CD4+ T cells and memory T cells (CD45RO/CD4 were dramatic increased after stimulation with phytohaemagglutinin in vitro. Next, we examined the GM1 expression on peripheral blood CD4+ T cells and CD8+ T cells from 44 patients with SLE and 28 healthy controls by flow cytometry. GM1 expression was further analyzed with serum soluble CD30 (sCD30, IL-10, TNF-alpha and clinical parameters. The mean fluorescence intensity of GM1 on CD4+ T cells from patients with SLE was significantly higher than those from healthy controls, but not on CD8+ T cells. Increased expression of GM1 was more marked on CD4+/CD45RO+ memory T cells from active SLE patients. Patients with SLE showed significantly elevated serum sCD30 and IL-10, but not TNF-alpha levels. In addition, we found that enhanced GM1 expression on CD4+ T cells from patients with SLE positively correlated with high serum levels of sCD30 and IgG as well as disease activity (SLEDAI scores. Our data suggested the potential role of aberrant lipid raft/GM1 on CD4+ T cells and sCD30 in the pathogenesis of SLE.

  19. Effects of ash forming temperature on water-soluble fraction of biomass ash and it’s elements%成灰温度对三种生物质灰及其元素水溶性的影响

    Institute of Scientific and Technical Information of China (English)

    何芳; 于如军; 张毅; 朱继英; 高振强; 孙鹏

    2015-01-01

    生物质灰及灰中化学元素的水溶特性是其是否能作为肥料应用的主要指标,成灰温度会影响这些特性。该文试验研究了成灰温度在400~800℃范围内,3种主要农业废弃物麦秸、玉米秸、稻壳的灰的水溶性和灰中各元素的水溶性。结果表明:1)麦秸灰、玉米秸灰的水溶性明显高于稻壳灰,三者水溶性都随成灰温度增高而显著降低,温度从400升高到800℃,水溶性分别从48%,35%和12%降至约12%,8%和0。2)灰中水溶元素主要有K,Cl和S,其中,K和Cl的水溶性随着成灰温度升高而降低,而S的水溶性几乎不受成灰温度的影响。%The implementation of biomass ash as a fertilizer is beneficial to the sustainable development of agriculture because it can return the elements taken by the plants from soil during the growth. Water solubility of biomass ash together with its elements is a vital property for the fertilizer’s utilization. In this paper, the effects of ash forming temperature on the water solubility of biomass ash and its elements were investigated experimentally. Three typical types of agro-residues in China, i.e. wheat straw, corn stover and rice husk, were chosen for investigation. Materials were collected and the corresponding proximate and elemental analyses were performed. In preparation process, wheat straw and corn stover were milled into powder with the particle size of less than 1 mm. Ashes were prepared in a muffle furnace at different ash forming temperatures in the scope from 400 to 800℃with the temperature interval of 50℃. About 4-5 g of each sample powder and rice husk were put in the crucibles, heated from ambient temperature to ash forming temperature, and then kept at the ash forming temperature for 4 hours in the muffle furnace. After the temperature of the furnace dropped to less than 200℃, the ashes were taken out to the cabinet dryer, cooled to the ambient temperature, and then

  20. nfluences of ammonium-nitrate, food waste compost and bacterial fertilizer on soluble soil nitrogen forms and on the growth of carrot (Daucus Carota L.

    Directory of Open Access Journals (Sweden)

    Andrea Balla Kovács

    2014-04-01

    Full Text Available This paper reports a greenhouse study to compare the effects of food waste compost, bacterial fertilizer and their combination with the effect of mineral fertilizer on yield of carrot and the available nutrient content of soils. The study was conducted on calcareous chernozem and acidic sandy soils and consisted of 8 treatments in a randomized complete block design with four replications. The NH4NO3 resulted in reduced growing of carrot plant in sandy soil, and the treatment effect of mineral fertilizer was not observed significantly in chernozem soil. Sandy soil showed higher response of growth of carrot to food waste compost fertilization than chernozem soil. Sole application of EM-1 bacterial fertilizer did not have marked effect on yield parameters and sizes of roots. When EM-1 bacterial fertilizer was applied together with ammonium-nitrate or with compost in chernozem soil, the weights of roots and the sizes of roots in some cases became higher compared to the values of appropriate treatments without inoculation. In sandy soil the diameter of roots slightly increased when EM-1 bacterial fertilizer was applied with ammonium-nitrate and with ammonium-nitrate+compost combination compared to appropriate treatment without inoculation. In chernozem soil the maximum weights and sizes of roots were achieved with the combined treatment of ammonium-nitrate+compost+EM-1 bacterial fertilizer and in sandy soil with compost treatment. Our results of soluble nitrogen content of soils are in good agreement with yield parameters of carrot. Results suggest that food waste compost could be a good substitute for mineral fertilizer application in carrot production mainly in sandy soil. EM-1 bacterial fertilizer did not cause marked effect on yield and yield parameters of carrot plant, but its combination with other fertilizers promises a little bit higher yield or plant available nutrient in the soil. These effects do not clear exactly, so further studies are

  1. High-performance CaMKI: A highly active and stable form of CaMKIδ produced by high-level soluble expression in Escherichia coli.

    Science.gov (United States)

    Senga, Yukako; Akizuki, Kazutoshi; Katayama, Syouichi; Shigeri, Yasushi; Kameshita, Isamu; Ishida, Atsuhiko; Sueyoshi, Noriyuki

    2016-07-01

    We describe here the expression and characterization of a constitutively active fragment of zebrafish Ca(2+)/calmodulin-dependent protein kinase (CaMK) Iδ designated zCaMKIδ(1-299) that lacks an autoinhibitory domain. We used a simple one-step purification method to isolate the recombinant enzyme at high yield (220 mg/l of the culture medium) from the soluble fraction of lysates prepared from Escherichia coli. Unlike the corresponding fragment of CaMKIα (CaMKΙα(1-294)), the kinase activity of zCaMKIδ(1-299), without activation procedures, was comparable to that of wild-type zCaMKIδ activated by CaMK kinase. zCaMKIδ(1-299) exhibited broad substrate specificity highly similar to that of wild-type zCaMKIδ, and complementary to that of the cAMP-dependent protein kinase catalytic subunit (PKAc). The protein kinase activity of zCaMKIδ(1-299) was higher compared with that of PKAc as well as CX-30K-CaMKII that comprises a constitutively active fragment of CaMKII fused to the N-terminal region of Xenopus CaMKI. Furthermore, kinase activity was highly stable against thermal inactivation and repeated freezing-thawing. Thus, zCaMKIδ(1-299) represents a readily available alternative that can be used as a "High-performance phosphorylating reagent" alone or in combination with PKAc in diverse experiments on protein phosphorylation and dephosphorylation. PMID:27207832

  2. Use of biorelevant media for assessment of a poorly soluble weakly basic drug in the form of liquisolid compacts: in vitro and in vivo study.

    Science.gov (United States)

    Badawy, Mahmoud A; Kamel, Amany O; Sammour, Omaima A

    2016-01-01

    The purpose of this work is to use biorelevant media to evaluate the robustness of a poorly water soluble weakly basic drug to variations along the gastrointestinal tract (GIT) after incorporation in liquisolid compacts and to assess the success of these models in predicting the in vivo performance. Liquisolid tablets were prepared using mosapride citrate as a model drug. A factorial design experiment was used to study the effect of three factors, namely: drug concentration at two levels (5% and 10%), carriers at three levels (avicel, mannitol and lactose) and powder excipients ratio (R) of the coating material at two levels (25 and 30). The in vitro dissolution media utilized were 0.1 N HCl, hypoacidic stomach model and a transfer model simulating the transfer from the stomach to the intestine. All compacts released above 95% of drug after 10 min in 0.1 N HCl. In the hypoacidic model, the compacts with R 30 were superior compared to R 25, where they released >90% of drug after 10 min compared to 80% for R 25. After the transfer of the optimum compacts from Simulated gastric fluid fast (SGFfast) to fasted state simulated intestinal fluid, slight turbidity appeared after 30 min, and the amount of drug dissolved slightly decreased from 96.91% to 90.59%. However, after the transfer from SGFfast to fed state simulated intestinal fluid, no turbidity or precipitation occurred throughout time of the test (60 min). In vivo pharmacokinetic study in human volunteers proved the success of the in vitro models with enhancement of the oral bioavailability (121.20%) compared to the commercial product. PMID:24892630

  3. Differential Ability of Maize and Soybean to Acquire and Utilize Phosphorus from Sparingly Soluble Forms in Low- and Medium-P Soils Using 32P

    International Nuclear Information System (INIS)

    A glasshouse pot experiment was conducted to evaluate the differential ability of maize (Zea mays) and soybean (Glycine max) to utilize soil phosphorus (P) for plant growth from total-P, available-P and inorganic (Ca-P, Al-P and Fe-P) soil P pools using a carrier-free 32P solution. A maize variety (DK 315) and a soybean variety (TGX 1910-4F) were grown in pots containing 1 kg of a low available P soil (Hungarian) or a medium available P (Waldviertel) soil labelled with 32P for 42 days or without 32P (unlabelled) for 42 and 60 days. The shoot and root biomass of maize and soybean were significantly greater when grown on the Waldviertel than on the Hungarian soils. The shoot P concentrations were higher for soybean (1.7-2.2 g kg-1) than for maize (1.1-1.4 g kg-1). The total radioactivity (dpm x 106) was higher in plants grown in Waldviertel than in Hungarian soil and the values reflected plant P uptake and shoot biomass of soybean and maize. The L-values (μg P g soil-1) of maize and soybean were higher in Waldviertel (72-78) than in Hungarian (9.6-20) soil. No significant differences in L-values were observed for maize and soybean grown on the Waldviertel soil, but for the Hungarian soil, the L-values were higher for maize (20.0) than for soybean (9.6) suggesting that in this low-P soil, maize was more efficient than soybean in taking up soil P. The available P (Bray II) and the Ca-P were the fractions most depleted by plants followed by the Fe-P fractions in the two soils, but differences between the crops were not significant. When soil P is limited, maize and soybean are able to access P mainly from the available P (Bray II), Fe- and Ca-P sparingly soluble fractions and not Al-P from the soil. (author)

  4. Quercetin represses apolipoprotein B expression by inhibiting the transcriptional activity of C/EBPβ.

    Directory of Open Access Journals (Sweden)

    Makoto Shimizu

    Full Text Available Quercetin is one of the most abundant polyphenolic flavonoids found in fruits and vegetables and has anti-oxidative and anti-obesity effects. Because the small intestine is a major absorptive organ of dietary nutrients, it is likely that highly concentrated food constituents, including polyphenols, are present in the small intestinal epithelial cells, suggesting that food factors may have a profound effect in this tissue. To identify novel targets of quercetin in the intestinal enterocytes, mRNA profiling using human intestinal epithelial Caco-2 cells was performed. We found that mRNA levels of some apolipoproteins, particularly apolipoprotein B (apoB, are downregulated in the presence of quercetin. On the exposure of Caco-2 cells to quercetin, both mRNA and protein levels of apoB were decreased. Promoter analysis of the human apoB revealed that quercetin response element is localized at the 5'-proximal promoter region, which contains a conserved CCAAT enhancer-binding protein (C/EBP-response element. We found that quercetin reduces the promoter activity of apoB, driven by the enforced expression of C/EBPβ. Quercetin had no effect on either mRNA or protein levels of C/EBPβ. In contrast, we found that quercetin inhibits the transcriptional activity of C/EBPβ but not its recruitment to the apoB promoter. On the exposure of Caco-2 cells to quercetin 3-O-glucuronide, which is in a cell-impermeable form, no notable change in apoB mRNA was observed, suggesting an intracellular action of quercetin. In vitro interaction experiments using quercetin-conjugated beads revealed that quercetin binds to C/EBPβ. Our results describe a novel regulatory mechanism of transcription of apolipoprotein genes by quercetin in the intestinal enterocytes.

  5. ¹H, ¹³C and ¹⁵N resonance assignment of the soluble form of the lipid-modified Azurin from Neisseria gonorrhoeae.

    Science.gov (United States)

    Nóbrega, Cláudia S; Matzapetakis, Manolis; Pauleta, Sofia R

    2013-10-01

    Lipid-modified azurin (Laz) from Neisseria gonorrhoeae is a type 1 copper protein proposed to be the electron donor to several enzymes involved in the resistance mechanism to reactive oxygen and nitrogen species. Here we report the backbone and side-chain resonance assignment of Laz in the reduced form, which has been complete at 97%. The predicted secondary structure indicates that this protein belongs to the azurin subfamily of type 1 copper proteins. PMID:23070845

  6. Plasma apolipoprotein A5 and triglycerides in type 2 diabetes

    NARCIS (Netherlands)

    Dallinga-Thie, GM; Van Tol, A; Hattori, H; van Vark-van de Zee, LC; Jansen, H; Sijbrands, EJG

    2006-01-01

    Aims/hypothesis: Variation in the human apolipoprotein (APO) A5 gene (APOA5) is associated with elevated plasma triglycerides. However, data on the exact role of plasma concentrations of APOA5 in human triglyceride homeostasis are lacking. In the present study, we estimated plasma APOA5 levels in pa

  7. Apolipoprotein a5 and hypertriglyceridemia in prague hypertriglyceridemic rats

    Czech Academy of Sciences Publication Activity Database

    Kadlecová, Michaela; Hojná, Silvie; Bohuslavová, R.; Hubáček, J. A.; Zicha, Josef; Kuneš, Jaroslav

    2006-01-01

    Roč. 55, č. 4 (2006), s. 373-379. ISSN 0862-8408 R&D Projects: GA MŠk(CZ) 1M0510; GA ČR(CZ) GA305/03/0769 Institutional research plan: CEZ:AV0Z50110509 Keywords : metabolic syndrome * apolipoprotein A5 * rat Subject RIV: ED - Physiology Impact factor: 2.093, year: 2006

  8. Human placenta secretes apolipoprotein B-100-containing lipoproteins

    DEFF Research Database (Denmark)

    Munk-Madsen, Eva; Lindegaard, Marie Louise Skakkebæk; Andersen, Claus B;

    2004-01-01

    Supply of lipids from the mother is essential for fetal growth and development. In mice, disruption of yolk sac cell secretion of apolipoprotein (apo) B-containing lipoproteins results in embryonic lethality. In humans, the yolk sac is vestigial. Nutritional functions are instead established very...... of lipid transfer from the mother to the developing fetus....

  9. Apolipoprotein E genotype, cardiovascular biomarkers and risk of stroke

    DEFF Research Database (Denmark)

    Khan, Tauseef A; Shah, Tina; Prieto, David;

    2013-01-01

    At the APOE gene, encoding apolipoprotein E, genotypes of the ε2/ε3/ε4 alleles associated with higher LDL-cholesterol (LDL-C) levels are also associated with higher coronary risk. However, the association of APOE genotype with other cardiovascular biomarkers and risk of ischaemic stroke is less c...

  10. Effects of apolipoproteins on the kinetics of cholesterol exchange

    Energy Technology Data Exchange (ETDEWEB)

    Letizia, J.Y.; Phillips, M.C. (Medical College of Pennsylvania, Philadelphia (USA))

    1991-01-22

    The effects of apolipoproteins on the kinetics of cholesterol exchange have been investigated by monitoring the transfer of ({sup 14}C)cholesterol from donor phospholipid/cholesterol complexes containing human apolipoproteins A, B, or C. Negatively charged discoidal and vesicular particles containing purified apolipoproteins complexed with lipid and a trace of ({sup 14}C)cholesterol were incubated with a 10-fold excess of neutral, acceptor, small unilamellar vesicles. The donor and acceptor particles were separated by chromatogrphy of DEAE-Sepharose, and the rate of movement of labeled cholesterol was analyzed as a first-order exchange process. The kinetics of exchange of cholesterol from both vesicular and discoidal complexes that contain apoproteins are consistent with an aqueous diffusion mechanism, as has been established previously for PC/cholesterol SUV. Apolipoproteins A-I, A-II, reduced and carboxymethylated A-11, and B-100 present in SUV at the same lipid/protein (w/w) ratio all enhance the rate of cholesterol exchange to about the same degree. Cholesterol molecules exchange more rapidly from discoidal complexes. Generally, as the diameter of apoprotein/phospholipid/cholesterol discs decreases, t{sub 1/2} for cholesterol exchange decreases. Since small bilayer discs have a relatively high ratio of boundary to face surface area, cholesterol molecules desorb more rapidly than from larger discs. The modulation of lipid packing by the apoprotein molecules present at the surface of lipoprotein particles affects the rate of cholesterol exchange from such particles.

  11. The gender-specific apolipoprotein E genotype influence on the distribution of plasma lipids and apolipoproteins in the population of Rochester, Minnesota. II. Regression relationships with concomitants

    Energy Technology Data Exchange (ETDEWEB)

    Reilly, S.L.; Sing, C.F. (Univ. of Michigan, Ann Arbor (United States)); Ferrell, R.E. (Univ. of Pittsburgh, PA (United States)); Kottke, B.A. (Mayo Clinic, Rochester, MN (United States))

    1992-12-01

    The influence of the apolipoprotein E (Apo E) polymorphism and gender on the regression relationships between each of nine plasma lipid and apolipoprotein traits (total cholesterol; ln triglycerides; high-density-lipoprotein chloesterol; apolipoproteins AI, AII, B, and CII; ln CIII; and ln E) and four concomitants (age, weight, waist-to-hip ratio, and smoking) was studied in 507 unrelated individuals representative of the adult population of Rochester, MN. Analyses are presented separately for females and males. Each lipid and apolipoprotein trait exhibited at least one Apo E genotype-specific regression relationship with the concomitants investigated in this study. In most cases the heterogeneity of regression was associated with differences between the [var epsilon]32 and [var epsilon]33 genotype. This study documents that the influence of Apo E genotype on average levels of plasma lipids and apolipoproteins varies among subdivisions of the population defined by age, body size, and smoking status. 61 refs., 1 fig., 5 tabs.

  12. Altered specificity of single-chain antibody fragments bound to pandemic H1N1-2009 influenza virus after conversion of the phage-bound to the soluble form

    Directory of Open Access Journals (Sweden)

    Kaku Yoshihiro

    2012-09-01

    Full Text Available Abstract Background In 2009, a novel influenza A/H1N1 virus (H1N1pdm quickly spread worldwide and co-circulated with then-existing seasonal H1N1 virus (sH1N1. Distinguishing between these 2 viruses was necessary to better characterize the epidemiological properties of the emergent virus, including transmission patterns, pathogenesis, and anti-influenza drug resistance. This situation prompted us to develop a point-of-care virus differentiation system before entering the 2009–2010 influenza season. Aiming to establish H1N1pdm-specific detection tools rapidly, we employed phage display libraries to select H1N1pdm-specific single-chain variable fragments (scFvs. Findings Human single-fold scFv libraries (Tomlinson I + J underwent selection for the ability to bind H1N1pdm virus particles. Three rounds of panning brought 1152 phage-bound scFvs, of which 58 clones reacted with H1N1pdm specifically or preferentially over sH1N1 in an enzyme-linked immunosorbent assay (ELISA. After conversion of the scFvs to soluble form, 7 clones demonstrating high/stable expression were finally obtained. However, all the soluble scFvs except No. 29 were found to have lost their specificity/preference for H1N1pdm in ELISA. The specificity/preference of No. 29 was also confirmed by immunofluorescence assay and immunoprecipitation, and the viral nucleoprotein was identified by ELISA as its target protein. The change in specificity associated with scFv conversion from phage-bound to soluble form could be due to loss of phage scaffold pIII protein, which likely provides structural support for the scFv antigen-binding site. It is also possible that the similar antigenic properties of H1N1pdm and sH1N1 led to the observed alterations in scFv specificity. Discussion Using a phage display library, we obtained 7 soluble scFv clones reactive against H1N1pdm; however, only 1 showed specificity/preference toward H1N1pdm. Our results confirmed that using phage display

  13. Association between a specific apolipoprotein B mutation and familial defective apolipoprotein B-100

    International Nuclear Information System (INIS)

    Familial defective apolipoprotein (apo) B-100 is a genetic disease that leads to hypercholesterolemia and to an increased serum concentration of low density lipoproteins that bind defectively to the apoB,E(LDL) receptor. The disorder appears to result from a mutation in the gene for apoB-100. Extensive sequence analysis of the two alleles of one subject heterozygous for the disorder has revealed a previously unreported mutation in the codon for amino acid 3500 that results in the substitution of glutamine for arginine. This same mutant allele occurs in six other, unrelated subjects and in eight affected relatives in two of these families. A partial haplotype of this mutant apoB-100 allele was constructed by sequence analysis and restriction enzyme digestion at positions where variations in the apoB-100 are known to occur. This haplotype is the same in three probands and four affected members of one family and lacks a polymorphic Xba I site whose presence has been correlated with high cholesterol levels. Thus, it appears that the mutation in the codon for amino acid 3500 (CGG → CAG), a CG mutational hot spot, defines a minor apoB-100 allele associated with defective low density lipoproteins and hypercholesterolemia

  14. Major lipids, apolipoproteins, and risk of vascular disease

    DEFF Research Database (Denmark)

    Collaboration, Emerging Risk Factors; Di Angelantonio, Emanuele; Sarwar, Nadeem;

    2009-01-01

    initial vascular disease from 68 long-term prospective studies, mostly in Europe and North America. During 2.79 million person-years of follow-up, there were 8857 nonfatal myocardial infarctions, 3928 coronary heart disease [CHD] deaths, 2534 ischemic strokes, 513 hemorrhagic strokes, and 2536......CONTEXT: Associations of major lipids and apolipoproteins with the risk of vascular disease have not been reliably quantified. OBJECTIVE: To assess major lipids and apolipoproteins in vascular risk. DESIGN, SETTING, AND PARTICIPANTS: Individual records were supplied on 302,430 people without...... mg/dL directly measured low-density lipoprotein cholesterol (LDL-C). Within-study regression analyses were adjusted for within-person variation and combined using meta-analysis. RESULTS: The rates of CHD per 1000 person-years in the bottom and top thirds of baseline lipid distributions, respectively...

  15. The Apolipoprotein E Antagonistic Pleiotropy Hypothesis: Review and Recommendations

    OpenAIRE

    Tuminello, Elizabeth R.; S Duke Han

    2011-01-01

    Research on apolipoprotein E (APOE) has consistently revealed a relationship between the gene's ε 4 allele and risk for development of Alzheimer's disease (AD). However, research with younger populations of ε 4 carriers has suggested that the APOE ε 4 allele may in fact be beneficial in earlier ages and may only confer risk of cognitive decline later in life. Accordingly, we and others have proposed that APOE may represent an example of antagonistic pleiotropy. Antagonistic pleiotropy is an e...

  16. The role of apolipoprotein AI domains in lipid binding

    OpenAIRE

    Davidson, W. Sean; Hazlett, Theodore; Mantulin, William W.; Jonas, Ana

    1996-01-01

    Apolipoprotein AI (apoAI) is the principal protein constituent of high density lipoproteins and it plays a key role in human cholesterol homeostasis; however, the structure of apoAI is not clearly understood. To test the hypothesis that apoAI is organized into domains, three deletion mutants of human apoAI expressed in Escherichia coli were studied in solution and in reconstituted high density lipoprotein particles. Each mutant lacked one of three specific regions ...

  17. Serum lipid and apolipoprotein distributions in Hong Kong Chinese.

    OpenAIRE

    Fong, P C; Tam, S C; Tai, Y. T.; Lau, C P; Lee, J.; Sha, Y Y

    1994-01-01

    STUDY OBJECTIVE--The aim was to describe the distribution of lipids and apolipoproteins in the Chinese population in Hong Kong. DESIGN--This was a prospective, cross sectional, population based survey. SETTINGS--The study was conducted in a single, self referred, out patient screening centre. PARTICIPANTS--Altogether 825 Chinese adults aged > or = 20 years were screened. One hundred subjects who had previously had lipid measurement and 29 who were taking lipid modifying drugs were excluded bu...

  18. Oligonucleotide-mediated gene editing of Apolipoprotein A-I.

    OpenAIRE

    Disterer, P

    2008-01-01

    Apolipoprotein A-I (ApoA-I) is the major protein constituent of high density lipoprotein (HDL) and controls reverse cholesterol transport, an important process in preventing atherosclerosis. A natural point mutation, ApoA-lMiiano (ApoA-Im) enhances the atheroprotective potential of HDL. Here, I attempt to introduce this specific modification into the genome of mammalian cells using the gene therapy strategy of oligonucleotide-mediated gene editing. I showed successful APOA-I gene editing in r...

  19. Hereditary Amyloid Cardiomyopathy Caused by a Variant Apolipoprotein A1

    OpenAIRE

    Hamidi Asl, Ladan; Liepnieks, Juris J.; Hamidi Asl, Kamran; Uemichi, Tomoyuki; Moulin, Georges; Desjoyaux, Emmanuel; Loire, Robert; Delpech, Marc; Grateau, Gilles; Benson, Merrill D.

    1999-01-01

    Autosomal dominant hereditary amyloidosis with a unique cutaneous and cardiac presentation and death from heart failure by the sixth or seventh decade was found to be associated with a previously unreported point mutation (thymine to cytosine, nt 1389) in exon 4 of the apolipoprotein A1 (apoA1) gene. The predicted substitution of proline for leucine at amino acid position 90 was confirmed by structural analysis of amyloid protein isolated from cardiac deposits of amyloid. The subunit protein ...

  20. Effect of fatty acids on the synthesis and secretion of apolipoprotein B by rat hepatocytes

    International Nuclear Information System (INIS)

    The modulation of apolipoprotein B synthesis and secretion by fatty acids in rat hepatocytes was studied. Maximum apolipoprotein B production was obtained in the case of oleic acid followed by linoleic, stearic and palmitic/linolenic acid when compared to control which was not supplemented with any fatty acids. Oleic acid was found to exert a concentration dependent increase in the secretion of [3H] apolipoprotein B into the medium while that associated with the cell layer was not affected. Pulse chase experiments in the presence of oleic acid showed that it caused an increase in the secretion of apolipoprotein B into the medium. 14C-acetate incorporation into cholesterol and cholesteryl ester associated with the cell layer and secreted very low density lipoproteins also showed an increase in the presence of oleic acid indicating an increase in cholesterogenesis. The effect of oleic acid on [3H] apolipoprotein B and very low density lipoprotein secretion appeared to be mediated through cholesterol as (i)ketoconazole, an inhibitor of cholesterol synthesis caused significant reduction in the stimulatory effect of oleic acid on apolipoprotein secretion and (ii) mevinolin, another inhibitor of cholesterol synthesis also reversed the stimulatory effect of oleic acid on apolipoprotein B secretion. These results indicated that oleic acid may influence apolipoprotein B synthesis and secretion in hepatocytes probably by affecting cholesterol/cholesteryl ester formation which may be a critical component in the secretion of apolipoprotein B as lipoproteins. (author). 21 refs., 4 figs., 2 tabs

  1. Gas solubilities widespread applications

    CERN Document Server

    Gerrard, William

    1980-01-01

    Gas Solubilities: Widespread Applications discusses several topics concerning the various applications of gas solubilities. The first chapter of the book reviews Henr's law, while the second chapter covers the effect of temperature on gas solubility. The third chapter discusses the various gases used by Horiuti, and the following chapters evaluate the data on sulfur dioxide, chlorine data, and solubility data for hydrogen sulfide. Chapter 7 concerns itself with solubility of radon, thoron, and actinon. Chapter 8 tackles the solubilities of diborane and the gaseous hydrides of groups IV, V, and

  2. Selective oxidation of methionine residues in apolipoprotein A-I and its potential biological consequences

    International Nuclear Information System (INIS)

    The earliest stages of HDL oxidation are accompanied by the oxidation of specific Met residues in apolipoprotein AI and AII and the formation of Met sulfoxides (Met(O)) has been proposed to play a significant role in the reduction and hence detoxification of lipid hydroperoxides associated with HDL. Oxidation of HDL may generally decrease the anti-atherogenic properties of this lipoprotein, although both, the inhibition and the enhancement of cholesterol removal from cells has been reported for different types of oxidation. In light of these findings we have investigated the secondary structure, lipid affinity, LCAT activation and cholesterol-efflux promoting properties of native and selectively oxidized apo A-I(apo A-I+32, containing Met(O) at Metl12 and Metl48) in purified or reconstituted forms. Data obtained by circular dichroism revealed that selective oxidation of Met residues 112 and 148 does not alter alpha helicity of the protein in solution, indicating that this oxidation is not sufficient to influence significantly this type of secondary structure of apo A-I in its 'lipid-free' form. The lipid affinity of native apo A-I and apo A-I+32 was determined as the rate of clearance of DMPC multilamellar to small unilamellar vesicles. Compared with the native protein, apo A-I+32 induced a 2-3 fold faster rate of clearance, suggesting that the increased hydrophilicity due Met(O) increased the rate for protein-lipid interactions. Met residues 112 and 148 reside in the hydrophobic faces of helices 5 and 7, and both these regions have been suggested to be important for both, LCAT activation and cholesterol efflux. Kinetic experiments have revealed that the affinity for LCAT is comparable for HDL reconstituted with either apo A-I or apo A-I+32. Efflux of [3H]-cholesterol from lipid-laden human monocytederived macrophages to isolated apolipoproteins was enhanced for apo A-I+32 compared with apo A-I, consistent with the DMPC clearance data. Together these findings

  3. Production and Analysis of Biological Properties of Recombinant Human Apolipoprotein A-I.

    Science.gov (United States)

    Ryabchenko, A V; Kotova, M V; Tverdohleb, N V; Knyazev, R A; Polyakov, L M

    2015-11-01

    Production of recombinant human apolipoprotein A-I (apoA-I) in E. coli cells is described and its biological properties are compared with those of natural protein. Recombinant apoA-I was isolated as a chimeric polypeptide and then processed to a mature form apoA-I (rapo-I). We studied the ability of the resulting protein to penetrate into hepatocyte nuclei and regulate the rate of DNA biosynthesis in complex with estriol. Penetration of rapoA-I conjugated with FITC into hepatocyte nuclei was demonstrated. rapoA-I-estriol and apoA-I-estriol complexes induced similar increase in DNA biosynthesis rate in isolated hepatocytes, which confi rms functional similarity of the obtained recombinant mature protein (rapoA-I) and native human apoA-I. PMID:26612626

  4. Crystal structure of truncated human apolipoprotein A-I suggests a lipid-bound conformation

    Science.gov (United States)

    Borhani, David W.; Rogers, Danise P.; Engler, Jeffrey A.; Brouillette, Christie G.

    1997-01-01

    The structure of truncated human apolipoprotein A-I (apo A-I), the major protein component of high density lipoprotein, has been determined at 4-Å resolution. The crystals comprise residues 44–243 (exon 4) of apo A-I, a fragment that binds to lipid similarly to intact apo A-I and that retains the lipid-bound conformation even in the absence of lipid. The molecule consists almost entirely of a pseudo-continuous, amphipathic α-helix that is punctuated by kinks at regularly spaced proline residues; it adopts a shape similar to a horseshoe of dimensions 125 × 80 × 40 Å. Four molecules in the asymmetric unit associate via their hydrophobic faces to form an antiparallel four-helix bundle with an elliptical ring shape. Based on this structure, we propose a model for the structure of apo A-I bound to high density lipoprotein. PMID:9356442

  5. Water soluble laser dyes

    Science.gov (United States)

    Hammond, Peter R.; Feeman, James F.; Field, George F.

    1998-01-01

    Novel water soluble dyes of the formula I are provided ##STR1## wherein R.sup.1 and R.sup.4 are alkyl of 1 to 4 carbon atoms or hydrogen; or R.sup.1 -R.sup.2 or R.sup.2 -R.sup.4 form part of aliphatic heterocyclic rings; R.sup.2 is hydrogen or joined with R.sup.1 or R.sup.4 as described above; R.sup.3 is --(CH.sub.2).sub.m --SO.sub.3.sup.-, where m is 1 to 6; X is N, CH or ##STR2## where Y is 2 --SO.sub.3.sup.- ; Z is 3, 4, 5 or 6 --SO.sub.3.sup.-. The novel dyes are particularly useful as the active media in water solution dye lasers.

  6. Homozygous familial hypobetalipoproteinemia: A Turkish case carrying a missense mutation in apolipoprotein B.

    Science.gov (United States)

    Yilmaz, Berna Seker; Mungan, Neslihan Onenli; Di Leo, Enza; Magnolo, Lucia; Artuso, Lucia; Bernardis, Isabella; Tumgor, Gokhan; Kor, Deniz; Tarugi, Patrizia

    2016-01-15

    The autosomal co-dominant disorder familial hypobetalipoproteinemia (FHBL) may be due to mutations in the APOB gene encoding apolipoprotein B (apoB), the main constituent peptide of chylomicrons, very low and low density lipoproteins. We describe an 11month-old child with failure to thrive, intestinal lipid malabsorption, hepatic steatosis and severe hypobetalipoproteinemia, suggesting the diagnosis of homozygous FHBL, abetalipoproteinemia (ABL) or chylomicron retention disease (CMRD). The analysis of candidate genes showed that patient was homozygous for a variant (c.1594 C>T) in the APOB gene causing arginine to tryptophan conversion at position 505 of mature apoB (Arg505Trp). No mutations were found in a panel of other potential candidate genes for hypobetalipoproteinemia. In vitro studies showed a reduced secretion of mutant apoB-48 with respect to the wild-type apoB-48 in transfected McA-RH7777 cells. The Arg505Trp substitution is located in the βα1 domain of apoB involved in the lipidation of apoB mediated by microsomal triglyceride transfer protein (MTP), the first step in VLDL and chylomicron formation. The patient's condition improved in response to a low fat diet supplemented with fat-soluble vitamins. Homozygosity for a rare missense mutation in the βα1 domain of apoB may be the cause of both severe hypobetalipoproteinemia and intestinal lipid malabsorption. PMID:26612772

  7. Apolipoprotein B is conformationally flexible but anchored at a triolein/water interface: A possible model for lipoprotein surfaces

    OpenAIRE

    Wang, Libo; Walsh, Mary T.; Small, Donald M.

    2006-01-01

    Apolipoprotein B (apoB) is one of a unique group of proteins that form and bind to fat droplets, stabilize the emulsified fat, and direct their metabolism. ApoB, secreted on lipoproteins (emulsions), remains bound during lipid metabolism yet exhibits conformational flexibility. It has amphipathic β-strand (AβS)-rich domains and amphipathic α-helix (AαH)-rich domains. We showed that two consensus AβS peptides of apoB bound strongly to hydrophobic interfaces [triolein/water (TO/W) and dodecane/...

  8. Pure Phase Solubility Limits: LANL

    International Nuclear Information System (INIS)

    , complex stability constants, and redox potentials for radionuclides in different oxidation states, form the underlying database to be used for those calculations. The potentially low solubilities of many radionuclides in natural waters constitute the first barrier for their migration from the repository into the environment. Evaluation of this effect requires a knowledge of the site-specific water chemistry and the expected spatial and temporal ranges of its variability. Quantitative determinations of radionuclide solubility in waters within the range of chemistry must be made. Speciation and molecular complexation must be ascertained to interpret and apply solubility results. The solubilities thus determined can be used to assess the effectiveness of solubility in limiting radionuclide migration. These solubilities can also be used to evaluate the effectiveness of other retardation processes expected to occur once dissolution of the source material and migration begin. Understanding the solubility behavior of radionuclides will assist in designing valuable sorption experiments that must be conducted below the solubility limit since only soluble species participate in surface reactions and sorption processes. The present strategy for radionuclide solubility tasks has been to provide a solubility model from bulk-experiments that attempt to bracket the estimate made for this Analysis and Modeling Report (AMR) of water conditions on site. The long-term goal must be to develop a thermodynamic database for solution speciation and solid-state determination as a prerequisite for transport calculations and interpretation of empirical solubility data. The model has to be self-consistent and tested against known solubility studies in order to predict radionuclide solubilities over the continuous distribution ranges of potential water compositions for performance assessment of the site. Solubility studies upper limits for radionuclide concentrations in natural waters. The

  9. Neptunium (IV) oxalate solubility

    International Nuclear Information System (INIS)

    The equilibrium solubility of neptunium (IV) oxalate in nitric/oxalic acid solutions was determined at 220C, 450C, and 600C. The concentrations of nitric/oxalic acid solutions represented a wide range of free oxalate ion concentration. A mathematical solubility model was developed which is based on the formation of the known complexes of neptunium (IV) oxalate. the solubility model uses a simplified concentration parameter which is proportional to the free oxalate ion concentration. The solubility model can be used to estimate the equilibrium solubility of neptunium (IV) oxalate over a wide range of oxalic and nitric acid concentrations at each temperature

  10. Specificity determinants in the interaction of apolipoprotein(a) kringles with tetranectin and LDL

    DEFF Research Database (Denmark)

    Caterer, Nigel R; Graversen, Jonas Heilskov; Jacobsen, Christian;

    2002-01-01

    Lipoprotein(a) is composed of low density lipoprotein and apolipoprotein(a). Apolipoprotein(a) has evolved from plasminogen and contains 10 different plasminogen kringle 4 homologous domains [KIV(1-110)]. Previous studies indicated that lipoprotein(a) non-covalently binds the N-terminal region of...

  11. Amyloid Fibril Solubility.

    Science.gov (United States)

    Rizzi, L G; Auer, S

    2015-11-19

    It is well established that amyloid fibril solubility is protein specific, but how solubility depends on the interactions between the fibril building blocks is not clear. Here we use a simple protein model and perform Monte Carlo simulations to directly measure the solubility of amyloid fibrils as a function of the interaction between the fibril building blocks. Our simulations confirms that the fibril solubility depends on the fibril thickness and that the relationship between the interactions and the solubility can be described by a simple analytical formula. The results presented in this study reveal general rules how side-chain-side-chain interactions, backbone hydrogen bonding, and temperature affect amyloid fibril solubility, which might prove to be a powerful tool to design protein fibrils with desired solubility and aggregation properties in general. PMID:26496385

  12. Amyloid Fibril Solubility

    CERN Document Server

    Rizzi, L G

    2015-01-01

    It is well established that amyloid fibril solubility is protein specific, but how solubility depends on the interactions between the fibril building blocks is not clear. Here we use a simple protein model and perform Monte Carlo simulations to directly measure the solubility of amyloid fibrils as a function of the interaction between the fibril building blocks. Our simulations confirms that the fibril solubility depends on the fibril thickness and that the relationship between the interactions and the solubility can be described by a simple analytical formula. The results presented in this study reveal general rules how side-chain side-chain interactions, backbone hydrogen bonding and temperature affect amyloid fibril solubility, which might prove a powerful tool to design protein fibrils with desired solubility and aggregation properties in general.

  13. The Effects of Ginger on Fasting Blood Sugar, Hemoglobin A1c, Apolipoprotein B, Apolipoprotein A-I and Malondialdehyde in Type 2 Diabetic Patients

    OpenAIRE

    Khandouzi, Nafiseh; Shidfar, Farzad; Rajab, Asadollah; Rahideh, Tayebeh; Hosseini, Payam; Mir Taheri, Mohsen

    2015-01-01

    Diabetes mellitus is the most common endocrine disorder, causes many complications such as micro- and macro-vascular diseases. Anti-diabetic, hypolipidemic and anti-oxidative properties of ginger have been noticed in several researches. The present study was conducted to investigate the effects of ginger on fasting blood sugar, Hemoglobin A1c, apolipoprotein B, apolipoprotein A-I, and malondialdehyde in type 2 diabetic patients. In a randomized, double-blind, placebo-controlled, clinical tria...

  14. Clinical, biopsy, and mass spectrometry characteristics of renal apolipoprotein A-IV amyloidosis.

    Science.gov (United States)

    Dasari, Surendra; Amin, Md Shahrier; Kurtin, Paul J; Vrana, Julie A; Theis, Jason D; Grogg, Karen L; Alexander, Mariam P; Nasr, Samih H; Fervenza, Fernando C; Leung, Nelson; Sethi, Sanjeev

    2016-09-01

    Apolipoprotein A-IV associated amyloidosis (AApoAIV amyloidosis) is a rare cause of amyloidosis with only a single reported case. Here we describe the clinical, biopsy, and mass spectrometry characteristics of 11 cases of renal AApoAIV amyloidosis encompassing 9 men and 2 women with a mean age at diagnosis of 63.5 years. Progressive chronic kidney disease (mean serum creatinine 2.9 mg/dl) was the most common cause for biopsy with proteinuria absent or minimal in all except one. Hematological and serological evaluation was negative in 9 patients, while 2 had a monoclonal gammopathy. The renal biopsy findings were striking and showed large amounts of eosinophilic Congo-red positive amyloid deposits restricted to the renal medulla with sparing of the renal cortex. In 6 cases, peritubular amyloid was noted in addition to the interstitial involvement. Immunofluorescence studies were negative for immunoglobulins. Electron microscopy showed nonbranching fibrils measuring 7 to 10 nm in diameter. Laser microdissection of the amyloid deposits followed by mass spectrometry showed large spectra number (a semiquantitative measure of abundance) for AApoAIV protein ranging from 49 to 169 (average 85), serum amyloid protein (average 19), and apolipoprotein E (average 48). Importantly, no peptides were detected for any other forms of known amyloidogenic precursor proteins. Thus, renal AApoAIV amyloidosis typically presents with progressive chronic kidney disease and histologically exhibits extensive medullary involvement with sparing of the cortex. The diagnosis is best established by mass spectrometry. Hence, a high degree of suspicion and examination of the renal medulla is required to make the diagnosis. PMID:27262366

  15. Characterization of the apolipoprotein AI and CIII genes in the domestic pig

    Energy Technology Data Exchange (ETDEWEB)

    Birchbauer, A.; Knipping, G.; Juritsch, B.; Zechner, R. (Univ. of Graz (Austria)); Aschauer, H. (Sandoz-Forschungs Institut Ges.m.b.H., Vienna (Austria))

    1993-03-01

    The apolipoproteins (apo) AI and CIII are important constituents of triglyceride-rich lipoproteins and high-density lipoproteins. In humans, apo AI is believed to play an important protective role in the pathogenesis of arteriosclerosis, whereas apo CIII might be involved in the development of hypertriglyceridemia. Both human genes are located within a gene cluster on chromosome 11. Although the domestic pig has been widely used as an animal model in arteriosclerosis and lipid research, the porcine apolipoproteins genes are poorly characterized. In this report, the complete nucleotide sequences of the porcine apo AI and CIII genes are presented and the authors demonstrate, for the first time, apo CIII expression in the pig. Both genes are composed of four exons and three introns and resemble closely their human counterparts with regard to the transcriptional start sites, exon sizes, intron sizes, exon-intron borders, and the size of the intergenic region. The predicted pig apo AI is a protein of 241 amino acids, which is 2 amino acids shorter than human apo AI. The protein sequence was found to be very homologous to apo AI sequences in other mammalian species. Apo AI expression was detected on the mRNA level in porcine liver and intestine. The apo CIII gene encodes a protein with 73 amino acids, which is 6 amino acids shorter than human apo CIII. In contrast to the three isoforms of apo CIII found in humans, only one major isoform was detected in the pig. Presumably this isoform is unglycosylated. In addition to apo CIII expression in the liver and the intestine, a truncated form of apo CIII mRNA was also found in porcine kidney. The studies demonstrate the presence of an apo CIII gene, an apo CIII mRNA, and an apo CIII protein in the pig and, therefore, exclude a hypothesized apo CIII deficiency in these animals. 53 refs., 5 figs.

  16. FTY720 Attenuates Acute Pancreatitis in Hypertriglyceridemic Apolipoprotein CIII Transgenic Mice.

    Science.gov (United States)

    Liu, Jinjiao; Xu, Pengfei; Zhang, Ling; Kayoumu, Abudurexiti; Wang, Yunan; Wang, Mengyu; Gao, Mingming; Zhang, Xiaohong; Wang, Yuhui; Liu, George

    2015-09-01

    Hypertriglyceridemic pancreatitis (HTGP) is often encountered clinically as a common form of recurrent acute pancreatitis (AP). It is important to evaluate the management of severe hypertriglyceridemia (HTG) or anti-inflammation in the prophylaxis of HTGP in the clinic. FTY720 (2-amino-2[2-(4-octylphenyl) ethyl]-1, 3-propanediol) is a new anti-inflammatory agent with low toxicity and reported to ameliorate lung injury with pancreatitis in rat. We evaluated its protective affection on AP induced by seven hourly intraperitoneal injection of cerulein in apolipoprotein CIII transgenic mice with severe HTG. FTY720 at 1.5 mg/kg was administered by gastric lavage daily for 3 days before induction of AP. The effects of FTY720 to protect against HTGP were assessed by serum amylase, pancreatic pathological scores, immunostaining, and the expression of inflammatory cytokine genes. As a result, injection of cerulein resulted in more severe pathological changes of AP and higher monocyte chemoattractant protein 1 expression in the pancreas in transgenic than in nontransgenic mice. FTY720 pretreatment improved the pathological severity of AP and decreased the expression of monocyte chemoattractant protein 1 in the pancreas significantly, especially near fourfold reduction in transgenic mice. However, FTY720 did not affect plasma triglyceride levels, and other inflammatory factors and plasma amylase were not correlated with the extent of pancreatic damage in AP with or without FTY720 administration. In summary, our study in a new model, apolipoprotein CIII transgenic mice, demonstrated that HTG mice are susceptible to induction of AP. Prophylactic treatment of FTY720 can significantly attenuate cerulein-induced AP and hence warrant further investigation of sphingosine-1-phosphate receptors agonist for potential clinical application in recurrent attacks of HTGP. PMID:25944794

  17. Reduced apolipoprotein glycosylation in patients with the metabolic syndrome.

    Directory of Open Access Journals (Sweden)

    Olga V Savinova

    Full Text Available The purpose of this study was to compare the apolipoprotein composition of the three major lipoprotein classes in patients with metabolic syndrome to healthy controls.Very low density (VLDL, intermediate/low density (IDL/LDL, hereafter LDL, and high density lipoproteins (HDL fractions were isolated from plasma of 56 metabolic syndrome subjects and from 14 age-sex matched healthy volunteers. The apolipoprotein content of fractions was analyzed by one-dimensional (1D gel electrophoresis with confirmation by a combination of mass spectrometry and biochemical assays.Metabolic syndrome patients differed from healthy controls in the following ways: (1 total plasma--apoA1 was lower, whereas apoB, apoC2, apoC3, and apoE were higher; (2 VLDL--apoB, apoC3, and apoE were increased; (3 LDL--apoC3 was increased, (4 HDL--associated constitutive serum amyloid A protein (SAA4 was reduced (p<0.05 vs. controls for all. In patients with metabolic syndrome, the most extensively glycosylated (di-sialylated isoform of apoC3 was reduced in VLDL, LDL, and HDL fractions by 17%, 30%, and 25%, respectively (p<0.01 vs. controls for all. Similarly, the glycosylated isoform of apoE was reduced in VLDL, LDL, and HDL fractions by 15%, 26%, and 37% (p<0.01 vs. controls for all. Finally, glycosylated isoform of SAA4 in HDL fraction was 42% lower in patients with metabolic syndrome compared with controls (p<0.001.Patients with metabolic syndrome displayed several changes in plasma apolipoprotein composition consistent with hypertriglyceridemia and low HDL cholesterol levels. Reduced glycosylation of apoC3, apoE and SAA4 are novel findings, the pathophysiological consequences of which remain to be determined.

  18. Apolipoprotein E*3-Leiden transgenic mice mode for hypolipidaemic drugs

    OpenAIRE

    Vlijmen, B.J.M. van; Pearce, N.J.; Bergö, M.; Staels, B.; Yates, J.W.; Gribble, A.D.; Bond, B.C.; Hofker, M H; Havekes, L. M.; Groot, P H E

    1998-01-01

    Apolipoprotein (APO) E*3-Leiden mice with impaired chylomicron and VLDL (very low density lipoprotein) remnant metabolism display hyperlipidaemia and atherosclerosis. In the present study, these mice were used for testing the hypolipidaemic effect of two marketed agents, lovastatin (CAS 75330-75-5) and gemfibrozil (CAS 25812-30-0) as well as a novel compound, SB 204990 (the 5- ring lactone of ±(3R*,5S*) 3-carboxy-11-(2,4-dichlorophenyl)-3,5- dihydroxyundecanoic acid, CAS 154566-12-8), a poten...

  19. An abundant dysfunctional apolipoprotein A1 in human atheroma

    OpenAIRE

    Huang, Ying; DiDonato, Joseph A.; Levison, Bruce S.; Schmitt, Dave; Li, Lin; Wu, Yuping; Buffa, Jennifer; Kim, Timothy; Gerstenecker, Gary; Gu, Xiaodong; Kadiyala, Chandra; Wang, Zeneng; Culley, Miranda K.; Hazen, Jennie E.; DiDonato, Anthony J.

    2014-01-01

    Recent studies indicate high density lipoproteins (HDL) and their major structural protein, apolipoprotein A1 (apoA1), recovered from human atheroma, are dysfunctional and extensively oxidized by myeloperoxidase (MPO), while in vitro oxidation of apoA1/HDL by MPO impairs its cholesterol acceptor function. We developed a high affinity monoclonal antibody (mAb) that specifically recognizes apoA1/HDL modified by the MPO/H2O2/Cl-system using phage display affinity maturation. An oxindolyl alanine...

  20. The characteristics of spontaneously forming physically cross-linked hydrogels composed of two water-soluble phospholipid polymers for oral drug delivery carrier I: hydrogel dissolution and insulin release under neutral pH condition.

    Science.gov (United States)

    Nam, Kwangwoo; Watanabe, Junji; Ishihara, Kazuhiko

    2004-11-01

    Hydrogels bearing a phospholipid polar group, 2-methacryloyloxyethyl phosphorylcholine (MPC), were prepared from two aqueous solutions of polymers, water-soluble poly[MPC-co-methacrylic acid (MA)] (PMA) and poly[MPC-co-n-butyl methacrylate (BMA)] (PMB). The hydrogel, which was formed by physical cross-linking spontaneously without any chemical reactions and/or any physical stimuli, showed a controllable insulin release through a pH change in the medium by changing the hydrogen bonds. In this study, the mechanical strength, erosion of the hydrogel caused by polymer dissociation, and the release of insulin were examined with attention to the following three parameters of the MPC polymer: molecular weight of the polymers, composition of PMA and PMB (PMA/PMB ratio), and polymer concentration inside the hydrogel. The hydrogel with the highest mechanical strength was obtained at a PMA/PMB ratio = 3/7 (v/v, by volume ratio) while the hydrogel with the slowest dissolution was obtained at a ratio of 5/5 (v/v). The release was in good match with the dissolution and followed anomalous transport for all, but the diffusion exponent n changed according to the PMA/PMB ratio. An increase in the polymer concentration inside the hydrogel caused an increase in the mechanical strength of the hydrogel. When the polymer concentration was more than 20 wt.%, the absorption of water under neutral pH condition (pH 6.8) was observed. The release of insulin was suppressed below 10% during the swelling process of the hydrogel under neutral pH condition, while release was accelerated during the erosion process of the hydrogel. The relationship between erosion of the hydrogel and the release of the insulin depended on the erosion process of the hydrogel but differed according to the PMA/PMB ratio. PMID:15489127

  1. Both serum apolipoprotein B and the apolipoprotein B/apolipoprotein A-I ratio are associated with carotid intima-media thickness.

    Directory of Open Access Journals (Sweden)

    Fei Huang

    Full Text Available BACKGROUND: Previous studies indicated that apolipoprotein measurements predicted cardiovascular disease (CVD risk; however, associations between apolipoproteins and carotid intima-media thickness (CIMT were less explored. METHODOLOGY AND PRINCIPAL FINDINGS: The cross-sectional study included 6069 participants aged 40 years or older with NGT from Shanghai, China. Serum fasting traditional lipids (total cholesterol [TC], low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C] and triglycerides [TG], apoA-I and apoB were assessed. A high-resolution B-mode ultrasonography was performed to measure CIMT. We found CIMT increased progressively across the quartiles of serum apoB (p for trend <0.0001. In logistic regression, concentrations of apoB (odds ratio [OR] 1.27, 95% confidence interval [CI] 1.18-1.36, TC (OR 1.23, 95% CI 1.14-1.32, LDL-C (OR 1.25, 95% CI 1.16-1.34 and TG (OR 1.11, 95% CI 1.04-1.20 were significantly related to elevated CIMT after adjusted for age and sex. Meanwhile, the apoB/apoA-I ratio (OR 1.25, 95% CI 1.17-1.34 related to elevated CIMT. ApoB (OR 1.23, 95% CI 1.00-1.51 and the apoB/apoA-I ratio (OR 1.19, 95% CI 1.04-1.36 remained significantly associated with elevated CIMT, after adjusted for the traditional CVD risk factors including traditional lipids. CONCLUSIONS AND SIGNIFICANCE: There were significant associations between serum apoB, the apoB/apoA-I ratio and elevated CIMT. Serum apoB and the apoB/apoA-I ratio might be independent predictors of early atherosclerosis in NGT.

  2. Wetting of soluble polymers

    OpenAIRE

    Dupas, Julien

    2012-01-01

    The wetting of a soluble substrate is a situation commonly encountered in day-to-day life. For instance, the practical motivation of this study concerns the preparation of beverages using dehydrated powders, consisting of water-soluble substances such as carbohydrates. Hydrodynamical theories describing wetting onto insoluble substrates cannot account for experimental observations in the case of a liquid spreading onto a soluble substrate. Tay et al.(1) made the hypothesis that the water cont...

  3. The intravenous injection of oxidized LDL- or Apolipoprotein B100 – Coupled splenocytes promotes Th1 polarization in wildtype and Apolipoprotein E – Deficient mice

    Energy Technology Data Exchange (ETDEWEB)

    Steinmetz, Martin, E-mail: martin.steinmetz@ukb.uni-bonn.de [INSERM, Unit 970, Paris Cardiovascular Research Center, 75015 Paris (France); Internal Medicine II, University Hospital Bonn, 53105 Bonn (Germany); Ponnuswamy, Padmapriya; Laurans, Ludivine; Esposito, Bruno; Tedgui, Alain [INSERM, Unit 970, Paris Cardiovascular Research Center, 75015 Paris (France); Mallat, Ziad [INSERM, Unit 970, Paris Cardiovascular Research Center, 75015 Paris (France); Division of Cardiovascular Medicine, University of Cambridge, Addenbrooke' s Hospital, Cambridge, CB2 2QQ (United Kingdom)

    2015-08-14

    Background: Th1 responses in atherosclerosis are mainly associated with the aggravation of atherosclerotic plaques, whereas Th2 responses lead to a less pronounced disease in mouse models. The fixation of antigens on cells by means of ethylene carbodiimide (ECDI), and subsequent injection of these antigen-coupled splenocytes (Ag-SP) to induce tolerance against the attached antigens, has been successfully used to treat murine type 1 diabetes or encephalomyelitis in. We analyzed this approach in a mouse model for atherosclerosis. Methods and results: OTII-transgenic mice that were treated with a single dose of 5 × 10{sup 7} OVA-coupled splenocytes (OVA-SP), had decreased splenocyte proliferation, and lower IFNγ production in vitro upon antigen recall. However, in vivo CD4 cell activation was increased. To try lipoprotein-derived, “atherosclerosis-associated” antigens, we first tested human oxidized LDL. In wild type mice, an increase of IFNγ production upon in vitro recall was detected in the oxLDL-SP group. In Apolipoprotein E − deficient (ApoE−/−) mice that received oxLDL-SP every 5 weeks for 20 weeks, we did not find any difference of atherosclerotic plaque burden, but again increased IFNγ production. To overcome xenogenous limitations, we then examined the effects of mouse Apolipoprotein B100 peptides P3 and P6. ApoB100-SP treatment again promoted a more IFNγ pronounced response upon in vitro recall. Flow cytometry analysis of cytokine secreting spleen cells revealed CD4 positive T cells to be mainly the source for IFNγ. In ApoE−/− mice that were administered ApoB100-SP during 20 weeks, the atherosclerotic plaque burden in aortic roots as well as total aorta was unchanged compared to PBS treated controls. Splenocyte proliferation upon antigen recall was not significantly altered in ApoB100-SP treated ApoE−/− mice. Conclusion: Although we did not observe a relevant anti-atherosclerotic benefit, the treatment with antigen

  4. The intravenous injection of oxidized LDL- or Apolipoprotein B100 – Coupled splenocytes promotes Th1 polarization in wildtype and Apolipoprotein E – Deficient mice

    International Nuclear Information System (INIS)

    Background: Th1 responses in atherosclerosis are mainly associated with the aggravation of atherosclerotic plaques, whereas Th2 responses lead to a less pronounced disease in mouse models. The fixation of antigens on cells by means of ethylene carbodiimide (ECDI), and subsequent injection of these antigen-coupled splenocytes (Ag-SP) to induce tolerance against the attached antigens, has been successfully used to treat murine type 1 diabetes or encephalomyelitis in. We analyzed this approach in a mouse model for atherosclerosis. Methods and results: OTII-transgenic mice that were treated with a single dose of 5 × 107 OVA-coupled splenocytes (OVA-SP), had decreased splenocyte proliferation, and lower IFNγ production in vitro upon antigen recall. However, in vivo CD4 cell activation was increased. To try lipoprotein-derived, “atherosclerosis-associated” antigens, we first tested human oxidized LDL. In wild type mice, an increase of IFNγ production upon in vitro recall was detected in the oxLDL-SP group. In Apolipoprotein E − deficient (ApoE−/−) mice that received oxLDL-SP every 5 weeks for 20 weeks, we did not find any difference of atherosclerotic plaque burden, but again increased IFNγ production. To overcome xenogenous limitations, we then examined the effects of mouse Apolipoprotein B100 peptides P3 and P6. ApoB100-SP treatment again promoted a more IFNγ pronounced response upon in vitro recall. Flow cytometry analysis of cytokine secreting spleen cells revealed CD4 positive T cells to be mainly the source for IFNγ. In ApoE−/− mice that were administered ApoB100-SP during 20 weeks, the atherosclerotic plaque burden in aortic roots as well as total aorta was unchanged compared to PBS treated controls. Splenocyte proliferation upon antigen recall was not significantly altered in ApoB100-SP treated ApoE−/− mice. Conclusion: Although we did not observe a relevant anti-atherosclerotic benefit, the treatment with antigen-coupled splenocytes

  5. Solubility limits on radionuclide dissolution

    Energy Technology Data Exchange (ETDEWEB)

    Kerrisk, J.F.

