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Sample records for characterize lipid lateral

  1. Lipids and membrane lateral organization

    Directory of Open Access Journals (Sweden)

    Sandro eSonnino

    2010-11-01

    Full Text Available Shortly after the elucidation of the very basic structure and properties of cellular membranes, it became evident that cellular membranes are highly organized structures with multiple and multi-dimensional levels of order. Very early observations suggested that the lipid components of biological membranes might be active players in the creations of these levels of order. In the late 80’s, several different and diverse experimental pieces of evidence coalesced together giving rise to the lipid raft hypothesis. Lipid rafts became enormously (and, in the opinion of these authors, sometimes acritically popular, surprisingly not just within the lipidologist community (who is supposed to be naturally sensitive to the fascination of lipid rafts. Today, a PubMed search using the key word lipid rafts returned a list of 3767 papers, including 690 reviews (as a term of comparison, searching over the same time span for a very hot lipid-related key word, ceramide returned 6187 hits with 799 reviews, and a tremendous number of different cellular functions have been described as lipid raft-dependent. However, a clear consensus definition of lipid raft has been proposed only in recent times, and the basic properties, the ruling forces, and even the existence of lipid rafts in living cells have been recently matter of intense debate. The scenario that is gradually emerging from the controversies elicited by the lipid raft hypothesis emphasize multiple roles for membrane lipids in determining membrane order, that encompasses their tendency to phase separation but are clearly not limited to this. In this review, we would like to re-focus the attention of the readers on the importance of lipids in organizing the fine structure of cellular membranes.

  2. Lateral pressure profiles in lipid monolayers

    NARCIS (Netherlands)

    Baoukina, Svetlana; Marrink, Siewert J.; Tieleman, D. Peter

    2010-01-01

    We have used molecular dynamics simulations with coarse-grained and atomistic models to study the lateral pressure profiles in lipid monolayers. We first consider simple oil/air and oil/water interfaces, and then proceed to lipid monolayers at air/water and oil/water interfaces. The results are qual

  3. Lateral mobility of plasma membrane lipids in dividing Xenopus eggs

    OpenAIRE

    de Laat, S W; Tetteroo, P.A.T.; Bluemink, J.G.; Dictus, W.J.A.G.; Zoelen, E.J.J. van

    1984-01-01

    The lateral mobility of plasma membrane lipids was analyzed during first cleavage of Xaopus Levis eggs by fluorescence photobleaching recovery (FPR) measurements, using the lipid analogs 5-(N-hexadecanoyl)aminofluorescein (“HEDAF”) and 5-(N-tetradecanoyl)aminofluorescein (“TEDAF”) as probes. The preexisting plasma membrane of the animal side showed an inhomogeneous, dotted fluorescence pattern after labeling and the lateral mobility of both probes used was below the detection limits of the FP...

  4. Lateral mobility of plasma membrane lipids in dividing Xenopus eggs

    NARCIS (Netherlands)

    Laat, S.W. de; Tetteroo, P.A.T.; Bluemink, J.G.; Dictus, W.J.A.G.; Zoelen, E.J.J. van

    1984-01-01

    The lateral mobility of plasma membrane lipids was analyzed during first cleavage of Xaopus Levis eggs by fluorescence photobleaching recovery (FPR) measurements, using the lipid analogs 5-(N-hexadecanoyl)aminofluorescein (“HEDAF”) and 5-(N-tetradecanoyl)aminofluorescein (“TEDAF”) as probes. The pre

  5. α-Synuclein senses lipid packing defects and induces lateral expansion of lipids leading to membrane remodeling.

    Science.gov (United States)

    Ouberai, Myriam M; Wang, Juan; Swann, Marcus J; Galvagnion, Celine; Guilliams, Tim; Dobson, Christopher M; Welland, Mark E

    2013-07-19

    There is increasing evidence for the involvement of lipid membranes in both the functional and pathological properties of α-synuclein (α-Syn). Despite many investigations to characterize the binding of α-Syn to membranes, there is still a lack of understanding of the binding mode linking the properties of lipid membranes to α-Syn insertion into these dynamic structures. Using a combination of an optical biosensing technique and in situ atomic force microscopy, we show that the binding strength of α-Syn is related to the specificity of the lipid environment (the lipid chemistry and steric properties within a bilayer structure) and to the ability of the membranes to accommodate and remodel upon the interaction of α-Syn with lipid membranes. We show that this interaction results in the insertion of α-Syn into the region of the headgroups, inducing a lateral expansion of lipid molecules that can progress to further bilayer remodeling, such as membrane thinning and expansion of lipids out of the membrane plane. We provide new insights into the affinity of α-Syn for lipid packing defects found in vesicles of high curvature and in planar membranes with cone-shaped lipids and suggest a comprehensive model of the interaction between α-Syn and lipid bilayers. The ability of α-Syn to sense lipid packing defects and to remodel membrane structure supports its proposed role in vesicle trafficking.