    1984-12-31

    This paper examines the effects of solubility in limiting dissolution rates of a number of important radionuclides from spent fuel and high-level waste. Two simple dissolution models were used for calculations that would be characteristics of a Yucca Mountain repository. A saturation-limited dissolution model, in which the water flowing through the repository is assumed to be saturated with each waste element, is very conservative in that it overestimates dissolution rates. A diffusion-limited dissolution model, in which element-dissolution rates are limited by diffusion of waste elements into water flowing past the waste, is more realistic, but it is subject to some uncertainty at this time. Dissolution rates of some elements (Pu, Am, Sn, Th, Zr, Sm) are always limited by solubility. Dissolution rates of other elements (Cs, Tc, Np, Sr, C, I) are never solubility limited; their release would be limited by dissolution of the bulk waste form. Still other elements (U, Cm, Ni, Ra) show solubility-limited dissolution under some conditions. 9 references, 3 tables.

  6. Amphotericin B induced interdigitation of apolipoprotein stabilized nanodisk bilayers

    Energy Technology Data Exchange (ETDEWEB)

    Nguyen, T; Weers, P M; Sulchek, T; Hoeprich, P D; Ryan, R O

    2006-12-07

    Amphotericin B nanodisks (AMB-ND) are ternary complexes of AMB, phospholipid (PL) and apolipoprotein organized as discrete nanometer scale disk-shaped bilayers. In gel filtration chromatography experiments, empty ND lacking AMB elute as a single population of particles with a molecular weight in the range of 200 kDa. AMB-ND formulated at a 4:1 PL:AMB weight ratio, separated into two peaks. Peak 1 eluted at the position of control ND lacking AMB while the second peak, containing all of the AMB present in the original sample, eluted in the void volume. When ND prepared with increased AMB (1:1 phospholipid:AMB molar ratio) were subjected to gel filtration chromatography, an increased proportion of phospholipid and apolipoprotein were recovered in the void volume with the AMB. Prior to gel filtration the AMB-ND sample could be passed through a 0.22 {micro}m filter without loss of AMB while the voided material was lost. Native gel electrophoresis studies corroborated the gel permeation chromatography data. Far UV circular dichroism analyses revealed that apoA-I associated with AMB-ND denatures at a lower guanidine HCl concentration than apoA-I associated with ND lacking AMB. Atomic force microscopy revealed that AMB induces compression of the ND bilayer thickness consistent with bilayer interdigitation, a phenomenon that is likely related to the ability of AMB to induce pore formation in susceptible membranes.

  7. Overexpression of Soluble Recombinant Human Lysyl Oxidase by Using Solubility Tags: Effects on Activity and Solubility

    Science.gov (United States)

    Smith, Madison A.; Gonzalez, Jesica; Hussain, Anjum; Oldfield, Rachel N.; Johnston, Kathryn A.; Lopez, Karlo M.

    2016-01-01

    Lysyl oxidase is an important extracellular matrix enzyme that has not been fully characterized due to its low solubility. In order to circumvent the low solubility of this enzyme, three solubility tags (Nus-A, Thioredoxin (Trx), and Glutathione-S-Transferase (GST)) were engineered on the N-terminus of mature lysyl oxidase. Total enzyme yields were determined to be 1.5 mg for the Nus-A tagged enzyme (0.75 mg/L of media), 7.84 mg for the Trx tagged enzyme (3.92 mg/L of media), and 9.33 mg for the GST tagged enzyme (4.67 mg/L of media). Enzymatic activity was calculated to be 0.11 U/mg for the Nus-A tagged enzyme and 0.032 U/mg for the Trx tagged enzyme, and no enzymatic activity was detected for the GST tagged enzyme. All three solubility-tagged forms of the enzyme incorporated copper; however, the GST tagged enzyme appears to bind adventitious copper with greater affinity than the other two forms. The catalytic cofactor, lysyl tyrosyl quinone (LTQ), was determined to be 92% for the Nus-A and Trx tagged lysyl oxidase using the previously reported extinction coefficient of 15.4 mM−1 cm−1. No LTQ was detected for the GST tagged lysyl oxidase. Given these data, it appears that Nus-A is the most suitable tag for obtaining soluble and active recombinant lysyl oxidase from E. coli culture. PMID:26942005

  8. Solubility of drugs in aqueous solutions. Part 5. Thermodynamic consistency test for the solubility data.

    Science.gov (United States)

    Ruckenstein, E; Shulgin, I

    2005-03-23

    This paper is devoted to the verification of the quality of experimental data regarding the solubility of sparingly soluble solids, such as drugs, environmentally important substances, etc. in mixed solvents. A thermodynamic consistency test based on the Gibbs-Duhem equation for ternary mixtures is suggested. This test has the form of an equation, which connects the solubilities of the solid, and the activity coefficients of the constituents of the solute-free mixed solvent in two mixed solvents of close compositions. The experimental data regarding the solubility of sparingly soluble substances can be verified with the suggested test if accurate data for the activity coefficients of the constituents of the solute-free mixed solvent are available. The test was applied to a number of systems representing the solubilities of sparingly soluble substances in mixed solvents. First, the test was scrutinized for four nonaqueous systems for which accurate solubility data were available. Second, the suggested test was applied to a number of systems representing experimental data regarding the solubility of sparingly soluble substances in aqueous mixed solvents. PMID:15725556

  9. Apolipoprotein Mimetic Peptides: A New Approach for the Treatment of Asthma

    Directory of Open Access Journals (Sweden)

    Xianglan eYao

    2012-03-01

    Full Text Available New treatments are needed for severe asthmatics to improve disease control and avoid severe toxicities associated with oral corticosteroids. We have used a murine model of house dust mite (HDM-induced asthma to identify steroid-unresponsive genes that might represent targets for new therapeutic approaches for severe asthma. This strategy identified apolipoprotein E as a steroid-unresponsive gene with increased mRNA expression in the lungs of HDM-challenged mice. Furthermore, apolipoprotein E functioned as an endogenous negative regulator of airway hyperreactivity and goblet cell hyperplasia in experimental HDM-induced asthma. The ability of apolipoprotein E, which is expressed by lung macrophages, to attenuate AHR and goblet cell hyperplasia is mediated by low density lipoprotein (LDL receptors expressed by airway epithelial cells. Consistent with this, administration of an apolipoprotein E mimetic peptide, corresponding to amino acids 130 to 149 of the LDL receptor-binding domain of the holo-apoE protein, significantly reduced AHR and goblet cell hyperplasia in HDM-challenged apoE-/- mice. These findings identified the apolipoprotein E - LDL receptor pathway as a new druggable target for asthma that can be activated by administration of apoE mimetic peptides. Similarly, apolipoprotein A-I may have therapeutic potential in asthma based upon its anti-inflammatory, anti-oxidative and anti-fibrotic properties. Furthermore, administration of apolipoprotein A-I mimetic peptides has attenuated airway inflammation, airway remodeling and airway hyperreactivity in murine models of experimental asthma. Thus, site-directed delivery of inhaled apolipoprotein E or apolipoprotein A-I mimetic peptides may represent novel treatment approaches that can be developed for asthma, including severe disease.

  10. Relationship between depression and apolipoproteins A and B: a case-control study

    Directory of Open Access Journals (Sweden)

    Masoumeh Sadeghi

    2011-01-01

    Full Text Available OBJECTIVE: To investigate the relation between major depressive disorder and metabolic risk factors of coronary heart disease. INTRODUCTION: Little evidence is available indicating a relationship between major depressive disorder and metabolic risk factors of coronary heart disease such as lipoprotein and apolipoprotein. METHODS: This case-control study included 153 patients with major depressive disorder who fulfilled the criteria of the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV, and 147 healthy individuals. All participants completed a demographic questionnaire and Hamilton rating scale for depression. Anthropometric characteristics were recorded. Blood samples were taken and total cholesterol, high-and low-density lipoproteins and apolipoproteins A and B were measured. To analyze the data, t-test, χ2 test, Pearson correlation test and linear regression were applied. RESULTS: Depression was a negative predictor of apolipoprotein A (β = -0.328, p<0.01 and positive predictor of apolipoprotein B (β = 0.290, p<0.05. Apolipoprotein A was inversely predicted by total cholesterol (β = -0.269, p<0.05 and positively predicted by high-density lipoprotein (β = 0.401, p<0.01. Also, low-density lipoprotein was a predictor of apolipoprotein B (β = 0.340, p<0.01. The severity of depression was correlated with the increment in serum apolipoprotein B levels and the decrement in serum apolipoprotein A level. CONCLUSION: In view of the relationship between apolipoproteins A and B and depression, it would seem that screening of these metabolic risk factors besides psychological interventions is necessary in depressed patients

  11. The Solubility of struvite

    DEFF Research Database (Denmark)

    Aage, H. K.; Andersen, Bertel Lohmann; Blom, A.;

    1997-01-01

    The solubility of magnesium-amonium-phosphate (struvite) has been studied emloying the radioisotope 32P as tracer. The amount of sample in solution is determined by measuring the Cherenkov radiation due to the beta-particles emitted from this radionuclide. The thermodynamic solubility product is...

  12. Applications of Solubility Data

    Science.gov (United States)

    Tomkins, Reginald P. T.

    2008-01-01

    This article describes several applications of the use of solubility data. It is not meant to be exhaustive but rather to show that knowledge of solubility data is required in a variety of technical applications that assist in the design of chemical processes. (Contains 3 figures and 1 table.)

  13. Characterization of the metabolic syndrome by apolipoproteins in the Oklahoma Cherokee.

    Science.gov (United States)

    Alaupovic, Petar; Blackett, Piers; Wang, Wenyu; Lee, Elisa

    2008-01-01

    Native Americans are susceptible to type 2 diabetes and associated cardiovascular risk that precedes the diabetes. Nondiabetic Cherokee adolescents and young adults were studied for association of apolipoproteins A-I, B, and C-III with the metabolic syndrome, homeostasis model assessment-insulin resistance (HOMA-IR), and body mass index. Apolipoproteins, lipids, selected ratios, and HOMA-IR changed adversely according to the number of metabolic syndrome criteria present (PCherokee have a high prevalence of the metabolic syndrome, which is associated with atherosclerotic lipoprotein particles containing apolipoprotein C-III and B. PMID:19040586

  14. Thermo-inductively Prokaryotic Expression in a Soluble Form and Easy Purification of Thymosin α1%胸腺肽α1的温度诱导原核可溶性表达与简易纯化

    Institute of Scientific and Technical Information of China (English)

    陈培富; 李红芳; 鲁琼芬; 陈俊

    2012-01-01

    An artificially synthesized gene of human thymosin a, (Tα1) was inserted into pBV222 and then thermo-inductively expressed as a fusion protein in a soluble form in transformed Escherichia coli strain DH5α at 42°C. The fusion protein purified through nickel affinity chromatography was cleaved with enterokinase. The cleavage mixture was returned to the nickel affinity chromatography column. Recombinant Tα1 (rTα1) in the flow-through reached a purity of 94. 5% as showed by sodium dode-cyl sulfate-polyacrylamide gel electrophoresis ( SDS-PAGE ) and 72% by reverse phase-high performance liquid chromatography (RP-HPLC), respectively. The finally purified rTα1, exhibited the same bioactivity as chemically synthesized Tα1, in rosette tests with peripheral blood lymphocytes from cancer patients.%将人工合成的人胸腺肽α1(Tα1)基因插入到载体pBV222,转化大肠杆菌DH5α菌株并置42℃诱导表达可溶性融合蛋白.融合蛋白经镍亲和层析柱纯化,加入肠激酶切割,再将酶切反应体系回到镍亲和层析柱.所获穿过液中的重组胸腺肽α1(rTα1),经十二烷基硫酸钠-聚苯烯酰胺凝胶电泳(SDS-PAGE)和反相高效液相色谱(RP-HPLC)分离及分析,纯度分别为94.5%和72%.以癌症患者外周血淋巴细胞开展玫瑰花环试验,所获rTα1纯品显示出与化学合成Tα1(sTα1)相同的生物学活性.

  15. Expression of the very low-density lipoprotein receptor (VLDL-r), an apolipoprotein-E receptor, in the central nervous system and in Alzheimer`s disease

    Energy Technology Data Exchange (ETDEWEB)

    Christie, R.H.; Chung, Haeyong; Rebeck, G.W.; Hyman, B.T. [Massachusetts General Hospital, Boston, MA (United States)] [and others

    1996-04-01

    The very low density lipoprotein receptor (VLDL-r) is a cell-surface molecule specialized for the internalization of multiple diverse ligands, including apolipoprotein E (apoE)-containing lipoprotein particles, via clathrin-coated pits. Its structure is similar to the low-density lipoprotein receptor (LDL-r), although the two have substantially different systemic distributions and regulatory pathways. The present work examines the distribution of VLDL-r in the central nervous system (CNS) and in relation to senile plaques in Alzheimer disease (AD). VLDL-r is present on resting and activated microglia, particularly those associated with senile plaques (SPs). VLDL-r immunoreactivity is also found in cortical neurons. Two exons of VLDL-r mRNA are differentially spliced in the mature receptor mRNA. One set of splice forms gives rise to receptors containing (or lacking) an extracellular O-linked glycosylation domain near the transmembrane portion of the molecule. The other set of splice forms appears to be brain-specific, and is responsible for the presence or absence of one of the cysteine-rich repeat regions in the binding region of the molecule. Ratios of the receptor variants generated from these splice forms do not differ substantially across different cortical areas or in AD. We hypothesize that VLDL-r might contribute to metabolism of apoE and apoE/A{beta} complexes in the brain. Further characterization of apoE receptors in Alzheimer brain may help lay the groundwork for understanding the role of apoE in the CNS and in the pathophysiology of AD. 43 refs., 5 figs.

  16. Human placenta secretes apolipoprotein B-100-containing lipoproteins

    DEFF Research Database (Denmark)

    Munk-Madsen, Eva; Lindegaard, Marie Louise Skakkebæk; Andersen, Claus B;

    2004-01-01

    Supply of lipids from the mother is essential for fetal growth and development. In mice, disruption of yolk sac cell secretion of apolipoprotein (apo) B-containing lipoproteins results in embryonic lethality. In humans, the yolk sac is vestigial. Nutritional functions are instead established very...... early during pregnancy in the placenta. To examine whether the human placenta produces lipoproteins, we examined apoB and microsomal triglyceride transfer protein (MTP) mRNA expression in placental biopsies. ApoB and MTP are mandatory for assembly and secretion of apoB-containing lipoproteins. Both...... lipoproteins secreted from placental tissue showed spherical particles with a diameter of 47 +/- 10 nm. These results demonstrate that human placenta expresses both apoB and MTP and consequently synthesize and secrete apoB-100-containing lipoproteins. Placental lipoprotein formation constitutes a novel pathway...

  17. Antiatherogenic effects of oleanolic acid in apolipoprotein E knockout mice

    DEFF Research Database (Denmark)

    Buus, Niels Henrik; Hansson, Nicolaj Christopher; Rodriguez-Rodriguez, Rosalia;

    2011-01-01

    Oleanolic acid (OA) is a plant triterpenoid steroid with potentially antiatherogenic properties. We investigated whether OA affected atherosclerosis development and vascular function in apolipoprotein E knockout (ApoE(-/-)) mice. ApoE(-/-) mice were fed a high cholesterol Western-type diet in...... combination with OA (100 mg/kg/day), fluvastatin (5 mg/kg/day) or vehicle, with wild type (WT) mice serving as controls. After 8 weeks of treatment atherosclerotic plaque areas in the aortic arch and plasma lipid concentrations were determined. Vasoconstriction and relaxation of the proximal part of aorta...... were investigated in vitro. Inducible nitric oxide synthase (iNOS) was visualized using immunoblotting. As opposed to WT and fluvastatin- and vehicle-treated mice, OA-fed ApoE(-/-) mice gained no weight during the treatment period. Plasma concentrations of total-cholesterol and triglyceride were not...

  18. Cardiovascular effects of uremia in apolipoprotein E-deficient mice

    DEFF Research Database (Denmark)

    Bro, Susanne

    2009-01-01

    of smooth muscle cell assigned genes indicates that besides intimal atherosclerosis, uremic vasculopathy in apoE-/- mice is characterized by a uremia-specific medial smooth muscle cell degeneration. Oxidative stress could also be important for the development of atherosclerotic lesions in uremia. In...... muscle cell degeneration. Furthermore, the studies suggested that vascular inflammation and systemic oxidative stress may explain some of the proatherogenic effects of uremia in mice. Interestingly, the accelerated atherosclerosis could be prevented by RAS inhibition, or markedly reduced by RAGE blockade......The purpose of this thesis work was to establish an experimental mouse model for studying the pathogenesis and therapy of accelerated atherosclerosis in uremia. Uremia was induced by surgical 5/6 nephrectomy in apolipoprotein E-deficient (apoE-/-) mice and led to development of severe aortic...

  19. Function and Comorbidities of Apolipoprotein E in Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Valérie Leduc

    2011-01-01

    Full Text Available Alzheimer's disease (AD—the most common type of dementia among the elderly—represents one of the most challenging and urgent medical mysteries affecting our aging population. Although dominant inherited mutation in genes involved in the amyloid metabolism can elicit familial AD, the overwhelming majority of AD cases, dubbed sporadic AD, do not display this Mendelian inheritance pattern. Apolipoprotein E (APOE, the main lipid carrier protein in the central nervous system, is the only gene that has been robustly and consistently associated with AD risk. The purpose of the current paper is thus to highlight the pleiotropic roles and the structure-function relationship of APOE to stimulate both the functional characterization and the identification of novel lipid homeostasis-related molecular targets involved in AD.

  20. Apolipoprotein B100 analysis in microchip with electrochemical detection

    Institute of Scientific and Technical Information of China (English)

    Cheng Cheng Liu; Yun Liu; Hui Xiang Wang; Yan Bo Qi; Peng Yuan Yang; Bao Hong Liu

    2011-01-01

    Apolipoprotein B100 (apoB-100) is a major protein of the cholesterol-rich low-density lipoprotein (LDL) and reflects a better assessment of total atherogenic burden to the vascular system than LDL. In this work, a simple and sensitive method has been developed to determine picoliter apoB-100s using the PMMA microfluidic chip coupled with electrochemical detection system. This method performs very well with a detectable linear range of 1-800 pg/mL and a detection limit of 1 pg/mL. A real serum sample has further been detected by this microchip-based biosensor. The results show that this kind of method is practicable and has the potential application in clinical analysis and diagnosis.

  1. Soluble macrophage-derived CD163

    DEFF Research Database (Denmark)

    Møller, Holger Jon; Nielsen, Marianne Jensby; Maniecki, Maciej Bogdan; Madsen, Mette; Moestrup, Søren Kragh

    2010-01-01

    BACKGROUND: The soluble form of the haptoglobin-hemoglobin (Hp-Hb) scavenger receptor (sCD163) is a specific plasma/serum marker for macrophage activity. Here, we have characterized molecular forms in serum and investigated a role of sCD163 as a binder of Hp-Hb complexes. METHODS: The sCD163...

  2. Hepatosteatosis and estrogen increase apolipoprotein O production in the chicken.

    Science.gov (United States)

    Schmidinger, Barbara; Weijler, Anna M; Schneider, Wolfgang J; Hermann, Marcela

    2016-08-01

    Apolipoprotein O (ApoO) is a recently discovered plasma apolipoprotein that may also play a role in the mitochondrial inner membrane. Possibly due to this complexity, its physiological functions have not been elucidated yet. To gain insight from a non-mammalian experimental system, we have investigated the regulation of ApoO levels in an alternative, well-suited model for studies on lipid metabolism, the chicken. qPCR using specific primer pairs and Western blot analysis with our rabbit anti-chicken ApoO antiserum demonstrated ApoO in the liver of chickens fed a control or a fat-enriched diet, as well as in 2 chicken hepatoma cell lines, LMH cells and the estrogen-responsive LMH-2A cells, under conditions of lipid loading by incubation with BSA-complexed oleic acid. Induced triglyceride accumulation in both the liver and the hepatic cells was associated with significantly increased levels of ApoO mRNA and protein. Furthermore, upon treatment for 24 h with estrogen of the estrogen receptor-expressing LMH-2A cells, quantitative analysis of ApoO transcripts and Western blotting revealed increases of ApoO expression. Finally, upon a single administration of estrogen to roosters that leads to hyperlipidemia, higher hepatic levels of both ApoO transcript and protein were observed within 24 h. Based on these data, we propose that hepatic expression of ApoO is tightly linked not only to diet-induced hepatosteatosis, but also to increased lipoprotein-production induced by, e.g., hormones. The findings support a role of ApoO as an effector of compromised mitochondrial function that likely accompanies the onset of non-alcoholic fatty liver disease. PMID:27126072

  3. Apolipoprotein and lipid abnormalities in chronic liver failure

    Directory of Open Access Journals (Sweden)

    Spósito A.C.

    1997-01-01

    Full Text Available Total serum lipids, as well as apolipoproteins A-I (apo A-I and B (apo B, were determined in 74 patients with chronic liver failure without cholestasis and in 82 normal subjects. The VLDL, LDL and HDL lipid fractions were reduced in the liver failure group by 36%, 24% and 46%, respectively (P<0.001. Apolipoproteins A-I and B were also reduced by 26% and 25%, respectively (P<0.001. However, the reduction of HDL cholesterol (HDLc was more pronounced than that of apo A-I and the HDLc:apo A-I ratio was significantly lower in the liver failure group. After separating these patients into groups with plasma albumin lower than 3.0, between 3.0 and 3.5, and higher than 3.5 g/dl, the HDLc:apo A-I ratio was proportional to plasma albumin, but the correlation was not statistically significant. When these patients were separated by the Child classification of liver function, there was a correlation between the HDLc:apo A-I ratio and liver function. The differences in the HDLc:apo A-I ratio between the Child groups B and C, and A and C were statistically significant (P<0.05. We conclude that there is a more pronounced reduction in HDL cholesterol than in apo A-I in liver failure patients. Therefore, the HDLc:apo A-I ratio is a marker of liver function, probably because there is a decreased lecithin-cholesterol acyltransferase production by the diseased liver

  4. Overexpression of apolipoprotein AII in transgenic mice converts high density lipoproteins to proinflammatory particles.

    OpenAIRE

    Castellani, L W; Navab, M; Van Lenten, B J; Hedrick, C. C.; Hama, S Y; Goto, A M; Fogelman, A M; Lusis, A J

    1997-01-01

    Previous studies showed that transgenic mice overexpressing either apolipoprotein AI (apoAI) or apolipoprotein AII (apoAII), the major proteins of HDL, exhibited elevated levels of HDL cholesterol, but, whereas the apoAI-transgenic mice were protected against atherosclerosis, the apoAII-transgenic mice had increased lesion development. We now examine the basis for this striking functional heterogeneity. HDL from apoAI transgenics exhibited an enhanced ability to promote cholesterol efflux fro...

  5. A mathematically defined motif for the radial distribution of charged residues on apolipoprotein amphipathic alpha helixes.

    OpenAIRE

    Hazelrig, J B; Jones, M. K.; Segrest, J P

    1993-01-01

    Multiple amphipathic alpha-helical candidate domains have been identified in exchangeable apolipoproteins by sequence analysis and indirect experimental evidence. The distribution of charged residues can differ within and between these apolipoproteins. Segrest et al. (Segrest, J. P., H. DeLoof, J. G. Dohlman, C. G. Brouillette, and G. M. Anantharamaiah. 1990. Proteins. 8:103-117.) argued that these differences are correlated with lipid affinity. A mathematically defined motif for the particul...

  6. Enhanced Diabetes Susceptibility in Community Dwelling Han Elders Carrying the Apolipoprotein E 3/3 Genotype

    OpenAIRE

    Ban, Chun-Xia; Zhong, Li; Wang, Tao; Zhu, Min-jie; Wang, Jing-Hua; Zhang, Zhen-lian; Wang, Zhe; Su, Ning; Liu, Yuan-Yuan; Shi, Yan-chen; Xiao, Shi-fu; Xia LI

    2016-01-01

    Despite Apolipoprotein E (ApoE) being one of the main apolipoproteins in the blood, the association between its genotype and the high cholesterol or blood glucose levels commonly seen in clinical practice is inconclusive. Such research is also lacking in the Han population. The aim of this study was to investigate the association between APOE genotype, diabetes, and plasma glucose and lipid levels. We included 243 community-dwelling elderly residents in this study. Participant APOE genotypes ...

  7. Mass spectral analyses of the two major apolipoproteins of great ape high density lipoproteins

    OpenAIRE

    Puppione, Donald L.; Della Donna, Lorenza; Laganowsky, Arthur D.; Bassilian, Sara; Souda, Puneet; Ryder, Oliver A.; Whitelegge, Julian P.

    2009-01-01

    The two major apolipoproteins associated with human and chimpanzee (Pan troglodytes) high density lipoproteins (HDL) are apoA-I and dimeric apoA-II. Although humans are closely related to great apes, apolipoprotein data do not exist for bonobos (Pan paniscus), western lowland gorillas (Gorilla gorilla gorilla) and the Sumatran orangutans (Pongo abelii). In the absence of any data, other great apes simply have been assumed to have dimeric apoA-II while other primates and most other mammals hav...

  8. Apolipoprotein A-V interaction with members of the low density lipoprotein receptor gene family

    DEFF Research Database (Denmark)

    Nilsson, Stefan K; Lookene, Aivar; Beckstead, Jennifer A; Gliemann, Jørgen

    2007-01-01

    Apolipoprotein A-V is a potent modulator of plasma triacylglycerol levels. To investigate the molecular basis for this phenomenon we explored the ability of apolipoprotein A-V, in most experiments complexed to disks of dimyristoylphosphatidylcholine, to interact with two members of the low densit...... to receptor-covered sensor chips. Our results indicate that apolipoprotein A-V may influence plasma lipid homeostasis by enhancing receptor-mediated endocytosis of triacylglycerol-rich lipoproteins. Udgivelsesdato: 2007-Mar-27......Apolipoprotein A-V is a potent modulator of plasma triacylglycerol levels. To investigate the molecular basis for this phenomenon we explored the ability of apolipoprotein A-V, in most experiments complexed to disks of dimyristoylphosphatidylcholine, to interact with two members of the low density...... lipoprotein receptor family, the low density lipoprotein receptor-related protein and the mosaic type-1 receptor, SorLA. Experiments using surface plasmon resonance showed specific binding of both free and lipid-bound apolipoprotein A-V to both receptors. The binding was calcium dependent and was inhibited by...

  9. Solution Conditions Affect the Ability of the K30D Mutation To Prevent Amyloid Fibril Formation by Apolipoprotein C-II: Insights from Experiments and Theoretical Simulations.

    Science.gov (United States)

    Mao, Yu; Todorova, Nevena; Zlatic, Courtney O; Gooley, Paul R; Griffin, Michael D W; Howlett, Geoffrey J; Yarovsky, Irene

    2016-07-12

    Apolipoproteins form amphipathic helical structures that bind lipid surfaces. Paradoxically, lipid-free apolipoproteins display a strong propensity to form cross-β structure and self-associate into disease-related amyloid fibrils. Studies of apolipoprotein C-II (apoC-II) amyloid fibrils suggest that a K30-D69 ion pair accounts for the dual abilities to form helix and cross-β structure. Consistent with this is the observation that a K30D mutation prevents fibril formation under standard fibril forming conditions. However, we found that fibril formation by K30D apoC-II proceeded readily at low pH and a higher salt or protein concentration. Structural analysis demonstrated that K30D apoC-II fibrils at pH 7 have a structure similar to that of the wild-type fibrils but are less stable. Molecular dynamics simulations of the wild-type apoC-II fibril model at pH 7 and 3 showed that the loss of charge on D69 at pH 3 leads to greater separation between residues K30 and D69 within the fibril with a corresponding reduction in β-strand content around residue 30. In contrast, in simulations of the K30D mutant model at pH 7 and 3, residues D30 and D69 moved closer at pH 3, accompanied by an increase in β-strand content around residue 30. The simulations also demonstrated a strong dominance of inter- over intramolecular contacts between ionic residues of apoC-II and suggested a cooperative mechanism for forming favorable interactions between the individual strands under different conditions. These observations demonstrate the important role of the buried K30-D69 ion pair in the stability and solution properties of apoC-II amyloid fibrils. PMID:27311794

  10. Estimating the Aqueous Solubility of Pharmaceutical Hydrates.

    Science.gov (United States)

    Franklin, Stephen J; Younis, Usir S; Myrdal, Paul B

    2016-06-01

    Estimation of crystalline solute solubility is well documented throughout the literature. However, the anhydrous crystal form is typically considered with these models, which is not always the most stable crystal form in water. In this study, an equation which predicts the aqueous solubility of a hydrate is presented. This research attempts to extend the utility of the ideal solubility equation by incorporating desolvation energetics of the hydrated crystal. Similar to the ideal solubility equation, which accounts for the energetics of melting, this model approximates the energy of dehydration to the entropy of vaporization for water. Aqueous solubilities, dehydration and melting temperatures, and log P values were collected experimentally and from the literature. The data set includes different hydrate types and a range of log P values. Three models are evaluated, the most accurate model approximates the entropy of dehydration (ΔSd) by the entropy of vaporization (ΔSvap) for water, and utilizes onset dehydration and melting temperatures in combination with log P. With this model, the average absolute error for the prediction of solubility of 14 compounds was 0.32 log units. PMID:27238488

  11. Mixed hydrotropy: Novel science of solubility enhancement

    Directory of Open Access Journals (Sweden)

    R K Maheshwari

    2011-01-01

    Full Text Available Conventional furosemide tablets are practically insoluble in water, have slow onset of action (45-60 min and poor bioavailability (39-53%, and therefore cannot be given in emergency clinical situations like hypertension or pulmonary edema. So purpose of research was to provide a fast dissolving oral dosage form of furosemide, which can provide quick onset of action by using concept of mixed hydrotropy. Initially solubility of furosemide was determined individually in 4 hydrotropic agents namely urea, sodium acetate, sodium benzoate, sodium citrate at concentration of 10, 20, 30 and 40% w/v solutions using purified water as solvent. Highest solubility was obtained in 40% sodium benzoate solution. Then different combinations of 2, 3 and 4 hydrotropic agents in different ratios were used to determine solubility, so that total concentration of hydrotropic agents was always 40%. Highest solubility was obtained in solution of urea+sodium benzoate+sodium citrate at optimum ratio of 15:20:5. This optimized combination was utilized in preparing solid dispersions by common solvent technique using distilled water as solvent. Solid dispersions were evaluated for flow properties, XRD, DSC, SEM and were also compressed to form tablets. Dissolution studies of conventional and prepared tablets were done using USP Type II apparatus. It was concluded that the concept of mixed hydrotropic solid dispersion is novel, safe and cost-effective technique for enhancing bioavailability of poorly water-soluble drugs by dissolving drug in nonionized form. The magical enhancement in solubility of furosemide is clear indication of its potential to be used in future for other poorly water-soluble drugs in which low bioavailability is major concern.

  12. Changes in plasma apolipoproteins following whole-body irradiation in rabbit

    Energy Technology Data Exchange (ETDEWEB)

    Feliste, R. (INSERM, Toulouse, France); Dousset, N.; Carton, M.; Douste-Blazy, L.

    1981-09-01

    Male New Zealand white rabbits were whole-body-irradiated with a linear electron accelerator at 800 rad (LD/sub 50/ in 30 days). This treatment induced a pronounced hypertriglyceridemia. The apoprotein composition of very low density lipoproteins (VLDL, d < 1.006 g/ml) and high-density lipoproteins (HDL, d = 1.063 - 1.21 g/ml) from irradiated rabbits was studied and compared to those of normal rabbits. Significant changes were observed in both very low density apolipoproteins and high-density apolipoproteins. (1) In the VLDL fraction from irradiated rabbits, there appeared in high proportion two apolipoproteins with electrophoretic mobility in urea/polyacrylamide gels similar to apoA-I and A-II but which were distinctly different in their apparent molecular weights, their isoelectric points, and their amino acid composition from these latter proteins. These proteins had apparent molecular weights of about 10,000. They focused into three bands with pI values of 6.1, 6.4, and 6.6. Their amino acid composition was characterized by a very low content of threonine and serine and a high content of aspartic acid, glycine, alanine, and arginine. In addition, a marked increase of an apolipoprotein with an apparent molecular weight of about 43,000 and with an amino acid composition similar to rat apoA-IV was also observed in rabbit VLDL after irradiation. Apolipoprotein C constituents with slowmobility decreased significantly. (2) The irradiated rabbit HDL apolipoproteins showed an important increase of the proteins with molecular weight 10,000 and isoelectric points 6.1, 6.4, and 6.6. Compared to normal rabbit HDL apolipoproteins, a significant decrease of apoA-IV occurred. These modifications were also observed with lower radiation doses (200 and 400 rad).

  13. Gender and age specific differences in the kinetic behavior of TRL, IDL and LDL apolipoprotein B-100 and HDL apolipoprotein A-I

    Science.gov (United States)

    Gender specific differences in lipid and lipoprotein profile, predominantly higher LDL-C, VLDL-C and TG, and lower HDL-C levels have been observed in males compared to females. These differences are influenced by menopausal status and age. To investigate mechanism(s) involved, apolipoprotein (apo) B...

  14. Apolipoprotein A-II Influences Apolipoprotein E-Linked Cardiovascular Disease Risk in Women with High Levels of HDL Cholesterol and C-Reactive Protein

    NARCIS (Netherlands)

    Corsetti, James P.; Bakker, Stephan J. L.; Sparks, Charles E.; Dullaart, Robin P. F.

    2012-01-01

    Background: In a previous report by our group, high levels of apolipoprotein E (apoE) were demonstrated to be associated with risk of incident cardiovascular disease in women with high levels of C-reactive protein (CRP) in the setting of both low (designated as HR1 subjects) and high (designated as

  15. Recombinant Neural Protein PrP Can Bind with Both Recombinant and Native Apolipoprotein E In Vitro

    Institute of Scientific and Technical Information of China (English)

    Chen GAO; Wei ZHOU; Xiao-Ping DONG; Yan-Jun LEI; Jun HAN; Qi SHI; Lan CHEN; Yan GUO; Yong-Jun GAO; Jian-Ming CHEN; Hui-Ying JIANG

    2006-01-01

    The most essential and crucial step during the pathogenesis of transmissible spongiform encephalopathy is the conformational change of cellular prion protein (PrPC) to pathologic isoform (prpSc). A lot of data revealed that caveolae-like domains (CLDs) in the cell surface were the probable place where the conversion of PrP proteins happened. Apolipoprotein E (ApoE) is an apolipoprotein which is considered to play an important role in the development of Alzheimer's disease and other neurodegenerative diseases by forming protein complex through binding to the receptor located in the clathrin-coated pits of the cell surface.In this study, a 914-bp cDNA sequence encoding human ApoE3 was amplified from neuroblastoma cell line SH-SY5Y. Three human ApoE isomers were expressed and purified from Escherichia coli. ApoE-specific antiserum was prepared by immunizing rabbits with the purified ApoE3. GST/His pull-down assay,immunoprecipitation and ELISA revealed that three full-length ApoE isomers interact with the recombinant full-length PrP protein in vitro. The regions corresponding to protein binding were mapped in the N-terminal segment of ApoE (amino acid 1-194) and the N-terminal of PrP (amino acid 23-90). Moreover, the recombinant PrP showed the ability to form a complex with the native ApoE from liver tissues. Our data provided direct evidence of molecular interaction between ApoE and PrP. It also supplied scientific clues for assessing the significance of CLDs on the surface of cellular membrane in the process of conformational conversion from PrPC to PrPSc and probing into the pathogenesis of transmissible spongiform encephalopathy.

  16. Soluble cytokine receptors in biological therapy.

    Science.gov (United States)

    Fernandez-Botran, Rafael; Crespo, Fabian A; Sun, Xichun

    2002-08-01

    Due to their fundamental involvement in the pathogenesis of many diseases, cytokines constitute key targets for biotherapeutic approaches. The discovery that soluble forms of cytokine receptors are involved in the endogenous regulation of cytokine activity has prompted substantial interest in their potential application as immunotherapeutic agents. As such, soluble cytokine receptors have many advantages, including specificity, low immunogenicity and high affinity. Potential disadvantages, such as low avidity and short in vivo half-lifes, have been addressed by the use of genetically-designed receptors, hybrid proteins or chemical modifications. The ability of many soluble cytokine receptors to inhibit the binding and biological activity of their ligands makes them very specific cytokine antagonists. Several pharmaceutical companies have generated a number of therapeutic agents based on soluble cytokine receptors and many of them are undergoing clinical trials. The most advanced in terms of clinical development is etanercept (Enbrel, Immunex), a fusion protein between soluble TNF receptor Type II and the Fc region of human IgG1. This TNF-alpha; antagonist was the first soluble cytokine receptor to receive approval for use in humans. In general, most agents based on soluble cytokine receptors have been safe, well-tolerated and have shown only minor side effects in the majority of patients. Soluble cytokine receptors constitute a new generation of therapeutic agents with tremendous potential for applications in a wide variety of human diseases. Two current areas of research are the identification of their most promising applications and characterisation of their long-term effects. PMID:12171504

  17. Folded Functional Lipid-Poor Apolipoprotein A-I Obtained by Heating of High-Density Lipoproteins: Relevance to HDL Biogenesis

    OpenAIRE

    Jayaraman, Shobini; Cavigiolio, Giorgio; Gursky, Olga

    2012-01-01

    High-density lipoproteins (HDL) remove cell cholesterol and protect from atherosclerosis. The major HDL protein is apolipoprotein A-I (apoA-I). Most plasma apoA-I circulates in lipoproteins, yet ~5% forms monomeric lipid-poor/free species. This metabolically active species is a primary cholesterol acceptor and is central to HDL biogenesis. Structural properties of lipid-poor apoA-I are unclear due to difficulties in isolating this transient species. We used thermal denaturation of human HDL t...

  18. Glucose Regulates the Expression of the Apolipoprotein A5 Gene

    Energy Technology Data Exchange (ETDEWEB)

    Fruchart, Jamila; Nowak, Maxime; Helleboid-Chapman, Audrey; Jakel, Heidelinde; Moitrot, Emmanuelle; Rommens, Corinne; Pennacchio, Len A.; Fruchart-Najib, Jamila; Fruchart, Jean-Charles

    2008-04-07

    The apolipoprotein A5 gene (APOA5) is a key player in determining triglyceride concentrations in humans and mice. Since diabetes is often associated with hypertriglyceridemia, this study explores whether APOA5 gene expression is regulated by alteration in glucose homeostasis and the related pathways. D-glucose activates APOA5 gene expression in a time- and dose-dependent manner in hepatocytes, and the glycolytic pathway involved was determined using D-glucose analogs and metabolites. Together, transient transfections, electrophoretic mobility shift assays and chromatin immunoprecipitation assays show that this regulation occurs at the transcriptional level through an increase of USF1/2 binding to an E-box in the APOA5 promoter. We show that this phenomenon is not due to an increase of mRNA or protein expression levels of USF. Using protein phosphatases 1 and 2A inhibitor, we demonstrate that D-glucose regulates APOA5 gene via a dephosphorylation mechanism, thereby resulting in an enhanced USF1/2-promoter binding. Last, subsequent suppressions of USF1/2 and phosphatases mRNA through siRNA gene silencing abolished the regulation. We demonstrate that APOA5 gene is up regulated by D-glucose and USF through phosphatase activation. These findings may provide a new cross talk between glucose and lipid metabolism.

  19. Visfatin Destabilizes Atherosclerotic Plaques in Apolipoprotein E-Deficient Mice.

    Directory of Open Access Journals (Sweden)

    Bo Li

    Full Text Available Although there is evidence that visfatin is associated with atherogenesis, the effect of visfatin on plaque stability has not yet been explored.In vivo, vulnerable plaques were established by carotid collar placement in apolipoprotein E-deficient (ApoE-/- mice, and lentivirus expressing visfatin (lenti-visfatin was locally infused in the carotid artery. The lipid, macrophage, smooth muscle cell (SMC and collagen levels were evaluated, and the vulnerability index was calculated. In vitro, RAW264.7 cells were stimulated with visfatin, and the MMPs expressions were assessed by western blot and immunofluorescence. And the mechanism that involved in visfatin-induced MMP-8 production was investigated.Transfection with lenti-visfatin significantly promoted the expression of visfatin which mainly expressed in macrophages in the plaque. Lenti-visfatin transfection significantly promoted the accumulation of lipids and macrophages, modulated the phenotypes of smooth muscle cells and decreased the collagen levels in the plaques, which significantly decreased the plaque stability. Simultaneously, transfection with lenti-visfatin significantly up-regulated the expression of MMP-8 in vivo, as well as MMP-1, MMP-2 and MMP-9. Recombinant visfatin dose- and time-dependently up-regulated the in vitro expression of MMP-8 in macrophages. Visfatin promoted the translocation of NF-κB, and inhibition of NF-κB significantly reduced visfatin-induced MMP-8 production.Visfatin increased MMP-8 expression, promoted collagen degradation and increased the plaques vulnerability index.

  20. Skeletal muscle apolipoprotein B expression reduces muscular triglyceride accumulation

    DEFF Research Database (Denmark)

    Bartels, Emil D; Ploug, Thorkil; Størling, Joachim;

    2014-01-01

    Abstract Background. Lipid accumulation in skeletal muscle is associated with impaired insulin sensitivity in type 2 diabetes. In cardiac myocytes, lipoprotein secretion controlled by apolipoproteinB (apoB) and microsomal triglyceride transfer protein (MTP) affects lipid homeostasis. Design....... In this study, we investigated whether expression of a human apoB transgene affects triglyceride accumulation and insulin sensitivity in skeletal muscle in fat fed obese mice. Results. Expression of apoB and MTP mRNA and the human apoB transgene was seen in skeletal muscle of the transgene mice. Human apo......B transgenic mice accumulated 28% less triglycerides in skeletal myocytes after one year of fat-feeding as compared with WT mice (32 ± 5, n = 10 vs. 44 ± 4 nmol/mg ww, n = 13, p = 0.04). Moreover, expression of human apoB in fat-fed mice was associated with 32% (p = 0.02) and 37% (p = 0.01) lower plasma...

  1. Optimisation and evaluation of restriction fragment length polimorfism method for apolipoprotein E

    Directory of Open Access Journals (Sweden)

    Drljević Nevena

    2014-01-01

    Full Text Available Introduction. Apolipoprotein E gene polymorphism is characterized by the presence of three common alleles, e2, e3 and e4, which encode three isoforms of apolipoprotein E in plasma E2, E3 and E4. Genetic polymorphisms of apolipoprotein E gene are predictive markers for the development of numerous disorders of lipid metabolism, already proven in a large number of clinical trials. This study was aimed at assessing the success rate of restriction fragment length polymorphism method for the detections of genes coding for isoenzymes E2, E3 and E4. Material and Methods. Deoxyribonucleic acid, used in this study, was extracted from blood by standard procedure using chloroform and phenol. The polymerase chain reaction method was used to amplify the coding sequence of fourth exon of the apolipoprotein E gene. Amplification products were digested with HhaI. The fragments obtained were separated by electrophoresis and visualized with ultraviolet light. Results. Our results showed that the restriction fragment length polymorphism method is optimal for detection of apolipoprotein E polymorphisms. The restriction enzyme HhaI achieved the cleavage of the gene on the specific loci, directly depend of presence or absence of mutations at positions 112 and 158, of different alleles. Conclusion. This method enables simple, rapid and efficient analysis of restriction fragment length polymorphisms, directly determining the patient’s genotype.

  2. Apolipoprotein A1 in channel catfish: Transcriptional analysis, antimicrobial activity, and efficacy as plasmid DNA immunostimulant against Aeromonas hydrophila infection

    Science.gov (United States)

    The objectives of this study were to: 1) determine transcriptional profiles of apolipoprotein A1 (ApoA1) in collected channel catfish tissues after infection with A. hydrophila by bath immersion; 2) investigate whether recombinant channel catfish apolipoprotein A1 produced in E. coli expression syst...

  3. Apolipoprotein A-I deficiency due to a codon 84 nonsense mutation of the apolipoprotein A-I gene

    International Nuclear Information System (INIS)

    The molecular genetic defect of a female patient with apolipoprotein A-I (apoA-I) deficiency and premature atherosclerosis was examined. Her parents were first cousins. Her plasma density fraction from 1.063 to 1.21 g/ml contained no apoA-I on SDS/PAGE and no measurable high density lipoprotein cholesterol. Southern blot hybridization showed no gross abnormality to be present in the patient's apoA-I gene and homozygosity for a haplotype of restriction fragment length polymorphisms in the apoA-I gene region. Sequencing after amplification by PCR revealed a codon 84 nonsense mutation (CAG → TAG, Gln → stop) of exon 4 and a codon 37 missense mutation (GCC→ ACC, Ala → Thr) of exon 3 in the patient's apoA-I gene. The data from dot-blot hybridization with allele-specific oligonucleotide probes indicated that she was homozygous for the apoA-I gene with regard to the two mutations. The codon 37 missense mutation was also detected in the apoA-I gene of 6 out of 60 controls, who all had normal levels of apoA-I and high density lipoprotein cholesterol, suggesting that the missense mutation is polymorphic and not associated with apoA-I deficiency. These finding indicate that homozygosity for the apoA-I gene with codon 84 nonsense mutation causes the deficiency of apoA-I and of high density lipoprotein cholesterol in the patient

  4. Water-soluble vitamins.

    Science.gov (United States)

    Konings, Erik J M

    2006-01-01

    Simultaneous Determination of Vitamins.--Klejdus et al. described a simultaneous determination of 10 water- and 10 fat-soluble vitamins in pharmaceutical preparations by liquid chromatography-diode-array detection (LC-DAD). A combined isocratic and linear gradient allowed separation of vitamins in 3 distinct groups: polar, low-polar, and nonpolar. The method was applied to pharmaceutical preparations, fortified powdered drinks, and food samples, for which results were in good agreement with values claimed. Heudi et al. described a separation of 9 water-soluble vitamins by LC-UV. The method was applied for the quantification of vitamins in polyvitaminated premixes used for the fortification of infant nutrition products. The repeatability of the method was evaluated at different concentration levels and coefficients of variation were simultaneous separations described. Vitamin B2.--Viñas et al. elaborated an LC analysis of riboflavin vitamers in foods. Vitamin B2 can be found in nature as the free riboflavin, but in most biological materials it occurs predominantly in the form of 2 coenzymes, flavin mononucleotide (FMN) and flavin-adenine dinucleotide (FAD). Several methods usually involve the conversion of these coenzymes into free riboflavin before quantification of total riboflavin. According to the authors, there is growing interest to know flavin composition of foods. The described method separates the individual vitamers isocratically. Accuracy of the method is tested with 2 certified reference materials (CRMs). Vitamin B5.-Methods for the determination of vitamin B5 in foods are limited because of their low sensitivity and poor selectivity. Pakin et al. proposed a post-column derivatization of pantothenic acid as a fluorescent compound and used this principle in a specific and sensitive method for the determination of free and bound pantothenic acid in a large variety of foods. A French laboratory invited European laboratories to participate in a series of

  5. Conformational and aggregation properties of the 1-93 fragment of apolipoprotein A-I

    DEFF Research Database (Denmark)

    Petrlova, Jitka; Bhattacherjee, Arnab; Boomsma, Wouter Krogh;

    2014-01-01

    Several disease-linked mutations of apolipoprotein A-I, the major protein in high-density lipoprotein (HDL), are known to be amyloidogenic, and the fibrils often contain N-terminal fragments of the protein. Here, we present a combined computational and experimental study of the fibril-associated ......Several disease-linked mutations of apolipoprotein A-I, the major protein in high-density lipoprotein (HDL), are known to be amyloidogenic, and the fibrils often contain N-terminal fragments of the protein. Here, we present a combined computational and experimental study of the fibril...... these conformational shifts match well with the effects of these mutations in thioflavin T fluorescence and transmission electron microscopy experiments. Together, our results point to molecular mechanisms that may have a key role in disease-linked aggregation of apolipoprotein A-I....

  6. Insulin resistance, dyslipidemia, and apolipoprotein E interactions as mechanisms in cognitive impairment and Alzheimer's disease.

    Science.gov (United States)

    Salameh, Therese S; Rhea, Elizabeth M; Banks, William A; Hanson, Angela J

    2016-09-01

    An increased risk for Alzheimer's disease is associated with dyslipidemia and insulin resistance. A separate literature shows the genetic risk for developing Alzheimer's disease is strongly correlated to the presence of the E4 isoform of the apolipoprotein E carrier protein. Understanding how apolipoprotein E carrier protein, lipids, amyloid β peptides, glucose, central nervous system insulin, and peripheral insulin interact with one another in Alzheimer's disease is an area of increasing interest. Here, we will review the evidence relating apolipoprotein E carrier protein, lipids, and insulin action to Alzheimer's disease and Aβ peptides and then propose mechanisms as to how these factors might interact with one another to impair cognition and promote Alzheimer's disease. PMID:27470930

  7. Modeling of Salt Solubilities in Mixed Solvents

    DEFF Research Database (Denmark)

    Chiavone-Filho, O.; Rasmussen, Peter

    2000-01-01

    A method to correlate and predict salt solubilities in mixed solvents using a UNIQUAC+Debye-Huckel model is developed. The UNIQUAC equation is applied in a form with temperature-dependent parameters. The Debye-Huckel model is extended to mixed solvents by properly evaluating the dielectric...... constants and the liquid densities of the solvent media. To normalize the activity coefficients, the symmetric convention is adopted. Thermochemical properties of the salt are used to estimate the solubility product. It is shown that the proposed procedure can describe with good accuracy a series of salt...

  8. Apolipoprotein E promotes lipid accumulation and differentiation in human adipocytes

    Energy Technology Data Exchange (ETDEWEB)

    Lasrich, Dorothee; Bartelt, Alexander [Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg (Germany); Grewal, Thomas, E-mail: thomas.grewal@sydney.edu.au [Faculty of Pharmacy A15, The University of Sydney, Sydney, NSW 2006 (Australia); Heeren, Joerg, E-mail: heeren@uke.de [Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg (Germany)

    2015-09-10

    Several studies in mice indicate a role for apolipoprotein E (APOE) in lipid accumulation and adipogenic differentiation in adipose tissue. However, little is yet known if APOE functions in a similar manner in human adipocytes. This prompted us to compare lipid loading and expression of adipocyte differentiation markers in APOE-deficient and control adipocytes using the differentiated human mesenchymal stem cell line hMSC-Tert as well as primary human and mouse adipocytes as model systems. Differentiated hMSC-Tert were stably transduced with or without siRNA targeting APOE while murine adipocytes were isolated from wild type and Apoe knockout mice. Human APOE knockdown hMSC-Tert adipocytes accumulated markedly less triglycerides compared to control cells. This correlated with strongly decreased gene expression levels of adipocyte markers such as adiponectin (ADIPOQ) and fatty acid binding protein 4 (FABP4) as well as the key transcription factor driving adipocyte differentiation, peroxisome proliferator activator receptor gamma (PPARG), in particular the PPARG2 isoform. Similarly, differentiation of murine Apoe-deficient adipocytes was characterized by reduced gene expression of Adipoq, Fabp4 and Pparg. Interestingly, incubation of APOE-deficient hMSC-Tert adipocytes with conditioned media from APOE3-overexpressing adipocytes or APOE-containing Very Low Density Lipoprotein (VLDL) partially restored triglyceride accumulation, but were unable to induce adipocyte differentiation, as judged by expression of adipocyte markers. Taken together, depletion of endogenous APOE in human adipocytes severely impairs lipid accumulation, which is associated with an inability to initiate differentiation. - Highlights: • Immortalized human mesenchymal stem cells were used to study adipocyte development. • Knockdown of endogenous APOE lead to impaired lipid accumulation and adipogenesis. • APOE supplementation partially restored lipid accumulation but not differentiation.

  9. Apolipoprotein E: from cardiovascular disease to neurodegenerative disorders.

    Science.gov (United States)

    Mahley, Robert W

    2016-07-01

    Apolipoprotein (apo) E was initially described as a lipid transport protein and major ligand for low density lipoprotein (LDL) receptors with a role in cholesterol metabolism and cardiovascular disease. It has since emerged as a major risk factor (causative gene) for Alzheimer's disease and other neurodegenerative disorders. Detailed understanding of the structural features of the three isoforms (apoE2, apoE3, and apoE4), which differ by only a single amino acid interchange, has elucidated their unique functions. ApoE2 and apoE4 increase the risk for heart disease: apoE2 increases atherogenic lipoprotein levels (it binds poorly to LDL receptors), and apoE4 increases LDL levels (it binds preferentially to triglyceride-rich, very low density lipoproteins, leading to downregulation of LDL receptors). ApoE4 also increases the risk for neurodegenerative diseases, decreases their age of onset, or alters their progression. ApoE4 likely causes neurodegeneration secondary to its abnormal structure, caused by an interaction between its carboxyl- and amino-terminal domains, called domain interaction. When neurons are stressed or injured, they synthesize apoE to redistribute cholesterol for neuronal repair or remodeling. However, because of its altered structure, neuronal apoE4 undergoes neuron-specific proteolysis, generating neurotoxic fragments (12-29 kDa) that escape the secretory pathway and cause mitochondrial dysfunction and cytoskeletal alterations, including tau phosphorylation. ApoE4-associated pathology can be prevented by small-molecule structure correctors that block domain interaction by converting apoE4 to a molecule that resembles apoE3 both structurally and functionally. Structure correctors are a potential therapeutic approach to reduce apoE4 pathology in both cardiovascular and neurological disorders. PMID:27277824

  10. IL-25 inhibits atherosclerosis development in apolipoprotein E deficient mice.

    Directory of Open Access Journals (Sweden)

    Polyxeni T Mantani

    Full Text Available IL-25 has been implicated in the initiation of type 2 immunity and in the protection against autoimmune inflammatory diseases. Recent studies have identified the novel innate lymphoid type 2 cells (ILC2s as an IL-25 target cell population. The purpose of this study was to evaluate if IL-25 has any influence on atherosclerosis development in mice.Administration of 1 μg IL-25 per day for one week to atherosclerosis-prone apolipoprotein (apoE deficient mice, had limited effect on the frequency of T cell populations, but resulted in a large expansion of ILC2s in the spleen. The expansion was accompanied by increased levels of anti-phosphorylcholine (PC natural IgM antibodies in plasma and elevated levels of IL-5 in plasma and spleen. Transfer of ILC2s to apoE deficient mice elevated the natural antibody-producing B1a cell population in the spleen. Treatment of apoE/Rag-1 deficient mice with IL-25 was also associated with extensive expansion of splenic ILC2s and increased plasma IL-5, suggesting ILC2s to be the source of IL-5. Administration of IL-25 in IL-5 deficient mice resulted in an expanded ILC2 population, but did not stimulate generation of anti-PC IgM, indicating that IL-5 is not required for ILC2 expansion but for the downstream production of natural antibodies. Additionally, administration of 1 μg IL-25 per day for 4 weeks in apoE deficient mice reduced atherosclerosis in the aorta both during initiation and progression of the disease.The present findings demonstrate that IL-25 has a protective role in atherosclerosis mediated by innate responses, including ILC2 expansion, increased IL-5 secretion, B1a expansion and natural anti-PC IgM generation, rather than adaptive Th2 responses.