  6. Lipid lateral organization on giant unilamellar vesicles containing lipopolysaccharides

    DEFF Research Database (Denmark)

    Kubiak, Jakub; Brewer, Jonathan R.; Hansen, Søren

    2011-01-01

    the presence of elongated micrometer-sized lipid domains for GUVs containing either LPS-Rc or LPS-Rd above 10 mol %. Laurdan GP images confirm this finding and show that this particular lateral scenario corresponds to the coexistence of fluid disordered and gel (LPS-enriched)-like micron-sized domains...

  7. Polyunsaturation in lipid membranes: dynamic properties and lateral pressure profiles.

    Science.gov (United States)

    Ollila, Samuli; Hyvönen, Marja T; Vattulainen, Ilpo

    2007-03-29

    We elucidate the influence of unsaturation on single-component membrane properties, focusing on their dynamical aspects and lateral pressure profiles across the membrane. To this end, we employ atomistic molecular dynamics simulations to study five different membrane systems with varying degrees of unsaturation, starting from saturated membranes and systematically increasing the level of unsaturation, ending up with a bilayer of phospholipids containing the docosahexaenoic acid. For an increasing level of unsaturation, we find considerable effects on dynamical properties, such as accelerated dynamics of the phosphocholine head groups and glycerol backbones and speeded up rotational dynamics of the lipid molecules. The lateral pressure profile is found to be altered by the degree of unsaturation. For an increasing number of double bonds, the peak in the middle of the bilayer decreases. This is compensated for by changes in the membrane-water interface region in terms of increasing peak heights of the lateral pressure profile. Implications of the findings are briefly discussed.

  8. Lipid characterization of human saliva.

    Science.gov (United States)

    Defagó, Maria Daniela; Valentich, Mirta Ana; Actis, Adriana Beatriz

    2011-12-01

    Salivary lipids have been scarcely studied, and the reported results present disparities. This literature review is presented based on the importance of saliva as a diagnostic and/or prognostic medium for various diseases, its lipid content, and on its potential use for the analysis of nutritional markers that contribute to the study of diseases related to lipid consumption and metabolism.

  9. Reduction in lateral lipid mobility of lipid bilayer membrane by atmospheric pressure plasma irradiation

    Science.gov (United States)

    Suda, Yoshiyuki; Tero, Ryugo; Yamashita, Ryuma; Yusa, Kota; Takikawa, Hirofumi

    2016-03-01

    Plasma medicine is an emerging research field in which various applications of electrical discharge, especially in the form of nonequilibrium plasma at atmospheric pressure, are examined, for example, the application of plasma to biological targets for various purposes such as selective killing of tumor cells and blood stanching. We have focused on the behavior of an artificial cell membrane system at the solid-liquid interface. To evaluate the lateral lipid mobility, we measured the diffusion coefficient of the supported lipid bilayer (SLB) composed of dioleoylphosphatidylcholine with fluorescence recovery after photobleaching by confocal laser scanning microscopy. It was found that the diffusion coefficient was decreased by plasma irradiation and that the diffusion coefficient decreasing rate proceeded with increasing plasma power. We investigated the effects of stimulation with an equilibrium chemical, H2O2, on the SLB and confirmed that the diffusion coefficient did not change at least up to a H2O2 concentration of 5 mM. These results indicate that transient active species generated by plasma play critical roles in the reduction in SLB fluidity. The effects of the two generated major oxidized lipid species, hydroxyl- or hydroperoxy-phosphatidylcholine (PC) and acyl-chain-truncated PCs terminated with aldehyde or carboxyl group, on lateral lipid mobility are discussed.

  10. Effects on lipid bilayer and nitrogen distribution induced by lateral pressure.

    Science.gov (United States)

    Wang, Yu; Chen, Liang; Wang, Xiaogang; Dai, Chaoqing; Chen, Junlang

    2015-05-01

    The lateral pressure exerted on cell membrane is of great importance to signal transduction. Here, we perform molecular dynamics simulation to explore how lateral pressure affects the biophysical properties of lipid bilayer as well as nitrogen distribution in the membrane. Our results show that both physical properties of cell membrane and nitrogen distribution are highly sensitive to the lateral pressure. With the increasing lateral pressure, area per lipid drops and thickness of membrane increases obviously, while nitrogen molecules are more congested in the center of lipid bilayer than those under lower lateral pressure. These results suggest that the mechanism of nitrogen narcosis may be related to the lateral pressure.

  11. Spatial Elucidation of Spinal Cord Lipid- and Metabolite- Regulations in Amyotrophic Lateral Sclerosis

    Science.gov (United States)

    Hanrieder, Jörg; Ewing, Andrew G.

    2014-06-01

    Amyotrophic lateral sclerosis (ALS) is a devastating, rapidly progressing disease of the central nervous system that is characterized by motor neuron degeneration in the brain stem and the spinal cord. We employed time of flight secondary ion mass spectrometry (ToF-SIMS) to profile spatial lipid- and metabolite- regulations in post mortem human spinal cord tissue from ALS patients to investigate chemical markers of ALS pathogenesis. ToF-SIMS scans and multivariate analysis of image and spectral data were performed on thoracic human spinal cord sections. Multivariate statistics of the image data allowed delineation of anatomical regions of interest based on their chemical identity. Spectral data extracted from these regions were compared using two different approaches for multivariate statistics, for investigating ALS related lipid and metabolite changes. The results show a significant decrease for cholesterol, triglycerides, and vitamin E in the ventral horn of ALS samples, which is presumably a consequence of motor neuron degeneration. Conversely, the biogenic mediator lipid lysophosphatidylcholine and its fragments were increased in ALS ventral spinal cord, pointing towards neuroinflammatory mechanisms associated with neuronal cell death. ToF-SIMS imaging is a promising approach for chemical histology and pathology for investigating the subcellular mechanisms underlying motor neuron degeneration in amyotrophic lateral sclerosis.

  12. Lateral Diffusion of Membrane Proteins : Consequences of Hydrophobic Mismatch and Lipid Composition

    NARCIS (Netherlands)

    Ramadurai, Sivaramakrishnan; Duurkens, Hinderika; Krasnikov, Victor V.; Poolman, Bert

    2010-01-01

    Biological membranes are composed of a large number lipid species differing in hydrophobic length, degree of saturation, and charge and size of the headgroup. We now present data on the effect of hydrocarbon chain length of the lipids and headgroup composition on the lateral mobility of the proteins

  13. Molecular dynamics simulations of lipid membranes with lateral force: rupture and dynamic properties.

    Science.gov (United States)

    Xie, Jun Yu; Ding, Guang Hong; Karttunen, Mikko

    2014-03-01

    Membranes' response to lateral tension, and eventual rupture, remains poorly understood. In this study, pure dipalmitoylphosphatidylcholine (DPPC) lipid bilayers, under tension/pressure, were studied using molecular dynamics (MD) simulations. The irreversible membrane breakdown is demonstrated to depend on the amplitude of lateral tension, loading rate, and the size of the bilayer. In all of our simulations, -200bar lateral pressure was found to be enough to rupture lipid membrane regardless of the loading rate or the membrane size. Loading rate and membrane size had a significant impact on rupture. A variety of dynamic properties of lipid molecules, probability distribution of area per lipid particularly, have been determined, and found to be fundamental for describing membrane behavior in detail, thus providing the quantitative description for the requirement of membrane rupture.

  14. Lipids in infant nutrition and their impact on later development

    NARCIS (Netherlands)

    Boersma, ER

    1996-01-01

    Numerous studies on infant nutrition show that breast-feeding has a beneficial effect on growth, morbidity, and neurological and cognitive functioning later in life, Moreover, there are indications that a relationship exists between the diet consumed during early childhood and morbidity in adulthood

  15. Lateral diffusion of membrane proteins: consequences of hydrophobic mismatch and lipid composition.

    Science.gov (United States)