  11. Apolipoprotein E promotes lipid accumulation and differentiation in human adipocytes

    International Nuclear Information System (INIS)

    Several studies in mice indicate a role for apolipoprotein E (APOE) in lipid accumulation and adipogenic differentiation in adipose tissue. However, little is yet known if APOE functions in a similar manner in human adipocytes. This prompted us to compare lipid loading and expression of adipocyte differentiation markers in APOE-deficient and control adipocytes using the differentiated human mesenchymal stem cell line hMSC-Tert as well as primary human and mouse adipocytes as model systems. Differentiated hMSC-Tert were stably transduced with or without siRNA targeting APOE while murine adipocytes were isolated from wild type and Apoe knockout mice. Human APOE knockdown hMSC-Tert adipocytes accumulated markedly less triglycerides compared to control cells. This correlated with strongly decreased gene expression levels of adipocyte markers such as adiponectin (ADIPOQ) and fatty acid binding protein 4 (FABP4) as well as the key transcription factor driving adipocyte differentiation, peroxisome proliferator activator receptor gamma (PPARG), in particular the PPARG2 isoform. Similarly, differentiation of murine Apoe-deficient adipocytes was characterized by reduced gene expression of Adipoq, Fabp4 and Pparg. Interestingly, incubation of APOE-deficient hMSC-Tert adipocytes with conditioned media from APOE3-overexpressing adipocytes or APOE-containing Very Low Density Lipoprotein (VLDL) partially restored triglyceride accumulation, but were unable to induce adipocyte differentiation, as judged by expression of adipocyte markers. Taken together, depletion of endogenous APOE in human adipocytes severely impairs lipid accumulation, which is associated with an inability to initiate differentiation. - Highlights: • Immortalized human mesenchymal stem cells were used to study adipocyte development. • Knockdown of endogenous APOE lead to impaired lipid accumulation and adipogenesis. • APOE supplementation partially restored lipid accumulation but not differentiation.

  12. An abundant dysfunctional apolipoprotein A1 in human atheroma.

    Science.gov (United States)

    Huang, Ying; DiDonato, Joseph A; Levison, Bruce S; Schmitt, Dave; Li, Lin; Wu, Yuping; Buffa, Jennifer; Kim, Timothy; Gerstenecker, Gary S; Gu, Xiaodong; Kadiyala, Chandra S; Wang, Zeneng; Culley, Miranda K; Hazen, Jennie E; Didonato, Anthony J; Fu, Xiaoming; Berisha, Stela Z; Peng, Daoquan; Nguyen, Truc T; Liang, Shaohong; Chuang, Chia-Chi; Cho, Leslie; Plow, Edward F; Fox, Paul L; Gogonea, Valentin; Tang, W H Wilson; Parks, John S; Fisher, Edward A; Smith, Jonathan D; Hazen, Stanley L

    2014-02-01

    Recent studies have indicated that high-density lipoproteins (HDLs) and their major structural protein, apolipoprotein A1 (apoA1), recovered from human atheroma are dysfunctional and are extensively oxidized by myeloperoxidase (MPO). In vitro oxidation of either apoA1 or HDL particles by MPO impairs their cholesterol acceptor function. Here, using phage display affinity maturation, we developed a high-affinity monoclonal antibody that specifically recognizes both apoA1 and HDL that have been modified by the MPO-H2O2-Cl(-) system. An oxindolyl alanine (2-OH-Trp) moiety at Trp72 of apoA1 is the immunogenic epitope. Mutagenesis studies confirmed a critical role for apoA1 Trp72 in MPO-mediated inhibition of the ATP-binding cassette transporter A1 (ABCA1)-dependent cholesterol acceptor activity of apoA1 in vitro and in vivo. ApoA1 containing a 2-OH-Trp72 group (oxTrp72-apoA1) is in low abundance within the circulation but accounts for 20% of the apoA1 in atherosclerosis-laden arteries. OxTrp72-apoA1 recovered from human atheroma or plasma is lipid poor, virtually devoid of cholesterol acceptor activity and demonstrated both a potent proinflammatory activity on endothelial cells and an impaired HDL biogenesis activity in vivo. Elevated oxTrp72-apoA1 levels in subjects presenting to a cardiology clinic (n = 627) were associated with increased cardiovascular disease risk. Circulating oxTrp72-apoA1 levels may serve as a way to monitor a proatherogenic process in the artery wall. PMID:24464187

  13. Apolipoprotein E isoform-specific effects on lipoprotein receptor processing.

    Science.gov (United States)

    Bachmeier, Corbin; Shackleton, Ben; Ojo, Joseph; Paris, Daniel; Mullan, Michael; Crawford, Fiona

    2014-12-01

    Recent findings indicate an isoform-specific role for apolipoprotein E (apoE) in the elimination of beta-amyloid (Aβ) from the brain. ApoE is closely associated with various lipoprotein receptors, which contribute to Aβ brain removal via metabolic clearance or transit across the blood–brain barrier (BBB). These receptors are subject to ectodomain shedding at the cell surface, which alters endocytic transport and mitigates Aβ elimination. To further understand the manner in which apoE influences Aβ brain clearance, these studies investigated the effect of apoE on lipoprotein receptor shedding. Consistent with prior reports, we observed an increased shedding of the low-density lipoprotein receptor (LDLR) and the LDLR-related protein 1 (LRP1) following Aβ exposure in human brain endothelial cells. When Aβ was co-treated with each apoE isoform, there was a reduction in Aβ-induced shedding with apoE2 and apoE3, while lipoprotein receptor shedding in the presence of apoE4 remained increased. Likewise, intracranial administration of Aβ to apoE-targeted replacement mice (expressing the human apoE isoforms) resulted in an isoform-dependent effect on lipoprotein receptor shedding in the brain (apoE4 > apoE3 > apoE2). Moreover, these results show a strong inverse correlation with our prior work in apoE transgenic mice in which apoE4 animals showed reduced Aβ clearance across the BBB compared to apoE3 animals. Based on these results, apoE4 appears less efficient than other apoE isoforms in regulating lipoprotein receptor shedding, which may explain the differential effects of these isoforms in removing Aβ from the brain. PMID:25015123

  14. Plasma Apolipoprotein-M (ApoM) Response to a Circuit Resistance Training Program

    OpenAIRE

    Abbass Ghanbari-Niaki

    2013-01-01

    Apolipoprotein M (Apo-M) is a human novel protein of apolipoprotein classes and highly expressed in liver and kidney tissues. ApoM is mainly associated with high-density lipoprotein (HDL), and act as a chaperone for sphingosine-1-phosphate (S1P), promotes mobilization of cellular cholesterol, formation of larger-size of pre β-HDL, and a new biomarker in sepsis. The level of apoM in plasma/serum is affected by several factors such as pregnancy, hyperglycemia, plasma leptin concentration, obe...

  15. Are soluble and membrane-bound rat brain acetylcholinesterase different

    International Nuclear Information System (INIS)

    Salt-soluble and detergent-soluble acetylcholinesterases (AChE) from adult rat brain were purified to homogeneity and studied with the aim to establish the differences existing between these two forms. It was found that the enzymatic activities of the purified salt-soluble AChE as well as the detergent-soluble AChE were dependent on the Triton X-100 concentration. Moreover, the interaction of salt-soluble AChE with liposomes suggests amphiphilic behaviour of this enzyme. Serum cholinesterase (ChE) did not bind to liposomes but its activity was also detergent-dependent. Detergent-soluble AChE remained in solution below critical micellar concentrations of Triton X-100. SDS polyacrylamide gel electrophoresis of purified, Biobeads-treated and iodinated detergent-soluble 11 S AChE showed, under non reducing conditions, bands of 69 kD, 130 kD and greater than 250 kD corresponding, respectively, to monomers, dimers and probably tetramers of the same polypeptide chain. Under reducing conditions, only a 69 kD band was detected. It is proposed that an amphiphilic environment stabilizes the salt-soluble forms of AChE in the brain in vivo and that detergent-soluble Biobeads-treated 11 S AChE possess hydrophobic domain(s) different from the 20 kD peptide already described

  16. Apolipoprotein(a) inhibits in vitro tube formation in endothelial cells: identification of roles for Kringle V and the plasminogen activation system.

    Science.gov (United States)

    Liu, Lei; Boffa, Michael B; Koschinsky, Marlys L

    2013-01-01

    Elevated plasma concentrations of lipoprotein(a) are associated with increased risk for atherothrombotic diseases. Apolipoprotein(a), the unique glycoprotein component of lipoprotein(a), is characterized by the presence of multiple kringle domains, and shares a high degree of sequence homology with the serine protease zymogen plasminogen. It has been shown that angiostatin, a proteolytic fragment of plasminogen containing kringles 1-4, can effectively inhibit angiogenesis. Moreover, proteolytic fragments of plasminogen containing kringle 5 are even more potent inhibitors of angiogenesis than angiostatin. Despite its strong similarity with plasminogen, the role of apolipoprotein(a) in angiogenesis remains controversial, with both pro- and anti-angiogenic effects reported. In the current study, we evaluated the ability of apolipoprotein(a) to inhibit VEGF- and angiopoietin-induced tube formation in human umbilical cord endothelial cells. A 17 kringle-containing form of recombinant apo(a) (17K), corresponding to a well-characterized, physiologically-relevant form of the molecule, effectively inhibited tube formation induced by either VEGF or angiopoietin-1. Using additional recombinant apolipoprotein(a) (r-apo(a)) variants, we demonstrated that this effect was dependent on the presence of an intact lysine-binding site in kringle V domain of apo(a), but not on the presence of the functional lysine-binding site in apo(a) kringle IV type 10; sequences within in the amino-terminal half of the molecule were also not required for the inhibitory effects of apo(a). We also showed that the apo(a)-mediated inhibition tube formation could be reversed, in part by the addition of plasmin or urokinase plasminogen activator, or by removal of plasminogen from the system. Further, we demonstrated that apo(a) treated with glycosidases to remove sialic acid was significantly less effective in inhibiting tube formation. This is the first report of a functional role for the glycosylation

  17. Apolipoprotein(a inhibits in vitro tube formation in endothelial cells: identification of roles for Kringle V and the plasminogen activation system.

    Directory of Open Access Journals (Sweden)

    Lei Liu

    Full Text Available Elevated plasma concentrations of lipoprotein(a are associated with increased risk for atherothrombotic diseases. Apolipoprotein(a, the unique glycoprotein component of lipoprotein(a, is characterized by the presence of multiple kringle domains, and shares a high degree of sequence homology with the serine protease zymogen plasminogen. It has been shown that angiostatin, a proteolytic fragment of plasminogen containing kringles 1-4, can effectively inhibit angiogenesis. Moreover, proteolytic fragments of plasminogen containing kringle 5 are even more potent inhibitors of angiogenesis than angiostatin. Despite its strong similarity with plasminogen, the role of apolipoprotein(a in angiogenesis remains controversial, with both pro- and anti-angiogenic effects reported. In the current study, we evaluated the ability of apolipoprotein(a to inhibit VEGF- and angiopoietin-induced tube formation in human umbilical cord endothelial cells. A 17 kringle-containing form of recombinant apo(a (17K, corresponding to a well-characterized, physiologically-relevant form of the molecule, effectively inhibited tube formation induced by either VEGF or angiopoietin-1. Using additional recombinant apolipoprotein(a (r-apo(a variants, we demonstrated that this effect was dependent on the presence of an intact lysine-binding site in kringle V domain of apo(a, but not on the presence of the functional lysine-binding site in apo(a kringle IV type 10; sequences within in the amino-terminal half of the molecule were also not required for the inhibitory effects of apo(a. We also showed that the apo(a-mediated inhibition tube formation could be reversed, in part by the addition of plasmin or urokinase plasminogen activator, or by removal of plasminogen from the system. Further, we demonstrated that apo(a treated with glycosidases to remove sialic acid was significantly less effective in inhibiting tube formation. This is the first report of a functional role for the

  18. Expression of apolipoprotein E during nerve degeneration and regeneration

    OpenAIRE

    Ignatius, M J; Gebicke-Härter, P J; Skene, J H; Schilling, J W; Weisgraber, K H; Mahley, R. W.; Shooter, E M

    1986-01-01

    A 37-kDa glycoprotein has been described recently, whose synthesis is dramatically increased after injury of the rat sciatic and optic nerves. Cells in the nerve sheath, distal to the site of injury, produce and secrete large amounts of this protein, so that by 3 weeks after injury, it represents 2-5% of the total soluble extracellular protein in the regenerating sciatic nerve sheath, although it fails to accumulate in damaged optic nerve. Results presented here reveal extensive homology betw...

  19. Soluble porphyrin polymers

    Science.gov (United States)

    Gust, Jr., John Devens; Liddell, Paul Anthony

    2015-07-07

    Porphyrin polymers of Structure 1, where n is an integer (e.g., 1, 2, 3, 4, 5, or greater) ##STR00001## are synthesized by the method shown in FIGS. 2A and 2B. The porphyrin polymers of Structure 1 are soluble in organic solvents such as 2-MeTHF and the like, and can be synthesized in bulk (i.e., in processes other than electropolymerization). These porphyrin polymers have long excited state lifetimes, making the material suitable as an organic semiconductor for organic electronic devices including transistors and memories, as well as solar cells, sensors, light-emitting devices, and other opto-electronic devices.

  20. Hyperglycemia-induced hyperinsulinemia acutely lowers plasma apolipoprotein B but not lipoprotein (a) in man

    NARCIS (Netherlands)

    Riemens, SC; Ligtenberg, JJM; Dullaart, RPF

    1997-01-01

    Acute hyperinsulinemia lowers plasma apolipoprotein B (apo B) and triglycerides by suppressing hepatic lipoprotein secretion and probably by enhancing catabolism of triglyceride-rich lipoproteins, but the effect of acute hyperinsulinemia on the plasma lipoprotein(a) (Lp(a)) level is unclear. We meas

  1. Trimerization of apolipoprotein A-I retards plasma clearance and preserves antiatherosclerotic properties

    DEFF Research Database (Denmark)

    Graversen, Jonas Heilskov; Laurberg, Jacob Marsvin; Andersen, Mikkel Holmen;

    2008-01-01

    An increased plasma level of the major high-density lipoprotein (HDL) component, apolipoprotein A-I (apoA-I) is the aim of several therapeutic strategies for combating atherosclerotic disease. HDL therapy by direct intravenous administration of apoA-I is a plausible way; however, a fast renal...

  2. Mutation in apolipoprotein B associated with hypobetalipoproteinemia despite decreased binding to the low density lipoprotein receptor

    DEFF Research Database (Denmark)

    Benn, Marianne; Nordestgaard, Børge G; Jensen, Jan Skov;

    2005-01-01

    Mutations in apolipoprotein B (APOB) may reduce binding of low density lipoprotein (LDL) to the LDL receptor and cause hypercholesterolemia. We showed that heterozygotes for a new mutation in APOB have hypobetalipoproteinemia, despite a reduced binding of LDL to the LDL receptor. APOB R3480P...

  3. Apolipoprotein D is associated with long-term outcome in patients with schizophrenia

    DEFF Research Database (Denmark)

    Hansen, T; Hemmingsen, R P; Wang, A G;

    2006-01-01

    Accumulating evidence implicates deficiencies in apolipoprotein D (ApoD) function and arachidonic acid signaling in schizophrenic disorders. We addressed two hypotheses in relation to ApoD: first, polymorphisms in the ApoD gene confer susceptibility to or are markers of disease, and, second, gene...

  4. Further studies of the influence of apolipoprotein B alleles on glucose and lipid metabolism

    DEFF Research Database (Denmark)

    Bentzen, Joan; Poulsen, Pernille; Vaag, Allan; Fenger, Mogens

    2003-01-01

    The effect of five genetic polymorphisms in the apolipoprotein B gene on parameters of lipid and glucose metabolism was assessed in 564 Danish mono- and dizygotic twins. Genotypes in apolipoprotein B T71I (ApaLI RFLP), A591V (AluI RFLP), L2712P (MvaI RFLP), R3611Q (MspI RFLP), and E4154K (EcoRI R...... five polymorphisms was seen in the dizygotic twins. The effect of the polymorphisms on lipid and glucose parameters could be mediated through linkage to genes with known effect on glucose metabolism or through free fatty acids exerting their effect on glucose metabolism.......The effect of five genetic polymorphisms in the apolipoprotein B gene on parameters of lipid and glucose metabolism was assessed in 564 Danish mono- and dizygotic twins. Genotypes in apolipoprotein B T71I (ApaLI RFLP), A591V (AluI RFLP), L2712P (MvaI RFLP), R3611Q (MspI RFLP), and E4154K (Eco......RI RFLP) were established using polymerase chain reaction and restriction enzyme digests. The effect of genotypes on lipid levels and on glucose, insulin, and HOMA (i.e., calculated parameters of beta-cell function and insulin resistance) was assessed by multivariate analyses of variance correcting for...

  5. The Apolipoprotein E/CI/CII Gene Cluster and Late-Onset Alzheimer Disease

    OpenAIRE

    Yu, Chang-En; Payami, Haydeh; Olson, Jane M.; Boehnke, Michael; Wijsman, Ellen M; Orr, Harry T.; Kukull, Walter A.; Goddard, Katrina A B; Nemens, Ellen; White, June A.; Alonso, M. Elisa; Taylor, Todd D.; Ball, Melvyn J.; Kaye, Jeffrey; Morris, John

    1994-01-01

    The chromosome 19 apolipoprotein E/CI/CII gene cluster was examined for evidence of linkage to a familial Alzheimer disease (FAD) locus. The family groups studied were Volga German (VG), early-onset non-VG (ENVG; mean age at onset

  6. Transcriptional Regulation of Apolipoprotein A5 Gene Expression by the Nuclear Receptor ROR alpha

    International Nuclear Information System (INIS)

    Apolipoprotein A5 has recently been identified as a crucial determinant of plasma triglyceride levels. Our results showed that RORa up-regulates human APOA5 but has no effect on mouse apoa5 promoter. These data suggest an additional important physiological role for RORa in the regulation of genes involved in plasma triglyceride homeostasis in human and probably in the development of atherosclerosis

  7. Apolipoprotein E4 reduces evoked hippocampal acetylcholine release in adult mice

    Czech Academy of Sciences Publication Activity Database

    Dolejší, Eva; Liraz, O.; Rudajev, Vladimír; Zimčík, Pavel; Doležal, Vladimír; Michaelson, D. M.

    Roč. 136, č. 3 ( 2016 ), s. 503-509. ISSN 0022-3042 R&D Projects: GA MŠk(CZ) LH13269 Institutional support: RVO:67985823 Keywords : acetylcholine release * Alzheimer's disease (AD) * apolipoprotein E4 (apoE4) * hippocampus Subject RIV: FH - Neurology Impact factor: 4.281, year: 2014

  8. Plasma apolipoprotein M responses to statin and fibrate administration in type 2 diabetes mellitus

    NARCIS (Netherlands)

    Kappelle, Paul J. W. H.; Ahnstrom, Josefin; Dikkeschei, Bert D.; de Vries, Rindert; Sluiter, Wim J.; Wolffenbuttel, Bruce H. R.; van Tol, Arie; Nielsen, Lars Bo; Dahlback, Bjorn; Dullaart, Robin P. F.

    2010-01-01

    Purpose: Plasma apolipoprotein M (apoM) is potentially anti-atherogenic, and has been found to be associated positively with plasma total, LDL and HDL cholesterol in humans. ApoM may, therefore, be intricately related to cholesterol metabolism. Here, we determined whether plasma apoM is affected by

  9. Improving prediction of ischemic cardiovascular disease in the general population using apolipoprotein B

    DEFF Research Database (Denmark)

    Benn, Marianne; Nordestgaard, Børge G; Jensen, Gorm Boje;

    2007-01-01

    Apolipoprotein B (apoB) levels predict fatal myocardial infarction. Whether apoB also predicts nonfatal ischemic cardiovascular events is unclear. We tested the following hypotheses: apoB predicts ischemic cardiovascular events, and apoB is a better predictor of ischemic cardiovascular events tha...

  10. PLASMA-LIPOPROTEINS AND RENAL APOLIPOPROTEINS IN RATS WITH CHRONIC ADRIAMYCIN NEPHROSIS

    NARCIS (Netherlands)

    JOLES, JA; VANTOL, A; JANSEN, EHJM; KOOMANS, HA; RABELINK, TJ; VANGOOR, H

    1993-01-01

    The relation between plasma lipoprotein composition and renal apolipoprotein deposition was studied in nephrotic rats in which stable renal function had been monitored for 7 months after a single low dose of adriamycin (ADR, 3 mg/kg). Proteinuria was observed 3 weeks after ADR and increased progress

  11. Apolipoprotein B genetic variants modify the response to fenofibrate: a GOLDN study

    Science.gov (United States)

    Hypertriglyceridemia, defined as a triglyceride measurement > 150 mg/dl, occurs in up to 34% of adults. Fenofibrate is a commonly used drug to treat hypertriglyceridemia, but response to fenofibrate varies considerably among individuals. We sought to determine if genetic variation in apolipoprotein...

  12. Transcriptional Regulation of Apolipoprotein A5 Gene Expression by the Nuclear Receptor ROR alpha

    Energy Technology Data Exchange (ETDEWEB)

    Genoux, Annelise; Dehondt, Helene; Helleboid-Chapman, Audrey; Duhem, Christian; Hum, Dean W.; Martin, Genevieve; Pennacchio, Len; Staels, Bart; Fruchart-Najib, Jamila; Fruchart, Jean-Charles

    2004-10-01

    Apolipoprotein A5 has recently been identified as a crucial determinant of plasma triglyceride levels. Our results showed that RORa up-regulates human APOA5 but has no effect on mouse apoa5 promoter. These data suggest an additional important physiological role for RORa in the regulation of genes involved in plasma triglyceride homeostasis in human and probably in the development of atherosclerosis

  13. APOLIPOPROTEIN E GENE POLYMORPHISMS ARE NOT ASSOCIATED WITH DIABETIC RETINOPATHY: THE ATHEROSCLEROSIS RISK IN COMMUNITIES STUDY

    Science.gov (United States)

    PURPOSE: Polymorphism of the apolipoprotein E (APOE) gene has been associated with dyslipidemia and cardiovascular disease. This study examines the association of APOE polymorphisms and diabetic retinopathy. DESIGN: Population-based cross-sectional study. METHODS: We studied 1,398 people aged 49 to ...

  14. Intracerebral adeno-associated virus gene delivery of apolipoprotein E2 markedly reduces brain amyloid pathology in Alzheimer's disease mouse models.

    Science.gov (United States)

    Zhao, Lingzhi; Gottesdiener, Andrew J; Parmar, Mayur; Li, Mingjie; Kaminsky, Stephen M; Chiuchiolo, Maria J; Sondhi, Dolan; Sullivan, Patrick M; Holtzman, David M; Crystal, Ronald G; Paul, Steven M

    2016-08-01

    The common apolipoprotein E alleles (ε4, ε3, and ε2) are important genetic risk factors for late-onset Alzheimer's disease, with the ε4 allele increasing risk and reducing the age of onset and the ε2 allele decreasing risk and markedly delaying the age of onset. Preclinical and clinical studies have shown that apolipoprotein E (APOE) genotype also predicts the timing and amount of brain amyloid-β (Aβ) peptide deposition and amyloid burden (ε4 >ε3 >ε2). Using several administration protocols, we now report that direct intracerebral adeno-associated virus (AAV)-mediated delivery of APOE2 markedly reduces brain soluble (including oligomeric) and insoluble Aβ levels as well as amyloid burden in 2 mouse models of brain amyloidosis whose pathology is dependent on either the expression of murine Apoe or more importantly on human APOE4. The efficacy of APOE2 to reduce brain Aβ burden in either model, however, was highly dependent on brain APOE2 levels and the amount of pre-existing Aβ and amyloid deposition. We further demonstrate that a widespread reduction of brain Aβ burden can be achieved through a single injection of vector via intrathalamic delivery of AAV expressing APOE2 gene. Our results demonstrate that AAV gene delivery of APOE2 using an AAV vector rescues the detrimental effects of APOE4 on brain amyloid pathology and may represent a viable therapeutic approach for treating or preventing Alzheimer's disease especially if sufficient brain APOE2 levels can be achieved early in the course of the disease. PMID:27318144

  15. The solubility of hen egg-white lysozyme

    Science.gov (United States)

    Howard, Sandra B.; Twigg, Pamela J.; Baird, James K.; Meehan, Edward J.

    1988-01-01

    The equilibrium solubility of chicken egg-white lysozyme in the presence of crystalline solid state was determined as a function of NaCl concentration, pH, and temperature. The solubility curves obtained represent a region of the lysozyme phase diagram. This diagram makes it possible to determine the supersaturation of a given set of conditions or to achieve identical supersaturations by different combinations of parameters. The temperature dependence of the solubility permits the evaluation of Delta-H of crystallization. The data indicate a negative heat of crystallization for the tetragonal crystal form but a positive heat of crystallization for the high-temperature orthorhombic form.

  16. Effect of apolipoprotein a-I complex with tetrahydrocortisone on protein biosynthesis and glucose absorption by rat hepatocytes.

    Science.gov (United States)

    Sumenkova, D V; Knyazev, R A; Guschya, R S; Polyakov, L M; Panin, L E

    2009-08-01

    We studied the effect of apolipoprotein A-I-tetrahydrocortisone complex on (14)C glucose absorption and lactate accumulation and on the rate of protein biosynthesis in isolated rat hepatocytes. The presence of apolipoprotein A-I-tetrahydrocortisone complex in the incubation medium increased absorption of labeled glucose by hepatocytes by 52%, while lactate content in the conditioning medium increased 4-fold. The rate of protein biosynthesis increased by 80% in comparison with control cells. It is hypothesized that the increase in protein biosynthesis rate in hepatocytes under the effect of apolipoprotein A-I-tetrahydrocortisone complex is due to stimulation of energy metabolism, specifically, of its glycolytic component. PMID:20027330

  17. Plasma proteome changes in cardiovascular disease patients: novel isoforms of apolipoprotein A1

    Directory of Open Access Journals (Sweden)

    Oravec Milan

    2011-06-01

    Full Text Available Abstract Background The aim of this proteomic study was to look for changes taking place in plasma proteomes of patients with acute myocardial infarction (AMI, unstable angina pectoris (UAP, and stable angina pectoris (SAP. Methods Depleted plasma proteins were separated by 2D SDS-PAGE (pI 4-7, and proteomes were compared using Progenesis SameSpots statistical software. Proteins were identified by nanoLC-MS/MS. Proteins were quantified using commercial kits. Apolipoprotein A1 was studied using 1D and 2D SDS-PAGE, together with western blotting. Results Reciprocal comparison revealed 46 unique, significantly different spots; proteins in 34 spots were successfully identified and corresponded to 38 different proteins. Discrete comparisons of patient groups showed 45, 41, and 8 significantly different spots when AMI, UAP, and SAP were compared with the control group. On the basis of our proteomic data, plasma levels of two of them, alpha-1 microglobulin and vitamin D-binding protein, were determined. The data, however, failed to prove the proteins to be suitable markers or risk factors in the studied groups. The plasma level and isoform representation of apolipoprotein A1 were also estimated. Using 1D and 2D SDS-PAGE, together with western blotting, we observed extra high-molecular weight apolipoprotein A1 fractions presented only in the patient groups, indicating that the novel high-molecular weight isoforms of apolipoprotein A1 may be potential new markers or possible risk factors of cardiovascular disease. Conclusion The reported data show plasma proteome changes in patients with AMI, UAP, and SAP. We propose some apolipoprotein A1 fractions as a possible new disease-associated marker of cardiovascular disorders.

  18. Mixed Hydrotropy: Novel Science of Solubility Enhancement

    OpenAIRE

    R K Maheshwari; Jagwani, Y.

    2011-01-01

    Conventional furosemide tablets are practically insoluble in water, have slow onset of action (45-60 min) and poor bioavailability (39-53%), and therefore cannot be given in emergency clinical situations like hypertension or pulmonary edema. So purpose of research was to provide a fast dissolving oral dosage form of furosemide, which can provide quick onset of action by using concept of mixed hydrotropy. Initially solubility of furosemide was determined individually in 4 hydrotropic agents na...

  19. Vitamin D deficiency and exogenous vitamin D excess similarly increase diffuse atherosclerotic calcification in apolipoprotein E knockout mice.

    Directory of Open Access Journals (Sweden)

    Timothy Ellam

    Full Text Available BACKGROUND: Observational data associate lower levels of serum vitamin D with coronary artery calcification, cardiovascular events and mortality. However, there is little interventional evidence demonstrating that moderate vitamin D deficiency plays a causative role in cardiovascular disease. This study examined the cardiovascular effects of dietary vitamin D deficiency and of vitamin D receptor agonist (paricalcitol administration in apolipoprotein E knockout mice. METHODS: Mice were fed atherogenic diets with normal vitamin D content (1.5 IU/kg or without vitamin D. Paricalcitol, or matched vehicle, was administered 3× weekly by intraperitoneal injection. Following 20 weeks of these interventions cardiovascular phenotype was characterized by histological assessment of aortic sinus atheroma, soluble markers, blood pressure and echocardiography. To place the cardiovascular assessments in the context of intervention effects on bone, structural changes at the tibia were assessed by microtomography. RESULTS: Vitamin D deficient diet induced significant reductions in plasma vitamin D (p<0.001, trabecular bone volume (p<0.01 and bone mineral density (p<0.005. These changes were accompanied by an increase in calcification density (number of calcifications per mm(2 of von Kossa-stained aortic sinus atheroma (461 versus 200, p<0.01. Paricalcitol administration suppressed parathyroid hormone (p<0.001, elevated plasma calcium phosphate product (p<0.005 and induced an increase in calcification density (472 versus 200, p<0.005 similar to that seen with vitamin D deficiency. Atheroma burden, blood pressure, metabolic profile and measures of left ventricular hypertrophy were unaffected by the interventions. CONCLUSION: Vitamin D deficiency, as well as excess, increases atherosclerotic calcification. This phenotype is induced before other measures of cardiovascular pathology associated clinically with vitamin D deficiency. Thus, maintenance of an optimal

  20. Uranium solubility. Part I: basic solubility criteria - initial study

    International Nuclear Information System (INIS)

    The thermodynamic properties of the metals are important to describe the solubility of one metal in other. In this work the criteria of solubility are discussed and possible uses are emphasized for metallic uranium. The sources of data selected for these calculations and the arrangement of the tables are also discussed. (author)

  1. Thermodynamic data development using the solubility method (Joint research)

    International Nuclear Information System (INIS)

    The solubility method is one of the most powerful tools to obtain reliable thermodynamic data for 1) solubility products of discrete solids and double salts, 2) complexation constants for various ligands, 3) development of data in a wide range of pH values, 4) evaluation of data for metals that form very insoluble solids (e.g. tetravalent actinides), 5) determining solubility-controlling solids in different types of wastes and 6) elevated temperatures for redox sensitive systems. This document is focused on describing various aspects of obtaining thermodynamic data using the solubility method. This manuscript deals with various aspects of conducting solubility studies, including selecting the study topic, modeling to define important variables, selecting the range of variables and experimental parameters, anticipating results, general equipment requirements, conducting experiments, and interpreting experimental data. (author)

  2. Pharmaceutical particle technologies: An approach to improve drug solubility, dissolution and bioavailability

    Directory of Open Access Journals (Sweden)

    Prakash Khadka

    2014-12-01

    Full Text Available Pharmaceutical particle technology is employed to improve poor aqueous solubility of drug compounds that limits in vivo bioavailability owing to their low dissolution rate in the gastrointestinal fluids following oral administration. The particle technology involves several approaches from the conventional size reduction processes to the newer, novel particle technologies that modify the solubility properties of the drugs and produce solid, powdered form of the drugs that are readily soluble in water and can be easily formulated into various dosage forms. This review highlights the solid particle technologies available for improving solubility, dissolution and bioavailability of drugs with poor aqueous solubility.

  3. A case report of hereditary apolipoprotein A-I amyloidosis associated with a novel APOA1 mutation and variable phenotype.

    Science.gov (United States)

    Tougaard, Birgitte G; Pedersen, Katja Venborg; Krag, Søren Rasmus; Gilbertson, Janet A; Rowczenio, Dorota; Gillmore, Julian D; Birn, Henrik

    2016-09-01

    Apolipoprotein A-I (apo A-I) amyloidosis is a non-AL, non-AA, and non-transthyretin type of amyloidosis associated with mutations in the APOA1 gene inherited in an autosomal dominant fashion. It is a form of systemic amyloidosis, but at presentation, can also mimic localized amyloidosis. The renal presentation generally involves interstitial and medullary deposition of apo A-I amyloid protein. We describe the identification of apo A-I amyloidosis by mass spectrometry in a 52-year old male, with no family history of amyloidosis, presenting with nephrotic syndrome and associated with heterozygosity for a novel APOA1 mutation (c.220 T > A) which encodes the known amyloidogenic Trp50Arg variant. Renal amyloid deposits in this case were confined to the glomeruli alone, and the patient developed progressive renal impairment. One year after diagnosis, the patient had a successful kidney transplant from an unrelated donor. Pathogenic mutations in the APOA1 gene are generally associated with symptoms of amyloidosis. In this family however, genotyping of family members identified several unaffected carriers suggesting a variable disease penetrance, which has not been described before in this form of amyloidosis and has implications when counselling those with APOA1 mutations. PMID:27240838

  4. Genetically elevated apolipoprotein A-I, high-density lipoprotein cholesterol levels, and risk of ischemic heart disease

    DEFF Research Database (Denmark)

    Lundegaard, Christiane; Tybjærg-Hansen, Anne; Grande, Peer;

    2010-01-01

    Epidemiologically, levels of high-density lipoprotein (HDL) cholesterol and its major protein constituent, apolipoprotein A-I (apoA-I), are inversely related to risk of ischemic heart disease (IHD).......Epidemiologically, levels of high-density lipoprotein (HDL) cholesterol and its major protein constituent, apolipoprotein A-I (apoA-I), are inversely related to risk of ischemic heart disease (IHD)....

  5. Overexpression of LolCDE Allows Deletion of the Escherichia coli Gene Encoding Apolipoprotein N-Acyltransferase ▿

    OpenAIRE

    Narita, Shin-ichiro; Tokuda, Hajime

    2011-01-01

    Bacterial lipoproteins represent a subset of membrane-associated proteins that are covalently modified with lipids at the N-terminal cysteine. The final step of lipoprotein modification, N-acylation of apolipoproteins, is mediated by apolipoprotein N-acyltransferase (Lnt). Examinations with reconstituted proteoliposomes and a conditional mutant previously indicated that N-acylation of lipoproteins is required for their efficient release from the inner membrane catalyzed by LolA and LolCDE, th...

  6. Apolipoprotein E ε4 allele and malondialdehyde level are independent risk factors for Alzheimer’s disease

    OpenAIRE

    López-Riquelme, Natividad; Alom-Poveda, Jordi; Viciano-Morote, Nuria; Llinares-Ibor, Isabel; Tormo-Díaz, Consuelo

    2016-01-01

    Background: The ε4 allele of Apolipoprotein E is involved in lipid metabolism. Oxidative stress produces an increase in lipid peroxidation that has been implicated in the pathogenic cascade in Alzheimer’s disease. This study estimated the effect of the ε4 allele, malondialdehyde and lipid levels on the risk for Alzheimer’s disease. Methods: A total of 41 control subjects and 73 patients with Alzheimer’s disease were recruited. The Apolipoprotein E genotype was determined by amplification of e...

  7. Apolipoprotein E4 influences growth and cognitive responses to micronutrient supplementation in shantytown children from northeast Brazil

    OpenAIRE

    Sumeet S Mitter; Oriá, Reinaldo B.; Kvalsund, Michelle P.; Paula Pamplona; Emanuella Silva Joventino; Rosa M. S. Mota; Davi C Gonçalves; Patrick, Peter D.; Guerrant, Richard L.; Lima, Aldo A. M.

    2012-01-01

    OBJECTIVE: Apolipoprotein E4 may benefit children during early periods of life when the body is challenged by infection and nutritional decline. We examined whether apolipoprotein E4 affects intestinal barrier function, thereby improving short-term growth and long-term cognitive outcomes in Brazilian shantytown children. METHODS: A total of 213 Brazilian shantytown children with below-median height-for-age z-scores (HAZ) received 200,000 IU of retinol (every four months), zinc (40 mg twice we...

  8. Acyclic cucurbit[n]uril molecular containers enhance the solubility and bioactivity of poorly soluble pharmaceuticals

    Science.gov (United States)

    Ma, Da; Hettiarachchi, Gaya; Nguyen, Duc; Zhang, Ben; Wittenberg, James B.; Zavalij, Peter Y.; Briken, Volker; Isaacs, Lyle

    2012-06-01

    The solubility characteristics of 40-70% of new drug candidates are so poor that they cannot be formulated on their own, so new methods for increasing drug solubility are highly prized. Here, we describe a new class of general-purpose solubilizing agents—acyclic cucurbituril-type containers—which increase the solubility of ten insoluble drugs by a factor of between 23 and 2,750 by forming container-drug complexes. The containers exhibit low in vitro toxicity in human liver, kidney and monocyte cell lines, and outbred Swiss Webster mice tolerate high doses of the container without sickness or weight loss. Paclitaxel solubilized by the acyclic cucurbituril-type containers kills cervical and ovarian cancer cells more efficiently than paclitaxel alone. The acyclic cucurbituril-type containers preferentially bind cationic and aromatic drugs, but also solubilize neutral drugs such as paclitaxel, and represent an attractive extension of cyclodextrin-based technology for drug solubilization and delivery.

  9. Cloud droplet activation: solubility revisited

    Directory of Open Access Journals (Sweden)

    L. T. Padró

    2007-02-01

    Full Text Available Soluble compounds present in atmospheric aerosol facilitate their transformation into cloud droplets by depressing the equilibrium vapor pressure required for activation. Their impact depends on the amount of dissolved substance in the aerosol aqueous phase, which in turn is controlled by its solubility. This study explores the impact of particle curvature on solubility, expressed in terms of a Kelvin enhancement. The augmented solubility, termed "Curvature Enhanced Solubility" (CES, is then introduced into Köhler theory for assessment of its impact on CCN activity for several organic compounds with a wide range of aqueous solubility. The interfacial energy between solute and aqueous phase required for quantification of CES is determined from existing correlations based on bulk solubility, and concurrent measurements of contact angle and surface tension. A number of important findings arise from this study: i CES can substantially increase solubility and impact CCN activity but only if the aerosol is initially wet, ii CES can stabilize highly supersaturated solutions, and provide a mechanism for retention of an aerosol aqueous phase even at very low relative humidity (RH, and, iii trace amounts of surfactant impurities can magnify the impact of CES.

  10. Solubility enhancement of rosiglitazone by using melt sonocrystallization technique.

    Science.gov (United States)

    Jagtap, Vaibhavkumar A; Vidyasagar, G; Dvivedi, S C

    2014-03-01

    The poor solubility and low dissolution rate in gastro-intestinal fluid, especially for class-II drugs according to Biopharmaceutics Classification System (BCS) the bioavailability enhanced by increasing the solubility and dissolution rate. A novel melt sonocrystallization technique of particle engineering to enhance solubility as well as dissolution of hydrophobic drug and to study its effect on crystal properties of drug. The present study leads to use investigate solubility of melt sonocrystallization technique to modify the undesirable properties of Rosiglitazone is antidiabetic drug in thiozolidione category with (BCS II) to forms agglomerates with number of shallow circular pits on the surface leads to increase solubility. Melt sonocrystallization process was developed for Rosiglitazone in which Rosiglitazone melt was poured in deionized water and simultaneously subjected to ultrasonic energy for 20 min at amplitude 80 %. The product obtained was evaluated using scanning electron microscopy, differential scanning calorimetry, X-ray powder diffractometry (XPRD), Fourier transformed infrared spectroscopy (FTIR), solubility and dissolution rate. The irregular agglomerates with porous surface were obtained having different crystal habit which increases solubility and dissolution rate. FTIR shows thermal behavior of untreated Rosiglitazone and treated Rosiglitazone have no significant difference low intensity peaks in XPRD of treated Rosiglitazone were noticed crystals habit changes and lattice defects during processing have causes favorable changes in the physicochemical properties of Rosiglitazone. The use of melt sonocrystallization technique is promising technique that may affords powder with improved flow as well as improved solubility and dissolution. PMID:24616749

  11. Water soluble fluor compositions

    International Nuclear Information System (INIS)

    Water soluble fluors useful in enhancing images obtained in autoradiography have the general formula: F is a moiety which acts as a fluor, e.g., a dehydro derivative of a compound which is a fluor; preferred examples include 4-(2,5-diphenyloxazolyl), 1-naphthylmethyl, 2-naphthyl, and 4-(5-(2-phenyloxazolyl))phenyl. S is a surfactant moiety which makes the molecule hydrophilic, e.g., dehydro derivatives of surfactants; preferred examples include polyethylene glycol derivatives, sulfonic acids or salts thereof, aryl sulfonates, amines and quaternary ammonium compounds. B is a binding moiety which chemically binds the fluor moiety F with the surfactant S, and may be a chemical bond, or a disubstituted moiety such as an alkylene, e.g., methylene group. The variables x, y and z are integers which can generally vary from 1 to 10. A number of such compounds are disclosed, as well as methods of using such compounds, as well as compositions and products for fluorographic analysis in connection with chromatography, electrophoresis etc

  12. Teaching Form as Form

    DEFF Research Database (Denmark)

    Keiding, Tina Bering

    2012-01-01

    understanding of form per se, or, to use an expression from this text, of form as form. This challenge can be reduced to one question: how can design teaching support students in achieving not only the ability to recognize and describe different form-related concepts in existing design (i.e. analytical and...

  13. Further studies of the influence of apolipoprotein B alleles on glucose and lipid metabolism

    DEFF Research Database (Denmark)

    Bentzen, Joan; Poulsen, Pernille; Vaag, Allan;

    2003-01-01

    The effect of five genetic polymorphisms in the apolipoprotein B gene on parameters of lipid and glucose metabolism was assessed in 564 Danish mono- and dizygotic twins. Genotypes in apolipoprotein B T71I (ApaLI RFLP), A591V (AluI RFLP), L2712P (MvaI RFLP), R3611Q (MspI RFLP), and E4154K (Eco...... on the insulin-to-glucose ratio (p = 0.04), and E4154K (EcoRI RFLP) influenced HOMAbeta (p = 0.04). Significant interactions were observed between genotype in T71I (ApaLI RFLP), A591V (AluI RFLP), R3611Q (MspI RFLP), and E4154K (EcoRI RFLP) and glucose tolerance on lipid-related parameters (0.03 < p...

  14. Soluble and stable zethrenebis(dicarboximide) and its quinone

    KAUST Repository

    Sun, Zhe

    2010-10-15

    Soluble and stable zethrenebis(dicarboximide) (1) was synthesized by an in situ Stille cross coupling/transannular cyclization reaction. 1 showed largely improved photostability and solubility compared with the very unstable zethrene and it also exhibited far-red absorption and emission with high photoluminescence quantum yield. Bromination of 1 with NBS/DMF gave its quinone form 2 via an unusual pathway. © 2010 American Chemical Society.

  15. Endothelial surface layer degradation by chronic hyaluronidase infusion induces proteinuria in apolipoprotein e-deficient mice

    OpenAIRE

    Meuwese, Marijn C.; Broekhuizen, Lysette N.; Mayella Kuikhoven; Sylvia Heeneman; Esther Lutgens; Marion J J Gijbels; Max Nieuwdorp; Peutz, Carine J; Stroes, Erik S.G.; Hans Vink; van den Berg, Bernard M.

    2010-01-01

    OBJECTIVE: Functional studies show that disruption of endothelial surface layer (ESL) is accompanied by enhanced sensitivity of the vasculature towards atherogenic stimuli. However, relevance of ESL disruption as causal mechanism for vascular dysfunction remains to be demonstrated. We examined if loss of ESL through enzymatic degradation would affect vascular barrier properties in an atherogenic model. METHODS: Eight week old male apolipoprotein E deficient mice on Western-type diet for 10 we...

  16. Expression analysis of apolipoprotein E and its associated genes in gastric cancer

    OpenAIRE

    Shi, Xiumin; Xu, Jianting; Wang, Jihan; CUI, MEIZI; Gao, Yushun; Niu, Haitao; Jin, Haofan

    2015-01-01

    Gastric cancer is a common type of cancer worldwide, and has a poor prognosis, in part due to the low rates of early diagnosis and the limited treatment methods available. Apolipoprotein E (ApoE) is involved in exogenous cholesterol transport and may be important in enabling tumor cells to fulfill their high cholesterol requirements. A number of reports have indicated that ApoE affects the development and prognosis of gastric cancer. Therefore, the aim of the present study was to investigate ...

  17. The Tangier disease gene product ABC1 controls the cellular apolipoprotein-mediated lipid removal pathway

    OpenAIRE

    Lawn, Richard M.; Wade, David P.; Garvin, Michael R.; Wang, Xingbo; Schwartz, Karen; Porter, J. Gordon; Seilhamer, Jeffrey J.; Ashley M Vaughan; Oram, John F.

    1999-01-01

    The ABC1 transporter was identified as the defect in Tangier disease by a combined strategy of gene expression microarray analysis, genetic mapping, and biochemical studies. Patients with Tangier disease have a defect in cellular cholesterol removal, which results in near zero plasma levels of HDL and in massive tissue deposition of cholesteryl esters. Blocking the expression or activity of ABC1 reduces apolipoprotein-mediated lipid efflux from cultured cells, and increasing expression of ABC...

  18. Apolipoprotein E gene polymorphism influences aggressive behavior in prostate cancer cells by deregulating cholesterol homeostasis

    OpenAIRE

    IFERE, GODWIN O.; Desmond, Renee; Demark-Wahnefried, Wendy; Nagy, Tim R.

    2013-01-01

    High circulating cholesterol and its deregulated homeostasis may facilitate prostate cancer progression. Genetic polymorphism in Apolipoprotein (Apo) E, a key cholesterol regulatory protein may effect changes in systemic cholesterol levels. In this investigation, we determined whether variants of the Apo E gene can trigger defective intracellular cholesterol efflux, which could promote aggressive prostate cancer. ApoE genotypes of weakly (non-aggressive), moderate and highly tumorigenic (aggr...

  19. Apolipoprotein A-I and its mimetics for the treatment of atherosclerosis

    OpenAIRE

    Smith, Jonathan D.

    2010-01-01

    Although statin treatment leads consistently to a reduction in major adverse coronary events and death in clinical trials, approximately 60 to 70% residual risk of these outcomes still remains. One frontier of investigational drug research is treatment to increase HDL, the ‘good cholesterol’ that is associated with a reduced risk of coronary artery disease. HDL and its major protein apolipoprotein A-I (apoAI) are protective against atherosclerosis through several mechanisms, including the abi...

  20. Association of apolipoprotein E allele {epsilon}4 with late-onset sporadic Alzheimer`s disease

    Energy Technology Data Exchange (ETDEWEB)

    Lucotte, G.; David, F.; Berriche, S. [Regional Center of Neurogenetics, Reims (France)] [and others

    1994-09-15

    Apolipoprotein E, type {epsilon}4 allele (ApoE {epsilon}4), is associated with late-onset sporadic Alzheimer`s disease (AD) in French patients. The association is highly significant (0.45 AD versus 0.12 controls for {epsilon}4 allele frequencies). These data support the involvement of ApoE {epsilon}4 allele as a very important risk factor for the clinical expression of AD. 22 refs., 1 fig., 3 tabs.

  1. Mutation in apolipoprotein B associated with hypobetalipoproteinemia despite decreased binding to the low density lipoprotein receptor

    DEFF Research Database (Denmark)

    Benn, Marianne; Nordestgaard, Børge G; Jensen, Jan Skov; Nilausen, Karin Skov; Meinertz, Hans; Tybjaerg-Hansen, Anne

    2005-01-01

    Mutations in apolipoprotein B (APOB) may reduce binding of low density lipoprotein (LDL) to the LDL receptor and cause hypercholesterolemia. We showed that heterozygotes for a new mutation in APOB have hypobetalipoproteinemia, despite a reduced binding of LDL to the LDL receptor. APOB R3480P hete...... in vitro studies with both human in vivo and population-based studies, as in vitro studies often have focused on very limited aspects of complex mechanisms taken out of their natural context....

  2. Apolipoprotein E Polymorphism and Colorectal Neoplasm: Results from a Meta-Analysis

    OpenAIRE

    Tian, Yun; Wang, Jirong; Ye, Ying; Sun, Liqun; Fan, Yingrui; Wang, Li; Juan LI; Wang, Zhaoxia; Wang, Keming

    2014-01-01

    To investigate the relationship of Apolipoprotein E (APOE) gene polymorphism to colorectal neoplasia (CRN), we performed a systematic review and meta-analysis. Eligible studies were identified through a systematic literature review from PubMed, EMBASE, and the Science Citation Index up to February 2014. A combined analysis was performed, followed by a subgroup analyses stratified by the study design. We used data collected from 8 prospective studies involving respectively a total of 9243 part...

  3. Perbedaan Kadar Apolipoprotein-B pada Diabetes Melitus Tipe 2 Terkontrol dan Tidak terkontrol

    OpenAIRE

    Sembiring, Budi Darmanta

    2015-01-01

    Background : Apolipoprotein-B (apo-B) is the major protein component of atherogenic lipoproteins such as VLDL, IDL, LDL. Type 2 DM apo-B act a better indicator of the progression of coronary artery disease compared with other lipids and lipoproteins . Objective : To determine differences in levels of apo-B in patients with type 2 diabetes mellitus controlled and uncontrolled blood sugar levels then for further can estimate the magnitude of the risk of coronary heart disease (CHD) in patien...

  4. The Apolipoprotein E Gene and Taq1A Polymorphisms in Childhood Obesity

    OpenAIRE

    Ergun, Mehmet Ali; Karaoguz, Meral Yirmibes; Koc, Altug; Camurdan, Orhun; Bideci, Aysun; Yazici, A. Canan; Cinaz, Peyami

    2010-01-01

    Obesity is a multifactorial disease that is influenced by genetic and environmental factors. The apolipoprotein E (Apo E) polymorphism has been reported to influence some lipid profile abnormalities associated with obesity in childhood. In this study, the relationship between the Apo E gene and Taq1A polymorphisms with childhood obesity has been studied. Regarding the Apo E genotypes, e3/4 was the most frequent in both the patient and control groups. Further, there was a significance between ...

  5. Apolipoprotein M binds oxidized phospholipids and increases the antioxidant effect of HDL

    DEFF Research Database (Denmark)

    Elsøe, Sara; Ahnström, Josefin; Christoffersen, Christina;

    2012-01-01

    Oxidation of LDL plays a key role in the development of atherosclerosis. HDL may, in part, protect against atherosclerosis by inhibiting LDL oxidation. Overexpression of HDL-associated apolipoprotein M (apoM) protects mice against atherosclerosis through a not yet clarified mechanism. Being a lip...... lipocalin, apoM contains a binding pocket for small lipophilic molecules. Here, we report that apoM likely serves as an antioxidant in HDL by binding oxidized phospholipids, thus enhancing the antioxidant potential of HDL....

  6. Association of hepatic nuclear factor-4 in the apolipoprotein B promoter: a preliminary report

    OpenAIRE

    Nóvak E.M.; Dantas K.C.; Charbel C.E.; Bydlowski S.P.

    1998-01-01

    Previous studies have examined the arrangement of regulatory elements along the apolipoprotein B (apoB) promoter region (-3067 to +940) and a promoter fragment extending from nucleotides -150 to +124 has been demonstrated to be essential for transcriptional activation of the apoB gene in hepatic and intestinal cells. It has also been shown that transcriptional activation of apoB requires a synergistic interaction between hepatic nuclear factor-4 (HNF-4) and CCAAT/enhancer-binding protein a (C...

  7. Guanosine effect on cholesterol efflux and apolipoprotein E expression in astrocytes.

    Science.gov (United States)

    Ballerini, Patrizia; Ciccarelli, Renata; Di Iorio, Patrizia; Buccella, Silvana; D'Alimonte, Iolanda; Giuliani, Patricia; Masciulli, Arianna; Nargi, Eleonora; Beraudi, Alina; Rathbone, Michel P; Caciagli, Francesco

    2006-11-01

    The main source of cholesterol in the central nervous system (CNS) is represented by glial cells, mainly astrocytes, which also synthesise and secrete apolipoproteins, in particular apolipoprotein E (ApoE), the major apolipoprotein in the brain, thus generating cholesterol-rich high density lipoproteins (HDLs). This cholesterol trafficking, even though still poorly known, is considered to play a key role in different aspects of neuronal plasticity and in the stabilisation of synaptic transmission. Moreover, cell cholesterol depletion has recently been linked to a reduction in amyloid beta formation. Here we demonstrate that guanosine, which we previously reported to exert several neuroprotective effects, was able to increase cholesterol efflux from astrocytes and C6 rat glioma cells in the absence of exogenously added acceptors. In this effect the phosphoinositide 3 kinase/extracellular signal-regulated kinase 1/2 (PI3K/ERK1/2) pathway seems to play a pivotal role. Guanosine was also able to increase the expression of ApoE in astrocytes, whereas it did not modify the levels of ATP-binding cassette protein A1 (ABCA1), considered the main cholesterol transporter in the CNS. Given the emerging role of cholesterol balance in neuronal repair, these effects provide evidence for a role of guanosine as a potential pharmacological tool in the modulation of cholesterol homeostasis in the brain. PMID:18404467

  8. Altered plasma apolipoprotein modifications in patients with pancreatic cancer: protein characterization and multi-institutional validation.

    Directory of Open Access Journals (Sweden)

    Kazufumi Honda

    Full Text Available BACKGROUND: Among the more common human malignancies, invasive ductal carcinoma of the pancreas has the worst prognosis. The poor outcome seems to be attributable to difficulty in early detection. METHODS: We compared the plasma protein profiles of 112 pancreatic cancer patients with those of 103 sex- and age-matched healthy controls (Cohort 1 using a newly developed matrix-assisted laser desorption/ionization (oMALDI QqTOF (quadrupole time-of-flight mass spectrometry (MS system. RESULTS: We found that hemi-truncated apolipoprotein AII dimer (ApoAII-2; 17252 m/z, unglycosylated apolipoprotein CIII (ApoCIII-0; 8766 m/z, and their summed value were significantly decreased in the pancreatic cancer patients [P = 1.36×10(-21, P = 4.35×10(-14, and P = 1.83×10(-24 (Mann-Whitney U-test; area-under-curve values of 0.877, 0.798, and 0.903, respectively]. The significance was further validated in a total of 1099 plasma/serum samples, consisting of 2 retrospective cohorts [Cohort 2 (n = 103 and Cohort 3 (n = 163] and a prospective cohort [Cohort 4 (n = 833] collected from 8 medical institutions in Japan and Germany. CONCLUSIONS: We have constructed a robust quantitative MS profiling system and used it to validate alterations of modified apolipoproteins in multiple cohorts of patients with pancreatic cancer.

  9. Apolipoproteins: Good Markers for Cardiovacular Risk in Patients with Chronic Kidney Disease and Dyslipidemia

    Directory of Open Access Journals (Sweden)

    Tudor Mirela - Nicoleta

    2014-09-01

    Full Text Available Background and aims. Dyslipidemia (DLP is a common complication of chronic kidney disease (CKD and may accelerate its progression. Circulating lipoproteins and their constituent proteins, apolipoproteins, are risk factors for CKD and cardiovascular diseases (CVD. The aim of the study was to determine whether there is a correlation between apolipoproteins and estimated glomerular filtration rate (eGFR or between apolipoproteins and anthropometrical and laboratory parameters or between evaluated cardiovascular risk (CV and dyslipidemia/CKD. Material and methods. We performed a study on 51 subjects from the Nephrology Department of Emergency Clinical County Hospital of Craiova, from November 2011 to July 2013. Results. We found statistically significant correlations between eGFR and Apo A1. Also we found a linear correlation between C-reactive protein (CRP and Apo B. When we evaluated the CV risk using CRP, we found statistically significant differences between the groups (CKD and DLP, only CKD, only DLP and control group, patients with CKD and DLP showing the highest levels of CRP. Conclusions. Elevated levels of Apo A1 are associated with a low rate of CKD. DLP and chronic inflammation play an important role in the progression of CKD. Patients with CKD and DLP had a high cardiovascular risk.

  10. Genetic variation of apolipoproteins, diet and other environmental interactions: an updated review

    Directory of Open Access Journals (Sweden)

    Mercedes Sotos-Prieto

    2013-08-01

    Full Text Available This paper summarizes the recent findings from studies investigating the potential environmental modulation of the genetic variation of apolipoprotein genes on metabolic traits. We reviewed nutrigenetic studies evaluating variations on apolipoproteins-related genes and its associated response to nutrients (mostly dietary fatty acids or any other dietary or environmental component. Most revised research studied single nucleotide polymorphism (SNP and specific nutrients through small intervention studies, and only few interactions have been replicated in large and independent populations (as in the case of -265T > C SNP in APOA2 gene. Although current knowledge shows that variations on apolipoprotein genes may contribute to the different response on metabolic traits due to dietary interventions, evidence is still scarce and results are inconsistent. Success in this area will require going beyond the limitations of current experimental designs and explore the hypotheses within large populations. Some of these limitations are being covered by the rapidly advance in high-throughput technologies and large scale-genome wide association studies.

  11. Amyloid-β colocalizes with apolipoprotein B in absorptive cells of the small intestine

    Directory of Open Access Journals (Sweden)

    Dhaliwal Satvinder S

    2009-10-01

    Full Text Available Abstract Background Amyloid-β is recognized as the major constituent of senile plaque found in subjects with Alzheimer's disease. However, there is increasing evidence that in a physiological context amyloid-β may serve as regulating apolipoprotein, primarily of the triglyceride enriched lipoproteins. To consider this hypothesis further, this study utilized an in vivo immunological approach to explore in lipogenic tissue whether amyloid-β colocalizes with nascent triglyceride-rich lipoproteins. Results In murine absorptive epithelial cells of the small intestine, amyloid-β had remarkable colocalization with chylomicrons (Manders overlap coefficient = 0.73 ± 0.03 (SEM, the latter identified as immunoreactive apolipoprotein B. A diet enriched in saturated fats doubled the abundance of both amyloid-β and apo B and increased the overlap coefficient of the two proteins (0.87 ± 0.02. However, there was no evidence that abundance of the two proteins was interdependent within the enterocytes (Pearson's Coefficient Conclusion The findings of this study are consistent with the possibility that amyloid-β is secreted by enterocytes as an apolipoprotein component of chylomicrons. However, secretion of amyloid-β appears to be independent of chylomicron biogenesis.

  12. Acute effects of moderate exercise on serum lipids, lipoproteins and apolipoproteins in sedentary young women.

    Science.gov (United States)

    Imamura, H; Katagiri, S; Uchid, K; Miyamoto, N; Nakano, H; Shirota, T

    2000-12-01

    1. The aim of the present study was to examine the effects of moderate exercise on serum lipids, lipoproteins and apolipoproteins in seven sedentary young women under controlled conditions. 2. The subjects exercised on separate days for 30 or 60 min at an intensity of 60% of maximal oxygen uptake on a cycle ergometer. Total cholesterol, triglycerides, high-density lipoprotein-cholesterol (HDL-C), HDL2-C, HDL3-C, low-density lipoprotein-cholesterol, apolipoproteins A-I, A-II and B were measured in the serum at the end of the 60 min rest period before each exercise, immediately after the performance of each exercise and at 30 min and 1, 2 and 24 h after each exercise. 3. The results showed that there were no significant differences between the pre- and postexercise samples for any of the parameters tested. 4. The results of the present study suggest that a single bout of exercise designed to simulate a typical training workout has no noticeable effect on serum lipids, lipoproteins and apolipoproteins in normal sedentary young women who have normal lipid profiles, are in the follicular phase of their menstrual cycle and who consume a relatively low-fat diet. PMID:11117233

  13. Effects of red grape juice consumption on high density lipoprotein-cholesterol, apolipoprotein AI, apolipoprotein B and homocysteine in healthy human volunteers.

    Science.gov (United States)

    Khadem-Ansari, Mohammad H; Rasmi, Yousef; Ramezani, Fatemeh

    2010-01-01

    It has suggested that grape juice consumption has lipid- lowering effect and it is associated with a decreased risk of heart disease. We aimed to evaluate the effects of red grape juice (RGj) consumption on high density lipoprotein-cholesterol (HDL-C), apolipoprotein AI (apoAI), apolipoprotein B (apoB) and homocysteine (Hcy) levels in healthy human volunteers. Twenty six healthy and nonsmoking males, aged between 25-60 years, who were under no medication asked to consume 150 ml of RGj twice per day for one month. Serum HDL-C, apoAI, apoB and plasma Hcy levels were measured before and after one month RGj consumption. HDL-C levels after RGj consumption were significantly higher than the corresponding levels before the RGj consumption (41.44 ± 4.50 and 44.37 ± 4.30 mg/dl; P0.05). Hcy levels were decreased after RGj consumption (7.70 ± 2.80 and 6.20 ± 2.30 µmol/l; P<0.001). The present study demonstrates that RGj consumption can significantly increase serum HDL-C levels and decrease Hcy levels. These findings may have important implications for the prevention of atherosclerosis in healthy individuals. PMID:21633724

  14. 17β-estradiol potentiates endothelium-dependent nitric oxide- and hyperpolarization-mediated relaxations in blood vessels of male but not female apolipoprotein-E deficient mice.

    Science.gov (United States)

    Kong, Billy W C; Vanhoutte, Paul M; Man, Ricky Y K; Leung, Susan W S

    2015-08-01

    The present study investigated the influence of gender on the changes underlying endothelial dysfunction in hyperlipidemia during aging. Isometric tension in rings (with endothelium) of the aortae and superior mesenteric arteries from apolipoprotein-E deficient mice was determined in wire myographs. Nitric oxide (NO)- and endothelium-dependent hyperpolarization (EDH)-mediated relaxations were smaller in the aortae and mesenteric arteries of 32weeks old males than eight weeks old males. In females, NO- and EDH-mediated relaxations were impaired only at 84weeks of age. The levels of reactive oxygen species were elevated in the blood vessels of 32weeks old males, but not females. Acute in vitro treatment with 17β-estradiol and apocynin improved NO- and EDH-mediated relaxations in 32weeks old males but not in 84weeks old males. Relaxations to SKA-31, activator of intermediate (IKCa) and small (SKCa) conductance calcium-activated potassium channels, were attenuated in the mesenteric arteries of 32weeks old males. Such impairment was restored by acute treatment with apocynin. These findings suggest that male hyperlipidemic mice develop endothelial dysfunction at an earlier age than females. This endothelial dysfunction is associated with impaired NO bioavailability and reduced IKCa and SKCa activity. Apocynin and 17β-estradiol restore the endothelial function only in younger male animals but not in older male or female animals. PMID:25869512

  15. Lipoprotein lipase activity and mass, apolipoprotein C-II mass and polymorphisms of apolipoproteins E and A5 in subjects with prior acute hypertriglyceridaemic pancreatitis

    Directory of Open Access Journals (Sweden)

    García-Arias Carlota

    2009-06-01

    Full Text Available Abstract Background Severe hypertriglyceridaemia due to chylomicronemia may trigger an acute pancreatitis. However, the basic underlying mechanism is usually not well understood. We decided to analyze some proteins involved in the catabolism of triglyceride-rich lipoproteins in patients with severe hypertriglyceridaemia. Methods Twenty-four survivors of acute hypertriglyceridaemic pancreatitis (cases and 31 patients with severe hypertriglyceridaemia (controls were included. Clinical and anthropometrical data, chylomicronaemia, lipoprotein profile, postheparin lipoprotein lipase mass and activity, hepatic lipase activity, apolipoprotein C II and CIII mass, apo E and A5 polymorphisms were assessed. Results Only five cases were found to have LPL mass and activity deficiency, all of them thin and having the first episode in childhood. No cases had apolipoprotein CII deficiency. No significant differences were found between the non-deficient LPL cases and the controls in terms of obesity, diabetes, alcohol consumption, drug therapy, gender distribution, evidence of fasting chylomicronaemia, lipid levels, LPL activity and mass, hepatic lipase activity, CII and CIII mass or apo E polymorphisms. However, the SNP S19W of apo A5 tended to be more prevalent in cases than controls (40% vs. 23%, NS. Conclusion Primary defects in LPL and C-II are rare in survivors of acute hypertriglyceridaemic pancreatitis; lipase activity measurements should be restricted to those having their first episode during chilhood.

  16. Noble gases solubility in water

    International Nuclear Information System (INIS)

    The available experimental data of solubility of noble gases in water for temperatures smaller than 3300C have been critically surveyed. Due to the unique structure of the solvent, the solubility of noble gases in water decreases with temperature passing through a temperature of minimum solubility which is different for each gas, and then increases at higher temperatures. As aresult of the analysis of the experimental data and of the features of the solute-solvent interaction, a generalized equation is proposed which enables thecalculation of Henry's coefficient at different temperatures for all noble gases. (author)

  17. Computational Design of Apolipoprotein E4 Inhibitors for Alzheimer’s Disease Therapy from Traditional Chinese Medicine

    Directory of Open Access Journals (Sweden)

    Hung-Jin Huang

    2014-01-01

    Full Text Available Apolipoprotein E4 (Apo E4 is the major genetic risk factor in the causation of Alzheimer’s disease (AD. In this study we utilize virtual screening of the world’s largest traditional Chinese medicine (TCM database and investigate potential compounds for the inhibition of ApoE4. We present the top three TCM candidates: Solapalmitine, Isodesacetyluvaricin, and Budmunchiamine L5 for further investigation. Dynamics analysis and molecular dynamics (MD simulation were used to simulate protein-ligand complexes for observing the interactions and protein variations. Budmunchiamine L5 did not have the highest score from virtual screening; however, the dynamics pose is similar to the initial docking pose after MD simulation. Trajectory analysis reveals that Budmunchiamine L5 was stable over all simulation times. The migration distance of Budmunchiamine L5 illustrates that docked ligands are not variable from the initial docked site. Interestingly, Arg158 was observed to form H-bonds with Budmunchiamine L5 in the docking pose and MD snapshot, which indicates that the TCM compounds could stably bind to ApoE4. Our results show that Budmunchiamine L5 has good absorption, blood brain barrier (BBB penetration, and less toxicity according to absorption, distribution, metabolism, excretion, and toxicity (ADMET prediction and could, therefore, be safely used for developing novel ApoE4 inhibitors.

  18. Mass spectrometry of transferrin and apolipoprotein C-III for diagnosis and screening of congenital disorder of glycosylation.

    Science.gov (United States)

    Wada, Yoshinao

    2016-06-01

    Congenital disorder of glycosylation (CDG), formerly representing a group of diseases due to defects in the biosynthetic pathway of protein N-glycosylation, currently covers a wide range of disorders affecting glycoconjugates. Since its first application to serum transferrin from a CDG patient with phosphomannomutase-2 deficiency in 1992, mass spectrometry (MS) has been playing a key role in identification and characterization of glycosylation defects affecting glycoproteins. MS of native transferrin detects a lack of glycans characteristic to the classical CDG-I type of molecular abnormality. Electrospray ionization MS of native transferrin, especially, allows glycoforms to be analyzed precisely but requires basic knowledge regarding deconvolution of multiply-charged ions which may generate ghost signals upon transformation into a singly-charged form. MS of glycopeptides from tryptic digestion of transferrin delineates site-specific glycoforms and reveals a delicate balance of donor/acceptor substrates or the conformational effect of nascent proteins in cells. Matrix-assisted laser desorption ionization MS of apolipoprotein C-III is a simple method of elucidating the profiles of mucin-type core 1 O-glycans including site occupancy and glycoforms. In this technological review, the principle and pitfalls of MS for CDG are discussed and mass spectra of various types of CDG are presented. PMID:26873821

  19. Solubility enhancement studies on lurasidone hydrochloride using mixed hydrotropy.

    Science.gov (United States)

    Madan, Jyotsana R; Pawar, Kiran T; Dua, Kamal

    2015-01-01

    Low aqueous solubility is a major problem faced during formulation development of new drug molecules. Lurasidone HCl (LRD) is an antipsychotic agent specially used in the treatments of schizophrenia and is a good example of the problems associated with low aqueous solubility. Lurasidone is practically insoluble in water, has poor bioavailability and slow onset of action and therefore cannot be given in emergency clinical situations like schizophrenia. Hence, purpose of this research was to provide a fast dissolving oral dosage form of Lurasidone. This dosage form can provide quick onset of action by using the concept of mixed hydrotropy. Initially, solubility of LRD was determined individually in nicotinamide, sodium citrate, urea and sodium benzoate at concentration of 10, 20, 30 and 40% w/v solutions using purified water as a solvent. Highest solubility was obtained in 40% sodium benzoate solution. In order to decrease the individual hydrotrope concentration mixed hydrotropic agents were used. Highest solubility was obtained in 15:20:5 ratio of Nicotinamide + sodium benzoate + sodium citrate. This optimized combination was utilized in the preparation of solid dispersions by using distilled water as a solvent. Solid dispersions were evaluated for X-ray diffraction, differential scanning calorimetry and Fourier-transform infrared to show no drug-hydrotropes interaction has occurred. This solid dispersion was compressed to form fast dissolving tablets. Dissolution studies of prepared tablets were done using USP Type II apparatus. The batch L3 tablets show 88% cumulative drug release within 14 min and in vitro dispersion time was 32 min. It was concluded that the concept of mixed hydrotropic solid dispersion is novel, safe and cost-effective technique for enhancing the bioavailability of poorly water-soluble drugs. The miraculous enhancement in solubility and bioavailability of Lurasidone is clear indication of the potential of mixed hydrotropy to be used in future

  20. Hypoxia is responsible for soluble vascular endothelial growth factor receptor-1 (VEGFR-1) but not for soluble endoglin induction in villous trophoblast

    OpenAIRE

    Munaut, Carine; Lorquet, Sophie; Pequeux, Christel; Blacher, Silvia; Berndt, Sarah; Frankenne, Francis; Foidart, Jean-Michel

    2008-01-01

    BACKGROUND: Pre-eclampsia is a pregnancy disorder characterized by a maternal endothelial cell dysfunction associated with low levels of circulating placental growth factor (PlGF) and increased levels of total vascular endothelial growth factor (VEGF), soluble VEGF receptor-1 (sVEGFR-1), and soluble endoglin, a transforming growth factor b1 and 3 coreceptor. Here, we tested the hypothesis that these altered levels of angiogenic cytokines and of the anti-angiogenic soluble forms of cytokine re...

  1. Calcite solubility in simulated geothermal brines

    Energy Technology Data Exchange (ETDEWEB)

    Pool, K.H.; Raney, P.J.; Shannon, D.W.

    1987-02-01

    The deposition of scale on geothermal piping surfaces has been recognized as a cause of increased pressure drop and diminished fluid flow. The two most common scales encountered in the geothermal energy field are silica and calcite. The main purpose of this study was to obtain accurate, reliable calcite solubility data in brines similar to natural geothermal brines over the temperature range of most known exploitable geothermal resources. In addition, geothermal fluid equilibrium modeling efforts and data bases can be refined and fine-turned with respect to the commercially important calcite-geothermal fluid stability problem with these data. The effect of sodium chloride and sodium bicarbonate on the solubility of CaCO/sub 3/ (calcite) in high temperature solutions was measured over the 100 to 300/sup 0/C temperature range. The brines studied contained 0 to 5 wt % NaCl, 0 to 5 mM NaHCO/sub 3/, and 0.003 to 0.1 M CO/sub 2/. The data detailing calcite solubility at various temperatures are presented in tabular, graphical, and regression-equation form for each brine composition tested.

  2. Stabilization of the bioactivity of tumor necrosis factor by its soluble receptors

    DEFF Research Database (Denmark)

    Aderka, D; Engelmann, H; Maor, Y; Brakebusch, C; Wallach, D

    1992-01-01

    The receptors for tumor necrosis factor (TNF) exist in cell-associated as well as soluble forms, both binding specifically to TNF. Since the soluble forms of TNF receptors (sTNF-Rs) can compete with the cell-associated TNF receptors for TNF, it was suggested that they function as inhibitors of TN...

  3. Review on theoretical calculation of the magnetite solubility

    International Nuclear Information System (INIS)

    FAC is influenced by many factors such as water chemistry (temperature, pH, dissolved oxygen (D. O.) in a solution, and etc.), chemical composition of carbon steel, and fluid dynamics. Magnetite is formed at the inner surface of carbon steel, and protects the integrity of pipes from the damage. The magnetite has a stable state at each equilibrium condition, so that it can be dissolved into the fluid under conditions that satisfy the equilibrium state. The iron solubility can be calculated by considering the reaction equilibrium constants for prediction of a change in the magnetite layer. In the present work, studies on the magnetite solubility were reviewed for the theoretical calculation of magnetite, and iron solubility data were compared to find the proper solubility values of each study

  4. Apolipoprotein A-II influences apolipoprotein E-linked cardiovascular disease risk in women with high levels of HDL cholesterol and C-reactive protein.

    Directory of Open Access Journals (Sweden)

    James P Corsetti

    Full Text Available BACKGROUND: In a previous report by our group, high levels of apolipoprotein E (apoE were demonstrated to be associated with risk of incident cardiovascular disease in women with high levels of C-reactive protein (CRP in the setting of both low (designated as HR1 subjects and high (designated as HR2 subjects levels of high-density lipoprotein cholesterol (HDL-C. To assess whether apolipoprotein A-II (apoA-II plays a role in apoE-associated risk in the two female groups. METHODOLOGY/PRINCIPAL: Outcome event mapping, a graphical data exploratory tool; Cox proportional hazards multivariable regression; and curve-fitting modeling were used to examine apoA-II influence on apoE-associated risk focusing on HDL particles with apolipoprotein A-I (apoA-I without apoA-II (LpA-I and HDL particles with both apoA-I and apoA-II (LpA-I:A-II. Results of outcome mappings as a function of apoE levels and the ratio of apoA-II to apoA-I revealed within each of the two populations, a high-risk subgroup characterized in each situation by high levels of apoE and additionally: in HR1, by a low value of the apoA-II/apoA-I ratio; and in HR2, by a moderate value of the apoA-II/apoA-I ratio. Furthermore, derived estimates of LpA-I and LpA-I:A-II levels revealed for high-risk versus remaining subjects: in HR1, higher levels of LpA-I and lower levels of LpA-I:A-II; and in HR2 the reverse, lower levels of LpA-I and higher levels of LpA-I:A-II. Results of multivariable risk modeling as a function of LpA-I and LpA-I:A-II (dichotomized as highest quartile versus combined three lower quartiles revealed association of risk only for high levels of LpA-I:A-II in the HR2 subgroup (hazard ratio 5.31, 95% CI 1.12-25.17, p = 0.036. Furthermore, high LpA-I:A-II levels interacted with high apoE levels in establishing subgroup risk. CONCLUSIONS/SIGNIFICANCE: We conclude that apoA-II plays a significant role in apoE-associated risk of incident CVD in women with high levels of HDL-C and CRP.

  5. SOLUBILITY ENHANCEMENT OF POORLY WATER SOLUBLE DRUGS BY SOLID DISPERSIO

    Directory of Open Access Journals (Sweden)

    Amita Verm

    2012-01-01

    Full Text Available Solid dispersions have been employed to enhance the dissolution rates of poorly water-soluble drugs. Many approaches have been investigated for the preparation of solid dispersions. This paper reports the various solubility enhancement strategies in solid dispersion. The approaches described are fusion (melting, solvent evaporation, lyophilization (freeze drying, melt agglomeration process, extruding method, spray drying technology, use of surfactant, electro static spinning method and super critical fluid technology. This paper also highlights the potential applications and limitations of theseapproaches in solid dispersions.

  6. Polymorphism of apolipoprotein E gene and post-stroke vascular dementia

    Institute of Scientific and Technical Information of China (English)

    Xinjing Lin; Changlin Hu; Yunlan Xie; Xin Zhang; Xiangping Liu; Ge Yan

    2006-01-01

    BACKGROUND: Studies have indicated that the more certain etiological factors of vascular dementia are the sites, size and number of cerebrovascular lesions, but there are arguments all the time in the relationship of genetic factors, especially apolipoprotein E gene, with the occurrence and development of vascular dementia. OBJECTIVE: To analyze the relationship between the polymorphism of apolipoprotein E gene and vascular dementia in stroke patients. DESIGN: A non-randomized grouped comparative observation at the same time. SETTING: The Laboratory of Neurology, the Second Affiliated Hospital of Chongqing University of Medical Sciences.PARTICIPANTS: Totally 121 inpatients with stroke were selected from the Department of Neurology, the Second Affiliated Hospital of Chongqing University of Medical Sciences from January 2000 to December 2001. All the patients were accorded with the diagnostic standards for cerebrovascular diseases set by the Second National Academic Meeting for Cerebrovascular Disease, and confirmed by cranial CT or MRI. According to with vascular dementia or not, they were divided into vascular dementia group (n =58) and non-vascular dementia group (n =63). In the vascular dementia group, there were 37 males and 21 females, the average age was (59±8) years. They were all in accordance with the standard of the third edition of Diagnostic and Statistical Manual of Mental Disorders (DMS-Ⅲ), without conscious disturbance and language disorder; hospitalized within 3 days after the attack of cerebrovascular disease. In the non-vascular dementia group, there were 37 males and 26 females, the average age was (59±9.5) years. They all had no intellectual disturbance within 3 months after the attack of cerebrovascular disease. All the subjects agreed to supply blood samples for the experiment. METHODS: ①Fasting venous blood (2 mL) was drawn from each patient in the morning to extract DNA. The frequencies of apolipoprotein E genotypes and alleles were

  7. Mechanistic studies of the oxidation of soluble species of ruthenium in nitric acid solutions. Application to the removal of ruthenium from nuclear fuel dissolution solutions; Etude du mecanisme d'oxydation des formes dissoutes du ruthenium dans les solutions d'acide nitrique. Application a l'elimination du ruthenium des solutions de dissolution des combustibles nucleaires irradies

    Energy Technology Data Exchange (ETDEWEB)

    Carron, V

    2001-07-01

    Ruthenium is one of the most troublesome fission products during nuclear fuel reprocessing. His removal from nitric acid fuel dissolution solutions, above the PUREX process, is under consideration. Electro-volatilization could be a possible way to eliminate this element. It consists in the oxidation of soluble ruthenium species coupled with the volatilization of formed RuO{sub 4}. Soluble species are nitrate and nitro complexes of nitrosyl ruthenium RuNO{sup 3+}. The first part of this work deals with the direct oxidation of RuNO{sup 3+} at a golden or a platinum anode. It has been investigated by cyclic voltammetry and infrared and UV-visible reflectance spectroscopy. The oxidation of RuNO{sup 3+} begins with an adsorption step, which precedes the formation of RuO{sub 4}. Then a reaction between RuO{sub 4} and RuNO{sup 3+} occurs to produce a Ru{sup IV} compound, which is also electro-oxidized to RuO{sub 4}. The second part concerns potentiostatic electro-volatilization experiences. The rate of electro-volatilization decreases with increasing HNO{sub 3} concentration. At low concentrations, kinetic is controlled by the volatilization of RuO{sub 4}. The rate-determining step is the oxidation of RuNO{sup 3+} at concentrations higher than 1 M. In HNO{sub 3} 4 M, the addition of AgNO{sub 3} is required to accelerate the oxidation of RuNO{sup 3+}. The last part is devoted to the study of the indirect oxidation of RuNO{sup 3+}. The electrocatalytic power of electro-generated Ag{sup II} is illustrated by voltammetric techniques and potentiostatic electrolysis. The existence of a limit concentration of AgNO{sub 3} is shown (which value depends on experimental conditions) beyond which kinetic is controlled by the RuO{sub 4} volatilization step. These results indicate that the electro-volatilization kinetic could be increased by optimizing the volatilization conditions. (author)

  8. Ectopic expression of clusterin/apolipoprotein J or Bcl-2 decreases the sensitivity of HaCaT cells to toxic effects of ropivacaine

    Institute of Scientific and Technical Information of China (English)

    2004-01-01

    Local anesthetics inhibit cell proliferation and induce apoptosis in various cell types. Ropivacaine, a unique, novel tertiary amine-type anesthetic, was shown to inhibit the proliferation of several cell types including keratinocytes. We found that Ropivacaine could inhibit the proliferation and induce apoptosis in an immortalized human keratinocyte line,HaCaT, in a dose- and time-dependent manner and with the deprivation of serum. The dose-dependent induction of apoptosis by ropivacaine was demonstrated by DNA fragmentation analysis and the proteolytic cleavage of a caspase-3substrate - poly (ADP-ribose) polymerase (PARP). In addition, ropivacaine downregulated the expression of clusterin/apoliporotein J, a protein with anti-apoptotic properties, in a dose-dependent manner, which well correlated with the induction of apoptosis of HaCaT cells. To investigate the role of clusterin/apoliporotein J in ropivacaine-induced apoptosis,HaCaT cells overexpressing clusterin/apoliporotein J were generated and compared to cells expressing the well established anti-apoptotic Bcl-2 protein. Ectopic overexpression of the secreted form of clusterin/apoliporotein J or Bcl-2decreased the sensitivity of HaCaT cells to toxic effects of ropivacaine as demonstrated by DNA fragmentation, the proteolytic cleavage of PARP and by a reduction in procaspase-3 expression. Furthermore, the downregulation of endogenous clusterin/apolipoprotein J levels by ropivacaine suggested that this might be one mechanism by which ropivacaine induced cell death in HaCaT cells. In conclusion, the ability of ropivacaine to induce antiproliferative responses and to suppress the expression of the anti-apoptotic protein clusterin/apolipoprotein J, combined with previously reported anti-inflammatory activity and analgesic property of the drug, suggests that ropivacaine may have potential utility in the local treatment of tumors.

  9. Solubility database for TILA-99

    International Nuclear Information System (INIS)

    The safety assessment of spent fuel disposal requires solubility values for several elements estimated in Finnish disposal conditions. In Finland four sites (Haestholmen, Kivetty, Olkiluoto and Romuvaara) are investigated for the disposal of spent fuel. Haestholmen and OLkiluoto are onshore sites, while Kivetty and Romuvaara are inland sites. Based on groundwater analysis and classification according to salinity at the planned disposal depth mainly fresh groundwater is encountered at Kivetty and Romuvaara, while brackish and saline water-types are met at Haestholmen and Olkiluoto. Very saline, almost brine-type water (∼70 g/l) has been found in the deepest parts of the investigated bedrock at one of the sites (Olkiluoto). The reference waters and conditions were chosen according to the water-types. The considered reference conditions incorporated both the near- and far-field, and both oxidizing and reducing conditions were considered. In the reference conditions, the changes in solubilities were also estimated as caused by possible variations in the pH, carbonate content and redox conditions. Uranium, which is the main component of spent fuel is dealt with in a separate report presenting the solubility of uranium and spent fuel dissolution. In this work the solubilities of all the other elements of concern (Am, Cu, Nb, Np, Pa, Pd, Pu, Ra, Se, Sn, Tc, Zr, Cm, Ni, Sr, Th, C, Cl, Cs, Fe, Ho, I, and Sm) in the safety assessment are considered. Some discussion on the corrosion of the spent fuel canister is also presented. For the estimation of solubilities of the elements in question, literature data was collected that mainly comprised experimentally measured concentrations. The sources used were spent fuel experiments, concentrations measured in solubility measurements, natural concentrations and concentrations from natural analogue sites (especially Palmottu and Hyrkkoelae in Finland) as well as the concentrations measured at the Finnish investigation sites. The

  10. Solubility database for TILA-99

    Energy Technology Data Exchange (ETDEWEB)

    Vuorinen, U.; Carlsson, T. [VTT Chemical Technology, Espoo (Finland); Kulmala, S.; Hakanen, M. [Helsinki Univ. (Finland). Lab. of Radiochemistry; Ahonen, L. [Geological Survey of Finland, Espoo (Finland)

    1998-11-01

    The safety assessment of spent fuel disposal requires solubility values for several elements estimated in Finnish disposal conditions. In Finland four sites (Haestholmen, Kivetty, Olkiluoto and Romuvaara) are investigated for the disposal of spent fuel. Haestholmen and OLkiluoto are onshore sites, while Kivetty and Romuvaara are inland sites. Based on groundwater analysis and classification according to salinity at the planned disposal depth mainly fresh groundwater is encountered at Kivetty and Romuvaara, while brackish and saline water-types are met at Haestholmen and Olkiluoto. Very saline, almost brine-type water ({approx}70 g/l) has been found in the deepest parts of the investigated bedrock at one of the sites (Olkiluoto). The reference waters and conditions were chosen according to the water-types. The considered reference conditions incorporated both the near- and far-field, and both oxidizing and reducing conditions were considered. In the reference conditions, the changes in solubilities were also estimated as caused by possible variations in the pH, carbonate content and redox conditions. Uranium, which is the main component of spent fuel is dealt with in a separate report presenting the solubility of uranium and spent fuel dissolution. In this work the solubilities of all the other elements of concern (Am, Cu, Nb, Np, Pa, Pd, Pu, Ra, Se, Sn, Tc, Zr, Cm, Ni, Sr, Th, C, Cl, Cs, Fe, Ho, I, and Sm) in the safety assessment are considered. Some discussion on the corrosion of the spent fuel canister is also presented. For the estimation of solubilities of the elements in question, literature data was collected that mainly comprised experimentally measured concentrations. The sources used were spent fuel experiments, concentrations measured in solubility measurements, natural concentrations and concentrations from natural analogue sites (especially Palmottu and Hyrkkoelae in Finland) as well as the concentrations measured at the Finnish investigation sites

  11. SOLID DISPERSION: STRATEGY TO ENHANCE SOLUBILITY

    OpenAIRE

    P B Dalvi; A B Gerange; P R INGALE

    2015-01-01

    The solubility behavior of drugs remains one of the most exigent aspects in formulation development.With the advent of combinatorial chemistry and high throughput screening, the number of poorly water soluble compounds has dramatically increased. Among all the newly discovered chemical entities, about 40-45% drugs fail to reach market due to their poor water solubility. Because of solubility problem, bioavailability of drugs gets affected and hence solubility enhancement becomes necessary. S...

  12. Immunolocalization of an Amino-Terminal Fragment of Apolipoprotein E in the Pick's Disease Brain

    OpenAIRE

    Rohn, Troy T.; Day, Ryan J; Catlin, Lindsey W; Brown, Raquel J.; Rajic, Alexander J.; Poon, Wayne W.

    2013-01-01

    Although the risk factor for apolipoprotein E (apoE) polymorphism in Alzheimer's disease (AD) has been well described, the role that apoE plays in other neurodegenerative diseases, including Pick's disease, is not well established. To examine a possible role of apoE in Pick's disease, an immunohistochemical analysis was performed utilizing a novel site-directed antibody that is specific for an amino-terminal fragment of apoE. Application of this antibody, termed the amino-terminal apoE cleava...

  13. Bioenergetic programming of macrophages by the apolipoprotein A-I mimetic peptide 4F

    OpenAIRE

    Datta, Geeta; Kramer, Philip A.; Johnson, Michelle S.; Sawada, Hirotaka; Smythies, Lesley E.; Crossman, David K.; Chacko, Balu; Ballinger, Scott W.; Westbrook, David G.; Mayakonda, Palgunachari; Anantharamaiah, G.M.; Darley-Usmar, Victor M.; White, C. Roger

    2015-01-01

    The apoA-I (apolipoprotein A-I) mimetic peptide 4F favours the differentiation of human monocytes to an alternatively activated M2 phenotype. The goal of the present study was to test whether the 4F-mediated differentiation of MDMs (monocyte-derived macrophages) requires the induction of an oxidative metabolic programme. 4F treatment induced several genes in MDMs that play an important role in lipid metabolism, including PPARγ (peroxisome-proliferator-activated receptor γ) and CD36. Addition ...

  14. Angiotensin II-Induced Hypertension in Apolipoprotein E-Deficient Rats

    OpenAIRE

    Gorman, Sydney N; Goergen, Craig J.; Blaize, A Nicole

    2015-01-01

    Abdominal aortic aneurysms (AAAs) are characterized by a weakened vessel wall and a diameter 50% greater than normal. AAA are usually asymptomatic until they are near rupturing, which can be fatal if not treated immediately. Apolipoprotein E-deficient (ApoE) mice are commonly used as a model to study aneurysm growth. Our lab has created a similar model using rats, which are more similar to humans. This study focuses on the analysis of blood pressures collected from ApoE rats for comparison wi...

  15. Abolished synthesis of cholic acid reduces atherosclerotic development in apolipoprotein E knockout mice[S

    OpenAIRE

    Slätis, Katharina; Gåfvels, Mats; Kannisto, Kristina; Ovchinnikova, Olga; Paulsson-Berne, Gabrielle; Parini, Paolo; Jiang, Zhao-Yan; Eggertsen, Gösta

    2010-01-01

    To investigate the effects of abolished cholic acid (CA) synthesis in the ApoE knockout model [apolipoprotein E (apoE) KO],a double-knockout (DKO) mouse model was created by crossbreeding Cyp8b1 knockout mice (Cyp8b1 KO), unable to synthesize the primary bile acid CA, with apoE KO mice. After 5 months of cholesterol feeding, the development of atherosclerotic plaques in the proximal aorta was 50% less in the DKO mice compared with the apoE KO mice. This effect was associated with reduced inte...

  16. Apolipoprotein E4 Domain Interaction Induces Endoplasmic Reticulum Stress and Impairs Astrocyte Function*

    OpenAIRE

    Zhong, Ning; Ramaswamy, Gayathri; Weisgraber, Karl H.

    2009-01-01

    Domain interaction, a structural property of apolipoprotein E4 (apoE4), is predicted to contribute to the association of apoE4 with Alzheimer disease. Arg-61 apoE mice, a gene-targeted mouse model specific for domain interaction, have lower brain apoE levels and synaptic, functional, and cognitive deficits. We hypothesized that domain interaction elicits an endoplasmic reticulum (ER) stress in astrocytes and an unfolded protein response that targets Arg-61 apoE for degradation. Primary Arg-61...

  17. Effect of Biliary Diversion on Rat Mesenteric Lymph Apolipoprotein-I and High Density Lipoprotein

    OpenAIRE

    Bearnot, H. Robert; Glickman, Robert M.; Weinberg, Lee; Green, Peter H.R.; Tall, Alan R.

    1982-01-01

    The effect of biliary diversion on intestinal apolipoprotein (apoA)-I and high density lipoprotein formation was studied in mesenteric lymph fistula rats. Bile diversion was produced by an exteriorized catheter that allowed interruption and reconstitution of the enterohepatic circulation. Bile diversion reduced lymph cholesterol output from 0.47±0.05 μmol/h to 0.17±0.03 μmol/h (P < 0.025), and lymph triglyceride output from 3.6±0.3μmol/h to 0.6±0.05 μmol/h (P < 0.025) after 24 h. This was due...

  18. Apolipoprotein E4 and a change in episodic memory functioning among normal aging Norwegian adults

    OpenAIRE

    2009-01-01

    The e4 allele of the apolipoprotein E (APOE) gene is a known risk factor for Alzheimer’s disease and may also affect cognitive performance in normal aging. The data presented in the current study represent the first two time points of an ongoing longitudinal study examining cognitive changes in genetically at-risk individuals with much emphasis on test of episodic recall as measured by the California Verbal Learning Test. A total of 110 of 139 people who participated in the first phase of the...

  19. The impact of plasma triglyceride and apolipoproteins concentrations on high-density lipoprotein subclasses distribution

    Directory of Open Access Journals (Sweden)

    Liu Yinghui

    2011-01-01

    Full Text Available Abstract Objective To investigate the effect of triglyceride (TG integrates with plasma major components of apolipoproteins in HDL subclasses distribution and further elicited the TG-apolipoproteins (apos interaction in the processes of high density lipoprotein (HDL mature metabolic and atherosclerosis related diseases. Methods Contents of plasma HDL subclasses were quantities by two-dimensional gel electrophoresis associated with immunodetection in 500 Chinese subjects. Results Contents of preβ1-HDL, HDL3a, and apoB-100 level along with apoB-100/A-I ratio were significantly increased, whereas there was a significant reduction in the contents of HDL2, apoA-I level as well as apoC-III/C-II ratio with increased TG concentration. Moreover, preβ1-HDL contents is elevated about 9 mg/L and HDL2b contents can be reduced 21 mg/L for 0.5 mmol/L increment in TG concentration. Moreover, with increase of apoA-I levels, HDL2b contents were marginally elevated in any TG concentration group. Furthermore, despite of in the apoB-100/A-I 1-HDL increased, and those of HDL2b decreased significantly for subjects in both high and very high TG levels compared to that in normal TG levels. Similarly, in the apoB-100/A-I ≥ 0.9 group, the distribution of HDL subclasses also showed abnormality for subjects with normal TG levels. Conclusions The particle size of HDL subclasses tend to small with TG levels increased which indicated that HDL maturation might be impeded and efficiency of reverse cholesterol transport(RCT might be weakened. These data suggest that TG levels were not only significantly associated with but liner with the contents of preβ1-HDL and HDL2b. They also raise the possibility that the TG levels effect on HDL maturation metabolism are subjected to plasma apolipoproteins and apolipoproteins ratios.

  20. Interactions of Apolipoprotein A-I with High-Density Lipoprotein Particles

    OpenAIRE

    Nguyen, David; Nickel, Margaret; Mizuguchi, Chiharu; Saito, Hiroyuki; Lund-Katz, Sissel; Phillips, Michael C.

    2013-01-01

    Although the partitioning of apolipoprotein A-I (apoA-I) molecules in plasma between high-density lipoprotein (HDL)-bound and -unbound states is an integral part of HDL metabolism, the factors that control binding of apoA-I to HDL particles are poorly understood. To address this gap in knowledge, we investigated how the properties of the apoA-I tertiary structure domains and surface characteristics of spherical HDL particles influence apoA-I binding. The abilities of 14C-labeled human and mou...

  1. Surface behavior of apolipoprotein A-I and its deletion mutants at model lipoprotein interfaces

    OpenAIRE

    Wang, Libo; Mei, Xiaohu; Atkinson, David; Small, Donald M.

    2014-01-01

    Apolipoprotein A-I (apoA-I) has a great conformational flexibility to exist in lipid-free, lipid-poor, and lipid-bound states during lipid metabolism. To address the lipid binding and the dynamic desorption behavior of apoA-I at lipoprotein surfaces, apoA-I, Δ(185-243)apoA-I, and Δ(1-59)(185-243)apoA-I were studied at triolein/water and phosphatidylcholine/triolein/water interfaces with special attention to surface pressure. All three proteins are surface active to both interfaces lowering th...

  2. The apolipoprotein A-I gene is actively expressed in the rapidly myelinating avian peripheral nerve

    OpenAIRE

    1989-01-01

    The expression of the apolipoprotein A-I (apo A-I) gene was investigated in the myelinating sciatic nerve. Hybridization analysis with an apo A-I cDNA probe obtained from a cDNA library of mRNA isolated from rapidly myelinating chick sciatic nerve indicated that apo A-I coding transcripts increase during development in the chick sciatic nerve in parallel with the increase of myelin lamellae. Substantial apo A-I-like immunoreactivity in chick sciatic nerve homogenates was detected by Western b...

  3. No severe bottleneck during human evolution: evidence from two apolipoprotein C-II deficiency alleles.

    OpenAIRE

    Xiong, W J; Li, W. H.; Posner, I; Yamamura, T.; Yamamoto, A.; Gotto, A M; Chan, L

    1991-01-01

    The DNA sequences of a Japanese and a Venezuelan apolipoprotein (apo) C-II deficiency allele, of a normal Japanese apo C-II gene, and of a chimpanzee apo C-II gene were amplified by PCR, and their nucleotide sequences were determined on multiple clones of the PCR products. The normal Japanese sequence is identical to--and the chimpanzee sequence differs by only three nucleotides from--a previously published normal Caucasian sequence. In contrast, the two human mutant sequences each differ fro...

  4. Crystal structure of truncated human apolipoprotein A-I suggests a lipid-bound conformation

    OpenAIRE

    Borhani, David W.; Rogers, Danise P.; Engler, Jeffrey A.; Brouillette, Christie G

    1997-01-01

    The structure of truncated human apolipoprotein A-I (apo A-I), the major protein component of high density lipoprotein, has been determined at 4-Å resolution. The crystals comprise residues 44–243 (exon 4) of apo A-I, a fragment that binds to lipid similarly to intact apo A-I and that retains the lipid-bound conformation even in the absence of lipid. The molecule consists almost entirely of a pseudo-continuous, amphipathic α-helix that is punctuated by kinks at regularly spaced proline residu...

  5. Human apolipoprotein C-II: complete nucleic acid sequence of preapolipoprotein C-II.

    OpenAIRE

    Fojo, S S; Law, S W; Brewer, H B

    1984-01-01

    Apolipoprotein (apo) C-II is a cofactor for lipoprotein lipase, the enzyme that catalyzes the hydrolysis of triglycerides on plasma triglyceride-rich lipoproteins. The complete coding sequence of apoC-II mRNA has been determined from an apoC-II clone isolated from a human liver cDNA library. A 17-base-long synthetic oligonucleotide based on amino acid residues 5-10 of apoC-II was utilized as a hybridization probe to select recombinant plasmids containing the apoC-II sequence. Two thousand fou...

  6. Erythrocyte-bound apolipoprotein B in relation to atherosclerosis, serum lipids and ABO blood group.

    Directory of Open Access Journals (Sweden)

    Boudewijn Klop

    Full Text Available INTRODUCTION: Erythrocytes carry apolipoprotein B on their membrane, but the determining factors of erythrocyte-bound apolipoprotein B (ery-apoB are unknown. We aimed to explore the determinants of ery-apoB to gain more insight into potential mechanisms. METHODS: Subjects with and without CVD were included (N = 398. Ery-apoB was measured on fresh whole blood samples using flow cytometry. Subjects with ery-apoB levels ≤ 0.20 a.u. were considered deficient. Carotid intima media thickness (CIMT was determined as a measure of (subclinical atherosclerosis. RESULTS: Mean ery-apoB value was 23.2% lower in subjects with increased CIMT (0.80 ± 0.09 mm, N = 140 compared to subjects with a normal CIMT (0.57 ± 0.08 mm, N = 258 (P = 0.007, adjusted P<0.001. CIMT and ery-apoB were inversely correlated (Spearman's r: -0.116, P = 0.021. A total of 55 subjects (13.6% were considered ery-apoB deficient, which was associated with a medical history of CVD (OR: 1.86, 95% CI 1.04-3.33; adjusted OR: 1.55; 95% CI 0.85-2.82. Discontinuation of statins in 54 subjects did not influence ery-apoB values despite a 58.4% increase in serum apolipoprotein B. Subjects with blood group O had significantly higher ery-apoB values (1.56 ± 0.94 a.u. when compared to subjects with blood group A (0.89 ± 1.15 a.u, blood group B (0.73 ± 0.1.12 a.u. or blood group AB (0.69 ± 0.69 a.u. (P-ANOVA = 0.002. CONCLUSION: Absence or very low values of ery-apoB are associated with clinical and subclinical atherosclerosis. While serum apolipoprotein B is not associated with ery-apoB, the ABO blood group seems to be a significant determinant.

  7. Inhibition of Endoplasmic Reticulum Stress and Atherosclerosis by 2-Aminopurine in Apolipoprotein E-Deficient Mice

    OpenAIRE

    Emmanuel Okoro; Zhong Mao Guo; Dong Fang Wu; Dezhi Yang; Lichun Zhou; Hong Yang

    2013-01-01

    We previously reported that the apolipoprotein (apo) B48-carrying lipoproteins obtained from apoE knockout (apoE −/− ) mice, so called E−/B48 lipoproteins, transformed mouse macrophages into foam cells and enhanced the phosphorylation of eukaryotic translation initiation factor 2 α (eIF-2 α ). Furthermore, the eIF-2 α phosphorylation inhibitor, 2-aminopurine (2-AP), attenuated E−/B48 lipoprotein-induced foam cell formation. The present report studied the effect of 2-AP on atherosclerosis in a...

  8. Apolipoprotein E gene and age-related macular degeneration in a Chinese population

    OpenAIRE

    Sun, Erdan; Lim, Apiradee; Liu, Xipu; Snellingen, Torkel; Wang, Ningli; Liu, Ningpu

    2011-01-01

    Purpose To examine the association between apolipoprotein E (APOE) polymorphisms and age-related macular degeneration (AMD) in a Chinese population. Methods The study consisted of 712 subjects, including 201 controls, 363 cases with early AMD, and 148 cases with exudative AMD. Genomic DNA was extracted from venous blood leukocytes. Common allelic variants of APOE (ε2, ε3, and ε4) were analyzed by PCR and direct sequencing. Results APOE ε3ε3 was the most frequent genotype, with a frequency of ...

  9. Apolipoprotein E genotypes do not influence the age of onset in Huntington's disease

    OpenAIRE

    Saft, C.; Andrich, J; Brune, N; Gencik, M; Kraus, P; Przuntek, H; Epplen, J

    2004-01-01

    Objective: The ε4 allele of the apolipoprotein E (ApoE) gene has been defined as a critical factor for early onset neurodegeneration in Pick's, Parkinson's, and Alzheimer's disease. Unexpectedly, the ε4 allele appeared to delay the age of onset in Huntington's disease (HD) patients. Furthermore, sex specific effects were reported on earlier age of onset due to the ApoE ε2ε3 genotype in males with HD. The age of onset of HD is known to be negatively correlated with increasing lengths of pathog...

  10. Apolipoprotein E allele-dependent pathogenesis: A model for age-related retinal degeneration

    OpenAIRE

    Malek, G; Johnson, L V; Mace, B E; Saloupis, P.; Schmechel, D E; Rickman, D. W.; Toth, C. A.; Sullivan, P. M.; Rickman, C. Bowes

    2005-01-01

    Age-related macular degeneration (AMD) is a late-onset, multifactorial, neurodegenerative disease of the retina and the leading cause of irreversible vision loss in the elderly in the Western world. We describe here a murine model that combines three known AMD risk factors: advanced age, high fat cholesterol-rich (HF-C) diet, and apolipoprotein E (apoE) genotype. Eyes of aged, targeted replacement mice expressing human apoE2, apoE3, or apoE4 and maintained on a HF-C diet show apoE isoform-dep...

  11. The allelic modulation of apolipoprotein E expression by oestrogen: potential relevance for Alzheimer's disease

    OpenAIRE

    Lambert, J; Coyle, N; Lendon, C

    2004-01-01

    Background: The ε4 allele of the apolipoprotein E (APOE) gene is a major genetic risk factor for Alzheimer's disease but appears to be associated with greater risk in women than in men. Some studies suggest that the level of APOE may of its own modulate the risk for Alzheimer's disease. Sex differences and an apparent benefit of oestrogen therapy suggest a role for oestrogen. APOE expression is influenced by oestrogen and oestrogen therapy may not benefit women bearing an APOE ε4 allele. Thes...

  12. Solubility modeling of refrigerant/lubricant mixtures

    Energy Technology Data Exchange (ETDEWEB)

    Michels, H.H.; Sienel, T.H.

    1996-12-31

    A general model for predicting the solubility properties of refrigerant/lubricant mixtures has been developed based on applicable theory for the excess Gibbs energy of non-ideal solutions. In our approach, flexible thermodynamic forms are chosen to describe the properties of both the gas and liquid phases of refrigerant/lubricant mixtures. After an extensive study of models for describing non-ideal liquid effects, the Wohl-suffix equations, which have been extensively utilized in the analysis of hydrocarbon mixtures, have been developed into a general form applicable to mixtures where one component is a POE lubricant. In the present study we have analyzed several POEs where structural and thermophysical property data were available. Data were also collected from several sources on the solubility of refrigerant/lubricant binary pairs. We have developed a computer code (NISC), based on the Wohl model, that predicts dew point or bubble point conditions over a wide range of composition and temperature. Our present analysis covers mixtures containing up to three refrigerant molecules and one lubricant. The present code can be used to analyze the properties of R-410a and R-407c in mixtures with a POE lubricant. Comparisons with other models, such as the Wilson or modified Wilson equations, indicate that the Wohl-suffix equations yield more reliable predictions for HFC/POE mixtures.

  13. Apolipoprotein E4 influences growth and cognitive responses to micronutrient supplementation in shantytown children from northeast Brazil

    Directory of Open Access Journals (Sweden)

    Sumeet S Mitter

    2012-01-01

    Full Text Available OBJECTIVE: Apolipoprotein E4 may benefit children during early periods of life when the body is challenged by infection and nutritional decline. We examined whether apolipoprotein E4 affects intestinal barrier function, improving short-term growth and long-term cognitive outcomes in Brazilian shantytown children. METHODS: A total of 213 Brazilian shantytown children with below-median height-for-age z-scores (HAZ received 200,000 IU of retinol (every four months, zinc (40 mg twice weekly, or both for one year, with half of each group receiving glutamine supplementation for 10 days. Height-for-age z-scores, weight-for-age z-scores, weight-forheight z-scores, and lactulose:mannitol ratios were assessed during the initial four months of treatment. An average of four years (range 1.4-6.6 later, the children underwent cognitive testing to evaluate non-verbal intelligence, coding, verbal fluency, verbal learning, and delayed verbal learning. Apolipoprotein E4 carriage was determined by PCR analysis for 144 children. RESULTS: Thirty-seven children were apolipoprotein E4(+, with an allele frequency of 13.9%. Significant associations were found for vitamin A and glutamine with intestinal barrier function. Apolipoprotein E4(+ children receiving glutamine presented significant positive Pearson correlations between the change in height-for-age z-scores over four months and delayed verbal learning, along with correlated changes over the same period in weight-for-age z-scores and weight-for-height z-scores associated with non-verbal intelligence quotients. There was a significant correlation between vitamin A supplementation of apolipoprotein E4(+ children and improved delta lactulose/mannitol. Apolipoprotein E4(- children, regardless of intervention, exhibited negative Pearson correlations between the change in lactulose-to-mannitol ratio over four months and verbal learning and non-verbal intelligence. CONCLUSIONS: During development, apolipoprotein E4 may

  14. Apolipoprotein B-containing lipoprotein particle assembly: Lipid capacity of the nascent lipoprotein particle

    Energy Technology Data Exchange (ETDEWEB)

    Manchekar, Medha; Forte, Trudy M.; Datta, Geeta; Richardson, Paul E.; Segrest, Jere P.; Dashti, Nassrin

    2003-12-01

    We previously proposed that the N-terminal 1000 residue {beta}{alpha}{sub 1} domain of apolipoprotein B (apoB) forms a bulk lipid pocket homologous to that of lamprey lipovitellin (LV). In support of this ''lipid pocket'' hypothesis, apoB:1000 (residues 1-1000) was shown to be secreted by a stable transformant of McA-RH7777 cells as a monodisperse particle with HDL{sub 3} density and Stokes diameter of 112 {angstrom}. In contrast, apoB:931 (residues 1-931), missing only 69 residues of the sequence homologous to LV, was secreted as a particle considerably more dense than HDL with Stokes diameter of 110 {angstrom}. The purpose of the present study was to determine the stoichiometry of the lipid component of the apoB:931 and apoB:1000 particles. This was accomplished by metabolic labeling of cells with either [{sup 14}C]oleic acid or [{sup 3}H]glycerol followed by immunoprecipitation (IP) or nondenaturing gradient gel electrophoresis (NDGGE) of secreted lipoproteins and by immunoaffinity chromatography of secreted unlabeled lipoproteins. The [{sup 3}H]-labeled apoB:1000-containing particles, isolated by NDGGE, contained 50 phospholipids (PL) and 11 triacylglycerols (TAG) molecules per particle. In contrast, apoB:931-containing particles contained only a few molecules of PL and were devoid of TAG. The unlabeled apoB:1000-containing particles isolated by immunoaffinity chromatography and analyzed for lipid mass, contained 56 PL, 8 TAG, and 7 cholesteryl ester molecules per particle. The surface:core lipid ratio of apoB:1000-containing particles was approximately 4:1 and was not affected by incubation of cells with oleate. Although small amounts of microsomal triglyceride transfer protein (MTP) were associated with apoB:1000-containing particles, it never approached a 1:1 molar ratio of MTP to apoB. These results support a model in which: (1) the first 1000 amino acid residues of apoB are competent to complete the ''lipid pocket

  15. Solubility of fluorides of alkaline earth metals and some rare earths in anhydrous trifluoroacetic acid

    International Nuclear Information System (INIS)

    Solubility of fluorides of alkaline earth and some rare earth metals in anhydrous trifluoroacetic acid is studied. For each type of fluoride solubility depends on the ionic radius of the cation. Solubility of fluorides of alkaline earth metals grows from magnesium to barium. All the fluorides in anhydrous trifluoroacetic acid form solvates. Solvates of strontium and scandium fluorides are shown to decompose at 110 and 150 deg C respectively

  16. Water-soluble polymers for recovery of metal ions from aqueous streams

    Science.gov (United States)

    Smith, Barbara F.; Robison, Thomas W.

    1998-01-01

    A process of selectively separating a target metal contained in an aqueous solution by contacting the aqueous solution containing a target metal with an aqueous solution including a water-soluble polymer capable of binding with the target metal for sufficient time whereby a water-soluble polymer-target metal complex is formed, and, separating the solution including the water-soluble polymer-target metal complex from the solution is disclosed.

  17. Soluble CD14 in periodontitis

    NARCIS (Netherlands)

    E.A. Nicu; M.L. Laine; S.A. Morre; U. van der Velden; B.G. Loos

    2009-01-01

    Lipopolysaccharide (LPS) binds to soluble (s)CD14. We investigated which factors contribute to variations in sCD14 levels in periodontitis, a chronic infectious disease of tooth-supporting tissues associated with endotoxemia and leading to inflammation and subsequently loss of teeth. The sCD14 level

  18. Teor de nitrogênio solúvel na água de erosão hídrica em cultura de aveia e ervilhaca em três formas de semeadura Soluble nitrogen content in runoff water from three forms of oat and vetch sowing

    Directory of Open Access Journals (Sweden)

    Fabrício Tondello Barbosa

    2009-04-01

    water contamination. Soluble N in the runoff is biologically available and contributes to eutrophication of the water and, depending on the form and content in the water, may be toxic to aquatic organisms. In order to evaluate the N content in the form of ammonium and nitrate in the runoff water, an experiment was conducted with simulated rainfall from April to November 2006, on an Inceptisol under conventional tillage. A combination of three factors was studied: crop type, sowing form and simulated rainfall test. The crops black oat (Avena strigosa and common vetch (Vicia sativa were studied, as well as the sowing forms: mechanical, along rows in slope direction; broadcast by hand; and mechanized along contour lines; and five simulated rainfall tests, at a constant and planned intensity of 64 mm h-1 and rainfall duration of 1 h. The first four rainfall tests were applied during the crop cycles and the fifth on the crop residues maintained on the soil surface. Nitrogen application to oat as urea cover dressing, immediately before rainfall test 1, resulted in a higher N-NH4+ content in the runoff water from oat than from vetch, exceeding the acceptable level for the aquatic community. Under rainfall on residues in decomposition on the soil surface, the content of soluble N-NO3- in the runoff water was higher in the crops of contour sowing than of slope sowing. The contents of soluble N-NH4+ and N-NO3- in the runoff water decreased from the beginning to the end of the crop cycles, but increased in the rainfall test on vetch mulch, to higher values than in the treatment with oat residue.