    Ramadurai, Sivaramakrishnan; Duurkens, Ria; Krasnikov, Victor V; Poolman, Bert

    2010-09-08

    Biological membranes are composed of a large number lipid species differing in hydrophobic length, degree of saturation, and charge and size of the headgroup. We now present data on the effect of hydrocarbon chain length of the lipids and headgroup composition on the lateral mobility of the proteins in model membranes. The trimeric glutamate transporter (GltT) and the monomeric lactose transporter (LacY) were reconstituted in giant unilamellar vesicles composed of unsaturated phosphocholine lipids of varying acyl chain length (14-22 carbon atoms) and various ratios of DOPE/DOPG/DOPC lipids. The lateral mobility of the proteins and of a fluorescent lipid analog was determined as a function of the hydrophobic thickness of the bilayer (h) and lipid composition, using fluorescence correlation spectroscopy. The diffusion coefficient of LacY decreased with increasing thickness of the bilayer, in accordance with the continuum hydrodynamic model of Saffman-Delbrück. For GltT, the mobility had its maximum at diC18:1 PC, which is close to the hydrophobic thickness of the bilayer in vivo. The lateral mobility decreased linearly with the concentration of DOPE but was not affected by the fraction of anionic lipids from DOPG. The addition of DOPG and DOPE did not affect the activity of GltT. We conclude that the hydrophobic thickness of the bilayer is a major determinant of molecule diffusion in membranes, but protein-specific properties may lead to deviations from the Saffman-Delbrück model.

  16. Correlated lateral phase separations in stacks of lipid membranes

    Energy Technology Data Exchange (ETDEWEB)

    Hoshino, Takuma, E-mail: hoshino-takuma@ed.tmu.ac.jp [Department of Chemistry, Graduate School of Science and Engineering, Tokyo Metropolitan University, Tokyo 192-0397 (Japan); Raymond and Beverly Sackler School of Physics and Astronomy, Tel Aviv University, Ramat Aviv, Tel Aviv 69978 (Israel); Kavli Institute for Theoretical Physics China, CAS, Beijing 100190 (China); Komura, Shigeyuki, E-mail: komura@tmu.ac.jp [Department of Chemistry, Graduate School of Science and Engineering, Tokyo Metropolitan University, Tokyo 192-0397 (Japan); Kavli Institute for Theoretical Physics China, CAS, Beijing 100190 (China); Andelman, David, E-mail: andelman@post.tau.ac.il [Raymond and Beverly Sackler School of Physics and Astronomy, Tel Aviv University, Ramat Aviv, Tel Aviv 69978 (Israel); Kavli Institute for Theoretical Physics China, CAS, Beijing 100190 (China)

    2015-12-28

    Motivated by the experimental study of Tayebi et al. [Nat. Mater. 11, 1074 (2012)] on phase separation of stacked multi-component lipid bilayers, we propose a model composed of stacked two-dimensional Ising spins. We study both its static and dynamical features using Monte Carlo simulations with Kawasaki spin exchange dynamics that conserves the order parameter. We show that at thermodynamical equilibrium, due to strong inter-layer correlations, the system forms a continuous columnar structure for any finite interaction across adjacent layers. Furthermore, the phase separation shows a faster dynamics as the inter-layer interaction is increased. This temporal behavior is mainly due to an effective deeper temperature quench because of the larger value of the critical temperature, T{sub c}, for larger inter-layer interaction. When the temperature ratio, T/T{sub c}, is kept fixed, the temporal growth exponent does not increase and even slightly decreases as a function of the increased inter-layer interaction.

  17. Lateral diffusion of bilayer lipids measured via (31)P CODEX NMR.

    Science.gov (United States)

    Saleem, Qasim; Lai, Angel; Morales, Hannah H; Macdonald, Peter M

    2012-10-01

    We have employed (31)P CODEX (centre-band-only-detection-of-exchange) NMR to measure lateral diffusion coefficients of phospholipids in unilamellar lipid bilayer vesicles consisting of 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC), alone or in mixtures with 30 mol% 1-palmitoyl-2-oleoyl-phosphatidylglycerol (POPG) or cholesterol (CHOL). The lateral diffusion coefficients of POPC and POPG were extracted from experimental CODEX signal decays as a function of increasing mixing time, after accounting for the vesicle's size and size distribution, as determined via dynamic light scattering, and the viscosity of the vesicular suspension, as determined via (1)H pulsed field gradient NMR. Lateral diffusion coefficients for POPC and POPG determined in this fashion fell in the range 1.0-3.2 × 10(-12) m(2) s(-1) at 10 °C, depending on the vesicular composition, in good agreement with accepted values. Thus, two advantages of (31)P CODEX NMR for phospholipid lateral diffusion measurements are demonstrated: no labelling of the molecule of interest is necessary, and multiple lateral diffusion coefficients can be measured simultaneously. It is expected that this approach will prove particularly useful in diagnosing heterogeneities in lateral diffusion behaviours, such as might be expected for specific lipid-lipid or lipid-protein interactions, and thermotropic or electrostatically induced phase inhomogeneities.

  18. Characterization of the thermotropic behavior and lateral organization of lipid-peptide mixtures by a combined experimental and theoretical approach: Effects of hydrophobic mismatch and role of flanking residues

    DEFF Research Database (Denmark)

    Morein, S.; Killian, J.A.; Sperotto, Maria Maddalena

    2002-01-01

    , of variable length, of alternating leucine and alanine residues, flanked on both ends with tryptophan and lysine residues, respectively. By systematically varying the peptide hydrophobic length it was thus possible to explore different matching conditions between the peptide's hydrophobic length and the lipid...... bilayer hydrophobic thickness, and to investigate the potential role of flanking residues. The results show that both the WALP and the KALP peptides tend to favor the liquid-crystal line (or fluid) phase of the system; i.e., they tend to depress the main-transition temperature, T-m, of pure DPPC. However...

  19. Acceleration of Lateral Equilibration in Mixed Lipid Bilayers Using Replica Exchange with Solute Tempering.

    Science.gov (United States)

    Huang, Kun; García, Angel E

    2014-10-14

    The lateral heterogeneity of cellular membranes plays an important role in many biological functions such as signaling and regulating membrane proteins. This heterogeneity can result from preferential interactions between membrane components or interactions with membrane proteins. One major difficulty in molecular dynamics simulations aimed at studying the membrane heterogeneity is that lipids diffuse slowly and collectively in bilayers, and therefore, it is difficult to reach equilibrium in lateral organization in bilayer mixtures. Here, we propose the use of the replica exchange with solute tempering (REST) approach to accelerate lateral relaxation in heterogeneous bilayers. REST is based on the replica exchange method but tempers only the solute, leaving the temperature of the solvent fixed. Since the number of replicas in REST scales approximately only with the degrees of freedom in the solute, REST enables us to enhance the configuration sampling of lipid bilayers with fewer replicas, in comparison with the temperature replica exchange molecular dynamics simulation (T-REMD) where the number of replicas scales with the degrees of freedom of the entire system. We apply the REST method to a cholesterol and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) bilayer mixture and find that the lateral distribution functions of all molecular pair types converge much faster than in the standard MD simulation. The relative diffusion rate between molecules in REST is, on average, an order of magnitude faster than in the standard MD simulation. Although REST was initially proposed to study protein folding and its efficiency in protein folding is still under debate, we find a unique application of REST to accelerate lateral equilibration in mixed lipid membranes and suggest a promising way to probe membrane lateral heterogeneity through molecular dynamics simulation.

  20. Improved characterization of EV preparations based on protein to lipid ratio and lipid properties.

    Directory of Open Access Journals (Sweden)

    Xabier Osteikoetxea

    Full Text Available In recent years the study of extracellular vesicles has gathered much scientific and clinical interest. As the field is expanding, it is becoming clear that better methods for characterization and quantification of extracellular vesicles as well as better standards to compare studies are warranted. The goal of the present work was to find improved parameters to characterize extracellular vesicle preparations. Here we introduce a simple 96 well plate-based total lipid assay for determination of lipid content and protein to lipid ratios of extracellular vesicle preparations from various myeloid and lymphoid cell lines as well as blood plasma. These preparations included apoptotic bodies, microvesicles/microparticles, and exosomes isolated by size-based fractionation. We also investigated lipid bilayer order of extracellular vesicle subpopulations using Di-4-ANEPPDHQ lipid probe, and lipid composition using affinity reagents to clustered cholesterol (monoclonal anti-cholesterol antibody and ganglioside GM1 (cholera toxin subunit B. We have consistently found different protein to lipid ratios characteristic for the investigated extracellular vesicle subpopulations which were substantially altered in the case of vesicular damage or protein contamination. Spectral ratiometric imaging and flow cytometric analysis also revealed marked differences between the various vesicle populations in their lipid order and their clustered membrane cholesterol and GM1 content. Our study introduces for the first time a simple and readily available lipid assay to complement the widely used protein assays in order to better characterize extracellular vesicle preparations. Besides differentiating extracellular vesicle subpopulations, the novel parameters introduced in this work (protein to lipid ratio, lipid bilayer order, and lipid composition, may prove useful for quality control of extracellular vesicle related basic and clinical studies.

  1. LIPID BIOMARKER CHARACTERIZATION OF BLOOM-RELATED DINOFLAGELLATES

    Science.gov (United States)

    Marine eukaryotic algae synthesize an array of lipids of chemotaxonomic utility that are potentially valuable in characterizing phytoplankton communities. Sterols and photopigments characteristic of dinoflagellates are rarely found in other algal classes. Long chain (C28) highly ...