  19. Solubility of crystalline thorium dioxide

    International Nuclear Information System (INIS)

    The solubility of thorium oxides of different crystallinity is investigated at 25 C by different experimental approaches. The dissolution of bulk crystalline ThO2(cr) is a very slow process and the Th(IV) concentrations measured after one year at pH 1-3 in 0.1 and 0.5 M HCl-NaCl solutions do not represent equilibrium data. Coulometric titration of thorium nitrate solutions in the low pH range of 1.5-2.5 leads to the formation of microcrystalline ThO2.xH2O(mcr) particles which subsequently agglomerate to a precipitate. The solubility of this solid, in equilibrium with Th4+(aq), is measured from the oversaturation direction. The solubility product is determined to be log K'sp = -49.9±0.4 in 0.5 M NaCl corresponding to log Kspo = -53.2±0.4 (converted to I = 0 with the SIT). It is close to the thermochemical value for ThO2(cr) and about 6 orders of magnitude lower than that of X-ray amorphous Th(IV) hydroxide or hydrous oxide. The differences in the solubility products are discussed with regard to the particle size and compared with analogous data for U(IV), Np(IV) and Pu(IV). Above the threshold of hydrolysis of Th4+ at pH > 2.5, the dissolution of microcrystalline ThO2.xH2O(mcr) is found to be irreversible. In near-neutral to alkaline solutions, the measured thorium concentrations approach those of amorphous Th(OH)4(am). Similar results are obtained with crystalline ThO2(cr) in 0.5 M NaCl-NaOH solutions. The solubility is not controlled by the bulk crystalline solid but by amorphous fractions on the surface. (orig.)

  20. CARVEDILOL SOLUBILITY ENHANCEMENT BY INCLUSION COMPLEXATION AND SOLID DISPERSION: REVIEW

    Directory of Open Access Journals (Sweden)

    Abdelmoumin Zoghbi

    2015-03-01

    Full Text Available Carvedilol is an antihypertensive drug characterized by itslow aqueous solubility, a major obstacle in drug formulation development to improve its bioavailability. To overcome problem of poor aqueous solubility of Carvedilol, various approaches have been investigated including physical and chemical modifications of the drug. Most of these investigations focused onmodifying the drug structurefrom crystalline insoluble form to amorphous soluble form, reducing drug particle size to provide high surface area subjected to solvent, enhancing porosity degree, and improving wettability. A wide variety of polymers was used in order to achieve these goals. Carvedilol inclusion complex with Cyclodextrin (CD and derivatives, solid dispersion with water-soluble carriers such as Polyvinylpyrrolidone K-30 (PVP K-30, Gelucire 50/13, porous silica (Sylysia 350, and Soluprus® (polyvinyl caprolactam–polyvinyl acetate–polyethylene glycol graft copolymer were previously investigated using different preparation methods such asSolvent evaporation method, fusion method, kneading method, and spray drying method. Analytical tests wereconducted to characterize these preparations. FTIR, SEM, DSC, XRD are among the most commonly used. The present paper summarizes different drug-carrier combinations used for solubility, dissolution rate and/or bioavailability enhancement of Carvedilol, with emphases on the preparation methods of Carvedilol inclusion complex and solid dispersions, and different tests used for their characterization.

  1. Plutonium Solubility In Simulated Savannah River Site Waste Solutions

    International Nuclear Information System (INIS)

    To address the accelerated disposition of the supernate and salt portions of Savannah River Site (SRS) high level waste (HLW), solubility experiments were performed to develop a predictive capability for plutonium (Pu) solubility. A statistically designed experiment was used to measure the solubility of Pu in simulated solutions with salt concentrations and temperatures which bounded those observed in SRS HLW solutions. Constituents of the simulated waste solutions included: hydroxide (OH-), aluminate (Al(OH)4-), sulfate (SO42-), carbonate (CO32-), nitrate (NO3-), and nitrite (NO2-) anions. Each anion was added to the waste solution in the sodium form. The solubilities were measured at 25 and 80 C. Five sets of samples were analyzed over a six month period and a partial sample set was analyzed after nominally fifteen months of equilibration. No discernable time dependence of the measured Pu concentrations was observed except for two salt solutions equilibrated at 80 C which contained OH- concentrations >5 mol/L. In these solutions, the Pu solubility increased with time. This observation was attributed to the air oxidation of a portion of the Pu from Pu(IV) to the more soluble Pu(V) or Pu(VI) valence states. A data driven approach was subsequently used to develop a modified response surface model for Pu solubility. Solubility data from this study and historical data from the literature were used to fit the model. The model predicted the Pu solubility of the solutions from this study within the 95% confidence interval for individual predictions and the analysis of variance indicated no statistically significant lack of fit. The Savannah River National Laboratory (SRNL) model was compared with predicted values from the Aqueous Electrolyte (AQ) model developed by OLI Systems, Inc. and a solubility prediction equation developed by Delegard and Gallagher for Hanford tank waste. The agreement between measured or values predicted by the SRNL model and values predicted by

  2. The study of relationship between the quantity of soluble forms of human leukocyte antigen - G ( sHLA - G ), tumor necrosis factor- α and recurrent spontaneous abortion%血清TNF-α及sHLA-G水平与习惯性流产的关联性分析

    Institute of Scientific and Technical Information of China (English)

    刘学云; 王霞

    2012-01-01

    Objective: To determine the levels of Soluble Forms of Human Leukocyte Antigen -G (sHLA-G), Tumor Necrosis Factor - a in human serum of patients with recurrent spontaneous abortion to explore relationship between sHLA - G and TNF - α and recurrent spontaneous abortion. Methods; A hundred women in early pregnancy were selected and divided into two groups; 58 in the RSA group and 42 in the control group who had at least one live birth without history of spontaneous abortion. The level of sHLA - G and TNF - α were detected by Enzyme - Linked Immuno Sorbent Assay. Results; The levels of Soluble Forms of Human Leukocyte Antigen-G (sHLA -G) in human serum of patients with recurrent spontaneous abortion were significantly decreased than those of normal early pregnant women. It had a significant difference (P < 0.05) , while the levels of Tumor Necrosis Factor - α by peripheral blood mononuclear cells were significantly higher. It reached a significant difference (P < 0.05). Conclusion; Both levels of sHLA -G and TNF - α are correlated with the results of pregnancy. The lack of sHLA - G and the excess of TNF - α in human serum may lead to the recurrent spontaneous abortion.%目的 通过定量方法研究测定习惯性流产(RSA)患者血清中的肿瘤坏死因子-α(TNF-α)及可溶性人白细胞抗原G(sHLA - G)的水平,探讨TNF -α及sHLA-G与习惯性流产有无相关性.方法 选择早期妊娠孕妇100例,正常对照组:无自然流产史早期妊娠健康孕妇42例,RSA组:有习惯性流产史二次及二次以上的早期妊娠妇女58例,采用酶联免疫(ELISA)法定量检测两组样本血清中TNF-α及sHLA-G的水平.结果 RSA组血清中外周血淋巴细胞的TNF-α表达水平则明显高于正常妊娠组差异有显著性(p<0.05),而sHLA -G的表达水平明显低于正常对照组,差异有显著性(P<0.05).结论 妊娠早期孕妇血清中TNF-α及sHLA-G与妊娠成功有直接关系,TNF-α升高及sHLA-G降低可能会导致习惯性流产的发生.

  3. Plasma Apolipoprotein-M (ApoM Response to a Circuit Resistance Training Program

    Directory of Open Access Journals (Sweden)

    Abbass Ghanbari-Niaki

    2013-12-01

    Full Text Available Apolipoprotein M (Apo-M is a human novel protein of apolipoprotein classes and highly expressed in liver and kidney tissues. ApoM is mainly associated with high-density lipoprotein (HDL, and act as a chaperone for sphingosine-1-phosphate (S1P, promotes mobilization of cellular cholesterol, formation of larger-size of pre β-HDL, and a new biomarker in sepsis. The level of apoM in plasma/serum is affected by several factors such as pregnancy, hyperglycemia, plasma leptin concentration, obesity, diabetes, insulin concentration and physical exercise. It has been shown that the level of plasma ApoM was significantly lower in strenuous exercise group when compared with the non-exercise group. In the present study a reduction was observed after the 4 weeks of circuit resistance training program. This reduction might be due to a decrease in ApoM expression in liver and kidney or an increase in ApoM clearance, degradation and excretion in urine.

  4. Familial defective apolipoprotein B-100: low density lipoproteins with abnormal receptor binding

    International Nuclear Information System (INIS)

    Previous in vivo turnover studies suggested that retarded clearance of low density lipoproteins (LDL) from the plasma of some hypercholesterolemic patients is due to LDL with defective receptor binding. The present study examined this postulate directly by receptor binding experiments. The LDL from a hypercholesterolemic patient (G.R.) displayed a reduced ability to bind to the LDL receptors on normal human fibroblasts. The G.R. LDL possessed 32% of normal receptor binding activity. Likewise, the G.R. LDL were much less effective than normal LDL in competing with 125I-labeled normal LDL for cellular uptake and degradation and in stimulating intracellular cholesteryl ester synthesis. The defect in LDL binding appears to be due to a genetic abnormality of apolipoprotein B-100: two brothers of the proband possess LDL defective in receptor binding, whereas a third brother and the proband's son have normally binding LDL. Further, the defect in receptor binding does not appear to be associated wit an abnormal lipid composition or structure of the LDL. Normal and abnormal LDL subpopulations were partially separated from plasma of two subjects by density-gradient ultracentrifugation, a finding consistent with the presence of a normal and a mutant allele. The affected family members appear to be heterozygous for this disorder, which has been designated familial defective apolipoprotein B-100. These studies indicate that the defective receptor binding results in inefficient clearance of LDL and the hypercholesterolemia observed in these patients

  5. Rapid radioimmunoassay of human apolipoproteins C-II and C-III

    Energy Technology Data Exchange (ETDEWEB)

    Gustafson, S.; Oestlund-Lindqvist, A.M.; Vessby, B. (Uppsala Univ. (Sweden))

    1984-06-01

    Apolipoprotein (apo) C-II is an activator of lipoprotein lipase, while apo C-III has the ability to inhibit apo C-II activated lipolysis. In order to study further the relationship between lipoprotein lipase mediated hydrolysis and the serum concentrations of apo C-II and apo C-III radioimmunoassays for these apolipoproteins have been developed. Formalin-treated Staphylococcus aureus Cowan I was used for immunoprecipitation and were shown to give rapid uptake of immune complexes that could easily be harvested by centrifugation. The assays were shown to be sensitive (10 ..mu..g/1), specific, precise (inter- and intra-assay coefficients of variation below 10%), rapid (completed in less than 6 h) and simple to perform. Delipidation of serum and lipoproteins had no effect on the results, indicating that the immunologically active sites of apo C-II and apo C-III are exposed to the aqueous environment under assay conditions. Serum apo C-II and apo C-III levels of normolipidaemic subjects were approximately 25 mg/1 and 110 mg/1, respectively. Highly significant positive correlations were found between VLDL apo C-II and VLDL apo C-III, respectively, and VLDL triglycerides, VLDL cholesterol and total serum TG. There was also a highly significant correlation between the HDL cholesterol concentration and the HDL apo C-III concentration.

  6. The apolipoprotein A-I mimetic peptide, ETC-642, reduces chronic vascular inflammation in the rabbit

    Science.gov (United States)

    2011-01-01

    Background High-density lipoproteins (HDL) and their main apolipoprotein, apoA-I, exhibit anti-inflammatory properties. The development of peptides that mimic HDL apolipoproteins offers a promising strategy to reduce inflammatory disease. This study aimed to compare the anti-inflammatory effects of ETC-642, an apoA-I mimetic peptide, with that of discoidal reconstituted HDL (rHDL), consisting of full-length apoA-I complexed with phosphatidylcholine, in rabbits with chronic vascular inflammation. Results New Zealand White rabbits (n = 10/group) were placed on chow supplemented with 0.2% (w/w) cholesterol for 6-weeks. The animals received two infusions of saline, rHDL (8 mg/kg apoA-I) or ETC-642 (30 mg/kg peptide) on the third and fifth days of the final week. The infusions of rHDL and ETC-642 were able to significantly reduce cholesterol-induced expression of intracellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in the thoracic aorta (p ETC-642 treated rabbits were more effective at inhibiting the TNF-α-induced increase in ICAM-1, VCAM-1 and p65 than HDL isolated from saline treated rabbits (p ETC-642 causes anti-inflammatory effects that are comparable to rHDL in an animal model of chronic vascular inflammation and highlights that apoA-I mimetic peptides present a viable strategy for the treatment of inflammatory disease. PMID:22128776

  7. Association of apolipoprotein E polymorphism in late-onset Alzheimer's disease and vascular dementia in Brazilians

    Directory of Open Access Journals (Sweden)

    D.R.S. Souza

    2003-07-01

    Full Text Available The genetic basis for dementias is complex. A common polymorphism in the apolipoprotein E (APOE gene is considered to be the major risk factor in families with sporadic and late-onset Alzheimer's disease as well as in the general population. The distribution of alleles and genotypes of the APOE gene in late-onset Alzheimer's disease (N = 68, other late-life dementias (N = 39, and in cognitively normal controls (N = 58 was determined, as also was the risk for Alzheimer's disease associated with the epsilon4 allele. Peripheral blood samples were obtained from a total of 165 individuals living in Brazil aged 65-82 years. Genomic DNA was amplified by the polymerase chain reaction and the products were digested with HhaI restriction enzyme. APOE epsilon2 frequency was considerably lower in the Alzheimer's disease group (1%, and the epsilon3 allele and epsilon3/epsilon3 genotype frequencies were higher in the controls (84 and 72%, respectively as were the epsilon4 allele and epsilon3/epsilon4 genotype frequencies in Alzheimer's disease (25 and 41%, respectively. The higher frequency of the epsilon4 allele in Alzheimer's disease confirmed its role as a risk factor, while epsilon2 provided a weak protection against development of the disease. However, in view of the unexpectedly low frequency of the epsilon4 allele, additional analyses in a more varied Brazilian sample are needed to clarify the real contribution of apolipoprotein E to the development of Alzheimer's disease in this population.

  8. One-pot synthesis and control of aqueous soluble and organic soluble carbon dots from a designable waterborne polyurethane emulsion

    Science.gov (United States)

    Gu, Jiangjiang; Hu, Donghua; Huang, Jin; Huang, Xin; Zhang, Qiuhong; Jia, Xudong; Xi, Kai

    2016-02-01

    Carbon dots (CDs) have a wide range of applications and have drawn great interest in the recent decade. The fabrication and control of CDs with different solubilities are still urgent problems for their practical use. In this paper, aqueous soluble and organic soluble CDs (ACDs, OCDs) were produced by one-pot hydrothermal treatment of a designable waterborne polyurethane (WPU) emulsion. The difference in the solubility and fluorescence of these two kinds of CDs was attributed to the various functional groups on the surface, which were derived from the different segment fragments formed by hydrothermal treatment of a block polymer. It was found that the yields of the ACDs and OCDs could be regulated by means of selecting different soft segments in WPU. The more hydrophobic soft segments could result in an increase of the OCDs and a decrease of the ACDs. While the soft segments were hydrophilic or hydrolysable under hydrothermal conditions, only ACDs were obtained. The ACDs had good fluorescence and showed low cytotoxicity for use in multicolour bio-imaging. The OCDs processed good solubility in a wide range of organic solvents and were suitable for preparing fluorescent composite films with polymers.Carbon dots (CDs) have a wide range of applications and have drawn great interest in the recent decade. The fabrication and control of CDs with different solubilities are still urgent problems for their practical use. In this paper, aqueous soluble and organic soluble CDs (ACDs, OCDs) were produced by one-pot hydrothermal treatment of a designable waterborne polyurethane (WPU) emulsion. The difference in the solubility and fluorescence of these two kinds of CDs was attributed to the various functional groups on the surface, which were derived from the different segment fragments formed by hydrothermal treatment of a block polymer. It was found that the yields of the ACDs and OCDs could be regulated by means of selecting different soft segments in WPU. The more

  9. The concentration of apolipoprotein A-I decreases during experimentally induced acute-phase processes in pigs

    DEFF Research Database (Denmark)

    Carpintero, R.; Pineiro, M.; Andres, M.;

    2005-01-01

    In this work, apolipoprotein A-I (ApoA-I) was purified from pig sera. The responses of this protein after sterile inflammation and in animals infected with Actinobacillus pleuropneumoniae or Streptococcus suis were investigated. Decreases in the concentrations of ApoA-I, two to five times lower...

  10. 9-CIS-RETINOIC ACID REPRESSES ESTROGEN-INDUCED EXPRESSION OF THE VERY-LOW-DENSITY APOLIPOPROTEIN-II GENE

    NARCIS (Netherlands)

    SCHIPPERS, IJ; KLOPPENBURG, M; SNIPPE, L; AB, G

    1994-01-01

    The chicken very low density apolipoprotein II (apoVLDLII) gene is estrogen-inducible and specifically expressed in liver. We examined the possible involvement of the retinoid X receptor (RXR) and its ligand 9-cis-retinoic acid (9-cis-RA) in the activation of the apoVLDLII promoter. We first concent

  11. Apolipoprotein E genotype status affects habitual human blood mononuclear cell gene expression and its response to fish oil intervention

    NARCIS (Netherlands)

    Matualatupauw, J.C.; Radonjic, M.; Nieuwerth-van de Rest, O.; Groot, de C.P.G.M.; Geleijnse, J.M.; Müller, M.R.; Afman, L.A.

    2016-01-01

    Scope
    People who carry the apolipoprotein E4 (APOE4) single nucleotide polymorphism have an increased risk of cardiovascular disease (CVD). Fish-oil supplementation may help in the prevention of CVD, though interindividual differences in the response to n-3 PUFAs have been observed. We aimed to

  12. Effect of Mediterranean diet with and without weight loss on apolipoprotein B100 metabolism in men with metabolic syndrome

    Science.gov (United States)

    The objective of this study was to assess the effect of a Mediterranean diet (MedDiet) with and without weight loss (WL) on apolipoprotein B100 (apoB100) metabolism in men with metabolic syndrome. The diet of 19 men with metabolic syndrome (age, 24–62 years) was first standardized to a North America...

  13. The apolipoprotein E epsilon4-allele and antihypertensive treatment are associated with increased risk of cerebral MRI white matter hyperintensities

    DEFF Research Database (Denmark)

    Høgh, P; Garde, Ellen; Mortensen, Erik Lykke;

    2007-01-01

    OBJECTIVE: Apolipoprotein E-epsilon4 (APOE-epsilon4) is a potential risk factor for cerebral vascular disease. The aim of the present study was to examine the relative importance of APOE-epsilon4 and other relevant risk factors for the extent of cerebral white matter hyperintensity (WMH) in a...

  14. Sorption, Diffusion and Solubility Databases for Performance Assessment

    International Nuclear Information System (INIS)

    This report presents a deterministic and probabilistic databases for application in Performance Assessment of a high-level radioactive waste disposal. This work includes a theoretical description of sorption, diffusion and solubility phenomena of radionuclides in geological media. The report presents and compares the databases of different nuclear wastes management agencies, describes the materials in the Spanish reference system, and the results of sorption diffusion and solubility in this system, with both the deterministic and probabilistic approximation. The probabilistic approximation is presented in the form of probability density functions (pdf). (Author) 52 refs

  15. Purification and characterization of a soluble calnexin from human placenta

    DEFF Research Database (Denmark)

    Olsen, Dorthe T; Peng, Li; Træholt, Sofie D;

    2013-01-01

    Calreticulin (Crt) and calnexin (Cnx) are homologous endoplasmic reticulum (ER) chaperones involved in protein folding and quality control. Crt is a soluble ER luminal Mr 46 kDa protein and Cnx is a Mr 67kDa ER membrane protein. During purification of Crt from human placenta a soluble form of Cnx...... extraction and initial purification steps were carried out in the presence of protease inhibitors, thus ruling out that the cleavage was an artefact of the isolation procedure. This indicates that sCnx may have a physiological chaperone function similar to that of Crt....

  16. Soluble and cell surface receptors for tumor necrosis factor

    DEFF Research Database (Denmark)

    Wallach, D; Engelmann, H; Nophar, Y;

    1991-01-01

    Tumor necrosis factor (TNF) initiates its multiple effects on cell function by binding at a high affinity to specific cell surface receptors. Two different molecular species of these receptors, which are expressed differentially in different cells, have been identified. The cDNAs of both receptors...... certain pathological situations. Release of the soluble receptors from the cells seems to occur by proteolytic cleavage of the cell surface forms and appears to be a way of down-regulating the cell response to TNF. Because of their ability to bind TNF, the soluble receptors exert an inhibitory effect on...

  17. Rocky core solubility in Jupiter and giant exoplanets

    CERN Document Server

    Wilson, Hugh F

    2011-01-01

    Gas giants are believed to form by the accretion of hydrogen-helium gas around an initial protocore of rock and ice. The question of whether the rocky parts of the core dissolve into the fluid H-He layers following formation has significant implications for planetary structure and evolution. Here we use ab initio calculations to study rock solubility in fluid hydrogen, choosing MgO as a representative example of planetary rocky materials, and find MgO to be highly soluble in H for temperatures in excess of approximately 10000 K, implying significant redistribution of rocky core material in Jupiter and larger exoplanets.

  18. Increasing the solubility characteristics of albendazole with dimethyl-beta-cyclodextrin.

    Science.gov (United States)

    Kata, M; Schauer, M

    1991-01-01

    Albendazole is a veterinary anthelminthic drug with excellent effect. Since it is only slightly soluble in water, it is processed in a suspension dosage form as a drench. The solubility and bioavailability of the pharmacon were successfully increased with cyclodextrin derivatives. PMID:1872189

  19. Collaborative form(s)

    DEFF Research Database (Denmark)

    Gunn, Wendy

    Gunn asks us to consider beauty as collaborative forms of action generated by moving between design by means of anthropology and anthropology by means of design. Specifically, she gives focus to play-like reflexions on practices of designing energy products, systems and infrastructure. Design...... anthropology engages groups of people within collaborative, interdisciplinary, inter-organizational design processes and co-analytic activities vs. the individual anthropologist conducting studies of people. In doing anthropology by means of design as Gatt and Ingold (2013) have shown, design is considered the...... premise designing as a social process and can be understood as a material engagement and constructive critique involving participant observation....

  20. Near-field solubility studies

    International Nuclear Information System (INIS)

    Experimental determinations of the solubilities of americium, plutonium, neptunium, protactinium, thorium, radium, lead, tin, palladium and zirconium are reported. These elements have radioactive isotopes of concern in assessments of radioactive waste disposal. All measurements were made under the highly alkaline conditions typical of the near field of a radioactive waste repository which uses cementitious materials for many of the immobilisation matrices, the backfill and the engineered structures. Low redox potentials, typical of those resulting from the corrosion of iron and steel, were simulated for those elements having more than one accessible oxidation state. The dissolved concentrations of the elements were defined using ultrafiltration. In addition, the corrosion of iron and stainless steel was shown to generate low redox potentials in solution and the solubility of iron(II) at high pH was measured and found to be sufficient for it to act as a redox buffer with respect to neptunium and plutonium. (author)

  1. Solubility of ammonia in rainwater

    OpenAIRE

    G. P. Ayers; Gras, J. L.; Adriaansen, A.; Gillett, R. W.

    2011-01-01

    Partitioning of ammonia between the gaseous and rainwater phases has been investigated at theAustralian Baseline Air Pollution Station during in-situ experiments in which rainwater andammonia gas were sampled concurrently. The relationship between ammonia concentrations inthe gaseous and aqueous phases did not follow either traditional solubility theory based onHenry’s Law, or a recent modified theory that includes secondary equilibria between dissolvedammonia and carbon dioxide.DOI: 10.1111/...

  2. SOLUBILITY AND DISSOLUTION PROFILE STUDIES OF GLICLAZIDE IN PHARMACEUTICAL FORMULATIONS BY RP-HPLC

    OpenAIRE

    Narasimha Swamy Lakka; Nishant Goswami

    2012-01-01

    This study describes the solubility and dissolution profile of Gliclazide. The solubility study was evaluated by using the shake flask method. The dissolution study has been carried out in different buffers for Gliclazide solid dosage form and estimated by using the RP-HPLC technique. In the present study a dissolution medium was developed and selected on the basis of solubility data of Gliclazide at 37 °C. The solubility data revealed that pH 7.4 phosphate buffer (0.6375 mg/ml) shall be sui...

  3. Metabolism of apolipoproteins C-II, C-III, and B in hypertriglyceridemic men. Changes after heparin-induced lipolysis

    International Nuclear Information System (INIS)

    The C apolipoproteins are normally transferred to high density lipoproteins (HDL) after lipolysis of very low density lipoprotein (VLDL) triglyceride. In previous studies, a loss of plasma C apolipoproteins was documented after heparin-induced lipolysis in hypertriglyceridemic subjects. The present studies were designed to determine if this decline in plasma C apolipoproteins was due to their clearance with VLDL remnants. Five Type IV hypertriglyceridemic and two normal subjects were injected with 125I-VLDL and 131I-low density lipoproteins (LDL) to document kinetically an excess of VLDL apolipoprotein (apo) B flux relative to LDL apo B flux in the Type IV subjects. A mean of 46% VLDL apo B was cleared from the circulation, without conversion to intermediate density lipoprotein (IDL) or LDL. Heparin was then infused (9000 IU over 4 hours) to generate an excess of VLDL remnants that were not converted to IDL or LDL. VLDL triglyceride, apo B, and apo C concentrations fell at a similar rate. VLDL apo B declined by 42% (p less than 0.01). However, no increases were observed in IDL or LDL apo B in the Type IV subjects. This resulted in a 14% (p less than 0.01) decline in plasma apo B concentrations, indicating a clearance of VLDL remnants. VLDL apo C-II and C-III concentrations fell by 42% (p less than 0.025) and 52% (p less than 0.01), respectively. During the first 2.5 hours of infusion, they were almost quantitatively recovered in HDL. Thereafter, the C apolipoproteins declined in HDL during which time VLDL apo C concentrations continued to decline

  4. Metabolism of apolipoproteins C-II, C-III, and B in hypertriglyceridemic men. Changes after heparin-induced lipolysis

    Energy Technology Data Exchange (ETDEWEB)

    Huff, M.W.; Breckenridge, W.C.; Strong, W.L.; Wolfe, B.M.

    1988-09-01

    The C apolipoproteins are normally transferred to high density lipoproteins (HDL) after lipolysis of very low density lipoprotein (VLDL) triglyceride. In previous studies, a loss of plasma C apolipoproteins was documented after heparin-induced lipolysis in hypertriglyceridemic subjects. The present studies were designed to determine if this decline in plasma C apolipoproteins was due to their clearance with VLDL remnants. Five Type IV hypertriglyceridemic and two normal subjects were injected with 125I-VLDL and 131I-low density lipoproteins (LDL) to document kinetically an excess of VLDL apolipoprotein (apo) B flux relative to LDL apo B flux in the Type IV subjects. A mean of 46% VLDL apo B was cleared from the circulation, without conversion to intermediate density lipoprotein (IDL) or LDL. Heparin was then infused (9000 IU over 4 hours) to generate an excess of VLDL remnants that were not converted to IDL or LDL. VLDL triglyceride, apo B, and apo C concentrations fell at a similar rate. VLDL apo B declined by 42% (p less than 0.01). However, no increases were observed in IDL or LDL apo B in the Type IV subjects. This resulted in a 14% (p less than 0.01) decline in plasma apo B concentrations, indicating a clearance of VLDL remnants. VLDL apo C-II and C-III concentrations fell by 42% (p less than 0.025) and 52% (p less than 0.01), respectively. During the first 2.5 hours of infusion, they were almost quantitatively recovered in HDL. Thereafter, the C apolipoproteins declined in HDL during which time VLDL apo C concentrations continued to decline.

  5. The effects of pH and mixed solvent systems on the solubility of oxytetracycline.

    Science.gov (United States)

    Tongaree, S; Flanagan, D R; Poust, R I

    1999-01-01

    The solubility of oxytetracycline (OTC) in aqueous and mixed solvent systems was studied. The effects of pH and cosolvent composition on the solubility and apparent dissociation constants (pKa') of OTC were determined by a solubility method. The pKa' values of OTC in each mixed solvent system were estimated and used to generate expressions for predicting drug solubility in each cosolvent as a function of pH. Cosolvent systems of PEG 400, propylene glycol, glycerin, and 2-pyrrolidone were studied in the pH range of 2.5-9. Solubility results showed increased solubility with increased cosolvent concentration, especially in 2-pyrrolidone solvent systems. These results also showed that cosolvents enhanced drug solubility through either their effects on polarity of the solvent medium or complex formation with OTC. Aqueous and mixed solvent systems at lower pH values resulted in higher OTC solubilization because the drug existed primarily in its cationic form. A mass balance equation including all ionic species of OTC allowed for estimation of the intrinsic solubilities and pKa' values in each solvent system. pKa' values and intrinsic solubility of the OTC zwitterion increased with increasing cosolvent content. These parameters allowed prediction of drug solubility within the pH range and cosolvent concentrations used in this study. PMID:10578512

  6. Study on Mixed Solvency Concept in Formulation Development of Aqueous Injection of Poorly Water Soluble Drug

    Directory of Open Access Journals (Sweden)

    Shailendra Singh Solanki

    2013-01-01

    Full Text Available In the present investigation, mixed-solvency approach has been applied for the enhancement of aqueous solubility of a poorly water- soluble drug, zaltoprofen (selected as a model drug, by making blends (keeping total concentrations 40% w/v, constant of selected water-soluble substances from among the hydrotropes (urea, sodium benzoate, sodium citrate, nicotinamide; water-soluble solids (PEG-4000, PEG-6000; and co-solvents (propylene glycol, glycerine, PEG-200, PEG-400, PEG-600. Aqueous solubility of drug in case of selected blends (12 blends ranged from 9.091 ± 0.011 mg/ml–43.055 ± 0.14 mg/ml (as compared to the solubility in distilled water 0.072 ± 0.012 mg/ml. The enhancement in the solubility of drug in a mixed solvent containing 10% sodium citrate, 5% sodium benzoate and 25 % S cosolvent (25% S cosolvent contains PEG200, PEG 400, PEG600, Glycerine and Propylene glycol was more than 600 fold. This proved a synergistic enhancement in solubility of a poorly water-soluble drug due to mixed cosolvent effect. Each solubilized product was characterized by ultraviolet and infrared techniques. Various properties of solution such as pH, viscosity, specific gravity and surface tension were studied. The developed formulation was studied for physical and chemical stability. This mixed solvency shall prove definitely a boon for pharmaceutical industries for the development of dosage form of poorly water soluble drugs.

  7. Extraction and analysis of soluble inositol polyphosphates from yeast.

    Science.gov (United States)

    Azevedo, Cristina; Saiardi, Adolfo

    2006-01-01

    Soluble inositol polyphosphates are implicated in the regulation of many important cellular functions. This protocol to extract and separate inositol polyphosphates from Saccharomyces cerevisiae is divided into three steps: labeling of yeast, extraction of soluble inositol polyphosphates and chromatographic separation. Yeast cells are incubated with tritiated inositol, which is taken up and metabolized into different phosphorylated forms. Soluble inositol polyphosphates are then acid-extracted and fractionated by high-performance liquid chromatography. The radioactivity of each fraction is determined by scintillation counting. This highly sensitive and reproducible method allows the accurate detection of subtle changes in the inositol polyphosphate profile and takes less than 48 h. It can easily be applied to other systems and we have included two adaptations of the protocol, one optimized for mammalian cells and the other for Arabidopsis thaliana. PMID:17406485

  8. Enzymatic hydrolysis of phytate and effects on soluble oxalate concentration in foods.

    Science.gov (United States)

    Israr, Beenish; Frazier, Richard A; Gordon, Michael H

    2017-01-01

    Soluble oxalate in foods is major concern for kidney stone formers due to its tendency to increase urinary oxalate concentration. Phytate forms complexes with cations, which increases soluble oxalate by making cations unavailable to precipitate oxalate. Thus, in order to reduce soluble oxalate, bran samples (wheat, oat and barley) and bean samples (red kidney bean and white bean) were treated with phytase. Release of phosphate after phytate degradation and its association with calcium was determined. Phosphate concentration increased after application of phytase in all samples, but effect on soluble oxalate concentration varied. Wheat and oat bran showed significant reduction (P<0.05) in soluble oxalate compared to bean samples. Wheat bran, oat bran and white bean had a lower calcium:phosphate ratio than barley bran and red kidney beans. Correlation of the calcium:phosphate molar ratio with release of phosphate depends on concentration of calcium ions and this influences soluble oxalate concentration. PMID:27507467

  9. Apolipoprotein B-100 Hopkins (arginine4019 → tryptophan): A new apolipoprotein B-100 variant in a family with premature atherosclerosis and hyperapobetalipoproteinemia

    International Nuclear Information System (INIS)

    A 43-year-old woman with severe coronary artery disease and hyperapobetalipoproteinemia was heterozygous for an abnormal Msp I apolipoprotein B (APOB) gene fragment because of the absence of the Msp I site around codon 4046 in exon 29 of the APOB gene. Using the polymerase chain reaction technique, 134 base pairs containing the mutant Msp I site were amplified, cloned, and sequenced. The mutation was a C to T transition, substituting tryptophan for arginine at amino acid position 4019 of the mature ApoB-100 protein. Seven relatives of the proband has the same mutation, which has been called ApoB-100 Hopkins. Only three of seven relatives with the mutation had hyperapobetalipoproteinemia. Mutant low-density lipoprotein (LDL) was bound and degraded to a greater extent than normal LDL in cultured human fibroblasts. In conclusion, a new mutation, ApoB-100 Hopkins, was not linked to the hyperapobetalipoproteinemia phenotype, which also was segregating in this family. The increased affinity of this mutant LDL for the LDL receptor may be due to a specific effect of ApoB-100 Hopkins or to altered LDL size and composition

  10. Apolipoprotein B-100 Hopkins (arginine sub 4019 yields tryptophan): A new apolipoprotein B-100 variant in a family with premature atherosclerosis and hyperapobetalipoproteinemia

    Energy Technology Data Exchange (ETDEWEB)

    Ladias, J.A.A.; Kwiterovich, P.O. Jr.; Smith, H.H.; Miller, M.; Bachorik, P.S.; Antonarakis, S.E. (Johns Hopkins Univ. School of Medicine, Baltimore, MD (USA)); Forte, T. (Univ. of California, Los Angeles (USA)); Lusis, A.J. (Donner Laboratory, Berkeley, CA (USA))

    1989-10-13

    A 43-year-old woman with severe coronary artery disease and hyperapobetalipoproteinemia was heterozygous for an abnormal Msp I apolipoprotein B (APOB) gene fragment because of the absence of the Msp I site around codon 4046 in exon 29 of the APOB gene. Using the polymerase chain reaction technique, 134 base pairs containing the mutant Msp I site were amplified, cloned, and sequenced. The mutation was a C to T transition, substituting tryptophan for arginine at amino acid position 4019 of the mature ApoB-100 protein. Seven relatives of the proband has the same mutation, which has been called ApoB-100 Hopkins. Only three of seven relatives with the mutation had hyperapobetalipoproteinemia. Mutant low-density lipoprotein (LDL) was bound and degraded to a greater extent than normal LDL in cultured human fibroblasts. In conclusion, a new mutation, ApoB-100 Hopkins, was not linked to the hyperapobetalipoproteinemia phenotype, which also was segregating in this family. The increased affinity of this mutant LDL for the LDL receptor may be due to a specific effect of ApoB-100 Hopkins or to altered LDL size and composition.

  11. Zirconium isopropoxide solvate solubility in isopropanol

    International Nuclear Information System (INIS)

    Stability of zirconium isopropoxide solvate was measured in isopropanol at 20-70 deg. The solubility increased with temperature elevation and depended on product part history. Solubility enthalpy was equal to 9±1 kJ/mol in the range of stable values of solubility

  12. Solubility of simulated PWR primary circuit corrosion products

    International Nuclear Information System (INIS)

    The solubility behavior of non-stoichiometric nickel ferrites, nickel-cobalt ferrites, and magnetite, as model substances for the corrosion products (''crud'') formed in nuclear pressurized water reactors, was studied in a flow system in aqueous solutions of lithium hydroxide, boric acid, and hydrogen with pH, temperature, and hydrogen concentrations as parameters. Below the temperature region of 300 to 3300C, at hydrogen concentrations of 25 to 40 cm3/kg H2O as used during reactor operation, the solubility of nickel-cobalt ferrite is the same as that of Ni and Co/sub x/Fe/sub 3-x/O4 (x 3/kg of hydrogen, the equilibrium iron and nickel solubilities increase congruently down to about 1000C, in a manner consistent with the solubility of Fe3O4, but sharply decline at lower temperatures, apparently due to formation of a borated layer. A cooldown experiment on a time scale of a typical Westinghouse reactor shutdown, as well as static experiments carried out on various ferrite samples at 600C show that after addition of oxygen or peroxide evolution of nickel (and possibly cobalt) above the equilibrium solubility in hydrogen depends on the presence of dissociation products prior to oxidation. Thermodynamic calculations of various reduction and oxidative decomposition reactions for stoichiometric and non-stoichiometric nickel ferrite and cobalt ferrite are presented. Their significance to evolutions of nickel and cobalt on reactor shutdown is discussed. 30 refs., 38 figs., 34 tabs

  13. Solubility of plutonium(VI) carbonate in saline solutions

    Science.gov (United States)

    Reilly, Sean D.; Runde, Wolfgang; Neu, Mary P.

    2007-06-01

    Among the plutonium oxidation states found to form in the environment, mobile plutonium(VI) can exist under oxidizing conditions and in waters with high chloride content due to radiolysis effects. We are investigating the solubility and speciation of plutonium(VI) carbonate under conditions relevant to natural waters and brines such as those found near some geologic radioactive waste repositories. The solid Pu(VI) phase PuO 2CO 3(s) was prepared and its solubility was measured in NaCl and NaClO 4 solutions in a CO 2 atmosphere as a function of pH and ionic strength (0.1-5.6 m). The concentration of soluble plutonium in solution was calculated from spectroscopic data and liquid scintillation counting. Spectroscopic measurements also revealed the plutonium oxidation state. The apparent solubility product of PuO 2CO 3(s) was determined at selected electrolyte concentrations to be, log Ks,0 = -13.95 ± 0.07 (0.1 m NaCl), log Ks,0 = -14.07 ± 0.13 (5.6 m NaCl), and log Ks,0 = -15.26 ± 0.11 (5.6 m NaClO 4). Specific ion interaction theory was used to calculate the solubility product at zero ionic strength, logKs,0∘=-14.82±0.05.

  14. Apolipoprotein M

    DEFF Research Database (Denmark)

    Christoffersen, Christina; Nielsen, Lars Bo

    2013-01-01

    chaperone for S1P. S1P is a bioactive lipid with effects on angiogenesis, lymphocyte trafficking, endothelial cell migration, and inflammation. A drug targeting the S1P-system (fingolimod) is now used for treatment of multiple sclerosis. It improves the blood–brain barrier and inhibits migration of...

  15. Association of Serum Apolipoprotein B with the Increased Risk of Diabetes in Korean Men

    Science.gov (United States)

    Lim, Hyo Hee

    2016-01-01

    This study aimed to investigate the association of Apolipoprotein B (ApoB) with the risk of diabetes in Koreans. Korean men (n = 790, 40-79 years) who had been never diagnosed for diabetes before participating were enrolled. Subjects were categorized into normal fasting glucose (NFG, n = 519), impaired fasting glucose (IFG, n = 188) and newly-onset diabetes (n = 83) according to fasting glucose levels. Age was not significantly different among the subgroups. Mean values of BMI, waist circumference, Blood pressure(BP), triglyceride, non-HDL cholesterol were significantly higher in IFG or newly-onset diabetic subjects compared to NFG subjects. The levels of glucose, insulin, free fatty acid, insulin resistance and ApoB were highest in diabetic patients and lowest in NFG subjects. According to ApoB level, subjects were divided into two groups (high-ApoB group: ≥ 87.0 mg/dL vs. low-ApoB group: Korean men.

  16. Study on relationship of apolipoprotein E gene polymorphism and genetic susceptibility of stress urinary incontinence

    Institute of Scientific and Technical Information of China (English)

    Tong Jia-li; Lang Jing-he; Zhu lan

    2010-01-01

    Objective: To explore the relationship between apolipoprotein E (ApoE) gene polymorphism and susceptibility of stress urinary incontinence (SUI).Methods: ApoE genotypes were examined by polymerase chain reaction-restricted fragment length polymorphism (PCR-RFLP) technique in 99 patients with SUI and 101 asymptomatic controls. Results: The frequency of allele e3 of ApoE was slightly lower in patients with anatomic SUI than that in controls (79.44% vs. 81.68%), while the frequency of allele e4 of ApoE was slightly higher in patients with anatomic SUI than that in controls (10.00% vs. 9.90%). No significant difference was found in frequency of allele e3 or e4 between SUI patients and controls (χ2=0.523, P=0.770).Conclusion: The gene polymorphism of ApoE is not independently involved in the development of SUI.

  17. Sex, but not Apolipoprotein E Polymorphism, Differences in Spatial Performance in Young Adults.

    Science.gov (United States)

    Yasen, Alia L; Raber, Jacob; Miller, Jeremy K; Piper, Brian J

    2015-11-01

    The purpose of this study was to examine how sex and apolipoprotein E (APOE) genotype contribute to individual differences in spatial learning and memory. The associations of APOE genotype with neurocognitive function have been well studied among the elderly but less is known at earlier ages. Young adults (n = 169, 88 females) completed three neurocognitive tasks: mental rotation, spatial span, and Memory Island, a spatial navigation test. Males outperformed females on all three tasks: finding the hidden targets more quickly on Memory Island (Cohen's d = 0.62) and obtaining higher scores on mental rotation (d = 0.54) and spatial span (d = 0.37). In contrast, no significant effects of APOE were observed. The identified sex differences elaborate upon past literature documenting sexually dimorphic performance on specific neurobehavioral tasks. PMID:25750133

  18. Identification of liver receptor homolog-1 as a novel regulator of apolipoprotein AI gene transcription.

    Science.gov (United States)

    Delerive, Philippe; Galardi, Cristin M; Bisi, John E; Nicodeme, Edwige; Goodwin, Bryan

    2004-10-01

    The orphan nuclear receptor liver receptor homolog-1 (LRH-1) has been reported to play a role in bile acid biosynthesis and reverse cholesterol transport. In this study, we examined the role of LRH-1 in the regulation of the apolipoprotein AI (APOAI) gene. Using RNA interference and adenovirus-mediated overexpression, we show that LRH-1 directly regulates APOAI gene transcription. Transient transfection experiments and EMSAs revealed that LRH-1 directly regulates APOAI transcription by binding to an LRH-1 response element located in the proximal APOAI promoter region. Chromatin immunoprecipitation experiments revealed that LRH-1 binds to the human APO AI promoter in vivo. Finally, we show that the transcriptional repressor SHP (small heterodimer partner) suppressed APOAI gene expression by inhibiting LRH-1 transcriptional activity. Taken together, our results demonstrate that LRH-1 is a novel regulator of APOAI transcription and underscore the role of this receptor in cholesterol homeostasis. PMID:15218078

  19. Impact of psychological stress on the associations between apolipoprotein E variants and metabolic traits: findings in an American sample of caregivers and controls

    DEFF Research Database (Denmark)

    Kring, Sofia Iqbal; Brummett, Beverly H; Barefoot, John;

    2010-01-01

    To examine the association between apolipoprotein E (APOE) gene variants and waist circumference, fasting plasma glucose, serum insulin, serum high-density lipoprotein cholesterol, and serum triglycerides, all metabolic traits known as cardiovascular disease (CVD) endophenotypes, in a population ...

  20. A strategy for solubilizing delipidated apolipoprotein with lysophosphatidylcholine and reconstitution with phosphatidylcholine

    International Nuclear Information System (INIS)

    The apolipoproteins of insect lipophorin were dissociated in guanidinium chloride and isolated by gel permeation chromatography. Over 98% of the total lipid in lipophorin was associated with apolipophorin I (apoLp-I), thus suggesting this apolipoprotein to be the lipid binding component of the particle. ApoLp-I was delipidated with ethanol/ether and solubilized in buffer that contained radioactive lysophosphatidylcholine ([3H]LPC) above the critical micellar concentration. Sonic irradiation of radioactive phosphatidylcholine ([14C]PC) with [3H]LPC-solubilized apoLp-I at a molar ratio of 318 resulted in reconstituted lipophorin I (RLp-I). [3H]LPC was bound to fatty acid free bovine serum albumin and was separated from RLp-I by density gradient ultracentrifugation and gel permeation chromatography. Negatively stained RLp-I particles were quasispherical with an average radius of 55 angstrom, and their overall morphology and secondary structure were similar to those of native hemolymph lipophorin. The RLp-I particle had a ρ = 1.137 g/mL, a Mr ∼ 5.2 x 105, and a [14C]PC:apoLp-I molar ratio of 308. From the compositional analysis, molecular size, trypsinization, and lipolysis with phospholipase A2, the authors concluded that each RLp-I particle contained one molecule of apoLp-I and a monomolecular layer of [14C]PC. When injected into the hemolymph of adult moths in vivo, RLp-I was loaded with lipid, as judged by a decrease in its density both in the presence and in the absence of adipokinetic hormone. The similarities in morphology and immunology of RLp-I and native lipophorin, together with the ability of RLp-I to load lipid, suggest that reconstituted lipophorins may serve as models to probe lipophorin structure and function

  1. A strategy for solubilizing delipidated apolipoprotein with lysophosphatidylcholine and reconstitution with phosphatidylcholine

    Energy Technology Data Exchange (ETDEWEB)

    Kawooya, J.K.; Wells, M.A.; Law, J.H. (Univ. of Arizona, Tucson (USA))

    1989-08-08

    The apolipoproteins of insect lipophorin were dissociated in guanidinium chloride and isolated by gel permeation chromatography. Over 98% of the total lipid in lipophorin was associated with apolipophorin I (apoLp-I), thus suggesting this apolipoprotein to be the lipid binding component of the particle. ApoLp-I was delipidated with ethanol/ether and solubilized in buffer that contained radioactive lysophosphatidylcholine (({sup 3}H)LPC) above the critical micellar concentration. Sonic irradiation of radioactive phosphatidylcholine (({sup 14}C)PC) with ({sup 3}H)LPC-solubilized apoLp-I at a molar ratio of 318 resulted in reconstituted lipophorin I (RLp-I). ({sup 3}H)LPC was bound to fatty acid free bovine serum albumin and was separated from RLp-I by density gradient ultracentrifugation and gel permeation chromatography. Negatively stained RLp-I particles were quasispherical with an average radius of 55{angstrom}, and their overall morphology and secondary structure were similar to those of native hemolymph lipophorin. The RLp-I particle had a {rho} = 1.137 g/mL, a M{sub r} {approx} 5.2 x 10{sup 5}, and a ({sup 14}C)PC:apoLp-I molar ratio of 308. From the compositional analysis, molecular size, trypsinization, and lipolysis with phospholipase A{sub 2}, the authors concluded that each RLp-I particle contained one molecule of apoLp-I and a monomolecular layer of ({sup 14}C)PC. When injected into the hemolymph of adult moths in vivo, RLp-I was loaded with lipid, as judged by a decrease in its density both in the presence and in the absence of adipokinetic hormone. The similarities in morphology and immunology of RLp-I and native lipophorin, together with the ability of RLp-I to load lipid, suggest that reconstituted lipophorins may serve as models to probe lipophorin structure and function.

  2. Elevated hepatic apolipoprotein A-I transcription is associated with diet-induced hyperalphalipoproteinemia in rabbits.

    Science.gov (United States)

    Schwab, D A; Rea, T J; Hanselman, J C; Bisgaier, C L; Krause, B R; Pape, M E

    2000-03-24

    Past studies have shown that a high saturated fatty acid diet containing coconut oil elevates plasma HDL cholesterol and apolipoprotein A-I (apoA-1) in rabbits through a mechanism involving increased synthesis. We have extended those studies by investigating expression of the hepatic apolipoprotein A-I gene and other lipid related genes in that model. Rabbits fed a diet containing 14% coconut oil for 4 weeks showed HDL-C elevations of 170% to 250% over chow-fed controls with peak differences occurring at 1 week. Plasma apoA-I levels were also increased over this time frame (160% to 180%) reflecting the HDL-C changes. After 4 weeks, there were no differences in plasma VLDL-C or LDL-C levels in chow versus coconut oil-fed rabbits. Hepatic levels of apoA-I mRNA in coconut oil-fed animals were elevated 150% after 4 weeks compared to chow-fed controls; hepatic mRNA levels for ten other genes either decreased slightly (apoB, LCAT, hepatic lipase, albumin, ACAT, and HMG CoA reductase) or were unchanged (CETP, apoE, LDL-receptor, and acyl CoA oxidase). Nuclear run-on transcription assays revealed that coconut oil feeding for 4 weeks caused a 220% increase in hepatic apoA-I transcription rate compared to controls; no change was observed for CETP and apoE. Treatment of cultured rabbit liver cells with various saturated fatty acids and sera from chow-fed and coconut oil-fed rabbits did not alter apoA-I mRNA levels as observed in vivo. These data demonstrate that coconut oil elevates plasma HDL-C and apoA-I by increasing hepatic apoA-I transcription while expression of other genes involved in lipid metabolism are reduced or unchanged in response to coconut oil feeding. PMID:10809165

  3. A cDNA-dependent scintillation proximity assay for quantifying apolipoprotein A-I.

    Science.gov (United States)

    Hanselman, J C; Schwab, D A; Rea, T J; Bisgaier, C L; Pape, M E

    1997-11-01

    We have developed a cDNA-dependent scintillation proximity assay (SPA) for rabbit apolipoprotein A-I that follows a classic radioimmunoassay scheme, in that antiserum and radiolabeled ligand are used in a process to quantify a source containing unlabeled ligand. To synthesize radiolabeled ligand we isolated a full-length rabbit apolipoprotein A-I (apoA-I) cDNA, transcribed the corresponding RNA in vitro, and synthesized radiolabeled apoA-I by including tritiated leucine in an in vitro translation reaction. Assay conditions were established which allowed quantification of unlabeled apoA-I over a range of 0.2 to 4 nanograms with intra- and interassay coefficients of variation of 5% and 10%, respectively. Purified rabbit apoA-I, apoA-I in rabbit liver parenchymal cell conditioned media, and apoA-I contained in rabbit plasma all generated parallel titration curves. Quantification of rabbit plasma apoA-I was not affected when sheep anti-rabbit apoA-I serum was mixed with sheep anti-rabbit apoB or apoE serum; thus, the antibody need not be specific to quantify the ligand of interest. To show utility of the assay, apoA-I mass was quantified in in vitro and in vivo models displaying altered apoA-I levels. In each model apoA-I values from the cDNA-dependent SPA and the established methodologies of Western blotting and electroimmunodiffusion were highly correlated. The approach outlined in this report should permit rapid development of scintillation proximity assays for other proteins given the widespread availability of full-length cDNAs. PMID:9392434

  4. Enhanced Diabetes Susceptibility in Community Dwelling Han Elders Carrying the Apolipoprotein E 3/3 Genotype.

    Science.gov (United States)

    Ban, Chun-Xia; Zhong, Li; Wang, Tao; Zhu, Min-Jie; Wang, Jing-Hua; Zhang, Zhen-Lian; Wang, Zhe; Su, Ning; Liu, Yuan-Yuan; Shi, Yan-Chen; Xiao, Shi-Fu; Li, Xia

    2016-01-01

    Despite Apolipoprotein E (ApoE) being one of the main apolipoproteins in the blood, the association between its genotype and the high cholesterol or blood glucose levels commonly seen in clinical practice is inconclusive. Such research is also lacking in the Han population. The aim of this study was to investigate the association between APOE genotype, diabetes, and plasma glucose and lipid levels. We included 243 community-dwelling elderly residents in this study. Participant APOE genotypes were assessed and were simultaneously tested for weight, height, blood glucose, triglycerides, cholesterol, and high- and low-density lipoprotein. In addition, gender, age, years of education, cognitive function, and medical history was recorded. Subjects were divided into 3 groups based on APOE genotype: APOE ε2 group (ε2/ε2 and ε2/ε3), APOE ε3 group (ε3/ε3), and APOE ε4 group (ε2/ε4, ε3/ε4 and ε4/ε4). Comparisons between groups were conducted for the incidence of diabetes, high blood pressure, and dementia, as well as for differences in body-mass index, fasting plasma glucose, and blood lipids. The APOE ε3/ε3 genotype exhibited the highest frequency (70.4%) among the subjects. Participants in the APOE ε3 group demonstrated significantly higher levels of fasting plasma glucose than those in the APOE ε2 and APOE ε4 groups (Pfasting plasma glucose values than did the APOE ε2 group (P = 0.065). Furthermore, the APOE3 genotype was significantly correlated with both fasting plasma glucose level and glucose abnormality (P< 0.05) and trended toward statistically significant correlation with diabetes (P = 0.082). The correlation between APOE2 and low low-density lipoprotein levels also approached statistical significance (P = 0.052). Thus, elderly community dwelling residents of Han ethnicity carrying the APOE ε3/ε3 genotype might have higher plasma glucose levels and a higher occurrence of diabetes. PMID:26998902

  5. Serum apolipoproteins in relation to intakes of fish in population of Arkhangelsk County

    Directory of Open Access Journals (Sweden)

    Petrenya Natalia

    2012-06-01

    Full Text Available Abstract Background Diets rich in omega-3 fatty acids and low in saturated fat were found beneficially associated with blood lipids and cardio-vascular health. Lean reindeer meet and local cold water white-fish species high in omega-3 are among the main sources of nutrients in the rural area of the Nenets Autonomous Okrug (NAO in Russia and are not normally consumed by the urban population from the same region. The aims of the study were firstly, to compare serum lipid profiles of residents of urban (Arkhangelsk city and rural (NAO regions of Arkhangelsk County, and secondly, to investigate the effects of fish consumption on the predictor of cardiovascular events apolipoprotein (Apo B/ApoA-I ratio in these populations. Methods A cross-sectional study conducted in Arkhangelsk County, Russia. Sample size of 249 adults: 132 subjects from Arkhangelsk city, aged 21–70 and 117 subject (87% Ethnic Nenets from NAO, aged 18–69. Results We observed more favorable lipid levels in NAO compared to Arkhangelsk participants. Age-adjusted geometric means of ApoB/ApoA-I ratio were 1.02 and 0.98 in men and women from Arkhangelsk; 0.84 and 0.91 in men and women from NAO respectively. Age and consumption of animal fat were positively associated with ApoB/ApoA-I ratio in women (pooled samples from Arkhangelsk and NAO. Body mass index and low levels of physical activity were positively associated with ApoB/ApoA-I ratio in men (pooled samples from Arkhangelsk and NAO. Reported oily fish consumption was not significantly correlated with ApoB/ApoA-I ratio. Conclusion The population sample from rural NAO, consisting largely of the indigenous Arctic population Nenets with healthier dietary sources, had a relatively less atherogenic lipid profile compared to the urban Arkhangelsk group. Fish consumption had no effect on apolipoproteins profile.

  6. Apolipoprotein C3 polymorphisms, cognitive function and diabetes in Caribbean origin Hispanics.

    Directory of Open Access Journals (Sweden)

    Caren E Smith

    Full Text Available Apolipoprotein C3 (APOC3 modulates triglyceride metabolism through inhibition of lipoprotein lipase, but is itself regulated by insulin, so that APOC3 represents a potential mechanism by which glucose metabolism may affect lipid metabolism. Unfavorable lipoprotein profiles and impaired glucose metabolism are linked to cognitive decline, and all three conditions may decrease lifespan. Associations between apolipoprotein C3 (APOC3 gene polymorphisms and impaired lipid and glucose metabolism are well-established, but potential connections between APOC3 polymorphisms, cognitive decline and diabetes deserve further attention.We examined whether APOC3 single nucleotide polymorphisms (SNPs m482 (rs2854117 and 3u386 (rs5128 were related to cognitive measures, whether the associations between cognitive differences and genotype were related to metabolic differences, and how diabetes status affected these associations. Study subjects were Hispanics of Caribbean origin (n = 991, aged 45-74 living in the Boston metropolitan area.Cognitive and metabolic measures differed substantially by type II diabetes status. In multivariate regression models, APOC3 m482 AA subjects with diabetes exhibited lower executive function (P = 0.009, Stroop color naming score (P = 0.014 and Stroop color-word score (P = 0.022 compared to AG/GG subjects. APOC3 m482 AA subjects with diabetes exhibited significantly higher glucose (P = 0.032 and total cholesterol (P = 0.028 compared to AG/GG subjects. APOC3 3u386 GC/GG subjects with diabetes exhibited significantly higher triglyceride (P = 0.004, total cholesterol (P = 0.003 and glucose (P = 0.016 compared to CC subjects.In summary, we identified significant associations between APOC3 polymorphisms, impaired cognition and metabolic dysregulation in Caribbean Hispanics with diabetes. Further research investigating these relationships in other populations is warranted.