  2. Strong influence of periodic boundary conditions on lateral diffusion in lipid bilayer membranes

    Energy Technology Data Exchange (ETDEWEB)

    Camley, Brian A. [Center for Theoretical Biological Physics and Department of Physics, University of California, San Diego, California 92093 (United States); Department of Physics, University of California, Santa Barbara, California 93106 (United States); Lerner, Michael G. [Department of Physics and Astronomy, Earlham College, Richmond, Indiana 47374 (United States); Laboratory of Computational Biology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892 (United States); Pastor, Richard W. [Laboratory of Computational Biology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892 (United States); Brown, Frank L. H. [Department of Physics, University of California, Santa Barbara, California 93106 (United States); Department of Chemistry and Biochemistry, University of California, Santa Barbara, California 93106 (United States)

    2015-12-28

    The Saffman-Delbrück hydrodynamic model for lipid-bilayer membranes is modified to account for the periodic boundary conditions commonly imposed in molecular simulations. Predicted lateral diffusion coefficients for membrane-embedded solid bodies are sensitive to box shape and converge slowly to the limit of infinite box size, raising serious doubts for the prospects of using detailed simulations to accurately predict membrane-protein diffusivities and related transport properties. Estimates for the relative error associated with periodic boundary artifacts are 50% and higher for fully atomistic models in currently feasible simulation boxes. MARTINI simulations of LacY membrane protein diffusion and LacY dimer diffusion in DPPC membranes and lipid diffusion in pure DPPC bilayers support the underlying hydrodynamic model.

  3. Strong influence of periodic boundary conditions on lateral diffusion in lipid bilayer membranes

    Science.gov (United States)

    Camley, Brian A.; Lerner, Michael G.; Pastor, Richard W.; Brown, Frank L. H.

    2015-12-01

    The Saffman-Delbrück hydrodynamic model for lipid-bilayer membranes is modified to account for the periodic boundary conditions commonly imposed in molecular simulations. Predicted lateral diffusion coefficients for membrane-embedded solid bodies are sensitive to box shape and converge slowly to the limit of infinite box size, raising serious doubts for the prospects of using detailed simulations to accurately predict membrane-protein diffusivities and related transport properties. Estimates for the relative error associated with periodic boundary artifacts are 50% and higher for fully atomistic models in currently feasible simulation boxes. MARTINI simulations of LacY membrane protein diffusion and LacY dimer diffusion in DPPC membranes and lipid diffusion in pure DPPC bilayers support the underlying hydrodynamic model.

  4. Lipid Lateral Segregation Driven by Diacyl Cyclodextrin Interactions at the Membrane Surface

    Science.gov (United States)

    Roux, Michel; Moutard, Stéphane; Perly, Bruno; Djedaini-Pilard, Florence

    2007-01-01

    Cyclodextrins are hydrophilic molecular cages with a hydrophobic interior allowing the inclusion of water-insoluble drugs. Amphiphilic cyclodextrins obtained by appending a hydrophobic anchor were designed to improve the cell targeting of the drug-containing cavities through their liposome transportation in the organism. After insertion in model membranes, they were found to induce a lateral phase separation into a pure lipid phase and a fluid cyclodextrin-rich phase (LCD) with reduced acyl chain order parameters, as observed with a derivative containing a cholesterol anchor (M. Roux, R. Auzely-Velty, F. Djedaïni-Pilard, and B. Perly. 2002. Biophysical Journal, 8:813–822). We present another class of amphiphilic cyclodextrins obtained by grafting aspartic acid esterified by two lauryl chains on the oligosaccharide core via a succinyl spacer. The obtained dilauryl-β-cyclodextrin (βDLC) was inserted in chain perdeuterated dimyristoylphosphatidylcholine (DMPC-d54) membranes and studied by deuterium NMR (2H-NMR). A laterally segregated mixed phase was found to sequester three times more lipids than the cholesteryl derivative (∼4–5 lipids per monomer of βDLC), and a quasipure LCD phase could be obtained with a 20% molar concentration of βDLC. When cooled below the main fluid-to-gel transition of DMPC-d54 the βDLC-rich phase stays fluid, coexisting with pure lipid in the gel state, and exhibits a sharp transition to a gel phase with frozen DMPC acyl chains at 12.5°C. No lateral phase separation was observed with partially or fully methylated βDLC, confirming that the stability of the segregated LCD phase was governed through hydrogen-bond-mediated intermolecular interactions between cyclodextrin headgroups at the membrane surface. As opposed to native βDLC, the methylated derivatives were found to strongly increase the orientational order of DMPC acyl chains as the temperature reaches the membrane fluid-to-gel transition. The results are discussed in

  5. Structural characterization and lipid composition of acquired cholesteatoma

    DEFF Research Database (Denmark)

    Bloksgaard, Maria; Svane-Knudsen, Viggo; Sørensen, Jens A

    2012-01-01

    along a depth of more than 200 μm and resembles the stratum corneum of hyperorthokeratotic skin. Lipid compositional analyses of the cholesteatoma show the presence of all major lipid classes found in normal skin stratum corneum (ceramides, long chain fatty acids, and cholesterol). Consistent with this......HYPOTHESIS: The goal of this work is to characterize the morphology and lipid composition of acquired cholesteatoma. We hypothesize that constitutive lipid membranes are present in the cholesteatoma and resemble those found in human skin stratum corneum. METHODS: We performed a comparative...... noninvasive structural and lipid compositional study of acquired cholesteatoma and control human skin using multiphoton excitation fluorescence microscopy-related techniques and high-performance thin-layer chromatography. RESULTS: The structural arrangement of the cholesteatoma is morphologically invariant...

  6. Cardiovascular risk, lipids and pregnancy: preeclampsia and the risk of later life cardiovascular disease.

    Science.gov (United States)

    Charlton, Francesca; Tooher, Jane; Rye, Kerry-Anne; Hennessy, Annemarie

    2014-03-01

    It has been widely thought that the effects of hypertension in pregnancy reversed after delivery and hypertension values returned to their pre-pregnancy level as it was seen as a disease of short duration in otherwise healthy young women. However, recent studies have demonstrated that the principal underlying abnormality, endothelial dysfunction, remains in women who had preeclampsia and that it is this damage that increases the risk of developing cardiovascular disease (CVD) in later life. The contributions of hypertension and dyslipidaemia before and during the pregnancy are also important and contribute to future risk. Serum lipids are complex and change dramatically in pregnancy. In general there is an increase in most plasma lipid components, notably triglycerides, total cholesterol and the major particles of HDL and LDL. Aberrations or exaggerations in this shift (i.e. decrease HDL and a greater increase in LDL) are associated with poor outcomes of pregnancy such as preeclampsia. Long term cardiovascular disease is influenced by preeclampsia and in part potentially by the lipid changes which escalate late in disease. Whether we can influence the risk of preeclampsia by controlling cardiovascular risk factors preceding or during preeclampsia, or cardiovascular disease after preeclampsia is yet to be determined. Ultimately, strategies to control lipid concentrations will only be viable when we understand the safety to the mother at the time of the pregnancy, and to the foetus both immediately and in the very long term. Strategies to control blood pressure are well established in the non-pregnant population, and previous preeclampsia and gestational hypertension should be considered in any cardiovascular risk profile. Whether control of blood pressure in the pregnancy per se is of any longer term benefit is also yet to be determined.

  7. Protein Crowding in Lipid Bilayers Gives Rise to Non-Gaussian Anomalous Lateral Diffusion of Phospholipids and Proteins

    Science.gov (United States)

    Jeon, Jae-Hyung; Javanainen, Matti; Martinez-Seara, Hector; Metzler, Ralf; Vattulainen, Ilpo

    2016-04-01

    Biomembranes are exceptionally crowded with proteins with typical protein-to-lipid ratios being around 1 ∶50 -1 ∶100 . Protein crowding has a decisive role in lateral membrane dynamics as shown by recent experimental and computational studies that have reported anomalous lateral diffusion of phospholipids and membrane proteins in crowded lipid membranes. Based on extensive simulations and stochastic modeling of the simulated trajectories, we here investigate in detail how increasing crowding by membrane proteins reshapes the stochastic characteristics of the anomalous lateral diffusion in lipid membranes. We observe that correlated Gaussian processes of the fractional Langevin equation type, identified as the stochastic mechanism behind lipid motion in noncrowded bilayer, no longer adequately describe the lipid and protein motion in crowded but otherwise identical membranes. It turns out that protein crowding gives rise to a multifractal, non-Gaussian, and spatiotemporally heterogeneous anomalous lateral diffusion on time scales from nanoseconds to, at least, tens of microseconds. Our investigation strongly suggests that the macromolecular complexity and spatiotemporal membrane heterogeneity in cellular membranes play critical roles in determining the stochastic nature of the lateral diffusion and, consequently, the associated dynamic phenomena within membranes. Clarifying the exact stochastic mechanism for various kinds of biological membranes is an important step towards a quantitative understanding of numerous intramembrane dynamic phenomena.

  8. Lateral diffusion of phospholipids in the plasma membrane of soybean protoplasts: Evidence for membrane lipid domains.