  7. Apolipoprotein J: A New Predictor and Therapeutic Target in Cardiovascular Disease?

    Directory of Open Access Journals (Sweden)

    Ning Yang

    2015-01-01

    Full Text Available Objective: To review the functional mechanism of apolipoprotein J (apoJ in the process of atherosclerosis and the feasibility of apoJ as a therapeutic endpoint. Data Sources: Relevant articles published in English from 1983 to present were selected from PubMed. The terms of "atherosclerosis, apolipoprotein J, clusterin (CLU, oxidative stress, and inflammation" were used for searching. Study Selection: Articles studying the role of apoJ with atherosclerosis and restenosis after injury were reviewed. Articles focusing on the intrinsic determinants of atherosclerosis were selected. The exclusion criteria of articles were that the studies on immunologic vasculitis. Results: ApoJ, involved in numerous physiological process important for lipid transportation and vascular smooth muscle cell differentiation, including apoptotic cell death, cell-cycle regulation, cell adhesion, tissue remodeling, immune system regulation, and oxidative stress, plays a role in the development of clinical atherosclerosis. In the process of relieving atherosclerosis, apoJ can promote cholesterol and phospholipid export from macrophage-foam cells, and exhibit cytoprotective and anti-inflammatory actions by interacting with lots of known inflammatory proteins which may predict the onset of clinical cardiovascular events and may actually play a causal role in mediating atherosclerotic disease such as C-reactive protein, paraoxonase, and leptin. As known as CLU, apoJ has been identified to play central roles in the process of vascular smooth cells migration, adhesion, and proliferation, which can contribute significantly to restenosis after vascular injury. Conclusions: Intense effort and substantial progress have been made to identify the apoJ that relieves atherosclerosis and vascular restenosis after percutaneous coronary intervention. More work is needed to elucidate the exact mechanisms of and the interrelationship between the actions of apoJ and to successfully achieve

  8. A new test for measuring soluble fibrin in plasma with a high predictive value for thrombotic disorders

    NARCIS (Netherlands)

    Bos, R.; Laterveer, R.; Lockwood, D.; Szewczyk, K.; Nieuwenhuizen, W.

    1998-01-01

    Fibrin formation is initiated by thrombin which releases the fibrinopeptides A and B from fibrinogen. In vivo, fibrin molecules form soluble complexes with fibrinogen. At a certain threshold concentration, fibrin-fibrin interactions prevail and insoluble aggregates are formed on site. Soluble fibrin

  9. Rapid and safe determination of human apolipoprotein E genotypes by miniaturised SDS-PAGE in non-insulin dependent diabetes mellitus.

    OpenAIRE

    C Clavel; Durlach, A.; Durlach, V; Birembaut, P

    1995-01-01

    AIMS--To present a non-isotopic procedure for the analysis of the different apolipoprotein E genotypes in normal subjects and patients with non-insulin dependent diabetes mellitus. METHODS--Apolipoprotein E genotypes were detected following polymerase chain reaction and miniaturised sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) (PhastSystem Pharmacia). RESULTS--The time taken from extraction of DNA from 6 microliters whole blood to the final result was eight hours. The...

  10. Carotid intima-media thickness and apolipoproteins in patients of ischemic stroke in a rural hospital setting in central India: A cross-sectional study

    OpenAIRE

    Jyoti Jain; Tejal Lathia; Om Prakash Gupta; Vishakha Jain

    2012-01-01

    Context: Carotid intima-media thickness (CIMT) and apolipoproteins have been found as a risk factor for ischemic stroke . Objective: The objective was to study the carotid intima-media thickness, apolipoproteins, and their relation in patients of ischemic stroke in central rural India. Settings and Design: A cross-sectional study was performed in a rural hospital in central India. Materials and Methods: In all patients of ischemic stroke proven by computerized tomography (CT), CIMT, apolipopr...

  11. Appreciation of concentration of lipoproteins and apolipoproteins in serum of male rats under the influence of diet change composition and its supplementation with group B vitamins

    OpenAIRE

    Zuzanna Goluch-Koniuszy; Aldona Wierzbicka

    2011-01-01

      Background. This study was aimed at exploring, on animal model, how the diet changes, which results in exceeding 5 times the amount of deficit of group B vitamins after diet change, which up to a certain extent imitates supplementation method in people, influences the concentration of apolipoprotein A-I and apolipoprotein B – the components of lipoprotein HDL-C and LDL-C. Material and methods. The research was conducted on 24 WISTAR male rats, aged ca 5 mo...

  12. Water-soluble chiral metallopeptoids.

    Science.gov (United States)

    Baskin, Maria; Maayan, Galia

    2015-09-01

    Metal ions play a significant role in the activity of biological systems including catalysis, recognition and folding. Therefore, introducing metal ions into peptidomimetic oligomers is a potential way for creating biomimetic metal complexes toward applications in sensing, recognition, drug design and catalysis. Herein we report the design, synthesis and characterization of water-soluble chiral N-substituted glycine oligomers, "peptoids," with one and two distinct intramolecular binding sites for metal ions such as copper and cobalt. We demonstrate for the first time the incorporation of the chiral hydrophilic group (S)-(+)-1-methoxy-2-propylamine (Nsmp) within peptoid sequences, which provides both chirality and water solubility. Two peptoids, a heptamer, and a dodecamer bearing two and four 8-hydroxyquinoline (HQ) groups respectively as metal-binding ligands, were synthesized on solid support using the submonomer approach. Using UV-titrations and ESI-MS analysis we demonstrate the creation of a novel metallopeptoid bearing two metal ions in distinct binding sites via intramolecular chelation. Exciton couplet circular dichroism (ECCD) demonstrated chiral induction from the chiral non-helical peptoids to the metal centers. PMID:25969151

  13. Solid state stability and solubility of triethylenetetramine dihydrochloride.

    Science.gov (United States)

    Henriet, Théo; Gana, Inès; Ghaddar, Carine; Barrio, Maria; Cartigny, Yohann; Yagoubi, Najet; Do, Bernard; Tamarit, Josep-Lluis; Rietveld, Ivo B

    2016-09-10

    The API triethylenetetramine dihydrochloride used as an alternative treatment of Wilson's disease is sensitive to water and it exhibits polymorphism. As this may become an issue for the drug formulation, the physical stability has been studied by differential scanning calorimetry, high-pressure thermal analysis, dynamic vapor sorption, and X-ray diffraction as a function of temperature. In addition, high-pressure liquid chromatography and mass spectrometry have been used to study the purity and chemical stability of the API. A pressure-temperature phase diagram of the pure compound has been constructed and it can be concluded that form II is monotropic in relation to form I, which is the only stable solid. The solubilities of the different solid forms have been determined with the help of a temperature - composition phase diagram. The API is very soluble, at 20° C about 10% of the saturated solution with respect to the dihydrate consists of API and the solubility of the pure form I is twice as high. Moreover, it has been shown that at 20°C, a relative humidity above 40% induces the formation of the dihydrate and at 70% a saturated solution appears. At higher temperatures, the formation of the dihydrate appears at lower relative humidity values. A clear link has been established between the API's chemical stability, its physical stability and the relative humidity in the air. Humidity levels above 40% are detrimental to the quality of the API. PMID:27377012

  14. Apolipoprotein AIF gene variant S347 is associated with increased risk of coronary heart disease and lower apolipoprotein AIV plasma concentrations

    Energy Technology Data Exchange (ETDEWEB)

    Wong, Wai-man R.; Hawe, Emma; Li, Lai K.; Miller, George J.; Nicaud, Viviane; Pennacchio, Len A.; Humphries, Steve E.; Talmud, Philippa J.

    2003-01-30

    The impact of common variants in the apolipoprotein gene cluster (APOC3-A4-A5) on prospective CHD risk was examined in healthy UK men. Of the 2808 men followed over nine years, 187 had a clinically defined CHD event. Examination of 9 single nucleotide polymorphisms (SNPs) in this group revealed that homozygotes for APOA4 S347 had significantly increased risk of CHD [Hazard ratio (HR) of 2.07 (95%CI 1.04-4.12)] while men homozygous for APOC3 1100T were protected (HR 0.28 (95%CI 0.09-0.87)). In stepwise multiple regression analysis, after entering all the variants and adjusting for established risk factors APOA4 T347S alone remained in the model. Using nine-SNP haplotype analysis, highest risk-estimate haplotypes carried APOA4 S347 and rare alleles of the two flanking intergenic markers. The protective effect of APOC31100T could be explained by negative linkage disequilibrium with these alleles. To determine the association of APOA4 T347S with apoAIVlevels, the relationship was examined in over 1600 healthy young European men and women. S347 homozygotes had significantly lower apoAIV plasma levels (13.48 + 0.6mg/dl) compared to carriers of the T347 allele (14.85 + 0.12 mg/dl) (p=0.025). These results demonstrate that genetic variation in and around APOA4, independent of effects of TG, is associated with risk of CHD and apoAIV levels, supporting an anti-atherogenic role for apoAIV.

  15. Pressure effect on subtilisin crystallization and solubility

    Science.gov (United States)

    Webb, J. N.; Waghmare, R. Y.; Carpenter, J. F.; Glatz, C. E.; Randolph, T. W.

    1999-09-01

    High pressures (135 and 200 MPa) arrested the crystallization process in unseeded batch crystallizations of subtilisin conducted at 25°C over a period of seven days. Crystallization resumed at the normal atmospheric pressure rate once batches were depressurized and the active soluble enzyme concentration decayed to the same value as seen in atmospheric crystallizations. Solubility experiments conducted at 25°C showed an exponential increase in apparent solubility with pressure. The solubility increased approximately five-fold at 200 MPa. The partial molar volume change of crystallization for this increase in solubility with pressure is +21±1 ml/mol. Solubility changes with pressure are largely responsible for the arrest in crystallization rate at high pressure. Experiments on pH-pressure and ionic strength-pressure interactions showed that the change in apparent solubility is not due to pressure-induced changes in pH and ionic strength. For comparative purposes, solubility data as a function of pressure were collected on lysozyme. A linear dependence of lysozyme solubility with pressure was observed, with a 40% increase in apparent solubility after incubation for seven days at 210 MPa and 25°C.

  16. Measurement of soluble nuclide dissolution rates from spent fuel

    International Nuclear Information System (INIS)

    Gaining a better understanding of the potential release behavior of water-soluble radionuclides is the focus of new laboratory spent fuel dissolution studies being planned in support of the Yucca Mountain Project. Previous studies have suggested that maximum release rates for actinide nuclides, which account for most of the long-term radioactivity in spent fuel, should be solubility-limited and should not depend on the characteristics or durability of the spent fuel waste form. Maximum actinide concentrations should be sufficiently low to meet the NRC (Nuclear Regulatory Commission) annual release limits. Potential release rates for soluble nuclides such as 99Tc, 135Cs, 14C and 129I, which account for about 1-2% of the activity in spent fuel at 1,000 years, are less certain and may depend on processes such as oxidation of the fuel in the repository air environment. Dissolution rates for several soluble nuclides have been measured from spent fuel specimens using static and semi-static methods. However, such tests do not provide a direct measurement of fuel matrix dissolution rates that may ultimately control soluble-nuclide release rates. Flow-through tests are being developed as a potential supplemental method for determining the matrix component of soluble-nuclide dissolution. Advantages and disadvantages of both semi-static and flow-through methods are discussed. Tests with fuel specimens representing a range of potential fuel states that may occur in the repository, including oxidized fuel, are proposed. Preliminary results from flow-through tests with unirradiated UO2 suggesting that matrix dissolution rates are very sensitive to water composition are also presented

  17. Fasting and nonfasting lipid levels: influence of normal food intake on lipids, lipoproteins, apolipoproteins, and cardiovascular risk prediction

    DEFF Research Database (Denmark)

    Langsted, A.; Freiberg, J.J.; Nordestgaard, Børge

    2008-01-01

    BACKGROUND: Lipid profiles are usually measured after fasting. We tested the hypotheses that these levels change only minimally in response to normal food intake and that nonfasting levels predict cardiovascular events. METHODS AND RESULTS: We cross-sectionally studied 33 391 individuals 20 to 95...... HDL cholesterol, and ratio of apolipoprotein B to apolipoprotein A1 did not change in response to normal food intake. The maximum changes after normal food and fluid intake from fasting levels were -0.2 mmol/L for total cholesterol, -0.2 mmol/L for low-density lipoprotein cholesterol, -0.1 mmol/L for...... years of age from the Copenhagen General Population Study. We also studied 9319 individuals 20 to 93 years of age from the Copenhagen City Heart Study, 1166 of whom developed cardiovascular events during 14 years of follow-up. Compared with fasting levels, total cholesterol, low-density lipoprotein...

  18. Bicarbonate-Regulated Soluble Adenylyl Cyclase

    Directory of Open Access Journals (Sweden)

    Wuttke MS

    2001-07-01

    Full Text Available Soluble adenylyl cyclase (sAC represents a novel form of mammalian adenylyl cyclase structurally, molecularly, and biochemically distinct from the G protein-regulated, transmembrane adenylyl cyclases (tmACs. sAC possesses no transmembrane domains and is insensitive to classic modulators of tmACs, such as heterotrimeric G proteins and P site ligands. Thus, sAC defines an independently regulated cAMP signaling system within mammalian cells. sAC is directly stimulated by bicarbonate ion both in vivo in heterologously expressing cells and in vitro using purified protein. sAC appears to be the predominant form of adenylyl cyclase (AC in mammalian sperm, and its direct activation by bicarbonate provides a mechanism for generating the cAMP required to complete the bicarbonate-induced processes necessary for fertilization, including hyperactivated motility, capacitation, and the acrosome reaction. Immunolocalization studies reveal sAC is also abundantly expressed in other tissues which respond to bicarbonate or carbon dioxide levels suggesting it may function as a general bicarbonate/CO(2 sensor throughout the body.

  19. TO901317 regulating apolipoprotein M expression mediates via the farnesoid X receptor pathway in Caco-2 cells

    OpenAIRE

    Berggren-Söderlund Maria; Shi Yuanping; Wei Jiang; Wang Zongchun; Luo Guanghua; Zhang Xiaoying; Di Dongmei; Zhu Chunhua; Nilsson-Ehle Peter; Xu Ning

    2011-01-01

    Abstract Background Apolipoprotein M (apoM) may have potential antiatherosclerotic properties. It has been reported that apoM expression could be regulated by many intracellar and extracellar factors. In the present study we further investigated regulation of apoM expression in Caco-2 cells stimulated by a liver X receptor (LXR) agonist, TO901317. Materials and methods Caco-2 cells were cultured in the presence of either TO901317, farnesoid X receptor (FXR) antagonist guggulsterone or TO90131...

  20. The influence of the polymorphism in apolipoprotein B codon 2488 on insulin and lipid levels in a Danish twin population

    DEFF Research Database (Denmark)

    Bentzen, J; Poulsen, P; Vaag, A; Beck-Nielsen, H; Fenger, M

    2002-01-01

    parameters associated with the insulin resistance syndrome in Danish twins. METHODS: The effect of the polymorphism on lipid, glucose and insulin measures was studied in 548 same sex twins aged 55-74 years. RESULTS: The codon 2488 polymorphism influenced fasting triglyceride levels, as well as insulin, as....... As the polymorphism is silent, these effects must be mediated through linkage to other polymorphisms in apolipoprotein B or other genes on chromosome 2....

  1. Effects of Bread with Nigella Sativa on Lipid Profiles, Apolipoproteins and Inflammatory Factor in Metabolic Syndrome Patients.

    Science.gov (United States)

    Mohtashami, Alireaz; Mahaki, Behzad; Azadbakht, Leila; Entezari, Mohammad Hasan

    2016-04-01

    Nigella sativa (N.sativa) has been used in traditional medicine and many studies have been performed in different communities in order to reveal the effects of it on medical disorders and chronic diseases. The aim of this study was to investigate the effects of bread with N. Sativa on lipid profiles, apolipoproteins, and inflammatory factors in metabolic syndrome (MetS) patients. A randomized, double-blind, cross-over and clinical trial was conducted in 51 MetS patients of both sexes with age group of 20-65 years old in Chaloos, north of Iran. Patients were randomly divided in two groups. In phase 1, intervention group (A, n = 27) received daily a bread with N. sativa and wheat bran and control group (B, n = 24) received the same bread without N. sativa for 2 months. After 2 weeks of wash out period, phase 2 was started with switch the intervention between two groups. Measuring of lipid profiles, apolipoproteins and inflammatory factor was performed for all patients before and after two phases. In this study, treatment, sequence and time effects of intervention were evaluated and revealed that consumption of bread with N. sativa has no significant treatment and time effects on triglyceride (TG), cholesterol (CHOL), low density lipoprotein (LDL), high density lipoprotein (HDL), apolipoprotein (APO)-A, APO-B and high-sensitivity C-reactive protein (p > 0.05). Sequence effect was significant on CHOL, LDL, APO-A, and APO-B (p 0.05). Consumption of bread with N. sativa has no a significant effect on lipid profiles, apolipoproteins and inflammatory factor in MetS patients. PMID:27152298

  2. Biological Monitoring of Hexavalent Chromium and Serum Levels of the Senescence Biomarker Apolipoprotein J/Clusterin in Welders

    OpenAIRE

    Vassilios Makropoulos; Gonos, Efstathios S.; Magda Lourda; Trougakos, Ioannis P.; Xenophon Cominos; Alexopoulos, Evangelos C.

    2008-01-01

    Welding fumes contain metals and other toxic substances known or strongly suspected to be related with oxidative stress and premature cellular senescence. Apolipoprotein J/Clusterin (ApoJ/CLU) is a glycoprotein that is differentially regulated in various physiological and disease states including ageing and age-related diseases. In vitro data showed that exposure of human diploid fibroblasts to hexavalent chromium (Cr(VI)) resulted in premature senescence and significant upregulation of the A...

  3. Endothelial Dysfunction in the Apolipoprotein E-deficient Mouse: insights into the influence of diet, gender and aging

    OpenAIRE

    Meyrelles Silvana S; Peotta Veronica A; Pereira Thiago MC; Vasquez Elisardo C

    2011-01-01

    Abstract Since the early 1990s, several strains of genetically modified mice have been developed as models for experimental atherosclerosis. Among the available models, the apolipoprotein E-deficient (apoE-/-) mouse is of particular relevance because of its propensity to spontaneously develop hypercholesterolemia and atherosclerotic lesions that are similar to those found in humans, even when the mice are fed a chow diet. The main purpose of this review is to highlight the key achievements th...

  4. The influence of parental history of Alzheimer's disease and apolipoprotein E ε4 on the BOLD signal during recognition memory

    OpenAIRE

    Xu, Guofan; McLaren, Donald G.; Ries, Michele L.; Fitzgerald, Michele E.; Barbara B. Bendlin; Howard A. Rowley; Sager, Mark A.; Atwood, Craig; Asthana, Sanjay; Johnson, Sterling C.

    2008-01-01

    First-degree family history (FH) of sporadic Alzheimer's disease and the apolipoprotein E ε4 allele (APOE4) are risk factors for Alzheimer's disease that may affect brain function prior to onset of clinical symptoms. In this functional MRI (fMRI) study, we used an episodic recognition task that required discrimination of previously viewed (PV) and novel (NV) faces to examine differences in blood oxygen level dependent (BOLD) signal due to risk factors in 74 middle-aged cognitively normal indi...

  5. Effects of Bread with Nigella Sativa on Lipid Profiles, Apolipoproteins and Inflammatory Factor in Metabolic Syndrome Patients

    Science.gov (United States)

    2016-01-01

    Nigella sativa (N.sativa) has been used in traditional medicine and many studies have been performed in different communities in order to reveal the effects of it on medical disorders and chronic diseases. The aim of this study was to investigate the effects of bread with N. Sativa on lipid profiles, apolipoproteins, and inflammatory factors in metabolic syndrome (MetS) patients. A randomized, double-blind, cross-over and clinical trial was conducted in 51 MetS patients of both sexes with age group of 20-65 years old in Chaloos, north of Iran. Patients were randomly divided in two groups. In phase 1, intervention group (A, n = 27) received daily a bread with N. sativa and wheat bran and control group (B, n = 24) received the same bread without N. sativa for 2 months. After 2 weeks of wash out period, phase 2 was started with switch the intervention between two groups. Measuring of lipid profiles, apolipoproteins and inflammatory factor was performed for all patients before and after two phases. In this study, treatment, sequence and time effects of intervention were evaluated and revealed that consumption of bread with N. sativa has no significant treatment and time effects on triglyceride (TG), cholesterol (CHOL), low density lipoprotein (LDL), high density lipoprotein (HDL), apolipoprotein (APO)-A, APO-B and high-sensitivity C-reactive protein (p > 0.05). Sequence effect was significant on CHOL, LDL, APO-A, and APO-B (p 0.05). Consumption of bread with N. sativa has no a significant effect on lipid profiles, apolipoproteins and inflammatory factor in MetS patients. PMID:27152298

  6. Vitamin D Deficiency and Exogenous Vitamin D Excess Similarly Increase Diffuse Atherosclerotic Calcification in Apolipoprotein E Knockout Mice

    OpenAIRE

    Ellam, Timothy; Hameed, Abdul; ul Haque, Risat; Muthana, Munitta; Wilkie, Martin; Francis, Sheila E.; Chico, Timothy J. A.

    2014-01-01

    Background Observational data associate lower levels of serum vitamin D with coronary artery calcification, cardiovascular events and mortality. However, there is little interventional evidence demonstrating that moderate vitamin D deficiency plays a causative role in cardiovascular disease. This study examined the cardiovascular effects of dietary vitamin D deficiency and of vitamin D receptor agonist (paricalcitol) administration in apolipoprotein E knockout mice. Methods Mice were fed athe...

  7. Role of apolipoprotein E4 in protecting children against early childhood diarrhea outcomes and implications for later development

    OpenAIRE

    Oriá, Reinaldo B.; Patrick, Peter D.; Blackman, James A.; Lima, Aldo A.M.; Guerrant, Richard L.

    2006-01-01

    Our group and others have reported a series of studies showing that heavy burdens of diarrheal diseases in the formative first two years of life in children in urban shantytowns have profound consequences of impaired physical and cognitive development lasting into later childhood and schooling. Based on these previous studies showing that apolipoprotein E4 (APOE4) is relatively common in favela children, we review recent data suggesting a protective role for the APOE4 allele in the cognitive ...

  8. Frequency of the apolipoprotein E epsilon 4 allele in a case-control study of early onset Parkinson's disease.

    OpenAIRE

    Whitehead, A S; Bertrandy, S.; Finnan, F; Butler, A; G. D. Smith(Edinburgh University); Ben-Shlomo, Y.

    1996-01-01

    OBJECTIVES: It has been suggested that Parkinson's disease and Alzheimer's disease may share a common or at least overlapping aetiology. The prevalence of dementia among cases of Parkinson's disease is known to be greater than expected in the general population. The frequency of the apolipoprotein epsilon 4 allele in a large case-control study of early onset Parkinson's disease has been examined. METHODS: 215 patients and 212 population based controls were recruited from the Republic of Irela...

  9. Apolipoprotein E4 Genotype and Depressive Symptoms as Risk Factors for Dementia in an Older Korean Population

    OpenAIRE

    Kim, Jae-Min; Kim, Seon-Young; Bae, Kyung-Yeol; Kim, Sung-Wan; Shin, Il-Seon; Yang, Su-Jin; Song, Young-Heon; Yoon, Jin-Sang

    2010-01-01

    Objective Growing evidence suggests the separate associations of apolipoprotein E e4 allele (apo E4) and depression with incident dementia. This study investigated the separate and combined effects of apo E4 and depression on the incidence of dementia in both men and women. Methods Of 625 elderly without dementia at baseline, 518 (83%) were followed over a 2.4-year period and were assessed clinically for incident dementia. The apo E polymorphism was ascertained, and depression was identified ...

  10. Solid lipid nanoparticles as a vehicle for brain-targeted drug delivery: two new strategies of functionalization with apolipoprotein E

    Science.gov (United States)

    Rute Neves, Ana; Fontes Queiroz, Joana; Weksler, Babette; Romero, Ignacio A.; Couraud, Pierre-Olivier; Reis, Salette

    2015-12-01

    Nanotechnology can be an important tool to improve the permeability of some drugs for the blood-brain barrier. In this work we created a new system to enter the brain by functionalizing solid lipid nanoparticles with apolipoprotein E, aiming to enhance their binding to low-density lipoprotein receptors on the blood-brain barrier endothelial cells. Solid lipid nanoparticles were successfully functionalized with apolipoprotein E using two distinct strategies that took advantage of the strong interaction between biotin and avidin. Transmission electron microscopy images revealed spherical nanoparticles, and dynamic light scattering gave a Z-average under 200 nm, a polydispersity index below 0.2, and a zeta potential between -10 mV and -15 mV. The functionalization of solid lipid nanoparticles with apolipoprotein E was demonstrated by infrared spectroscopy and fluorimetric assays. In vitro cytotoxic effects were evaluated by MTT and LDH assays in the human cerebral microvascular endothelial cells (hCMEC/D3) cell line, a human blood-brain barrier model, and revealed no toxicity up to 1.5 mg ml-1 over 4 h of incubation. The brain permeability was evaluated in transwell devices with hCMEC/D3 monolayers, and a 1.5-fold increment in barrier transit was verified for functionalized nanoparticles when compared with non-functionalized ones. The results suggested that these novel apolipoprotein E-functionalized nanoparticles resulted in dynamic stable systems capable of being used for an improved and specialized brain delivery of drugs through the blood-brain barrier.

  11. FORM development

    OpenAIRE

    Vermaseren, J. A. M.

    2011-01-01

    I give an overview of FORM development based on a few pilot projects, explaining how they have influenced the FORM capabilities. Next I explain what is happnening right now in the field of Open Sourcing and the FORM Forum.

  12. Self-assembly of water-soluble nanocrystals

    Science.gov (United States)

    Fan, Hongyou; Brinker, C. Jeffrey; Lopez, Gabriel P.

    2012-01-10

    A method for forming an ordered array of nanocrystals where a hydrophobic precursor solution with a hydrophobic core material in an organic solvent is added to a solution of a surfactant in water, followed by removal of a least a portion of the organic solvent to form a micellar solution of nanocrystals. A precursor co-assembling material, generally water-soluble, that can co-assemble with individual micelles formed in the micellar solution of nanocrystals can be added to this micellar solution under specified reaction conditions (for example, pH conditions) to form an ordered-array mesophase material. For example, basic conditions are used to precipitate an ordered nanocrystal/silica array material in bulk form and acidic conditions are used to form an ordered nanocrystal/silica array material as a thin film.

  13. Estimation of plasma apolipoprotein B concentration using routinely measured lipid biochemical tests in apparently healthy Asian adults

    Directory of Open Access Journals (Sweden)

    Cho Dong-Sik

    2012-05-01

    Full Text Available Abstract Background Increased low-density lipoprotein cholesterol (LDL concentration is associated with increased risk of coronary heart disease (CHD but a substantial risk of cardiovascular disease often remains after LDL concentrations have been treated to target. Apolipoprotein B (apo B is the major apolipoprotein contained within atherogenic lipoproteins such as LDL, and apo B is a more reliable indicator of cardiovascular risk than LDL concentration. Aim and methods Our aim was to develop a formula for calculating apo B using lipid biochemistry measurements that are commonly available in clinical practice. We examined the clinical and laboratory data from 73,047 Koreans who underwent a medical health check that included apolipoprotein B concentration. The study sample was randomly divided into a training set for prediction model building and a validation set of equal size. Multivariable linear regression analysis was used to develop a prediction model equation for estimating apo B and to validate the developed model. Results The best results for estimating apo B were derived from an equation utilising LDL and triglyceride (TG concentrations [ApoB = −33.12 + 0.675*LDL + 11.95*ln(tg]. This equation predicted the apo B result with a concordance correlation coefficient (CCC and 95%CIs = 0.936 (0.935,0.937. Conclusion Our equation for predicting apo B concentrations from routine analytical lipid biochemistry provides a simple method for obtaining precise information about an important cardiovascular risk marker.

  14. Synthesis gas solubility in Fischer-Tropsch slurry: Final report

    Energy Technology Data Exchange (ETDEWEB)

    Chao, K.C.; Lin, H.M.

    1988-01-01

    The objective is to investigate the phase equilibrium behavior of synthesis gases and products in a Fischer-Tropsch slurry reactor. A semi-flow apparatus has been designed and constructed for this purpose. Measurements have been made for hydrogen, cabon monoxide, methane, ethane, ethylene, and carbon dioxide in a heavy n-paraffin at temperatures from 100 to 300)degree)C and pressures 10 to 50 atm. Three n-paraffin waxes: n-eicosane (n-C/sub 20/), n-octacosane )n-C/sub 28/), and n-hexatriacontane (n-C/sub 36/), were studied to model the industrial wax. Solubility of synthesis gas mixtures of H/sub 2/ and CO in n-C/sub 28/ was also determined at two temperatures (200 and 300)degree)C) for each of three gas compositions (40.01, 50.01, and 66.64 mol%) of hydrogen). Measurements were extended to investigate the gas solubility in two industrial Fischer-Tropsch waxes: Mobilwax and SASOL wax. Observed solubility increases in the order: H/sub 2/, CO, CH/sub 4/, CO/sub 2/, C/sub 2/H/sub 4/, C/sub 2/H/sub 6/, at a given temperature pressure, and in the same solvent. Solubility increases with increasing pressure for all the gases. Lighter gases H/sub 2/ and CO show increased solubility with increasing temperature, while the heavier gases CO/sub 2/, ethane, and ethylene show decreased solubility with increasing temperature. The solubility of methane, the intermediate gas, changes little with temperature, and shows a shallow minimum at about 200)degrees)C or somewhat above. Henry's constant and partial molal volume of the gas solute at infinite dilution are determinedfrom the gas solubility data. A correlation is developed from the experimental data in the form on an equation of state. A computer program has been prepared to implement the correlation. 19 refs., 66 figs., 39 tabs.

  15. Estudo de custo-rendimento do precessamento de queijos tipo minas frescal com derivado de soja e diferentes agentes coagulantes Study of cost and yield of minas like fresh cheese produced with added fat freee soybean hydro-soluble extract powder with curd formed by different coagulants agents

    Directory of Open Access Journals (Sweden)

    R. D. Neves-Souza

    2005-03-01

    Full Text Available O desenvolvimento de alimentos é uma constante nas indústrias, nas universidades e nos institutos de pesquisa visando otimizar processamentos, agregar diferentes ingredientes em produtos já existentes, entre outros fatores. Após o desenvolvimento de um produto, informações adicionais podem ser obtidas pela determinação do rendimento e do custo do produto final. O objetivo deste trabalho foi estimar o rendimento e o custo de queijos Minas frescal tradicionais e adicionados de extrato hidrossolúvel de soja desengordurado (EHS processados com coalho bovino e com coagulante microbiano (Aspergillus niger var. awamori. A introdução de 8% do EHS (em relação ao teor de sólidos totais do leite no queijo Minas frescal processado com coalho bovino proporcionou rendimento em gramas de sólidos totais por litro de leite (g ST/L superior de 16,67% em relação ao queijo Minas frescal tradicional processado com o mesmo coalho. O queijo tipo Minas frescal processado com coagulante microbiano e com 8% de EHS apresentou rendimento (g ST/L superior de 16,54%, quando comparado ao seu tradicional. O custo das formulações-base (kg de queijo/100L de leite processadas com coalho bovino e com coagulante microbiano foi US$ 36,75 e US$ 37,50, respectivamente, ao passo que os queijos tradicionais processados com os mesmos agentes coagulantes apresentaram custo equivalente a US$ 35,12 e US$ 35,36.Food products development occur in industries, universities and research centers with the aim of optimizing processes, to include different ingredients to existing products or for other reasons. After developing a product, additional information may be obtained by determining yield and cost of the final product. The objective of this research was to estimate yield and cost of traditional Minas fresh cheese and those produced with added fat free soybean hydro-soluble extract powder (SEP, with curd formed by rennet or microbial coagulant (Aspergillus niger var

  16. Water-soluble sacrificial layers for surface micromachining.

    Science.gov (United States)

    Linder, Vincent; Gates, Byron D; Ryan, Declan; Parviz, Babak A; Whitesides, George M

    2005-07-01

    This manuscript describes the use of water-soluble polymers for use as sacrificial layers in surface micromachining. Water-soluble polymers have two attractive characteristics for this application: 1) They can be deposited conveniently by spin-coating, and the solvent removed at a low temperature (95-150 degrees C), and 2) the resulting layer can be dissolved in water; no corrosive reagents or organic solvents are required. This technique is therefore compatible with a number of fragile materials, such as organic polymers, metal oxides and metals-materials that might be damaged during typical surface micromachining processes. The carboxylic acid groups of one polymer-poly(acrylic acid) (PAA)-can be transformed by reversible ion-exchange from water-soluble (Na+ counterion) to water-insoluble (Ca2+ counterion) forms. The use of PAA and dextran polymers as sacrificial materials is a useful technique for the fabrication of microstructures: Examples include metallic structures formed by the electrodeposition of nickel, and freestanding, polymeric structures formed by photolithography. PMID:17193516

  17. Solid solubility and residual resistivity of scandium in aluminum

    International Nuclear Information System (INIS)

    The solid solubility and the residual resistivity of Sc in Al were determined by means of the measurement of the electrical resistivity at 77 K of Al-Sc alloys air cooled after annealing at various temperatures for a time sufficient to complete the precipitation of the equilibrium phase (ScAl3). Moreover, the solidus line of the Al-rich alloys was determined by thermal analysis. The solid solubilities of Sc in Al were found to vary from 0.186 at.% at 913 K to 0.033 at.% at 743 K. From the temperature dependence of the solid solubility the excess entropy of mixing Δs and the heat of mixing Δh associated with the solid solution of Sc in Al were calculated to be 6.0 R and 59 kJ mol-1, respectively. The compound ScAl3 reacts eutectically with Al to form an Al-rich solid solution. The eutectic temperature is 823 +- 1 K. Using the values of Δs and Δh, the maximum solid solubility of Sc in Al was estimated as 0.21 at.% at the eutectic temperature. The resistivity increment caused by Sc atoms in solution is linearly proportional to the concentration of Sc. The residual resistivity for Sc in Al is (3.4 +- 0.1) X 10-8 Ω m (at.%)-1. (Auth.)

  18. Biological significance of soluble IL-2 receptor

    Directory of Open Access Journals (Sweden)

    Calogero Caruso

    1993-01-01

    Full Text Available A NUMBER of receptors for growth factors and differentiation antigens have been found to be secreted or released by cells. Following mononuclear cell (MNC activation and interleukin-2 receptor (IL-2R expression, a soluble form of the Alpha;-chain of IL-2R (sIL-2R is released. The sIL-2R has been shown to be present in the culture supernatants of activated MNCs as well as in normal sera and, in higher amounts, in sera from subjects affected by several diseases including neoplastic, infectious and autoimmune ones, and in sera from transplanted patients suffering allograft rejection. The blood sIL-2R levels depend on the number of producing cells and the number of molecules per cell, so that sIL-2R blood values may represent an index of the number and the functional state of producing cells, both normal and neoplastic. Thus, monitoring of the immune system, mostly T-cells and haematological malignancies might be targets for the measurement of sIL-2R. Since many conditions may influence sIL-2R production, little diagnostic use may result from these measurements. However, since blood sIL-2R levels may correlate with disease progression and/or response to therapy, their measurement may be a useful index of activity and extent of disease. The precise biological role of the soluble form of the IL-2R is still a matter of debate. However, we know that increased sIL-2R levels may be observed in association with several immunological abnormalities and that sIL-2R is able to bind IL-2. It is conceivable then that in these conditions the excess sIL-2R released in vivo by activated lymphoid cells or by neoplastic cells may somehow regulate IL-2-dependent processes. On the other hand, it cannot exclude that sIL-2R is a by-product without biological significance. Finally, it is puzzling that in many conditions in which an increase of blood sIL-2R values has been observed, MNCs display a decreased in vitro capacity to produce sIL-2R. These seemingly contrasting

  19. Production of soluble Neprilysin by endothelial cells

    International Nuclear Information System (INIS)

    Highlights: • A soluble full-length form of Neprilysin exists in media of endothelial cells. • Exosomal release is the key mechanism for the production of soluble Neprilysin. • Inhibition of ADAM-17 by specific inhibitors reduce Neprilysin release. • Exosome mediated release of Neprilysin is dependent on ADAM-17 activity. - Abstract: A non-membrane bound form of Neprilysin (NEP) with catalytic activity has the potential to cleave substrates throughout the circulation, thus leading to systemic effects of NEP. We used the endothelial cell line Ea.hy926 to identify the possible role of exosomes and A Disintegrin and Metalloprotease 17 (ADAM-17) in the production of non-membrane bound NEP. Using a bradykinin based quenched fluorescent substrate (40 μM) assay, we determined the activity of recombinant human NEP (rhNEP; 12 ng), and NEP in the media of endothelial cells (10% v/v; after 24 h incubation with cells) to be 9.35 ± 0.70 and 6.54 ± 0.41 μmols of substrate cleaved over 3 h, respectively. The presence of NEP in the media was also confirmed by Western blotting. At present there are no commercially available inhibitors specific for ADAM-17. We therefore synthesised two inhibitors TPI2155-14 and TPI2155-17, specific for ADAM-17 with IC50 values of 5.36 and 4.32 μM, respectively. Treatment of cells with TPI2155-14 (15 μM) and TPI2155-17 (4.3 μM) resulted in a significant decrease in NEP activity in media (62.37 ± 1.43 and 38.30 ± 4.70, respectively as a % of control; P < 0.0001), implicating a possible role for ADAM-17 in NEP release. However, centrifuging media (100,000g for 1 h at 4 °C) removed all NEP activity from the supernatant indicating the likely role of exosomes in the release of NEP. Our data therefore indicated for the first time that NEP is released from endothelial cells via exosomes, and that this process is dependent on ADAM-17

  20. Production of soluble Neprilysin by endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Kuruppu, Sanjaya, E-mail: Sanjaya.Kuruppu@monash.edu [Department of Biochemistry and Molecular Biology, Building 77, Monash University, Wellington Rd, Clayton, Vic 3800 (Australia); Rajapakse, Niwanthi W. [Department of Physiology, Building 13F, Monash University, Wellington Rd, Clayton, Vic 3800 (Australia); Minond, Dmitriy [Torrey Pines Institute for Molecular Studies, 11350 SW Village Parkway, Port Saint Lucie, FL 34987 (United States); Smith, A. Ian [Department of Biochemistry and Molecular Biology, Building 77, Monash University, Wellington Rd, Clayton, Vic 3800 (Australia)

    2014-04-04

    Highlights: • A soluble full-length form of Neprilysin exists in media of endothelial cells. • Exosomal release is the key mechanism for the production of soluble Neprilysin. • Inhibition of ADAM-17 by specific inhibitors reduce Neprilysin release. • Exosome mediated release of Neprilysin is dependent on ADAM-17 activity. - Abstract: A non-membrane bound form of Neprilysin (NEP) with catalytic activity has the potential to cleave substrates throughout the circulation, thus leading to systemic effects of NEP. We used the endothelial cell line Ea.hy926 to identify the possible role of exosomes and A Disintegrin and Metalloprotease 17 (ADAM-17) in the production of non-membrane bound NEP. Using a bradykinin based quenched fluorescent substrate (40 μM) assay, we determined the activity of recombinant human NEP (rhNEP; 12 ng), and NEP in the media of endothelial cells (10% v/v; after 24 h incubation with cells) to be 9.35 ± 0.70 and 6.54 ± 0.41 μmols of substrate cleaved over 3 h, respectively. The presence of NEP in the media was also confirmed by Western blotting. At present there are no commercially available inhibitors specific for ADAM-17. We therefore synthesised two inhibitors TPI2155-14 and TPI2155-17, specific for ADAM-17 with IC{sub 50} values of 5.36 and 4.32 μM, respectively. Treatment of cells with TPI2155-14 (15 μM) and TPI2155-17 (4.3 μM) resulted in a significant decrease in NEP activity in media (62.37 ± 1.43 and 38.30 ± 4.70, respectively as a % of control; P < 0.0001), implicating a possible role for ADAM-17 in NEP release. However, centrifuging media (100,000g for 1 h at 4 °C) removed all NEP activity from the supernatant indicating the likely role of exosomes in the release of NEP. Our data therefore indicated for the first time that NEP is released from endothelial cells via exosomes, and that this process is dependent on ADAM-17.

  1. Apolipoprotein A-I localization and dipalmitoylphosphatidylcholine dynamics in reconstituted high density lipoproteins.

    Science.gov (United States)

    Dergunov, A D; Dobretsov, G E

    2000-02-01

    The structure and molecular dynamics of recombinant high density lipoproteins (rHDL) were studied by non-radiative energy transfer (NRET), fluorescence anisotropy and intensity measurements. The rHDL particles contained human plasma apolipoprotein (apo) A-I and dipalmitoylphosphatidylcholine (DPPC). Fluorescent cis- and trans-parinaric acids were used both as probes of molecular motion in the particle lipid phase and as acceptors in the Forster's energy transfer from apo A-I tryptophan residues to determine particle dimensions, apolipoprotein localization and lipid dynamics. The probes are sensitive to thermal wobbling (macromobility) and conformational deformations (micromobility) of phospholipid acyl chains. The experimental data fitted to various models of the particle structure are compatible with the following: (a) at T DPPC molecules in rHDL were more rapid due to a significant disorder of the boundary lipid molecules close to the apo A-I molecule. This disorder led to the increase of the specific surface area per one lipid molecule, S(o). The lipid phase can be divided into three regions: (i) zone I of the most tightly packed lipid (0-1.7 nm from the disc axis) with a S(o) value small as 0.5 nm2; (ii) intermediate zone II (from 1.7 to 4.0 nm); and (iii) boundary lipid zone III (4-5 nm) of significantly disordered lipid with a S(o) value large as 0.65 nm2. (b) at T> Tt the S(o) heterogeneity disappeared, the radius of the lipid phase did not increase significantly, not exceeding 5.2-5.4 nm, but protein-induced immobilization of lipid molecules which affected about half or more of the total lipid, became remarkable. The overall effect was the suppression of the transition amplitude in rHDL compared to liposomes. The structural inhomogeneity might underlie the function of the native plasma HDL as the key component of the transport and metabolism of plasma lipids. PMID:10669308

  2. Enhanced Diabetes Susceptibility in Community Dwelling Han Elders Carrying the Apolipoprotein E 3/3 Genotype.

    Directory of Open Access Journals (Sweden)

    Chun-Xia Ban

    Full Text Available Despite Apolipoprotein E (ApoE being one of the main apolipoproteins in the blood, the association between its genotype and the high cholesterol or blood glucose levels commonly seen in clinical practice is inconclusive. Such research is also lacking in the Han population. The aim of this study was to investigate the association between APOE genotype, diabetes, and plasma glucose and lipid levels. We included 243 community-dwelling elderly residents in this study. Participant APOE genotypes were assessed and were simultaneously tested for weight, height, blood glucose, triglycerides, cholesterol, and high- and low-density lipoprotein. In addition, gender, age, years of education, cognitive function, and medical history was recorded. Subjects were divided into 3 groups based on APOE genotype: APOE ε2 group (ε2/ε2 and ε2/ε3, APOE ε3 group (ε3/ε3, and APOE ε4 group (ε2/ε4, ε3/ε4 and ε4/ε4. Comparisons between groups were conducted for the incidence of diabetes, high blood pressure, and dementia, as well as for differences in body-mass index, fasting plasma glucose, and blood lipids. The APOE ε3/ε3 genotype exhibited the highest frequency (70.4% among the subjects. Participants in the APOE ε3 group demonstrated significantly higher levels of fasting plasma glucose than those in the APOE ε2 and APOE ε4 groups (P<0.05. The APOE ε3 group had slightly higher abnormal fasting plasma glucose values than did the APOE ε2 group (P = 0.065. Furthermore, the APOE3 genotype was significantly correlated with both fasting plasma glucose level and glucose abnormality (P< 0.05 and trended toward statistically significant correlation with diabetes (P = 0.082. The correlation between APOE2 and low low-density lipoprotein levels also approached statistical significance (P = 0.052. Thus, elderly community dwelling residents of Han ethnicity carrying the APOE ε3/ε3 genotype might have higher plasma glucose levels and a higher occurrence of

  3. Escherichia coli maltose-binding protein is uncommonly effective at promoting the solubility of polypeptides to which it is fused.

    OpenAIRE

    Kapust, R B; Waugh, D. S.

    1999-01-01

    Although it is usually possible to achieve a favorable yield of a recombinant protein in Escherichia coli, obtaining the protein in a soluble, biologically active form continues to be a major challenge. Sometimes this problem can be overcome by fusing an aggregation-prone polypeptide to a highly soluble partner. To study this phenomenon in greater detail, we compared the ability of three soluble fusion partners--maltose-binding protein (MBP), glutathione S-transferase (GST), and thioredoxin (...

  4. Inhibition of soluble tumour necrosis factor is therapeutic in experimental autoimmune encephalomyelitis and promotes axon preservation and remyelination

    OpenAIRE

    Brambilla, Roberta; Ashbaugh, Jessica Jopek; Magliozzi, Roberta; Dellarole, Anna; Karmally, Shaffiat; Szymkowski, David E; John R Bethea

    2011-01-01

    Tumour necrosis factor is linked to the pathophysiology of various neurodegenerative disorders including multiple sclerosis. Tumour necrosis factor exists in two biologically active forms, soluble and transmembrane. Here we show that selective inhibition of soluble tumour necrosis factor is therapeutic in experimental autoimmune encephalomyelitis. Treatment with XPro1595, a selective soluble tumour necrosis factor blocker, improves the clinical outcome, whereas non-selective inhibition of bot...

  5. ApolipoproteinE ε4 allelic variant, cognitive decline and psychosis in Alzheimer disease: a review of the literature and suggestions for upcoming studies

    Directory of Open Access Journals (Sweden)

    Ilaria Spoletini

    2006-06-01

    Full Text Available Apolipoprotein E (ApoE ε4 allele represents a well known vascular risk factor for developing Alzheimer disease (AD and differences in ApoE genotypes may explain a part of the variability in AD phenotypes. In fact, ApoE ε4 allele possession seems to be associated with a more precocious age of onset, greater episodic memory impairment, and psychotic symptoms. The first question we discuss regards the role of ApoE ε4 on cognitive progression of AD. In fact, while a general agreement exists about the role played by ApoE ε4 on the precocious onset of AD, cognitive decline has been differently associated with ApoE ε4 allele possession in AD patients in a continuum of faster decline, no effect, and slower decline. An attemptable interpretation is that the biological processes leading to the onset of AD are different from those involved in determining its clinical course. The second question regards the possible relationship between the presence of the degenerative pathological hallmarks of the disease in specific cerebral areas and different cognitive or behavioural symptoms. In fact, there is evidence that degenerative pathology in hippocampal formation and frontal cortex reflects the progression of cognitive deficits in brain aging and AD and that hypometabolism in right frontal lobe and greater frontal neuropsychological deficits occur in AD patients with psychosis in comparison to those without. The third question regards, specifically, the relationship between ApoE ε4 variant and behavioural symptoms. In fact, there is evidence supporting the link between being carriers of ApoE ε4 allele and severity of delusions, mostly at the early stage of the illness. In an interpretative challenge, we suggest that the link between being carriers of ApoE ε4 allele and suffering from delusions in AD may be explained by frontal lobe dysfunctions. Finally, we hypothesize that the most precocious onset of AD illness, described in carriers of ApoE ε4

  6. In vitro solubility of uranium tetrafluoride with oxidizing medium compared with in vivo solubility in rats

    International Nuclear Information System (INIS)

    A simple in vitro solubility test for UF4 was developed to investigate effects of addition of enzymes, proteins or gases (eg O2) to synthetic biological fluid or Gamble solvent. Tests were made concomitantly with an in vivo inhalation study using male rats. With Gamble solvent alone, UF4 showed class Y behaviour with dissolution half-time 300-500 days. When O2 or carbonates were added to Gamble solvent, UF4 showed class W behaviour (half-time 25-50 days). In the presence of oxygen and pyrogallol, the superoxide ion was formed and UF4 behaved as class D (half-time 2-3 days). Results correlated with those of the inhalation experiment in which dissolution half-time was 2.5 and 5.2 days. Data also agree with urine monitoring data for workers exposed to UF4 over 20 years. (author)

  7. Applications of soluble dietary fibers in beverages

    OpenAIRE

    C. I. Beristain; M. E. Rodríguez-Huezo; C. Lobato-Calleros; F. Cruz-Sosa; R. Pedroza-Islas; J. R. Verde-Calvo

    2006-01-01

    In this work the importance of soluble dietary fibers in the human diet is discussed. Traditional and new sources of soluble dietary fiber are mentioned, and a description of how to apply them in different types of beverages such as energy drinks, sport drinks, carbonated beverages and protein-based beverages in order to achieve enhanced functional properties is given.

  8. Determination of soluble protein contents from RVNRL

    International Nuclear Information System (INIS)

    This project was carried out to determine the soluble protein contents on RVNRL film vulcanisates, with respect to the RVNRL storage time, gamma irradiation dose absorbed by the latex and the effect of different leaching time and leaching conditions. These three factors are important in the hope to determine the best possible mean of minimizing the soluble protein contents in products made from RVNRL. Within the nine months storage period employed in the study, the results show that, the longer the storage period the less the soluble protein extracted from the film samples. Gamma irradiation dose absorbed by the samples, between 5.3 kGy to 25.2 kGy seems to influence the soluble protein contents of the RVNRL films vulcanisates. The higher the dose the more was the soluble protein extracted from the film samples. At an absorbed dose of 5.3 kGy and 25.2 kGy, the soluble contents were 0. 198 mg/ml and 0.247 mg/ml respectively. At a fixed leaching temperature, the soluble proteins increases with leaching time and at a fixed leaching time, the soluble proteins increases with leaching temperature. ne highest extractable protein contents was determined at a leaching time of 10 minutes and leaching temperature of 90'C The protein analysis were done by using Modified Lowry Method

  9. Solubility Products of M(II) - Carbonates

    International Nuclear Information System (INIS)

    Many solubility data for M(II) carbonates commonly compiled in tables are contradictory and sometimes obviously wrong. The quality of such data has been evaluated based on the original publications and reliable solubility constants have been selected for the carbonates of Mn, Fe, Co, Ni, Cu, Zn, Cd and Pb with the help of cross-comparisons. (author)

  10. A Colorful Solubility Exercise for Organic Chemistry

    Science.gov (United States)

    Shugrue, Christopher R.; Mentzen, Hans H., II; Linton, Brian R.

    2015-01-01

    A discovery chemistry laboratory has been developed for the introductory organic chemistry student to investigate the concepts of polarity, miscibility, solubility, and density. The simple procedure takes advantage of the solubility of two colored dyes in a series of solvents or solvent mixtures, and the diffusion of colors can be easily…

  11. Folded functional lipid-poor apolipoprotein A-I obtained by heating of high-density lipoproteins: relevance to high-density lipoprotein biogenesis.

    Science.gov (United States)

    Jayaraman, Shobini; Cavigiolio, Giorgio; Gursky, Olga

    2012-03-15

    HDL (high-density lipoproteins) remove cell cholesterol and protect from atherosclerosis. The major HDL protein is apoA-I (apolipoprotein A-I). Most plasma apoA-I circulates in lipoproteins, yet ~5% forms monomeric lipid-poor/free species. This metabolically active species is a primary cholesterol acceptor and is central to HDL biogenesis. Structural properties of lipid-poor apoA-I are unclear due to difficulties in isolating this transient species. We used thermal denaturation of human HDL to produce lipid-poor apoA-I. Analysis of the isolated lipid-poor fraction showed a protein/lipid weight ratio of 3:1, with apoA-I, PC (phosphatidylcholine) and CE (cholesterol ester) at approximate molar ratios of 1:8:1. Compared with lipid-free apoA-I, lipid-poor apoA-I showed slightly altered secondary structure and aromatic packing, reduced thermodynamic stability, lower self-associating propensity, increased adsorption to phospholipid surface and comparable ability to remodel phospholipids and form reconstituted HDL. Lipid-poor apoA-I can be formed by heating of either plasma or reconstituted HDL. We propose the first structural model of lipid-poor apoA-I which corroborates its distinct biophysical properties and postulates the lipid-induced ordering of the labile C-terminal region. In summary, HDL heating produces folded functional monomolecular lipid-poor apoA-I that is distinct from lipid-free apoA-I. Increased adsorption to phospholipid surface and reduced C-terminal disorder may help direct lipid-poor apoA-I towards HDL biogenesis. PMID:22150513

  12. Proteomic Analysis of Plasma from California Sea Lions (Zalophus californianus Reveals Apolipoprotein E as a Candidate Biomarker of Chronic Domoic Acid Toxicosis.

    Directory of Open Access Journals (Sweden)

    Benjamin A Neely

    Full Text Available Domoic acid toxicosis (DAT in California sea lions (Zalophus californianus is caused by exposure to the marine biotoxin domoic acid and has been linked to massive stranding events and mortality. Diagnosis is based on clinical signs in addition to the presence of domoic acid in body fluids. Chronic DAT further is characterized by reoccurring seizures progressing to status epilepticus. Diagnosis of chronic DAT is often slow and problematic, and minimally invasive tests for DAT have been the focus of numerous recent biomarker studies. The goal of this study was to retrospectively profile plasma proteins in a population of sea lions with chronic DAT and those without DAT using two dimensional gel electrophoresis to discover whether individual, multiple, or combinations of protein and clinical data could be utilized to identify sea lions with DAT. Using a training set of 32 sea lion sera, 20 proteins and their isoforms were identified that were significantly different between the two groups (p<0.05. Interestingly, 11 apolipoprotein E (ApoE charge forms were decreased in DAT samples, indicating that ApoE charge form distributions may be important in the progression of DAT. In order to develop a classifier of chronic DAT, an independent blinded test set of 20 sea lions, seven with chronic DAT, was used to validate models utilizing ApoE charge forms and eosinophil counts. The resulting support vector machine had high sensitivity (85.7% with 92.3% negative predictive value and high specificity (92.3% with 85.7% positive predictive value. These results suggest that ApoE and eosinophil counts along with machine learning can perform as a robust and accurate tool to diagnose chronic DAT. Although this analysis is specifically focused on blood biomarkers and routine clinical data, the results demonstrate promise for future studies combining additional variables in multidimensional space to create robust classifiers.

  13. Expression of the human apolipoprotein E gene suppresses steroidogenesis in mouse Y1 adrenal cells

    International Nuclear Information System (INIS)

    The lipid transport protein, apolipoprotein E (apoE), is expressed in many peripheral tissues in vivo including the adrenal gland and testes. To investigate the role of apoE in adrenal cholesterol homeostasis, the authors have expressed a human apoE genomic clone in the Y1 mouse adrenocortical cell line. Y1 cells do not express endogenous apoE mRNA or protein. Expression of apoE in Y1 cells resulted in a dramatic decrease in basal steroidogenesis; secretion of fluorogenic steroid was reduced 7- to >100-fold relative to Y1 parent cells. Addition of 5-cholesten-3β,25-idol failed to overcome the suppression of steroidogenesis in these cells. Cholesterol esterification under basal conditions, as measured by the production of cholesteryl [14C]oleate, was similar in the Y1 parent and the apoE-transfected cell lines. Upon incubation with adrenocorticotropin or dibutyryl cAMP, production of cholesteryl [14C]oleate decreased 5-fold in the Y1 parent cells but was unchanged in the apoE-transfected cell lines. These results suggest that apoE may be an important modulator of cholesterol utilization and steroidogenesis in adrenal cells

  14. Association of apolipoprotein E polymorphism with plasma lipids and Alzheimer's disease in a Southern Brazilian population

    Directory of Open Access Journals (Sweden)

    de-Andrade F.M.

    2000-01-01

    Full Text Available Apolipoprotein E (protein: apo E; gene: APOE plays an important role in the multifactorial etiology of both Alzheimer's disease (AD and lipid level concentrations. The polymerase chain reaction (PCR was used to investigate the APOE gene polymorphism in 446 unrelated Caucasians, among them 23 AD patients, and 100 Afro-Brazilians living in Porto Alegre, Brazil. The frequencies of the APOE*2, APOE*3 and APOE*4 alleles were 0.075, 0.810 and 0.115 in Caucasians and 0.075, 0.700 and 0.225 in Afro-Brazilians, respectively (c2 = 8.72, P = 0.013. A highly significant association was observed between the APOE*4 allele and AD in this population-based sample. The APOE*4 frequency in AD patients (39% was about four times higher than in the general Caucasian population (11.5%. The influence of each of the three common APOE alleles on lipid traits was evaluated by the use of the average excess statistic. The E*2 allele is associated with lower levels of triglycerides and of total and non-HDL cholesterol in both men and women. Conversely, the E*4 allele is associated with higher levels of these traits in women only. The effect of APOE alleles was of greater magnitude in women.

  15. Apolipoprotein E Gene Polymorphisms in Saudi Patients with Systemic Lupus Erythematosus

    Science.gov (United States)

    Al-Rayes, Hannan; Huraib, Ghaleb; Julkhuf, Saeed; Arfin, Misbahul; Tariq, Mohammad; Al-Asmari, Abdulrahman

    2016-01-01

    Apolipoprotein E (APOE) is a glycosylated protein with multiple biological properties. APOE gene polymorphism plays a central role in lipid metabolism and has recently been suggested to regulate inflammation. Our objective is to evaluate whether APOE polymorphism affects susceptibility to SLE. APOE genotyping was performed using ApoE StripAssay™ kit. Results indicated significantly higher frequencies of allele ε4 and genotype ε3/ε4 and lower frequencies of allele ε3 and genotype ε3/ε3 in SLE patients than controls. APOE ε2 allele was found in three patients, whereas it was absent in controls. The frequencies of allele ε4 and genotype ε3/ε4 were significantly higher in SLE patients with renal involvement and those of alleles ε2, ε4 and genotypes ε2/ε3, ε3/ε4 were higher in patients with neuropsychiatric symptoms. It is concluded that APOE allele ε4 is associated with susceptibility risk/clinical manifestations of SLE and ε2 may increase its severity while ε3 is protective for SLE in Saudis. PMID:27257397

  16. Apolipoprotein E-specific innate immune response in astrocytes from targeted replacement mice

    Directory of Open Access Journals (Sweden)

    Montine Thomas J

    2006-04-01

    Full Text Available Abstract Background Inheritance of the three different alleles of the human apolipoprotein (apo E gene (APOE are associated with varying risk or clinical outcome from a variety of neurologic diseases. ApoE isoform-specific modulation of several pathogenic processes, in addition to amyloid β metabolism in Alzheimer's disease, have been proposed: one of these is innate immune response by glia. Previously we have shown that primary microglia cultures from targeted replacement (TR APOE mice have apoE isoform-dependent innate immune activation and paracrine damage to neurons that is greatest with TR by the ε4 allele (TR APOE4 and that derives from p38 mitogen-activated protein kinase (p38MAPK activity. Methods Primary cultures of TR APOE2, TR APOE3 and TR APOE4 astrocytes were stimulated with lipopolysaccharide (LPS. ApoE secretion, cytokine production, and nuclear factor-kappa B (NF-κB subunit activity were measured and compared. Results Here we showed that activation of primary astrocytes from TR APOE mice with LPS led to TR APOE-dependent differences in cytokine secretion that were greatest in TR APOE2 and that were associated with differences in NF-κB subunit activity. Conclusion Our results suggest that LPS activation of innate immune response in TR APOE glia results in opposing outcomes from microglia and astrocytes as a result of TR APOE-dependent activation of p38MAPK or NF-κB signaling in these two cell types.

  17. Apolipoprotein E isotype-dependent modulation of microRNA-146a in plasma and brain.

    Science.gov (United States)

    Teter, Bruce; LaDu, Mary Jo; Sullivan, Patrick M; Frautschy, Sally A; Cole, Greg M

    2016-08-01

    The Apolipoprotein E (ApoE) isotype ApoE4 is a prevalent genetic risk factor for Alzheimer's disease (AD) that can modulate systemic and central inflammation, independent of amyloid accumulation. Although disruption of innate immune toll receptor signaling is modulated by ApoE and observed in AD, ApoE isotype-specific effects remain poorly understood. Therefore, we examined the effect of the ApoE isotype on the brain levels of major regulators of TLR signaling including miR146a, a microRNA enriched in the brain. We used 6-month-old ApoE3 or ApoE4 targeted replacement mice with and without mutant familial AD transgenes. ApoE4 reduced the levels of miR146a compared with ApoE3, both in the brain (29%; Pimmune stimuli (including Aβ) in ApoE4 carriers. Thus, ApoE4 causes early dysregulation of a central controller of the innate immune system both centrally and systemically. This defect persists with familial AD pathology and may be relevant to ApoE4 AD risk. PMID:27281274

  18. Mechanism of lipid lowering in mice expressing human apolipoprotein A5

    Energy Technology Data Exchange (ETDEWEB)

    Fruchart-Najib, Jamila; Bauge, Eric; Niculescu, Loredan-Stefan; Pham, Tatiana; Thomas, Benoit; Rommens, Corinne; Majd, Zouher; Brewer, Bryan; Rubin, Edward M.; Pennacchio, Len A.; Fruchart, Jean-Charles

    2004-01-15

    Recently, we reported that apoAV plays key role in triglycerides lowering. Here, we attempted to determine the mechanism underlying this hypotriglyceridemic effect. We showed that triglyceride turnover is faster in hAPOA5 transgenic compared to wild type mice. Moreover, both apoB and apoCIII are decreased and LPL activity is increased in postheparin plasma of hAPOA5 transgenic mice. These data suggest a decrease in size and number of VLDL. To further investigate the mechanism of hAPOA5 in hyperlipidemic background, we intercrossed hAPOA5 and hAPOC3 transgenic mice. The effect resulted in a marked decreased of VLDL triglyceride, cholesterol, apolipoproteins B and CIII. In postprandial state, the triglyceride response is abolished in hAPOA5 transgenic mice. We demonstrated that in response to the fat load in hAPOA5XhAPOC3 mice, apoAV shifted from HDL to VLDL, probably to limit the elevation of triglycerides. In vitro, apoAV activates lipoprotein lipase. However, apoAV does not interact with LPL but interacts physically with apoCIII. This interaction does not seem to displace apoCIII from VLDL but may induce conformational change in apoCIII and consequently change in its function leading the activation of lipoprotein lipase.

  19. Screening for the familial defective apolipoprotein B-100 R3500W by mutagenic primers PCR

    Institute of Scientific and Technical Information of China (English)

    冯纪安; 冯铮

    2002-01-01

    Objective A method combining the mutagenic primers PCR and restriction enzyme digestion was designed to facilitate the detection of gene mutation in familial defective apolipoprotein B-1O0 R3500W. Methods A pair of primer was designed and a mismatch nucleotide was introduced in its upstream primer. A segment of target DNA including the possibly mutated nucleotide was amplified by PCR and the products were digested by restriction enzyme Nco 1. To overcome the potential false negative results due to improper digestion conditions, a segment of DNA with Ncol cut size was added as reference.Results The target sequence was successfully amplified by PCR, producing a 144 bp DNA fragment as expected. When incubated with Ncol, the enzyme could digest the DNA, producing a 114 bp segment,only if it was amplified from the mutated gene, but not from the normal allele. This difference in length of DNA could be separated by electrophoresis on a 2 %agarose gel. Thus we successfully detected two carriers of heterozygous FDB R3500W in 162 hypercholesterolemic patients. Conclusions Mutagenic primers PCR can be used to detect the gene mutation of apo B-100 R3500W, two cases were detected among 162patients with hypercholesterolemia. It suggests that this mutation is not rare in mainland China.

  20. Correlation between haplotype of apolipoprotein B gene and natural longevity persons in Uygur Nationality

    Institute of Scientific and Technical Information of China (English)

    JIANG WenXi; QIU ChangChun; CHENG ZuHeng; ZHOU WenYu; GU MingLiang; XU Qun; FANG MingWu; NIU WenQuan

    2007-01-01

    This paper investigated the correlation between polymorphisms and haplotypes in the apolipoprotein B (apoB) gene (SP-I/D, XbaI-RFLP, VNTR) and natural longevity persons among the Uygur people in Xinjiang. For this purpose, 191 healthy Uygur individuals aged above 90 from Hetian area of Xinjiang were recruited, and another 53 persons aged 65-70 from the same nationality, the same region and with the same gender ratio, served as the control group. Genotyping was performed by PCR-SSP, PCR-RFLP and PCR-sequencing methods. Logistic regression analyses revealed that the frequencies of X+X+ genotype, M and L alleles and the genetypes composed of M and L were significantly higher in the longevity group than in the control group. In haplotype analyses, we found that, in the long-lived people, the frequency of haplotypes composed of the X+ and M alleles was significantly higher whereas the frequency of haplotypes composed of the X- and S alleles was significantly lower (both P<0.05) I than those of their controls. These results indicated that the S allele, SS genotype and X+-S, D-S, D-X+-S haplotypes were the possible adverse factors, whereas the M, L alleles, X+X+, MM, ML, LL genotypes and I-X+-M, X+-M haplotypes were the possibe protective factors for the naturally long-lived Uygur people in China.

  1. Correlation between haplotype of apolipoprotein B gene and natural longevity persons in Uygur Nationality

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    This paper investigated the correlation between polymorphisms and haplotypes in the apolipoprotein B (apoB) gene (SP-I/D, XbaI-RFLP, VNTR) and natural longevity persons among the Uygur people in Xin-jiang. For this purpose, 191 healthy Uygur individuals aged above 90 from Hetian area of Xinjiang were recruited, and another 53 persons aged 65—70 from the same nationality, the same region and with the same gender ratio, served as the control group. Genotyping was performed by PCR-SSP, PCR-RFLP and PCR-sequencing methods. Logistic regression analyses revealed that the frequencies of X+X+ genotype, M and L alleles and the genetypes composed of M and L were significantly higher in the longevity group than in the control group. In haplotype analyses, we found that, in the long-lived people, the frequency of haplotypes composed of the X+ and M alleles was significantly higher whereas the frequency of haplotypes composed of the X- and S alleles was significantly lower (both P<0.05) I than those of their controls. These results indicated that the S allele, SS genotype and X+-S, D-S, D-X+-S haplotypes were the possible adverse factors, whereas the M, L alleles, X+X+, MM, ML, LL genotypes and I-X+-M, X+-M haplotypes were the possibe protective factors for the naturally long-lived Uygur people in China.

  2. Longitudinal Trajectories of Cholesterol from Midlife through Late Life according to Apolipoprotein E Allele Status

    Directory of Open Access Journals (Sweden)

    Brian Downer

    2014-10-01

    Full Text Available Background: Previous research indicates that total cholesterol levels increase with age during young adulthood and middle age and decline with age later in life. This is attributed to changes in diet, body composition, medication use, physical activity, and hormone levels. In the current study we utilized data from the Framingham Heart Study Original Cohort to determine if variations in apolipoprotein E (APOE, a gene involved in regulating cholesterol homeostasis, influence trajectories of total cholesterol, HDL cholesterol, and total: HDL cholesterol ratio from midlife through late life. Methods: Cholesterol trajectories from midlife through late life were modeled using generalized additive mixed models and mixed-effects regression models. Results: APOE e2+ subjects had lower total cholesterol levels, higher HDL cholesterol levels, and lower total: HDL cholesterol ratios from midlife to late life compared to APOE e3 and APOE e4+ subjects. Statistically significant differences in life span cholesterol trajectories according to gender and use of cholesterol-lowering medications were also detected. Conclusion: The findings from this research provide evidence that variations in APOE modify trajectories of serum cholesterol from midlife to late life. In order to efficiently modify cholesterol through the life span, it is important to take into account APOE allele status.

  3. Taurine reduces the secretion of apolipoprotein B100 and lipids in HepG2 cells

    Directory of Open Access Journals (Sweden)

    Nagao Koji

    2008-10-01

    Full Text Available Abstract Background Higher concentrations of serum lipids and apolipoprotein B100 (apoB are major individual risk factors of atherosclerosis and coronary heart disease. Therefore ameliorative effects of food components against the diseases are being paid attention in the affluent countries. The present study was undertaken to investigate the effect of taurine on apoB secretion and lipid metabolism in human liver model HepG2 cells. Results The results demonstrated that an addition of taurine to the culture media reduces triacylglycerol (TG-mass in the cells and the medium. Similarly, cellular cholesterol-mass was decreased. Taurine inhibited the incorporation of [14C] oleate into cellular and medium TG, suggesting the inhibition of TG synthesis. In addition, taurine reduced the synthesis of cellular cholesterol ester and its secretion, suggesting the inhibition of acyl-coenzyme A:cholesterol acyltransferase activity. Furthermore, taurine reduced the secretion of apoB, which is a major protein component of very low-density lipoprotein. Conclusion This is a first report to demonstrate that taurine inhibits the secretion of apoB from HepG2 cells.

  4. Apolipoprotein E in the genetics and epidemiology of Alzheimer`s disease

    Energy Technology Data Exchange (ETDEWEB)

    Hardy, J. [Univ. of South Florida, Tampa, FL (United States)

    1995-10-09

    The role of apolipoprotein E (ApoE) alleles and isoforms in the etiology and pathogenesis of Alzheimer`s disease is discussed. The possibility that ApoE itself is not involved in the disease pathogenesis but is merely in genetic disequilibrium with the real locus is discussed and dismissed. The data showing that the {epsilon}4 allele is associated with an increased risk of developing the disease and with an earlier onset age are reviewed. The data showing that, at least in some circumstances, the {epsilon}2 allele is associated with a decrease in the risk of developing the disease, and with a later onset age are also reviewed. Data from the genetic analysis of other disorders are reviewed and presented, and it is suggested that the genetic data support the notion that the role of ApoE in the etiology of the disease directly relates to {beta}-amyloid deposition and plaque formation. This suggestion is in concordance with the most likely mechanism for the role of P-amyloid precursor protein gene mutations as other risk factors for the disease. 68 refs.

  5. Possible role of apolipoprotein A1 in healing and cell death after neuronal injury.

    Science.gov (United States)

    Sengupta, Mohor B; Mukhopadhyay, Debashis

    2016-01-01

    Limited axonal regeneration after traumatic injuries to the CNS presents a challenge in neuroscience. Investigation of CSF from subjects with spinal cord injury (SCI) has found that the lipid catabolism pathway is implicated in the post injury scenario. Sequestration of the CNS by the blood brain barrier ensures a mechanism of cholesterol metabolism and recycling distinct from that in the peripheral tissues. Apolipoprotein A1, the protein component of high density lipoprotein (HDL), is an abundant protein in the mammalian cerebrospinal fluid. Interaction of ApoA1 with its cellular receptor, ABCA1, gives rise to several signaling events, such as the activation of Cdc42 protein leading to actin polymerisation. Emerging evidences suggest that ApoA1 mediates anti-inflammatory effects and conversely, is negatively regulated by inflammatory cytokines. Collating these findings, added to the clinical evidences of using HDL as a therapeutic target for cardio vascular diseases, we hypothesize that ApoA1 could be useful in neurite outgrowth after mechanical injury by 1) mediating polymerisation of actin and 2) restricting inflammatory responses after injury which are deleterious to healing. PMID:27100352

  6. Plasma levels of apolipoprotein E and risk of dementia in the general population

    DEFF Research Database (Denmark)

    Rasmussen, Katrine L; Tybjaerg-Hansen, Anne; Nordestgaard, Børge G; Frikke-Schmidt, Ruth

    2015-01-01

    OBJECTIVE: The apolipoprotein E (APOE) ε4 allele is a major genetic risk factor for Alzheimer disease and dementia. However, it remains unclear whether plasma levels of apoE confer additional risk. We tested this hypothesis. METHODS: Using 75,708 participants from the general population, we tested...... whether low plasma levels of apoE at study enrollment were associated with increased risk of future Alzheimer disease and all dementia, and whether this association was independent of ε2/ε3/ε4 APOE genotype. RESULTS: Multifactorially adjusted hazard ratios (HRs) for Alzheimer disease and all dementia...... increased from the highest to the lowest apoE tertile (p for trends < 1 × 10(-6) ). Multifactorially adjusted HRs for lowest versus highest tertile were 2.68 (95% confidence interval [CI] = 2.04-3.52) and 1.80 (95% CI = 1.52-2.13) for Alzheimer disease and all dementia, respectively. After further...

  7. The Hsp110 molecular chaperone stabilizes apolipoprotein B from endoplasmic reticulum-associated degradation (ERAD).

    Science.gov (United States)

    Hrizo, Stacy L; Gusarova, Viktoria; Habiel, David M; Goeckeler, Jennifer L; Fisher, Edward A; Brodsky, Jeffrey L

    2007-11-01

    Apolipoprotein B (apoB) is the most abundant protein in low density lipoproteins and plays key roles in cholesterol homeostasis. The co-translational degradation of apoB is controlled by fatty acid levels in the endoplasmic reticulum (ER) and is mediated by the proteasome. To define the mechanism of apoB degradation, we employed a cell-free system in which proteasome-dependent degradation is recapitulated with yeast cytosol, and we developed an apoB yeast expression system. We discovered that a yeast Hsp110, Sse1p, associates with and stabilizes apoB, which contrasts with data indicating that select Hsp70s and Hsp90s facilitate apoB degradation. However, the Ssb Hsp70 chaperones have no effect on apoB turnover. To determine whether our results are relevant in mammalian cells, Hsp110 was overexpressed in hepatocytes, and enhanced apoB secretion was observed. This study indicates that chaperones within distinct complexes can play unique roles during ER-associated degradation (ERAD), establishes a role for Sse1/Hsp110 in ERAD, and identifies Hsp110 as a target to lower cholesterol. PMID:17823116

  8. Apolipoprotein e genotype, plasma cholesterol, and cancer: a Mendelian randomization study.

    LENUS (Irish Health Repository)

    Trompet, Stella

    2009-12-01

    Observational studies have shown an association between low plasma cholesterol levels and increased risk of cancer, whereas most randomized clinical trials involving cholesterol-lowering medications have not shown this association. Between 1997 and 2002, the authors assessed the association between plasma cholesterol levels and cancer risk, free from confounding and reverse causality, in a Mendelian randomization study using apolipoprotein E (ApoE) genotype. ApoE genotype, plasma cholesterol levels, and cancer incidence and mortality were measured during a 3-year follow-up period among 2,913 participants in the Prospective Study of Pravastatin in the Elderly at Risk. Subjects within the lowest third of plasma cholesterol level at baseline had increased risks of cancer incidence (hazard ratio (HR) = 1.90, 95% confidence interval (CI): 1.34, 2.70) and cancer mortality (HR = 2.03, 95% CI: 1.23, 3.34) relative to subjects within the highest third of plasma cholesterol. However, carriers of the ApoE2 genotype (n = 332), who had 9% lower plasma cholesterol levels than carriers of the ApoE4 genotype (n = 635), did not have increased risk of cancer incidence (HR = 0.86, 95% CI: 0.50, 1.47) or cancer mortality (HR = 0.70, 95% CI: 0.30, 1.60) compared with ApoE4 carriers. These findings suggest that low cholesterol levels are not causally related to increased cancer risk.

  9. Mammalian embryonic cerebrospinal fluid proteome has greater apolipoprotein and enzyme pattern complexity than the avian proteome.

    Science.gov (United States)

    Parada, Carolina; Gato, Angel; Bueno, David

    2005-01-01

    During early stages of embryo development, the brain cavity is filled with Embryonic Cerebro-Spinal Fluid, which has an essential role in the survival, proliferation and neurogenesis of the neuroectodermal stem cells. We identified and analyzed the proteome of Embryonic Cerebro-Spinal Fluid from rat embryos (Rattus norvegicus), which includes proteins involved in the regulation of Central Nervous System development. The comparison between mammalian and avian Embryonic Cerebro-Spinal Fluid proteomes reveals great similarity, but also greater complexity in some protein groups. The pattern of apolipoproteins and enzymes in CSF is more complex in the mammals than in birds. This difference may underlie the greater neural complexity and synaptic plasticity found in mammals. Fourteen Embryonic Cerebro-Spinal Fluid gene products were previously identified in adult human Cerebro-Spinal Fluid proteome, and interestingly they are altered in patients with neurodegenerative diseases and/or neurological disorders. Understanding these molecules and the mechanisms they control during embryonic neurogenesis may contribute to our understanding of Central Nervous System development and evolution, and these human diseases. PMID:16335996

  10. Substituted Benzamides Containing Azaspiro Rings as Upregulators of Apolipoprotein A-I Transcription

    Directory of Open Access Journals (Sweden)

    Bin Hong

    2012-06-01

    Full Text Available Apolipoprotein A-I (Apo A-I is the principal protein component of high density lipoprotein (HDL, which is generally considered as a potential therapeutic target against atherosclerosis. The understanding of the Apo A-I regulation mechanism has fuelled the development of novel HDL targeted therapeutic approaches. To identify novel agents that can upregulate Apo A-I expression, we performed a cell-based reporter assay to screen 25,600 small molecules. Based on the dataset obtained from screening, a series of novel analogs of substituted benzamides containing azaspiro rings were assessed for their ability to induce the transcription of the Apo A-I gene, and the structure-activity relationship (SAR around these analogs was also proposed. The results indicated that the trifluoromethyl substituted benzamide containing an azaspiro ring is a promising backbone for designing Apo A-I transcriptional upregulator and could be viable leads for development of new drugs to prevent and treat atherosclerosis in the future.

  11. Determination of lipoprotein(a) concentrations and apolipoprotein(a) molecular weights in diabetic patients.

    Science.gov (United States)

    Ribault, A; Durou, M R; Letellier, C; Wojcik, F; Poirier, J Y; Ruelland, A

    2000-04-01

    Lipoprotein(a) (Lp(a)) with atherogenic and thrombotic properties has been frequently studied in diabetes, because a high cardiovascular risk has been reported both in type 1 and type 2 diabetes. Few studies have considered genetic factors, especially the isoforms of apolipoprotein(a). The aim of this work is to determine the distribution of apo(a) phenotypes in the serum of 148 diabetic patients (59 type 1, 89 type 2) with or without vascular complications. Apo(a) phenotypes are determined using 4-15% sodium dodecyl sulfate polyacrylamide gel electrophoresis followed by immunoblotting (PhastSystem - Pharmacia). An inverse relationship is observed between Lp(a) serum concentration and the apparent molecular mass of apo(a) isoforms: type 1 r=- 0.61, p<0.01; type 2 r=- 0.55, p<0.01. The frequency of apo(a) isoforms is significantly different between type 1 and type 2 diabetes mellitus. A higher prevalence of isoforms of low molecular weight was observed in the type 2 diabetic population. PMID:10804324

  12. Apolipoprotein A5: A newly identified gene impacting plasmatriglyceride levels in humans and mice

    Energy Technology Data Exchange (ETDEWEB)

    Pennacchio, Len A.; Rubin, Edward M.

    2002-09-15

    Apolipoprotein A5 (APOA5) is a newly described member of theapolipoprotein gene family whose initial discovery arose from comparativesequence analysis of the mammalian APOA1/C3/A4 gene cluster. Functionalstudies in mice indicated that alteration in the level of APOA5significantly impacted plasma triglyceride concentrations. Miceover-expressing human APOA5 displayed significantly reducedtriglycerides, while mice lacking apoA5 had a large increase in thislipid parameter. Studies in humans have also suggested an important rolefor APOA5 in determining plasma triglyceride concentrations. In theseexperiments, polymorphisms in the human gene were found to define severalcommon haplotypes that were associated with significant changes intriglyceride concentrations in multiple populations. Several separateclinical studies have provided consistent and strong support for theeffect with 24 percent of Caucasians, 35 percent of African-Americans and53 percent of Hispanics carrying APOA5 haplotypes associated withincreased plasma triglyceride levels. In summary, APOA5 represents anewly discovered gene involved in triglyceride metabolism in both humansand mice whose mechanism of action remains to be deciphered.

  13. Psyllium husk. II: Effect on the metabolism of apolipoprotein B in African green monkeys.

    Science.gov (United States)

    McCall, M R; Mehta, T; Leathers, C W; Foster, D M

    1992-08-01

    Dietary psyllium's ability to reduce low-density-lipoprotein (LDL) cholesterol is presumably mediated by increased LDL catabolism and/or reduced LDL synthesis. To distinguish between these possibilities, apolipoprotein B (apo B) metabolism was studied in adult male African green monkeys consuming one of three semipurified diets: low-cholesterol cellulose (LCC), high-cholesterol cellulose (HCC), or high-cholesterol psyllium (HCP). 131I-labeled LDL and 125I-labeled VLDL were injected simultaneously into animals; blood samples were drawn at selected times and apo B specific activity determined in VLDL, IDL, and LDL. Based on a multicompartmental model, LDL apo B pool size and de novo apo B transport were elevated significantly in HCC animals compared with HCP and LCC animals. Differences in LDL transport, although not significant, paralleled differences observed in LDL apo B pool size. Fractional catabolic rates were similar among groups (HCC 0.040 +/- 0.010; HCP 0.042 +/- 0.009, and LCC 0.043 +/- 0.004 pools/h). These data suggest that dietary psyllium reduces plasma cholesterol concentrations by decreasing LDL synthesis. PMID:1322033

  14. Evaluation of Apolipoprotein A5 Polymorphism in Coronary- Heart Disease Patients

    Directory of Open Access Journals (Sweden)

    Somayeh Haqparast

    2012-02-01

    Full Text Available Background and Objectives: Apolipoprotein A5 (APOA5 gene is important in determining plasma triglyceride levels, a major cardiovascular disease risk factor. Mutation in this gene affected plasma triglyceride level. We looked for possible associations of the APOA5 gene polymorphism S19W with coronary heart disease (CHD in a sample of Iranian population. Materials and Methods: A total of 73 CHD patients and 55 controls were genotyped by polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP for this single nucleotide polymorphism. Serum lipids and Fast Blood Sugar concentrations were measured in all subjects with enzymatic method. Results: Allele frequencies observed in our population were 0.041 for the W allele and 0.959 for the S allele which are similar to other populations (p>0.05. There is no evidence that APOA5 S19W, is a risk factor of CHD in our sample (p>0.05. In addition, we observed no association between the APOA5 W allele and elevated plasma TG levels (p>0.05 in the CHD group. This result was also present in the control group (p>0.05. Conclusion: The APO A5 gene polymorphism in S19W gene has no association with the high susceptibility to CHD.

  15. Capture and concentration of viral and bacterial foodborne pathogens using apolipoprotein H.

    Science.gov (United States)

    Almand, Erin A; Goulter, Rebecca M; Jaykus, Lee-Ann

    2016-09-01

    The need for improved pathogen separation and concentration methods to reduce time-to-detection for foodborne pathogens is well recognized. Apolipoprotein H (ApoH) is an acute phase human plasma protein that has been previously shown to interact with viruses, lipopolysaccharides (LPS) and bacterial proteins. The purpose of this study was to determine if ApoH was capable of binding and efficiently capturing two representative human norovirus strains (GI.1 and GII.4), a cultivable surrogate, and four bacterial pathogens (Escherichia coli O157:H7, Listeria monocytogenes, Salmonella enterica serovar Enteritidis, and Staphylococcus aureus). Experiments were carried out using an ApoH-conjugated magnetic bead-based capture followed by pathogen detection using nucleic acid amplification. For all three viruses studied, >10% capture efficiency (microflora. A complementary plate-based capture assay showed that ApoH bound to a variety of human norovirus virus-like particles. ApoH has the potential to be a broadly reactive ligand for separating and concentrating representative foodborne pathogens, both bacteria and viruses. PMID:27439140

  16. Deletion of sirtuin 6 accelerates endothelial dysfunction and atherosclerosis in apolipoprotein E-deficient mice.

    Science.gov (United States)

    Liu, Zhiping; Wang, Jiaojiao; Huang, Xiaoyang; Li, Zhuoming; Liu, Peiqing

    2016-06-01

    Sirtuin 6 (SIRT6) is a chromatin-associated deacetylase that plays a leading role in genomic stability and aging. However, the precise role of SIRT6 in atherosclerosis, an aging-associated cardiovascular disease, remains elusive. This study aims at defining the role of SIRT6 in atherosclerotic lesion development. SIRT6 messenger RNA and protein expression are markedly decreased in atherosclerotic aortas of apolipoprotein E-deficient (ApoE(-/-)) mice fed a high-cholesterol diet. SIRT6 was knocked down in ApoE(-/-) mice using small hairpin RNAs (shRNAs) lentivirus injection. SIRT6-shRNA-treated ApoE(-/-) mice showed impaired endothelium-dependent vasodilation, increased plaque size (in aortic sinus, aortic root and en face aorta), and augmented plaque vulnerability (evidenced by increased necrotic core areas and macrophage accumulation and reduced collagen content). At the cellular level, SIRT6 depletion by RNA interference in human umbilical vein endothelial cells significantly increased monocyte adhesion to endothelial cells by inducing the expression of intracellular adhesion molecule-1. Consistently, intracellular adhesion molecule-1 expression was significantly upregulated in aortic endothelium of SIRT6-shRNA-treated ApoE(-/-) mice compared with controls. In sum, the aforementioned findings suggest that SIRT6 is a primary negative regulation factor in endothelial dysfunction and atherosclerosis development. As a result, SIRT6 is a promising therapeutic target for treating atherosclerosis and its cardiovascular complications. PMID:26924042

  17. Effects of Simvastatin on adiponectin and endothelial function in apolipoprotein E-deficient mice

    Institute of Scientific and Technical Information of China (English)

    Meng Liu; Donghua Yin; Ming Gui; Kejiang Cao

    2009-01-01

    0bjective:To investigate the effects of simvastatin,a 3-hydroxy-3-methylglutaryl coenzyme A(HMG-CoA) reductase inhibitor,on adiponectin and markers of endothelial function in apolipoprotein E-deficient mice at an early stage of atherosclerosis.Methods:Twenty-four 6-week old male apoE-deficient mice were randomly divided into two groups:control group(normal saline) and treatment group[simvastatin(5 mg/(kg·d)].Simvastatin was administered to treatment group mice by gavage and the same volume of normal saline was administered to control group mice by the same method for 4 weeks.Total cholesterol(TC),superoxide dismutase(SOD),malondialdehyde (MDA),and nitric oxide(NO) were measured by biochemical analysis,and adiponectin was measured by an ABC-ELISA method.Results:There was no significant difference in serum TC between control and treatment groups.Compared with the control animals,simvastafin-treated animals exhibited a significant increase in serurn levels of adponectin,SOD and NO,and decrease in serum MDA(P <0.01).Conclusion:Simvastatin protects endothelial function by increasing serum adiponectin,which may increase serum SOD and NO,and decrease serum MDA.This study suggests that sirnvastatin has therapeutic advantages,unrelated to its cholesterol-lowering effect,that are mediated by adiponectin.

  18. Molecular cloning and characterization of the promoter region of the porcine apolipoprotein E gene.

    Science.gov (United States)

    Xia, Jihan; Hu, Bingjun; Mu, Yulian; Xin, Leilei; Yang, Shulin; Li, Kui

    2014-05-01

    Apolipoprotein E (APOE), a component of lipoproteins plays an important role in the transport and metabolism of cholesterol, and is associated with hyperlipoproteinemia and Alzheimer's disease. In order to further understand the characterization of APOE gene, the promoter of APOE gene of Landrace pigs was analyzed in the present study. The genomic structure and amino acid sequence in pigs were analyzed and found to share high similarity in those of human but low similarity in promoter region. Real-time PCR revealed the APOE gene expression pattern of pigs in diverse tissues. The highest expression level was observed in liver, relatively low expression in other tissues, especially in stomach and muscle. Furthermore, the promoter expressing in Hepa 1-6 was significantly better at driving luciferase expression compared with C2C12 cell. After analysis of porcine APOE gene promoter regions, potential transcription factor binding sites were predicted and two GC signals, a TATA box were indicated. Results of promoter activity analysis indicated that one of potential regulatory elements was located in the region -669 to -259, which was essential for a high expression of the APOE gene. Promoter mutation and deletion analysis further suggested that the C/EBPA binding site within the APOE promoter was responsible for the regulation of APOE transcription. Electrophoretic mobility shift assays also showed the binding site of the transcription factor C/EBPA. This study advances our knowledge of the promoter of the porcine APOE gene. PMID:24464129

  19. Apolipoprotein E ε4 allele modulates the immediate impact of acute exercise on prefrontal function.

    Science.gov (United States)

    De Marco, Matteo; Clough, Peter J; Dyer, Charlotte E; Vince, Rebecca V; Waby, Jennifer S; Midgley, Adrian W; Venneri, Annalena

    2015-01-01

    The difference between Apolipoprotein E ε4 carriers and non-carriers in response to single exercise sessions was tested. Stroop and Posner tasks were administered to young untrained women immediately after walking sessions or moderately heavy exercise. Exercise had a significantly more profound impact on the Stroop effect than on the Posner effect, suggesting selective involvement of prefrontal function. A significant genotype-by-exercise interaction indicated differences in response to exercise between ε4 carriers and non-carriers. Carriers showed facilitation triggered by exercise. The transient executive down-regulation was construed as due to exercise-dependent hypofrontality. The facilitation observed in carriers was interpreted as better management of prefrontal metabolic resources, and explained within the antagonistic pleiotropy hypothesis framework. The findings have implications for the interpretation of differences between ε4 carriers and non-carriers in the benefits triggered by long-term exercise that might depend, at least partially, on mechanisms of metabolic response to physical activity. PMID:25218559

  20. Apolipoprotein E Genotype Linked to Spatial Gait Characteristics: Predictors of Cognitive Dual Task Gait Change

    Science.gov (United States)

    MacAulay, Rebecca K.; Allaire, Ted; Brouillette, Robert; Foil, Heather; Bruce-Keller, Annadora J.; Keller, Jeffrey N.

    2016-01-01

    Background Developing measures to detect preclinical Alzheimer’s Disease is vital, as prodromal stage interventions may prove more efficacious in altering the disease’s trajectory. Gait changes may serve as a useful clinical heuristic that precedes cognitive decline. This study provides the first systematic investigation of gait characteristics relationship with relevant demographic, physical, genetic (Apolipoprotein E genotype), and health risk factors in non-demented older adults during a cognitive-load dual task walking condition. Methods The GAITRite system provided objective measurement of gait characteristics in APOE-e4 “carriers” (n = 75) and “non-carriers” (n = 224). Analyses examined stride length and step time gait characteristics during simple and dual-task (spelling five-letter words backwards) conditions in relation to demographic, physical, genetic, and health risk factors. Results Slower step time and shorter stride length associated with older age, greater health risk, and worse physical performance (ps attention decrements and structural brain changes in older adults. Our results indicate that stride length is a useful behavioral marker of cognitive change that is associated with genetic risk for AD. Sex disparities in motor decline may be a function of health risk factors. PMID:27486898

  1. Phosphorylation-dependent down-regulation of apolipoprotein A5 by insulin

    Energy Technology Data Exchange (ETDEWEB)

    Nowak, Maxine; Helleboid-Chapman, Audrey; Jakel, Heidelinde; Rommens, Corinne; Martin, Genevieve; Duran-Sandoval, Daniel; Staels, Bart; Rubin, Edward M.; Pennacchio, Len A.; Taskinen, Marja-Riitta; Fruchart-Najib, Jamila; Fruchart, Jean-Charles

    2004-02-15

    The apolipoprotein A5 (APOA5) gene has been shown to be important in lowering plasma triglyceride levels. Since several studies have shown that hyperinsulinemia is associated with hypertriglyceridemia, we sought to determine whether APOA5 gene is regulated by insulin. We show here that cell and mouse treatments with insulin down-regulated APOA5 expression in a dose-dependent manner. Furthermore, we determined that insulin decreases APOA5 promoter activity and subsequent deletion analyses revealed an E-box-containing fragment. We showed that Upstream Stimulatory Factors, USF1/USF2, bind to the identified E-box in the APOA5 promoter. Moreover, in cotransfection studies, USF1 stimulates APOA5 promoter activity. The treatment with insulin reduces the binding of USF1/USF2 to APOA5 promoter. The inhibition of PI3K pathway with wortmannin abolished the insulin s effect on APOA5 gene transcription. Using oligoprecipitation method of USF from nuclear extracts, we demonstrated that phosphorylated USF1 failed to bind to APOA5 promoter. This indicates that the APOA5 gene transrepression by insulin involves a phosphorylation of USF through PI3K, that modulate their binding to APOA5 promoter and results in APOA5 down-regulation. The effect of exogenous hyperinsulinemia in healthy men shows a decrease of the plasma ApoAV level. These data suggest a potential mechanism involving APOA5 gene in hypertriglyceridemia associated with hyperinsulinemia.

  2. Intracellular trafficking of recycling apolipoprotein E in Chinese hamster ovary cells.

    Science.gov (United States)

    Braun, Nicole A; Mohler, Peter J; Weisgraber, Karl H; Hasty, Alyssa H; Linton, MacRae F; Yancey, Patricia G; Su, Yan Ru; Fazio, Sergio; Swift, Larry L

    2006-06-01

    We have investigated apolipoprotein E (apoE) recycling in Chinese hamster ovary (CHO) cells, a peripheral cell that does not produce lipoproteins or express apoE. Using a pulse-chase protocol in which cells were pulsed with 125I-apoE-VLDL and chased for different periods, approximately 30% of the apoE internalized during the pulse was resecreted within a 4 h chase in a relatively lipid-free state. The addition of lysosomotropic agents or brefeldin A had no effect on apoE recycling. Unlike previous results with hepatocytes and macrophages, neither apoA-I nor upregulation of ABCA1 stimulated apoE recycling. However, cyclodextrin, which extracts cholesterol from plasma membrane lipid rafts, increased recycling. Confocal studies revealed that apoE, internalized during a 1 h pulse, colocalizes with early endosomal antigen-1, Rab5, Rab11a, and lysobisphosphatidic acid but not with lysosomal-associated membrane protein-1. Colocalization of apoE and Rab11a persisted even after cells had been chased for 1 h, suggesting a pool of apoE within the endosomal recycling compartment (ERC). Our data suggest that apoE recycling in CHO cells is linked to cellular cholesterol removal via the ERC and phospholipid-containing acceptors in a pathway alternative to the ABCA1-apoA-I axis. PMID:16534141

  3. Relationship Between Plasma Insulin Level and Apolipoprotein E Gene Polymorphysm in Alzheimer′s Disease

    Institute of Scientific and Technical Information of China (English)

    Luo Zhuming; Yuan Qiang

    2000-01-01

    Objective: To study relationship between plasma insulin level and apolipoprotein E Gene polymorphysm in Alzheimcr′s Disease. Background: Recent researches have shown that there was a close relationship between ApoE- ε 4 allele and AD. Because of the discovery of hyperinsulineamia in AD patients, the study of insulin on the pathogenesis of AD become a hot point of AD reseearch. Methods: We apply PCR-RFLP to the ApoE genotype study of 45 AD paticnts and 32 normal controls. At the same time, plasma insulin and glucose level was measured in the abovc objects. Results and Discussion: The frequency of ApoE- ε 4 in AD (32.2%) is much higher than in controls (10.9%). On the contrary, the frequency of ApeE- ε 4 is relatively lower in AD than in thc controls. The resistence of hyperinsulineamia in AD. Insulin sensitivity decreased in AD. Conclusion: When gene dose of ApoE- ε 4 increases, the prcvalance of AD increase, while the on-set ages of AD decrease (P<0.05). These findings indicatc that AD patients may have insulin resistance anbd insulin probably play a role in AD pathogenesis. In addition, the s 4 homozygote AD patients seem to have loweer plasma insulin level that the non- ε 4 homozygote AD patients (P<0.05). But this situation need to be replicated in studies of larger sample.

  4. Meta-analysis of peripheral blood apolipoprotein E levels in Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Chong Wang

    Full Text Available BACKGROUND: Peripheral blood Apolipoprotein E (ApoE levels have been proposed as biomarkers of Alzheimer's disease (AD, but previous studies on levels of ApoE in blood remain inconsistent. This meta-analysis was designed to re-examine the potential role of peripheral ApoE in AD diagnosis and its potential value as a candidate biomarker. METHODS: We conducted a systematic literature search of MEDLINE, EMBASE, the Cochrane library, and BIOSIS previews for case-control studies measuring ApoE levels in serum or plasma from AD subjects and healthy controls. The pooled weighted mean difference (WMD and 95% confidence interval (CI were used to estimate the association between ApoE levels and AD risk. RESULTS: Eight studies with a total of 2250 controls and 1498 AD cases were identified and analyzed. The pooled WMD from a random-effect model of AD participants compared with the healthy controls was -5.59 mg/l (95% CI: [-8.12, -3.06]. The overall pattern in WMD was not varied by characteristics of study, including age, country, assay method, publication year, and sample type. CONCLUSIONS: Our meta-analysis supports a lowered level of blood ApoE in AD patients, and indicates its potential value as an important risk factor for AD. Further investigation employing standardized assay for ApoE measurement are still warranted to uncover the precise role of ApoE in the pathophysiology of AD.

  5. Droplet evaporation on a soluble substrate

    Science.gov (United States)

    Mailleur, Alexandra; Pirat, Christophe; Colombani, Jean; CNES Collaboration

    2015-11-01

    Stains left by evaporated droplets are ubiquitous in everyday life as well as in industrial processes. Whatever the composition of the evaporating liquid (colloidal suspensions, biological fluids...), the stains are mostly constituted by a deposit at the periphery of the dried drop, similar to a coffee stain (Deegan, 1997). All these studies have been carried with non-reacting solids. In this presentation, we focus on the behavior of a pure-water droplet evaporating on a soluble substrate which is more complex, since three phenomena are strongly interacting: the dissolution of the substrate, the diffusion/convection of the dissolved species into the drop and the evaporation of the liquid. NaCl and KCl single crystals have been chosen for this experimental study as they are fast-dissolving solids. We have observed that the dissolution induces a pinning of the triple line from the beginning of the evaporation, leading to a decrease of the contact angle in time. At the end of the evaporation, a peripheral deposit is always formed, proof of an outward flow inside the drop (coffee-ring effect). The authors would like to thank the CNES for the financial support.

  6. Solid dispersion: A promising technique to enhance solubility of poorly water soluble drug

    Directory of Open Access Journals (Sweden)

    Anshu Sharma

    2011-05-01

    Full Text Available Poorly water soluble compounds have solubility and dissolution related bioavailability problems. The present review deals in detail about solid dispersion technology and its manufacturing techniques at laboratory and industrial level. This highlight about various hydrophilic polymers used in this technique to enhance solubility of poorly soluble drugs. It also discusses about modern characterization technique to characterize solid dispersion. In this review, it is intended to discuss the recent advances related on the area of solid dispersion technology.Keywords: Solid dispersion; Carriers; Solubility; Dissolution; Bioavailability.

  7. CYCLODEXTRIN INCLUSION COMPLEX TO ENHANCE SOLUBILITY OF POORLY WATER SOLUBLE DRUGS: A REVIEW

    Directory of Open Access Journals (Sweden)

    V.B. Chaudhary * 1 and J. K. Patel 2

    2013-01-01

    Full Text Available Low solubility compounds show dissolution rate limited absorption and hence poor absorption, distribution and target organ delivery. Improvement of aqueous solubility in such a case is valuable goal to improve therapeutic efficacy. Complexation with CDs by different methods like physical mixing, melting, kneding, spray drying, freeze drying, co-evaporation has been reported to enhance the solubility, dissolution rate and bioavability of poorly water soluble drugs. The formation of inclusion complex can be confirmed by DSC, FTIR, XRD and SEM study. This review aims to assess the use of cyclodextrines as complexing agents to enhance the solubility of poorly soluble drugs and hence to resolve the many issues associated with developing and commercializing poorly water soluble drugs.

  8. OZONE TREATMENT OF SOLUBLE ORGANICS IN PRODUCED WATER

    Energy Technology Data Exchange (ETDEWEB)

    Klasson, KT

    2002-03-14

    This project was an extension of previous research to improve the applicability of ozonation and will help address the petroleum-industry problem of treating produced water containing soluble organics. The goal of this project was to maximize oxidation of hexane-extractable organics during a single-pass operation. The project investigated: (1) oxidant production by electrochemical and sonochemical methods, (2) increasing the mass transfer rate in the reactor by forming microbubbles during ozone injection into the produced water, and (3) using ultraviolet irradiation to enhance the reaction if needed. Several types of methodologies for treatment of soluble organics in synthetic and actual produced waters have been performed. The technologies tested may be categorized as follows: (1) Destruction via sonochemical oxidation at different pH, salt concentration, ultraviolet irradiation, and ferrous iron concentrations. (2) Destruction via ozonation at different pH, salt concentration, hydrogen peroxide concentrations, ultraviolet irradiation, temperature, and reactor configurations.

  9. Preparation of soluble molybdenum catalysts for epoxidation of olefins

    International Nuclear Information System (INIS)

    This patent describes the process of regenerating a soluble molybdenum composition to obtain a stable catalyst solution capable of being employed as a catalyst in the process for the epoxidation of an olefin with an organic hydroperoxide. Thermally precipitating and separating a molybdenum-containing solid contains up to about 50 percent by weight, of molybdenum from a spent catalyst solution derived from a molybdenum-catalyzed olefin epoxidation reaction. The molybdenum-containing solid has been contained by heating the spent catalyst solution with either solid solubilizating. The separated precipitated solid forms a soluble molybdenum composition by contacting at a temperature of between about 200C and about 1300C, and removing any undesired solid material remaining with the solubilized molybdenum composition

  10. Solubility of thorium under oxygen-free conditions

    International Nuclear Information System (INIS)

    Thorium solubility in 0.1 mol/l NaCl in oxygen- and carbonate-free conditions was studied. Equilibrium was established both in terms of unsaturated and oversaturated solutions. Crystallization of amorphous and microcrystal thorium-containing solid phases was controlled roentgenographically. Thorium concentration in solutions in the range of 10-11-10-8 mol/l was determined by means of mass spectrometry. Study by the methods of electron microscopy of the precipitate and solution after ultrafiltration suggests that in the system studied thorium does not form colloids. Experimentally obtained value of thorium solubility in carbonate-free medium agrees well with the calculated value (EQ3/6 code); i.e. approximately 2x10-3 mol/l

  11. UO2 solubility in NaPO3-NaCl melts

    International Nuclear Information System (INIS)

    Solubility of uranium dioxide in metaphosphate-chloride melts has been studied by the method of isothermal saturation at 700, 800, and 900 deg C. With increasing concentration of NaCl in a salt phase up to 20 ml% oxide solubility grows and attains 20.2 wt.% at 900 deg C. Infrared spectroscopy data allow an assumption that sodium uranates are formed in the process of dissolution

  12. The beta-globin domain in immature chicken erythrocytes: enhanced solubility is coincident with histone hyperacetylation.

    OpenAIRE

    Nelson, D. A.; Ferris, R C; Zhang, D E; Ferenz, C R

    1986-01-01

    A 60 minute exposure of chicken immature erythrocytes to n-butyrate shifts actively acetylated and deacetylated histones to hypermodified forms. Micrococcal nuclease digestion of nuclei from n-butyrate treated cells and subsequent fractionation of the chromatin releases 40-45% of the adult beta-globin (beta A) nucleohistone into a soluble fraction. This is an eleven fold enrichment over the soluble chromatin from untreated cells (Ferenz and Nelson (1985) Nucleic Acids Res. 13, 1977-1995). The...

  13. Solubility of MgO in chloride melts containing NdCl3 or LaCl3

    OpenAIRE

    Li, Bing; Li, Jun; Chen, Jinzhong; Yu, Jianguo

    2009-01-01

    Due to extremely low solubility in conventional magnesium electrolyte, MgO tends to attach to cathode and causes cathodic passivation, which will dramatically lower current efficiency of magnesium electrolysis. In this paper, NdCl3 or LaCl3 was added to conventional magnesium electrolyte to increase MgO solubility. We investigated the effects of NdCl3 or LaCl3 content, the form of MgO, and temperature on the dissolution rate of MgO and on MgO solubility. MgO solubility increased with increasi...

  14. Solubilities of uranium for TILA-99

    Energy Technology Data Exchange (ETDEWEB)

    Ollila, K. [VTT Chemical Technology, Espoo (Finland); Ahonen, L. [Geological Survey of Finland, Espoo (Finland)

    1998-11-01

    This report presents the evaluation of the uranium solubilities in the reference waters of TILA-99. The behaviour of uranium has been discussed separately in the near-field and far-field conditions. The bentonite/groundwater interactions have been considered in the compositions of the fresh and saline near-field reference waters. The far-field groundwaters` compositions include fresh, brackish, saline and very saline, almost brine-type compositions. The pH and redox conditions, as the main parameters affecting the solubilities, are considered. A literature study was made in order to obtain information on the recent dissolution and leaching experiments of UO{sub 2} and spent fuel. The latest literature includes studies on UO{sub 2} solubility under anoxic conditions, in which the methods for simulating the reducing conditions of deep groundwater have been improved. Studies on natural uraninite and its alteration products give a valuable insight into the long-term behaviour of spent fuel. Also the solubility equilibria for some relevant poorly known uranium minerals have been determined. The solubilities of the selected solubility-limiting phases were calculated using the geochemical code, EQ3/6. The NEA database for uranium was the basis for the modelling. The recently extended and updated SR `97 database was used for comparison. The solubility products for uranophane were taken from the latest literature. The recommended values for solubilities were given after a comparison between the calculated solubilities, experimental information and measured concentrations in natural groundwaters. The experiments include several UO{sub 2} dissolution studies in synthetic groundwaters with compositions close to the reference groundwaters. (author) 81 refs.

  15. Mouillage de polymères solubles

    OpenAIRE

    Dupas, Julien

    2012-01-01

    Le mouillage d'un substrat soluble est une situation couramment rencontrée dans la vie de tous les jours les jours. Par exemple, les motivations pratiques de cette étude concernent la préparation de boissons à partir de poudres déshydratées, constituées de substances solubles dans l'eau telles que les glucides. Les modèles hydrodynamiques décrivant le mouillage sur un substrat non soluble ne peuvent pas expliquer les observations expérimentales dans le cas d'un liquide s'étalant sur un substr...

  16. Molecular Thermodynamic Modeling of Mixed Solvent Solubility

    DEFF Research Database (Denmark)

    Ellegaard, Martin Dela; Abildskov, Jens; O’Connell, John P.

    2010-01-01

    A method based on statistical mechanical fluctuation solution theory for composition derivatives of activity coefficients is employed for estimating dilute solubilities of 11 solid pharmaceutical solutes in nearly 70 mixed aqueous and nonaqueous solvent systems. The solvent mixtures range from...... nearly ideal to strongly nonideal. The database covers a temperature range from 293 to 323 K. Comparisons with available data and other existing solubility methods show that the method successfully describes a variety of observed mixed solvent solubility behaviors using solute−solvent parameters from...

  17. Two novel heat-soluble protein families abundantly expressed in an anhydrobiotic tardigrade.

    Directory of Open Access Journals (Sweden)

    Ayami Yamaguchi

    Full Text Available Tardigrades are able to tolerate almost complete dehydration by reversibly switching to an ametabolic state. This ability is called anhydrobiosis. In the anhydrobiotic state, tardigrades can withstand various extreme environments including space, but their molecular basis remains largely unknown. Late embryogenesis abundant (LEA proteins are heat-soluble proteins and can prevent protein-aggregation in dehydrated conditions in other anhydrobiotic organisms, but their relevance to tardigrade anhydrobiosis is not clarified. In this study, we focused on the heat-soluble property characteristic of LEA proteins and conducted heat-soluble proteomics using an anhydrobiotic tardigrade. Our heat-soluble proteomics identified five abundant heat-soluble proteins. All of them showed no sequence similarity with LEA proteins and formed two novel protein families with distinct subcellular localizations. We named them Cytoplasmic Abundant Heat Soluble (CAHS and Secretory Abundant Heat Soluble (SAHS protein families, according to their localization. Both protein families were conserved among tardigrades, but not found in other phyla. Although CAHS protein was intrinsically unstructured and SAHS protein was rich in β-structure in the hydrated condition, proteins in both families changed their conformation to an α-helical structure in water-deficient conditions as LEA proteins do. Two conserved repeats of 19-mer motifs in CAHS proteins were capable to form amphiphilic stripes in α-helices, suggesting their roles as molecular shield in water-deficient condition, though charge distribution pattern in α-helices were different between CAHS and LEA proteins. Tardigrades might have evolved novel protein families with a heat-soluble property and this study revealed a novel repertoire of major heat-soluble proteins in these anhydrobiotic animals.

  18. Cyclodextrins and ternary complexes: technology to improve solubility of poorly soluble drugs

    Directory of Open Access Journals (Sweden)

    Janisse Crestani de Miranda

    2011-12-01

    Full Text Available Cyclodextrins (CDs are cyclic oligosaccharides composed of D-glucopyranoside units linked by glycosidic bonds. Their main property is the ability to modify the physicochemical and biological characteristics of low-soluble drugs through the formation of drug:CD inclusion complexes. Inclusion complexation requires that host molecules fit completely or partially within the CD cavity. This adjustment is directly related to the physicochemical properties of the guest and host molecules, easy accommodation of guest molecules within the CD cavity, stoichiometry, therapeutic dose, and toxicity. However, dosage forms may achieve a high volume, depending on the amount of CD required. Thus, it is necessary to increase solubilization efficiency in order to use smaller amounts of CD. This can be achieved by adding small amounts of water-soluble polymers to the system. This review addresses aspects related to drug complexation with CDs using water-soluble polymers to optimize the amount of CD used in the formulation in order to increase drug solubility and reduce dosage form volume.Ciclodextrinas (CDs são oligossacarídeos cíclicos, compostos por unidades D-glicopiranosídicas ligadas entre si por meio de ligações glicosídicas e sua principal propriedade está na capacidade de alterar as características físico-químicas e biológicas de fármacos com baixa solubilidade por meio da formação de complexos de inclusão fármaco:CD. Para a formação dos complexos de inclusão a molécula hospedeira necessita ajustar-se total ou parcialmente no interior da cavidade da CD, onde este ajuste está diretamente ligado a propriedades físico-químicas da molécula hóspede e hospedeira, facilidade de alojamento da molécula hóspede no interior da cavidade da CD, estequiometria, dose terapêutica e toxicidade. No entanto, as formas farmacêuticas podem atingir um elevado volume, em função da quantidade de CD requerida, sendo necessário aumentar sua efici

  19. Prevalence of the apolipoprotein E Arg145Cys dyslipidemia at-risk polymorphism in African-derived populations.

    Science.gov (United States)

    Abou Ziki, Maen D; Strulovici-Barel, Yael; Hackett, Neil R; Rodriguez-Flores, Juan L; Mezey, Jason G; Salit, Jacqueline; Radisch, Sharon; Hollmann, Charleen; Chouchane, Lotfi; Malek, Joel; Zirie, Mahmoud A; Jayyuosi, Amin; Gotto, Antonio M; Crystal, Ronald G

    2014-01-15

    Apolipoprotein E, a protein component of blood lipid particles, plays an important role in lipid transport. Different mutations in the apolipoprotein E gene have been associated with various clinical phenotypes. In an initiated study of Qataris, we observed that 17% of the African-derived genetic subgroup were heterozygotes for a rare Arg145Cys (R145C) variant that functions as a dominant trait with incomplete penetrance associated with type III hyperlipoproteinemia. On the basis of this observation, we hypothesized that the R145C polymorphism might be common in African-derived populations. The prevalence of the R145C variant was assessed worldwide in the "1000 Genomes Project" and in 1,012 whites and 1,226 African-Americans in New York, New York. The 1000 Genomes Project data demonstrated that the R145C polymorphism is rare in non-African-derived populations but present in 5% to 12% of Sub-Saharan African-derived populations. The R145C polymorphism was also rare in New York whites (1 of 1,012, 0.1%); however, strikingly, 53 of the 1,226 New York African-Americans (4.3%) were R145C heterozygotes. The lipid profiles of the Qatari and New York R145C heterozygotes were compared with those of controls. The Qatari R145C subjects had higher triglyceride levels than the Qatari controls (p worldwide derived from Sub-Saharan Africans are apolipoprotein E R145C. In conclusion, although larger epidemiologic studies are necessary to determine the long-term consequences of this polymorphism, the available evidence suggests it is a common cause of a mild triglyceride dyslipidemia. PMID:24239320

  20. Comparison of deuterated leucine, valine, and lysine in the measurement of human apolipoprotein A-I and B-100 kinetics

    International Nuclear Information System (INIS)

    The production rates of apolipoprotein (apo)B-100 in very low density lipoprotein and in low density lipoprotein and apolipoprotein A-I in high density lipoprotein were determined using a primed-constant infusion of [5,5,5,-2H3]leucine, [4,4,4,-2H3]valine, and [6,6-2H2,1,2-13C2]lysine. The three stable isotope-labeled amino acids were administered simultaneously to determine whether absolute production rates calculated using a stochastic model were independent of the tracer species utilized. Three normolipidemic adult males were studied in the constantly fed state over a 15-h period. The absolute production rates of very low density lipoprotein apoB-100 were 11.4 +/- 5.8 (leucine), 11.2 +/- 6.8 (valine), and 11.1 +/- 5.4 (lysine) mg per kg per day (mean +/- SDM). The absolute production rates for low density lipoprotein apoB-100 were 8.0 +/- 4.7 (leucine), 7.5 +/- 3.8 (valine), and 7.5 +/- 4.2 (lysine) mg per kg per day. The absolute production rates for high density lipoprotein apoA-I were 9.7 +/- 0.2 (leucine), 9.4 +/- 1.7 (valine), and 9.1 +/- 1.3 (lysine) mg per kg per day. There were no statistically significant differences in absolute synthetic rates of the three apolipoproteins when the plateau isotopic enrichment values of very low density lipoprotein apoB-100 were used to define the isotopic enrichment of the intracellular precursor pool. Our data indicate that deuterated leucine, valine, or lysine provided similar results when used for the determination of apoA-I and apoB-100 absolute production rates within plasma lipoproteins as part of a primed-constant infusion protocol

  1. DEVELOPMENT OF SOLUBILITY PRODUCT VISUALIZATION TOOLS

    Energy Technology Data Exchange (ETDEWEB)

    T.F. Turner; A.T. Pauli; J.F. Schabron

    2004-05-01

    Western Research Institute (WRI) has developed software for the visualization of data acquired from solubility tests. The work was performed in conjunction with AB Nynas Petroleum, Nynashamn, Sweden who participated as the corporate cosponsor for this Jointly Sponsored Research (JSR) task. Efforts in this project were split between software development and solubility test development. The Microsoft Windows-compatible software developed inputs up to three solubility data sets, calculates the parameters for six solid body types to fit the data, and interactively displays the results in three dimensions. Several infrared spectroscopy techniques have been examined for potential use in determining bitumen solubility in various solvents. Reflectance, time-averaged absorbance, and transmittance techniques were applied to bitumen samples in single and binary solvent systems. None of the techniques were found to have wide applicability.

  2. Relevance of apolipoprotein E4 for the lipid profile of Brazilian patients with coronary artery disease

    Directory of Open Access Journals (Sweden)

    D.R.S. Souza

    2007-02-01

    Full Text Available Apolipoprotein E (apoE - e2, e3, e4 alleles plays a role in the regulation of lipid metabolism, with the e4 considered to be a risk factor for coronary artery disease (CAD. We aimed to evaluate the apoE polymorphisms in Brazilians with CAD and their influence on the lipid profile and other risk factors (hypertension, diabetes mellitus, smoking. Two hundred individuals were examined: 100 patients with atherosclerosis confirmed by coronary angiography and 100 controls. Blood samples were drawn to determine apoE polymorphisms and lipid profile. As expected, the e3 allele was prevalent in the CAD (0.87 and non-CAD groups (0.81; P = 0.099, followed by the e4 allele (0.09 and 0.14, respectively; P = 0.158. The e3/3 (76 and 78% and e3/4 (16 and 23% were the most common genotypes for patients and controls, respectively. The lipid profile was altered in patients compared to controls (P < 0.05, independently of the e4 allele. However, in the controls this allele was prevalent in individuals with elevated LDL-cholesterol levels only (odds ratio = 2.531; 95% CI = 1.028-6.232. The frequency of risk factors was higher in the CAD group (P < 0.05, but their association with the lipid profile was not demonstrable in e4 carriers. In conclusion, the e4 allele is not associated with CAD or lipid profile in patients with atherosclerosis. However, its frequency in the non-CAD group is associated with increased levels of LDL-cholesterol, suggesting an independent effect of the e4 allele on lipid profile when the low frequency of other risk factors in this group is taken into account.

  3. Apolipoprotein E polymorphism influences postprandial retinyl palmitate but not triglyceride concentrations

    Energy Technology Data Exchange (ETDEWEB)

    Boerwinkle, E. (Univ. of Texas Health Science Center, Houston, TX (United States)); Brown, S.; Patsch, W. (Methodist Hospital and Baylor College of Medicine, Houston, TX (United States)); Sharrett, A.R. (National Heart, Lung, and Blood Institute, Bethesda, MD (United States)); Heiss, G. (Univ. of North Carolina, Chapel Hill, NC (United States))

    1994-02-01

    To quantify the effect of the apolipoprotein (apo) E polymorphism on the magnitude of postprandial lipemia, the authors have defined its role in determining the response to a single high-fat meal in a large sample of (N = 474) individuals taking part in the biethnic Atherosclerosis Risk in Communities Study. The profile of postprandial response in plasma was monitored over 8 h by triglyceride, triglyceride-rich lipoprotein (TGRL)-triglyceride, apo B-48/apo B-100 ratio, and retinyl palmitate concentrations, and the apo E polymorphism was determined by DNA amplification and digestion. The frequency of the apo E alleles and their effects on fasting lipid levels in this sample with vitamin A was significantly different among apo E genotypes, with delayed clearance in individuals with an [var epsilon]2 allele, compared with [var epsilon]3/3 and [var epsilon]3/4 individuals. In the sample of 397 Caucasians, average retinyl palmitate response was 1,489 [mu]g/dl in [var epsilon]2/3 individuals, compared with 1,037 [mu]g/dl in [var epsilon]3/3 individuals and 1,108 [mu]g/dl in [var epsilon]3/4 individuals. The apo E polymorphism accounted for 7.1% of the interindividual variation in postprandial retinyl palmitate response, a contribution proportionally greater than its well-known effect on fasting LDL-cholesterol. However, despite this effect on postprandial retinyl palmitate, the profile of postprandial triglyceride response was not significantly different among apo E genotypes. The profile of postprandial response was consistent between the sample of Caucasians and a smaller sample of black subjects. While these data indicate that the removal of remnant particles from circulation is delayed in subjects with the [var epsilon]2/3 genotype, there is no reported evidence that the [var epsilon]2 allele predisposes to coronary artery disease (CAD). 82 refs., 6 figs., 4 tabs.

  4. p53 family members regulate the expression of the apolipoprotein D gene.

    Science.gov (United States)

    Sasaki, Yasushi; Negishi, Hideaki; Koyama, Ryota; Anbo, Naoki; Ohori, Kanae; Idogawa, Masashi; Mita, Hiroaki; Toyota, Minoru; Imai, Kohzoh; Shinomura, Yasuhisa; Tokino, Takashi

    2009-01-01

    p73 and p63 are members of the p53 gene family that play an important role in development and homeostasis, mainly by regulating transcription of a variety of genes. We report here that apolipoprotein D (apoD), a member of the lipocalin superfamily of lipid transport proteins, is a direct transcriptional target of the p53 family member genes. We found that the expression of apoD was specifically up-regulated by either TAp73 or TAp63 but not significantly by p53. In addition, apoD transcription is activated in response to cisplatin in a manner dependent on endogenous p73. By using small interference RNA designed to target p73, we demonstrated that silencing endogenous p73 abolishes induction of apoD transcription following cisplatin treatment. We also identified a p73/p63-binding site in the promoter of the apoD gene that is responsive to the p53 family members. The ectopic expression of TAp73 as well as the addition of recombinant human apoD to culture medium induced the osteoblastic differentiation of the human osteosarcoma cell line Saos-2, as assessed by alkaline phosphatase activity. Importantly, apoD knockdown abrogated p73-mediated alkaline phosphatase induction. Moreover, TAp73-mediated apoD expression was able to induce morphological differentiation, as well as expression of neuronal markers, in the human neuroblastoma cell line SH-SY5Y. These results suggest that apoD induction may mediate the activity of p73 in normal development. PMID:19001418

  5. Clusterin/apolipoprotein J attenuates angiotensin II-induced renal fibrosis.

    Directory of Open Access Journals (Sweden)

    Gwon-Soo Jung

    Full Text Available The blockade of angiotensin II (Ang II is a major therapeutic strategy for diabetic nephropathy. The main roles of Ang II in renal disease are mediated via the Ang type 1 receptor (AT1R. Upregulation of clusterin/apolipoprotein J has been reported in nephropathy models, suggesting it has a protective role in nephropathogenesis. Here, we studied how clusterin acts against Ang II-induced renal fibrosis. Levels of AT1R and fibrotic markers in clusterin-/- mice and Ang II infused rats transfected with an adenovirus encoding clusterin were evaluated by immunoblot analysis, real time RT-PCR, and immunohistochemical staining. The effect of clusterin on renal fibrosis was evaluated in NRK-52E cells, a cultured renal tubular epithelial cell line, using immunoblot analysis and real time RT-PCR. Nuclear localization of NF-κB was evaluated using immunofluorecence and co-immunoprecipitation. Renal fibrosis and expression of AT1R was higher in the kidneys of clusterin-/- mice than in those of wild-type mice. Furthermore, loss of clusterin accelerated Ang II-stimulated renal fibrosis and AT1R expression. Overexpression of clusterin in proximal tubular epithelial cells decreased the levels of Ang II-stimulated fibrotic markers and AT1R. Moreover, intrarenal delivery of clusterin attenuated Ang II-mediated expression of fibrotic markers and AT1R in rats. Fluorescence microscopy and co-immunoprecipitation in conjunction with western blot revealed that clusterin inhibited Ang II-stimulated nuclear localization of p-NF-κB via a direct physical interaction and subsequently decreased the AT1R level in proximal tubular epithelial cells. These data suggest that clusterin attenuates Ang II-induced renal fibrosis by inhibition of NF-κB activation and subsequent downregulation of AT1R. This study raises the possibility that clusterin could be used as a therapeutic target for Ang II-induced renal diseases.

  6. Kaempferol regulates OPN-CD44 pathway to inhibit the atherogenesis of apolipoprotein E deficient mice

    Energy Technology Data Exchange (ETDEWEB)

    Xiao, Hong-Bo, E-mail: xhbzhb@yahoo.com [College of Veterinary Medicine, Hunan Agricultural University, Changsha 410128 (China); Lu, Xiang-Yang; Sun, Zhi-Liang [Hunan Agricultural University, Changsha 410128 (China); Zhang, Heng-Bo [Furong District Red Cross Hospital, Changsha 410126 (China)

    2011-12-15

    Recent studies show that osteopontin (OPN) and its receptor cluster of differentiation 44 (CD44) are two pro-inflammatory cytokines contributing to the development of atherosclerosis. The objective of this study was to explore the inhibitory effect of kaempferol, a naturally occurring flavonoid compound, on atherogenesis and the mechanisms involved. The experiments were performed in aorta and plasma from C57BL/6J control and apolipoprotein E-deficient (ApoE{sup -/-}) mice treated or not with kaempferol (50 or 100 mg/kg, intragastrically) for 4 weeks. Kaempferol treatment decreased atherosclerotic lesion area, improved endothelium-dependent vasorelaxation, and increased the maximal relaxation value concomitantly with decrease in the half-maximum effective concentration, plasma OPN level, aortic OPN expression, and aortic CD44 expression in ApoE{sup -/-} mice. In addition, treatment with kaempferol also significantly decreased reactive oxygen species production in mice aorta. The present results suggest that kaempferol regulates OPN-CD44 pathway to inhibit the atherogenesis of ApoE{sup -/-} mice. -- Graphical abstract: Kaempferol regulates OPN-CD44 pathway to inhibit the atherogenesis of ApoE{sup -/-} mice. Highlights: Black-Right-Pointing-Pointer OPN-CD44 pathway plays a critical role in the development of atherosclerosis. Black-Right-Pointing-Pointer We examine lesion area, OPN and CD44 changes after kaempferol treatment. Black-Right-Pointing-Pointer Kaempferol treatment decreased atherosclerotic lesion area in ApoE{sup -/-} mice. Black-Right-Pointing-Pointer Kaempferol treatment decreased aortic OPN and CD44 expressions in ApoE{sup -/-} mice. Black-Right-Pointing-Pointer Kaempferol regulates OPN-CD44 pathway to inhibit the atherogenesis.

  7. Blue-Green Algae Inhibit the Development of Atherosclerotic Lesions in Apolipoprotein E Knockout Mice.

    Science.gov (United States)

    Ku, Chai Siah; Kim, Bohkyung; Pham, Tho X; Yang, Yue; Wegner, Casey J; Park, Young-Ki; Balunas, Marcy; Lee, Ji-Young

    2015-12-01

    Hyperlipidemia and inflammation contribute to the development of atherosclerotic lesions. Our objective was to determine antiatherogenic effect of edible blue-green algae (BGA) species, that is, Nostoc commune var. sphaeroides Kützing (NO) and Spirulina platensis (SP), in apolipoprotein E knockout (ApoE(-/-)) mice, a well-established mouse model of atherosclerosis. Male ApoE(-/-) mice were fed a high-fat/high-cholesterol (HF/HC, 15% fat and 0.2% cholesterol by wt) control diet or a HF/HC diet supplemented with 5% (w/w) of NO or SP powder for 12 weeks. Plasma total cholesterol (TC) and triglycerides (TG) were measured, and livers were analyzed for histology and gene expression. Morphometric analysis for lesions and immunohistochemical analysis for CD68 were conducted in the aorta and the aortic root. NO supplementation significantly decreased plasma TC and TG, and liver TC, compared to control and SP groups. In the livers of NO-fed mice, less lipid droplets were present with a concomitant decrease in fatty acid synthase protein levels than the other groups. There was a significant increase in hepatic low-density lipoprotein receptor protein levels in SP-supplemented mice than in control and NO groups. Quantification of aortic lesions by en face analysis demonstrated that both NO and SP decreased aortic lesion development to a similar degree compared with control. While lesions in the aortic root were not significantly different between groups, the CD68-stained area in the aortic root was significantly lowered in BGA-fed mice than controls. In conclusion, both NO and SP supplementation decreased the development of atherosclerotic lesions, suggesting that they may be used as a natural product for atheroprotection. PMID:26566121

  8. Apolipoprotein A-I Helsinki promotes intracellular acyl-CoA cholesterol acyltransferase (ACAT) protein accumulation.

    Science.gov (United States)

    Toledo, Juan D; Garda, Horacio A; Cabaleiro, Laura V; Cuellar, Angela; Pellon-Maison, Magali; Gonzalez-Baro, Maria R; Gonzalez, Marina C

    2013-05-01

    Reverse cholesterol transport is a process of high antiatherogenic relevance in which apolipoprotein AI (apoA-I) plays an important role. The interaction of apoA-I with peripheral cells produces through mechanisms that are still poorly understood the mobilization of intracellular cholesterol depots toward plasma membrane. In macrophages, these mechanisms seem to be related to the modulation of the activity of acyl-CoA cholesterol acyltransferase (ACAT), the enzyme responsible for the intracellular cholesterol ester biosynthesis that is stored in lipid droplets. The activation of ACAT and the accumulation of lipid droplets play a key role in the transformation of macrophages into foam cells, leading to the formation of atheroma or atherosclerotic plaque. ApoA-I Helsinki (or ∆K107) is a natural apoA-I variant with a lysine deletion in the central protein region, carriers of which have increased atherosclerosis risk. We herein show that treatment of cultured RAW macrophages or CHOK1 cells with ∆K107, but not with wild-type apoA-I or a variant containing a similar deletion at the C-terminal region (∆K226), lead to a marked increase (more than 10 times) in the intracellular ACAT1 protein level as detected by western blot analysis. However, we could only detect a slight increase in cholesteryl ester produced by ∆K107 mainly when Chol loading was supplied by low-density lipoprotein (LDL). Although a similar choline-phospholipid efflux is evoked by these apoA-I variants, the change in phosphatidylcholine/sphyngomyelin distribution produced by wild-type apoA-I is not observed with either ∆K107 or ∆K226. PMID:23456478

  9. Apolipoprotein A-I metabolism in cynomolgus monkey. Identification and characterization of beta-migrating pools

    International Nuclear Information System (INIS)

    Fresh plasma from control (C) and hypercholesterolemic (HC) cynomolgus monkeys was analyzed by agarose electrophoresis-immunoblotting with antibody to cynomolgus monkey apolipoprotein (apo) A-I. Two bands were evident on the autoradiogram: an alpha-migrating band (high density lipoprotein) and a beta-migrating band that comigrated exactly with cynomolgus monkey low density lipoprotein (LDL). The presence of beta-migrating apo A-I in the plasma of these monkeys was confirmed by Geon-Pevikon preparative electrophoresis, crossed immunoelectrophoresis, and isotope dilution studies in which radiolabeled apo A-I was found to equilibrate also with alpha- and beta-migrating pools of apo A-I in the plasma. Subfractionation of C and HC plasma by agarose column chromatography (Bio-Gel A-0.5M and A-15M) followed by agarose electrophoresis-immunoblotting indicated that the beta-migrating apo A-I in C was relatively homogeneous and eluted with proteins of Mr approximately 50 kD [apo A-I(50 kD)], whereas two beta-migrating fractions were identified in HC, one that eluted with the 50-kD proteins, and the other that eluted in the LDL Mr range [apo A-I(LDL)]. The apo A-I(LDL) was precipitated by antibody to cynomolgus monkey apo B. The apo A-I(50 kD) accounted for 5 +/- 1% (mean +/- SD) of the plasma apo A-I in C plasma, and 15 +/- 7% in HC plasma. No apo A-I(LDL) was detected in C plasma, but that fraction accounted for 9 +/- 7% of the apo A-I in HC plasma. These data establish the presence of multiple pools of apo A-I in the cynomolgus monkey, which must be taken into consideration in any comprehensive model of apo A-I metabolism in this species

  10. CHRNA7 Polymorphisms and Dementia Risk: Interactions with Apolipoprotein ε4 and Cigarette Smoking.

    Science.gov (United States)

    Weng, Pei-Hsuan; Chen, Jen-Hau; Chen, Ta-Fu; Sun, Yu; Wen, Li-Li; Yip, Ping-Keung; Chu, Yi-Min; Chen, Yen-Ching

    2016-01-01

    α7 nicotinic acetylcholine receptor (α7nAChR, encoded by CHRNA7) is involved in dementia pathogenesis through cholinergic neurotransmission, neuroprotection and interactions with amyloid-β. Smoking promotes atherosclerosis and increases dementia risk, but nicotine exerts neuroprotective effect via α7nAChR in preclinical studies. No studies explored the gene-gene, gene-environment interactions between CHRNA7 polymorphism, apolipoprotein E (APOE) ε4 status and smoking on dementia risk. This case-control study recruited 254 late-onset Alzheimer's disease (LOAD) and 115 vascular dementia (VaD) cases (age ≥65) from the neurology clinics of three teaching hospitals in Taiwan during 2007-2010. Controls (N = 435) were recruited from health checkup programs and volunteers during the same period. Nine CHRNA7 haplotype-tagging single nucleotide polymorphisms representative for Taiwanese were genotyped. Among APOE ε4 non-carriers, CHRNA7 rs7179008 variant carriers had significantly decreased LOAD risk after correction for multiple tests (GG + AG vs. AA: adjusted odds ratio = 0.29, 95% confidence interval = 0.13-0.64, P = 0.002). Similar findings were observed for carriers of GT haplotype in CHRNA7 block4. A significant interaction was found between rs7179008, GT haplotype in block4 and APOE ε4 on LOAD risk. rs7179008 variant also reduced the detrimental effect of smoking on LOAD risk. No significant association was found between CHRNA7 and VaD. These findings help to understand dementia pathogenesis. PMID:27249957

  11. Apolipoprotein E expression and behavioral toxicity of high charge, high energy (HZE) particle radiation

    International Nuclear Information System (INIS)

    Apolipoprotein E (apoE) is a lipid binding protein that plays an important role in tissue repair following brain injury. In the present studies, we have investigated whether apoE affects the behavioral toxicity of high charge, high energy (HZE) particle radiation. Sixteen male apoE knockout (KO) mice and sixteen genetically matched wild-type (WT) C57BL mice were used in this experiment. Half of the KO and half of the WT animals were irradiated with 600 MeV/amu iron particles (2 Gy whole body). The effect of irradiation on motor coordination and stamina (Rotarod test), exploratory behavior (open field test), and spatial working and reference memory (Morris water maze) was assessed. Rotarod test: Performance was adversely affected by radiation exposure in both KO and WT groups at 30 d after irradiation. By 60 d after radiation, the radiation effect was lost in WT, but still apparent in irradiated KO mice. Open field test: Radiation reduced open field exploratory activity 14, 28, 56, 84, and 168 d after irradiation of KO mice, but had no effect on WT mice. Morris water maze: Radiation adversely affected spatial working memory in the KO mice, but had no discernible effect in the WT mice as assessed 180 d after irradiation. In contrast, irradiated WT mice showed marked impairment of spatial reference memory in comparison to non-irradiated mice, while no effect of radiation was observed in KO mice. These studies show that apoE expression influences the behavioral toxicity of HZE particle radiation and suggest that apoE plays a role in the repair/recovery from radiation injury of the central nervous system (CNS). ApoE deficiency may exacerbate the previously reported effects of HZE particle radiation in accelerating the brain aging process. (author)

  12. Two independent apolipoprotein a5 Haplotypes influence human plasma triglyceride levels

    Energy Technology Data Exchange (ETDEWEB)

    Pennacchio, Len A.; Olivier, Michael; Hubacek, Jaroslav A.; Krauss, Ronald M.; Rubin, Edward M.; Cohen, Jonathan C.

    2002-09-16

    The recently identified apolipoprotein A5 gene (APOA5) has been shown to play an important role in determining plasma triglyceride concentrations in humans and mice. We previously identified an APOA5 haplotype (designated APOA5*2) that is present in {approx}16 percent of Caucasians and is associated with increased plasma triglyceride concentrations. In this report we describe another APOA5 haplotype (APOA5*3) containing the rare allele of the single nucleotide polymorphism c.56C>G that changes serine to tryptophan at codon 19 and is independently associated with high plasma triglyceride levels in three different populations. In a sample of 264 Caucasian men and women with plasma triglyceride concentrations above the 90th percentile or below the 10th percentile, the APOA5*3 haplotype was more than three-fold more common in the group with high plasma triglyceride levels. In a second independently ascertained sample of Caucasian men and women (n 1/4 419) who were studied while consuming their self-selected diets as well as after high-carbohydrate diets and high-fat diets, the APOA5*3 haplotype was associated with increased plasma triglyceride levels on all three dietary regimens. In a third population comprising 2660 randomly selected individuals, the APOA5*3 haplotype was found in 12 percent of Caucasians, 14 percent of African-Americans and 28 percent of Hispanics and was associated with increased plasma triglyceride levels in both men and women in each ethnic group. These findings establish that the APOA5 locus contributes significantly to inter-individual variation in plasma triglyceride levels in humans. Together, the APOA5*2 and APOA5*3 haplotypes are found in 25 50 percent of African-Americans, Hispanics and Caucasians and support the contribution of common human variation to quantitative phenotypes in the general population.

  13. Effects of simvastatin on early oxidative stress and endothelial function in apolipoprotein E-deficient mice

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective:To investigate the mechanisms that Simvastatin,a 3-ydroxy-3-methylglutaryl coenzyme A(HMG-CoA)reductase inhibitor,plays an important role in primary prevention of atherosclerosis independently of its lipid-lowering effect in Apolipoprotein E-deficient mice in the early stage of atherosclerosis.Methods:Twenty-four 6-week old male apoE-deficient mice were randomly divided into two groups:control group(normal saline)and treatment group[simvastatin(5 mg/(kg·d))].Simvastatin was administered to treatment group mice by gavage and the same volume of normal saline was administered to control group mice by the same method for 2 or 4 weeks.Total cholesterol(TC),super-oxide dismutase(SOD),malondialdehyde(MDA)and serum nitric oxide(NO)were measured by biochemical analysis.Results:There was no significant difference in serum TC between control and treatment groups.Compared with the control's,the effects of simvastatin were more signiticant in decreasing serum MDA level(P<0.01 vs control's at 2-week;P<0.006 vs control's at 4-week),increasing serum SOD level(P<0.03 vs control's at 2-week;P<0.003 vs control's at 4-week)and NO level (P<0.01 control's at 2-week;P<0.001 vs control's at 4-week)either at 2 or 4 weeks.Conclusion:Simvastatin attenuates oxidative stress and protects endothelial function by the mechanisms of decreasing serum MDA level,increasing serum SOD level and NO level,which were inconsistent with its cholesterol-lowering effect.It may play an important role in primary(if not all)prevention of atherosclerosis and might be independent of lipid-regulation mechanism.

  14. Inhibition of endoplasmic reticulum stress and atherosclerosis by 2-aminopurine in apolipoprotein e-deficient mice.

    Science.gov (United States)

    Zhou, Lichun; Yang, Dezhi; Wu, Dong Fang; Guo, Zhong Mao; Okoro, Emmanuel; Yang, Hong

    2013-01-01

    We previously reported that the apolipoprotein (apo) B48-carrying lipoproteins obtained from apoE knockout (apoE (-/-) ) mice, so called E(-)/B48 lipoproteins, transformed mouse macrophages into foam cells and enhanced the phosphorylation of eukaryotic translation initiation factor 2 α (eIF-2 α ). Furthermore, the eIF-2 α phosphorylation inhibitor, 2-aminopurine (2-AP), attenuated E(-)/B48 lipoprotein-induced foam cell formation. The present report studied the effect of 2-AP on atherosclerosis in apoE (-/-) mice. Our results showed that the level of food intake, bodyweight, plasma cholesterol, and triglycerides was comparable in apoE (-/-) mice treated with or without 2-AP. However, the mean size of atherosclerotic lesions in the aorta sinus as well as the surface area of the entire aorta of 2-AP-treated apoE (-/-) mice were reduced by about 55% and 39%, respectively, compared to samples from untreated control apoE (-/-) mice. In addition, the 2-AP-treated apoE (-/-) mice showed a significant decrease in glucose-regulated protein 78 (GRP78) and phosphorylated eIF-2 α in their aortic samples as compared to levels in untreated control apoE (-/-) mice. These observations suggest that endoplasmic reticulum stress is a causal mechanism for the development of atherosclerosis in apoE (-/-) mice and that therapeutic strategies can be developed for using eIF-2 α phosphorylation inhibitors, such as 2-AP, to prevent or treat atherosclerosis. PMID:23984090

  15. Synergistic effects of high fat feeding and apolipoprotein E deletion on enterocytic amyloid-beta abundance

    Directory of Open Access Journals (Sweden)

    Dhaliwal Satvinder S

    2008-04-01

    Full Text Available Abstract Background Amyloid-β (Aβ, a key protein found in amyloid plaques of subjects with Alzheimer's disease is expressed in the absorptive epithelial cells of the small intestine. Ingestion of saturated fat significantly enhances enterocytic Aβ abundance whereas fasting abolishes expression. Apolipoprotein (apo E has been shown to directly modulate Aβ biogenesis in liver and neuronal cells but it's effect in enterocytes is not known. In addition, apo E modulates villi length, which may indirectly modulate Aβ as a consequence of differences in lipid absorption. This study compared Aβ abundance and villi length in wild-type (WT and apo E knockout (KO mice maintained on either a low-fat or high-fat diet. Wild-type C57BL/6J and apo E KO mice were randomised for six-months to a diet containing either 4% (w/w unsaturated fats, or chow comprising 16% saturated fats and 1% cholesterol. Quantitative immunohistochemistry was used to assess Aβ abundance in small intestinal enterocytes. Apo E KO mice given the low-fat diet had similar enterocytic Aβ abundance compared to WT controls. Results The saturated fat diet substantially increased enterocytic Aβ in WT and in apo E KO mice, however the effect was greater in the latter. Villi height was significantly greater in apo E KO mice than for WT controls when given the low-fat diet. However, WT mice had comparable villi length to apo E KO when fed the saturated fat and cholesterol enriched diet. There was no effect of the high-fat diet on villi length in apo E KO mice. Conclusion The findings of this study are consistent with the notion that lipid substrate availability modulates enterocytic Aβ. Apo E may influence enterocytic lipid availability by modulating absorptive capacity.

  16. Leptospiral LruA is required for virulence and modulates an interaction with mammalian apolipoprotein AI.

    Science.gov (United States)

    Zhang, Kunkun; Murray, Gerald L; Seemann, Torsten; Srikram, Amporn; Bartpho, Thanatchaporn; Sermswan, Rasana W; Adler, Ben; Hoke, David E

    2013-10-01

    Leptospirosis is a worldwide zoonosis caused by spirochetes of the genus Leptospira. While understanding of pathogenesis remains limited, the development of mutagenesis in Leptospira has provided a powerful tool for identifying novel virulence factors. LruA is a lipoprotein that has been implicated in leptospiral uveitis as a target of the immune response. In this study, two lruA mutants, M754 and M765, generated by transposon mutagenesis from Leptospira interrogans serovar Manilae, were characterized. In M754, the transposon inserted in the middle of lruA, resulting in no detectable expression of LruA. In M765, the transposon inserted toward the 3' end of the gene, resulting in expression of a truncated protein. LruA was demonstrated to be on the cell surface in M765 and the wild type (WT). M754, but not M765, was attenuated in a hamster model of acute infection. A search for differential binding to human serum proteins identified a serum protein of around 30 kDa bound to the wild type and the LruA deletion mutant (M754), but not to the LruA truncation mutant (M765). Two-dimensional separation of proteins from leptospiral cells incubated with guinea pig serum identified the 28-kDa apolipoprotein A-I (ApoA-I) as a major mammalian serum protein that binds Leptospira in vitro. Interestingly, M754 (with no detectable LruA) bound more ApoA-I than did the LruA-expressing strains Manilae wild type and M765. Our data thus identify LruA as a surface-exposed leptospiral virulence factor that contributes to leptospiral pathogenesis, possibly by modulating cellular interactions with serum protein ApoA-I. PMID:23918777

  17. Liver expression of steroid hormones and Apolipoprotein D receptors in hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    FJ Vizoso; L Rodrigo; M Rodriguez; A Altadill; ML González-Diéguez; A Linares; LO González; S Junquera; F Fresno-Forcelledo; MD Corte

    2007-01-01

    AIM: To evaluate the tissular expression of Androgen (A), Estrogen (E) and Progesterone (Pg) receptors, and Apolipoprotein D (ApoD), in liver tumors from resected hepatocellular carcinoma (HCC) cases in order to assess their possible relationship to prognosis.METHODS We performed an immunohistochemical study using tissue microarrays (containing more than 260 cancer specimens, from 31 HCC patients and controls)to determine the presence of specific antibodies against AR, ER, PgR and ApoD, correlating their findings with several clinico-pathological and biological variables. The staining results were categorized using a semi-quantitive score based on their intensity, and the percentage of immunostained cells was measured.RESULTS: A total of 21 liver tumors (67.7%) were positive for AR; 16 (51.6%) for ER; 26 (83.9%) for PgR and 12 (38.7%) stained for ApoD. We have found a wide variability in the immunostaining score values for each protein, with a median (range) of 11.5 (11.5-229.5) for AR; 11.1 (8.5-65) for ER; 14.2 (4-61) for PgR; and 37.7 (13.8-81.1) for ApoD. A history of heavy ethanol consumption, correlated positively with AR and PgR and negatively with ER status. HCV chronic infection also correlated positively with AR and PgR status. However,the presence of ApoD immunostaining did not correlate with any of these variables. Tumors with a positive immuno-staining for PgR showed a better prognosis.CONCLUSION: Our results indicate a moderate clinical value of the steroid receptor status in HCC, emphasizing the need to perform further studies in order to evaluate the possible role of new hormonal-based therapies.

  18. Functional network endophenotypes unravel the effects of apolipoprotein E epsilon 4 in middle-aged adults.

    Directory of Open Access Journals (Sweden)

    Joseph S Goveas

    Full Text Available Apolipoprotein E-ε4 (APOE-ε4 accentuates memory decline, structural volume loss and cerebral amyloid deposition in cognitively healthy adults. We investigated whether APOE-ε4 carriers will show disruptions in the intrinsic cognitive networks, including the default mode (DMN, executive control (ECN and salience (SN networks, relative to noncarriers in middle-aged healthy adults; and the extent to which episodic-memory performance is related to the altered functional connectivity (Fc in these networks. Resting-state functional connectivity MRI (R-fMRI was used to measure the differences in the DMN, ECN and SN Fc between 20 APOE-ε4 carriers and 26 noncarriers. Multiple linear regression analyses were performed to determine the relationship between episodic-memory performance and Fc differences in the three resting-state networks across all subjects. There were no significant differences in the demographic and neuropsychological characteristics and the gray-matter volumes in the carriers and noncarriers. While mostly diminished DMN and ECN functional connectivities were seen, enhanced connections to the DMN structures were found in the SN in ε4 carriers. Altered DMN and ECN were associated with episodic memory performance. Significant Fc differences in the brain networks implicated in cognition were seen in middle-aged individuals with a genetic risk for AD, in the absence of cognitive decline and gray-matter atrophy. Prospective studies are essential to elucidate the potential of R-fMRI technique as a biomarker for predicting conversion from normal to early AD in healthy APOE-ε4 carriers.

  19. Radiative-SPR platform for the detection of apolipoprotein E for use in medical diagnostics

    Science.gov (United States)

    Sciacca, Beniamino; Francois, Alexandre; Penno, Megan A. S.; Brazzatti, Julie A.; Klingler-Hoffmann, Manuela; Hoffmann, Peter; Monro, Tanya M.

    2012-03-01

    Surface Plasmon Resonance (SPR) based sensors enable the rapid, label-free and highly sensitive detection of a large range of biomolecules. We have previously shown that, using silver coated optical fibres with an high surface roughness, a re-scattering of the surface plasmons is possible, turning SPR into a radiative process. This approach overcomes limitations associated with current SPR technologies such as the tight tolerance on the metallic coating thickness, and results in a more compact, versatile, robust and cost-effective approach. However, the specific detection of small molecules is a challenge in SPR systems, regardless of the SPR architecture that is used. This new sensing platform, which has proved effective for the detection of large molecules such as viruses, is now demonstrated to be able to detect small proteins thanks to an improved surface functionalization procedure, a key point for reliable and robust immunosensors. Avidin, a tetrameric biotin-binding protein, was used to link biotinylated antibodies to the biotinylated surface, with a given orientation, to enable efficient sensing of the analyte. This approach may offer significant advantages compared to protein A surface functionalization strategies such as a limited cross reactivity with free IgG antibodies in clinical samples. We demonstrate that by bringing together this novel emission-based fibre SPR platform, with an improved surface functionalization process, is possible to rapidly and specifically detect human apolipoprotein E, a low molecular weight protein (~39kDa) known to be involved in cardiovascular diseases, in Alzheimer's disease and in gastric cancer. The results obtained clearly show that this new sensing platform has the potential to serve as a tool for point-of-decision medical diagnostics.

  20. Postmenopausal Osteoporosis Is Associated with Serum Chemerin and Irisin but Not with Apolipoprotein M Levels

    Science.gov (United States)

    Çağlayan, Emel Kıyak; Göçmen, Ayşe Yeşim; Polat, Muhammed Fevzi

    2016-01-01

    Objectives The objective of this study was to describe the levels of chemerin, irisin and apolipoprotein M (apoM) in women with postmenopausal osteoporosis. Methods The study included 88 women with postmenopausal osteoporosis. Based on World Health Organization criteria, women with a T-score of ≤ –2.5 were defined as osteoporotic. In this case-control study, postmenopausal women with T-score > –1 were selected as controls (n = 88) and case-matched in a 1:1 ratio based on age (within 2 years) and body mass index (BMI) (within 1.0 kg/m2). ApoM, irisin and chemerin levels were determined by a commercially available enzyme-linked immunosorbent assay (ELISA) kit. Results There were no significant differences in age, BMI, parity, cholesterol and apoM levels between the two groups. C-reactive protein levels were significantly increased in women with osteoporosis. Serum chemerin levels (240.1 ± 46.1 vs. 261.5 ± 50.8 ng/mL) were significantly lower in the women with osteoporosis, as compared to the controls (P = 0.004). Serum irisin levels were also decreased in women with osteoporosis (0.7 ± 0.2 vs. 0.8 ± 0.2 ng/mL; P = 0.007). Conclusion In the present study, osteoporosis was associated with decreased levels of circulating chemerin and irisin. These findings suggested that adipokines might play a role in the pathogenesis of osteoporosis.

  1. Quercetin stabilizes apolipoprotein E and reduces brain Aβ levels in amyloid model mice.

    Science.gov (United States)

    Zhang, Xilin; Hu, Jin; Zhong, Li; Wang, Na; Yang, Longyu; Liu, Chia-Chen; Li, Huifang; Wang, Xin; Zhou, Ying; Zhang, Yunwu; Xu, Huaxi; Bu, Guojun; Zhuang, Jiangxing

    2016-09-01

    Apolipoprotein E (apoE) is a major cholesterol carrier that regulates lipid homeostasis by mediating lipid transport from one tissue or cell type to another. In the central neural system (CNS), apoE is mainly produced by astrocytes, and transports cholesterol to neurons via apoE receptors, which are members of the low-density lipoprotein receptor family. The APOEε4 gene is a strong genetic risk factor for late-onset sporadic Alzheimer's disease (AD), likely through its strong effect on the accumulation of amyloid-β (Aβ) peptide. ApoE protein levels in cerebrospinal fluid (CSF) and plasma are reduced in APOEε4 carriers and in patients with AD. Furthermore, altered cholesterol levels are also associated with the risk of AD. Aβ accumulation, oligomerization and deposition in the brain are central to the pathogenesis of AD. Mounting evidence demonstrates that apoE and apoE receptors play important roles in these processes. Astrocyte-derived apoE is pivotal for cerebral cholesterol metabolism and clearance of Aβ. Thus, we hypothesized that increased apoE in the brain may be an effective therapeutic strategy for AD. We report here that quercetin can significantly increase apoE levels by inhibiting apoE degradation in immortalized astrocytes. Importantly, we show that oral administration of quercetin significantly increased brain apoE and reduced insoluble Aβ levels in the cortex of 5xFAD amyloid model mice. Our results demonstrate that quercetin increases apoE levels through a novel mechanism and can be explored as a novel class of drug for AD therapy. PMID:27114256

  2. Apolipoprotein B-containing lipoprotein assembly in microsomal triglyceride transfer protein-deficient McA-RH7777 cells

    OpenAIRE

    Liu, Yanwen; Manchekar, Medha; Sun, Zhihuan; Richardson, Paul E.; Dashti, Nassrin

    2010-01-01

    Microsomal triglyceride transfer protein (MTP) is required for the assembly and secretion of apolipoprotein (apo) B-containing lipoproteins. Previously, we demonstrated that the N-terminal 1,000 residues of apoB (apoB:1000) are necessary for the initiation of apoB-containing lipoprotein assembly in rat hepatoma McA-RH7777 cells and that these particles are phospholipid (PL) rich. To determine if the PL transfer activity of MTP is sufficient for the assembly and secretion of primordial apoB:10...

  3. Apolipoprotein E Variation at the Sequence Haplotype Level: Implications for the Origin and Maintenance of a Major Human Polymorphism

    OpenAIRE

    Fullerton, Stephanie M.; Clark, Andrew G.; Weiss, Kenneth M.; Nickerson, Deborah A.; Taylor, Scott L.; Stengård, Jari H.; Salomaa, Veikko; Vartiainen, Erkki; Perola, Markus; Boerwinkle, Eric; Sing, Charles F.

    2000-01-01

    Three common protein isoforms of apolipoprotein E (apoE), encoded by the ε2, ε3, and ε4 alleles of the APOE gene, differ in their association with cardiovascular and Alzheimer's disease risk. To gain a better understanding of the genetic variation underlying this important polymorphism, we identified sequence haplotype variation in 5.5 kb of genomic DNA encompassing the whole of the APOE locus and adjoining flanking regions in 96 individuals from four populations: blacks from Jackson, MS (n=4...

  4. High 99mTc-DPD myocardial uptake in a patient with apolipoprotein AI-related amyloidotic cardiomyopathy.

    Science.gov (United States)

    Quarta, Candida Cristina; Obici, Laura; Guidalotti, Pier Luigi; Pieroni, Maurizio; Longhi, Simone; Perlini, Stefano; Verga, Laura; Merlini, Giampaolo; Rapezzi, Claudio

    2013-03-01

    Amyloidotic cardiomyopathy is still a widely underdiagnosed condition that usually requires endomyocardial biopsy (EMB) for a definite diagnosis. 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) has proven highly sensitive for detecting amyloidotic cardiomyopathy due to transthyretin-related amyloid deposition. Herein we report the first description of the (99mTc-DPD scintigraphy profile in a patient with suspected amyloidotic cardiomyopathy and a final EMB- and genetically-proven diagnosis of familial apolipoprotein AI amyloidosis due to Leu174Ser variant. PMID:23231421

  5. Depression and Plasma Amyloid β Peptides in the Elderly with and without the Apolipoprotein E4 Allele

    OpenAIRE

    Sun, Xiaoyan; Chiu, Chi Chia; Liebson, Elizabeth; Crivello, Natalia A.; Wang, Lixia; Caunch, Joshua; Folstein, Marshal; Rosenberg, Irwin; Mwamburi, D. Mkaya; Peter, Inga; Qiu, Wei Qiao

    2009-01-01

    Depression associated with low plasma Amyloid-β peptide 42 (Aβ42) leading to a high ratio of Aβ40/Aβ42, a biomarker of Alzheimer’s disease (AD), may represent a unique depression subtype. The relationship between low plasma Aβ42 in depression and the major risk factor of AD, Apolipoprotein E4 (ApoE4), is unknown. With the goal of clarifying this relationship, we analyzed 1060 homebound elders with ApoE characterization and depression status in a cross-sectional study. Plasma Aβ40 and Aβ42 wer...

  6. Kringle-containing fragments of apolipoprotein(a) circulate in human plasma and are excreted into the urine.

    OpenAIRE

    Mooser, V.; Marcovina, S. M.; A L White; Hobbs, H H

    1996-01-01

    Apolipoprotein(a) [apo(a)] contains multiple kringle 4 repeats and circulates as part of lipoprotein(a) [Lp(a)]. Apo(a) is synthesized by the liver but its clearance mechanism is unknown. Previously, we showed that kringle 4-containing fragments of apo(a) are present in human urine. To probe their origin, human plasma was examined and a series of apo(a) immunoreactive peptides larger in size than urinary fragments was identified. The concentration of apo(a) fragments in plasma was directly re...

  7. Lactobacillus acidophilus ATCC 4356 Prevents Atherosclerosis via Inhibition of Intestinal Cholesterol Absorption in Apolipoprotein E-Knockout Mice

    OpenAIRE

    Huang, Ying; WANG, Jinfeng; Quan, Guihua; Wang, Xiaojun; Yang, Longfei; Zhong, Lili

    2014-01-01

    The objective of this study was to investigate the effect of Lactobacillus acidophilus ATCC 4356 on the development of atherosclerosis in apolipoprotein E-knockout (ApoE−/−) mice. Eight-week-old ApoE−/− mice were fed a Western diet with or without L. acidophilus ATCC 4356 daily for 16 weeks. L. acidophilus ATCC 4356 protected ApoE−/− mice from atherosclerosis by reducing their plasma cholesterol levels from 923 ± 44 to 581 ± 18 mg/dl, likely via a marked decrease in cholesterol absorption cau...

  8. A gel-based method for purification of apolipoprotein A-I from small volumes of plasma

    OpenAIRE

    Brace, Rachel J.; Sorrenson, Brie; Sviridov, Dmitri; McCormick, Sally P. A.

    2010-01-01

    We present here a gel-based method for rapid purification of apolipoprotein A-I (apoA-I) from small volumes of human plasma. After isolation of high density lipoprotein from plasma, the apoA-I protein was separated by electrophoresis and the apoA-I band excised from the gel. The apoA-I was then eluted from the gel strip, concentrated, and delipidated ready for use. The structure and function of the gel-purified apoA-I protein was compared against apoA-I purified by the traditional size-exclus...

  9. Apolipoprotein B Is Related to Metabolic Syndrome Independently of Low Density Lipoprotein Cholesterol in Patients with Type 2 Diabetes

    OpenAIRE

    Lim, Younghyup; Yoo, Soyeon; Lee, Sang Ah; Chin, Sang Ouk; Heo, Dahee; Moon, Jae Cheol; Moon, Shinhang; Boo, Kiyoung; Kim, Seong Taeg; Seo, Hye Mi; Jwa, Hyeyoung; Koh, Gwanpyo

    2015-01-01

    Background Increased low density lipoprotein cholesterol (LDL-C) level and the presence of metabolic syndrome (MetS) are important risk factors for cardiovascular disease (CVD) in type 2 diabetes mellitus (T2DM). Recent studies demonstrated apolipoprotein B (apoB), a protein mainly located in LDL-C, was an independent predictor of the development of CVD especially in patients with T2DM. The aim of this study was to investigate the relationship between apoB and MetS in T2DM patients. Methods W...

  10. Comparison of immunoturbidimetric and Lowry methods for measuring concentration of very low density lipoprotein apolipoprotein B-100 in plasma.

    OpenAIRE

    Cummings, M H; Watts, G F; Lumb, P J; Slavin, B M

    1994-01-01

    To assess whether the Lowry-tetramethylurea method for measuring apolipoprotein B-100 (apo-B) in very low density lipoprotein (VLDL) could be replaced by direct assay of VLDL apo-B using a highly practicable immunological method. Seventy five fasting blood samples were collected from patients attending the lipid clinic at this hospital. Plasma was separated immediately and VLDL isolated by preparative ultracentrifugation at solution density 0.93-1.006 kg/l. Apo-B was precipitated from an aliq...

  11. Regeneration-associated high level expression of apolipoprotein D mRNA in endoneurial fibroblasts of peripheral nerve.

    OpenAIRE

    Spreyer, P; Schaal, H; Kuhn, G.; Rothe, T; Unterbeck, A; Olek, K; Müller, H. W.

    1990-01-01

    A cDNA clone containing the entire coding region of rat apolipoprotein D (Apo D) was isolated from a cDNA library of regenerating sciatic nerve by differential hybridization. Only small amounts of Apo D mRNA were detected in noninjured mature nerve. Moderately increased levels of Apo D transcripts were found in transected nerves, which were prevented from regeneration by ligation. In contrast, in regenerating crushed nerve, the steady-state level of Apo D mRNA transiently increased at least 4...

  12. Transcriptional regulation of the apolipoprotein B100 gene: purification and characterization of trans-acting factor BRF-2.

    OpenAIRE

    Zhuang, H.; Chuang, S S; Das, H. K.

    1992-01-01

    Apolipoprotein B100 (apoB), the only protein of low-density lipoprotein, is produced primarily in the liver and serves as a ligand for the low-density lipoprotein receptor. Hepatic cell-specific expression of the human apoB gene is controlled by at least two cis-acting positive elements located between positions-128 and -70 (H. K. Das, T. Leff, and J.L. Breslow, J. Biol. Chem. 263:11452-11458, 1988). The distal element (-128 to -85) appears to be liver specific since it shows positive activit...

  13. Susceptibility of Mice to Trypanosoma evansi Treated with Human Plasma Containing Different Concentrations of Apolipoprotein L-1

    OpenAIRE

    Aleksandro S. Da Silva; Fanfa, Vinicius R.; Otto, Mateus A.; Gressler, Lucas T.; Tavares, Kaio C.S.; Lazzarotto, Cícera R.; Alexandre A Tonin; Miletti, Luiz C.; Duarte, Marta M. M. F.; Silvia G. Monteiro

    2011-01-01

    The aim of this study was to test the susceptibility of mice to Trypanosoma evansi treated with human plasma containing different concentrations of apolipoprotein L-1 (APOL1). For this experiment, a strain of T. evansi and human plasma (plasmas 1, 2, and 3) from 3 adult males clinically healthy were used. In vivo test used 50 mice divided in 5 groups (A to E) with 10 animals in each group. Animals of groups B to E were infected, and then treated with 0.2 ml of human plasma in the following ou...

  14. Reconstituted high-density lipoproteins acutely reduce soluble brain Aβ levels in symptomatic APP/PS1 mice.

    Science.gov (United States)

    Robert, Jérôme; Stukas, Sophie; Button, Emily; Cheng, Wai Hang; Lee, Michael; Fan, Jianjia; Wilkinson, Anna; Kulic, Iva; Wright, Samuel D; Wellington, Cheryl L

    2016-05-01

    Many lines of evidence suggest a protective role for high-density lipoprotein (HDL) and its major apolipoprotein (apo)A-I in Alzheimer's Disease (AD). HDL/apoA-I particles are produced by the liver and intestine and, in addition to removing excess cholesterol from the body, are increasingly recognized to have vasoprotective functions. Here we tested the ability of reconstituted HDL (rHDL) consisting of human apoA-I reconstituted with soy phosphatidylcholine for its ability to lower amyloid beta (Aβ) levels in symptomatic APP/PS1 mice, a well-characterized preclinical model of amyloidosis. Animals were treated intravenously either with four weekly doses (chronic study) or a single dose of 60mg/kg of rHDL (acute study). The major finding of our acute study is that soluble brain Aβ40 and Aβ42 levels were significantly reduced within 24h of a single dose of rHDL. By contrast, no changes were observed in our chronic study with respect to soluble or deposited Aβ levels in animals assessed 7days after the final weekly dose of rHDL, suggesting that beneficial effects diminish as rHDL is cleared from the body. Further, rHDL-treated animals showed no change in amyloid burden, cerebrospinal fluid (CSF) Aβ levels, neuroinflammation, or endothelial activation in the chronic study, suggesting that the pathology-modifying effects of rHDL may indeed be acute and may be specific to the soluble Aβ pool. That systemic administration of rHDL can acutely modify brain Aβ levels provides support for further investigation of the therapeutic potential of apoA-I-based agents for AD. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock. PMID:26454209

  15. Apolipoprotein E Regulates the Integrity of Tight Junctions in an Isoform-dependent Manner in an in Vitro Blood-Brain Barrier Model*

    OpenAIRE

    Nishitsuji, Kazuchika; Hosono, Takashi; Nakamura, Toshiyuki; Bu, Guojun; Michikawa, Makoto

    2011-01-01

    Apolipoprotein E (apoE) is a major apolipoprotein in the brain. The ϵ4 allele of apoE is a major risk factor for Alzheimer disease, and apoE deficiency in mice leads to blood-brain barrier (BBB) leakage. However, the effect of apoE isoforms on BBB properties are as yet unknown. Here, using an in vitro BBB model consisting of brain endothelial cells and pericytes prepared from wild-type (WT) mice, and primary astrocytes prepared from human apoE3- and apoE4-knock-in mice, we show that the barri...

  16. Immunotherapeutic and toxic effects of a triple fusion protein encompassing apolipoprotein A-I, IL-15 and IL-15Rα sushi domain

    OpenAIRE

    María C Ochoa; Inmaculada Rodriguez; Guillermo Mazzolini

    2013-01-01

    Interleukin 15 (IL-15) effects on CD8 T and NK lymphocytes hold promise to treat cancer. Fusion proteins have been engineered to provide IL-15 receptor alpha (IL-15Rα) mediated trans-presentation to lymphocytes and extend the plasma half-life of the cytokine. In this study, we report on a triple fusion protein combining apolipoprotein A-I, IL-15 and IL-15Rα’s sushi domain. Apolipoprotein A-I conveys IL-15 to high-density lipoproteins (HDL), from which the cytokine is trans-presented by the IL...

  17. Zebrafish as a model for apolipoprotein biology: comprehensive expression analysis and a role for ApoA-IV in regulating food intake

    Directory of Open Access Journals (Sweden)

    Jessica P. Otis

    2015-03-01

    Full Text Available Improved understanding of lipoproteins, particles that transport lipids throughout the circulation, is vital to developing new treatments for the dyslipidemias associated with metabolic syndrome. Apolipoproteins are a key component of lipoproteins. Apolipoproteins are proteins that structure lipoproteins and regulate lipid metabolism through control of cellular lipid exchange. Constraints of cell culture and mouse models mean that there is a need for a complementary model that can replicate the complex in vivo milieu that regulates apolipoprotein and lipoprotein biology. Here, we further establish the utility of the genetically tractable and optically clear larval zebrafish as a model of apolipoprotein biology. Gene ancestry analyses were implemented to determine the closest human orthologs of the zebrafish apolipoprotein A-I (apoA-I, apoB, apoE and apoA-IV genes and therefore ensure that they have been correctly named. Their expression patterns throughout development were also analyzed, by whole-mount mRNA in situ hybridization (ISH. The ISH results emphasized the importance of apolipoproteins in transporting yolk and dietary lipids: mRNA expression of all apolipoproteins was observed in the yolk syncytial layer, and intestinal and liver expression was observed from 4–6 days post-fertilization (dpf. Furthermore, real-time PCR confirmed that transcription of three of the four zebrafish apoA-IV genes was increased 4 hours after the onset of a 1-hour high-fat feed. Therefore, we tested the hypothesis that zebrafish ApoA-IV performs a conserved role to that in rat in the regulation of food intake by transiently overexpressing ApoA-IVb.1 in transgenic larvae and quantifying ingestion of co-fed fluorescently labeled fatty acid during a high-fat meal as an indicator of food intake. Indeed, ApoA-IVb.1 overexpression decreased food intake by approximately one-third. This study comprehensively describes the expression and function of eleven zebrafish

  18. Solubility Products of M(II) - Carbonates

    Energy Technology Data Exchange (ETDEWEB)

    Grauer, Rolf; Berner, Urs [ed.

    1999-01-01

    Many solubility data for M(II) carbonates commonly compiled in tables are contradictory and sometimes obviously wrong. The quality of such data has been evaluated based on the original publications and reliable solubility constants have been selected for the carbonates of Mn, Fe, Co, Ni, Cu, Zn, Cd and Pb with the help of cross-comparisons. (author) translated from a PSI internal report written in German in 1994 (TM-44-94-05). 5 figs., 1 tab., 68 refs.

  19. Correlation of Helium Solubility in Liquid Nitrogen

    Science.gov (United States)

    VanDresar, Neil T.; Zimmerli, Gregory A.

    2012-01-01

    A correlation has been developed for the equilibrium mole fraction of soluble gaseous helium in liquid nitrogen as a function of temperature and pressure. Experimental solubility data was compiled and provided by National Institute of Standards and Technology (NIST). Data from six sources was used to develop a correlation within the range of 0.5 to 9.9 MPa and 72.0 to 119.6 K. The relative standard deviation of the correlation is 6.9 percent.

  20. Soluble CD14 and fracture risk

    OpenAIRE

    Bethel, M; Bůžková, P; Fink, HA; Robbins, JA; Cauley, JA; Lee, J.; Barzilay, JI; Jalal, DI; Carbone, LD

    2016-01-01

    © 2015 International Osteoporosis Foundation and National Osteoporosis Foundation Summary: Soluble CD14 (sCD14) is an inflammatory marker associated with osteoclasts. Using Cox proportional hazards models, we found a positive association between plasma levels of sCD14 and risk of incident fracture among participants in the Cardiovascular Health Study. sCD14 may be useful in identifying those at risk for fracture. Introduction: Soluble CD14, a proinflammatory cytokine, is primarily derived fro...