    Science.gov (United States)

    Metcalf, T N; Wang, J L; Schindler, M

    1986-01-01

    Fluorescent lipid and phospholipid probes were incorporated at 4 degrees C into soybean protoplasts prepared from cultured soybean (SB-1) cells. Fluorescence microscopy showed that the plasma membrane as well as the nucleus were labeled. Fluorescence redistribution after photobleaching (FRAP) analysis was performed on these cells at 18 degrees C to monitor the lateral mobility of the incorporated probes. After labeling at low concentrations (40 mug/ml) of phosphatidyl-N-(4-nitrobenzo-2-oxa-1,3-diazolyl)ethanolamine (NBD-PtdEtn), a single mobile component was observed with a diffusion coefficient (D) of approximately 3 x 10(-9) cm(2)/sec. After labeling at higher probe concentrations (>/=100 mug/ml), two diffusing species were observed, with diffusion coefficients of approximately 3 x 10(-9) cm(2)/sec ("fast") and approximately 5 x 10(-10) cm(2)/sec ("slow"). Similar results were observed with fluorescent derivatives of phosphatidylcholine and fatty acids. In contrast to these results, parallel analysis of 3T3 fibroblasts, using the same probes and conditions, yielded only a single diffusion component. These results suggest that the soybean plasma membrane may contain two distinct lipid domains in terms of lipid mobility. Consistent with this idea, experiments with soybean protoplasts yielded a single diffusion component under the following conditions: (i) labeling with NBD-PtdEtn (100 mug/ml), FRAP analysis at 37 degrees C (D = 1.1 x 10(-8) cm(2)/sec); (ii) labeling with NBD-PtdEtn (100 mug/ml), FRAP analysis at 18 degrees C in the presence of 2 mM EGTA (D = 4.2 x 10(-9) cm(2)/sec); (iii) labeling with 5-(N-dodecanoyl)aminofluorescein (a short-chain lipid probe), FRAP analysis at 18 degrees C or 37 degrees C (D = 2.5 x 10(-8) cm(2)/sec). These results suggest that the plasma membrane of soybean cells may contain stable immiscible domains of fluid and gel-like lipids.

  9. Characterization of the fate of lipids in activated sludge

    Institute of Scientific and Technical Information of China (English)

    Kangala B.Chipasa; Krystyna Medrzycka

    2008-01-01

    Experiments were carried out to characterize the transformation of lipids in activated sludge under aerobic conditions. Results showed that the overall lipid content in the effluent could not be reduced to values below 300 mg/L from an initial content of 2, 000 mg/L. However, the contents of individual fatty acids underwent drastic decreases and increases during all microbial growth phases. These changes in contents of individual fatty acids showed that fatty acids were used as substrates by microorganisms as well as released into the wastewater as by-products. We have therefore suggested a novel model of transformation of lipids in activated sludge, showing that utilization of microbial activity for complete removal of lipids from wastewater is limited.

  10. Lateral mobility of plasma membrane lipids in a molluscan egg: Evidence for an animal/vegetal polarity

    NARCIS (Netherlands)

    Laat, S.W. de; Speksnijder, J.E.; Dohmen, M.R.; Zoelen, E. van; Tertoolen, L.G.J.; Bluemink, J.G.

    1984-01-01

    The lateral diffusion of the lipid analog C₁₄-diI (3', 3'-dihexadecylindocarbocyanine iodide) was measured in the plasma membrane of early embryos of the mollusc Nassarius reticulatus using the FPR-(Fluorescence Photobleaching Recovery) method. At almost all stages measured (from fertilized egg up t

  11. Formulation and in vitro characterization of domperidone loaded solid lipid nanoparticles and nanostructured lipid carriers

    Directory of Open Access Journals (Sweden)

    RP Thatipamula

    2011-03-01

    Full Text Available Background and the purpose of the study: Domperidone (DOM is a dopamine- receptor (D2 antagonist, widely used in the treatment of motion-sickness. The pharmacokinetic parameters of DOM make it a suitable candidate for development of Solid Lipid Nanoparticle (SLN and Nanostructured Lipide Carrier (NLC. The purpose of the present investigation was to prepare and evaluate DOM loaded solid lipid nanoparticles (DOM-SLN and DOM loaded nanostructured lipid carriers (DOM-NLC. Methods: DOM loaded SLN and NLC were prepared by hot homogenization followed by ultrasonication technique, using trimyristin as solid lipid, cetyl recinoleate as liquid lipid and a mixture of soy phosphatidylcholine (99% and tween 80 as surfactant. SLN and NLC were characterized for particle size, polydispersity index (PDI, zeta potential and entrapment efficiency. The effects of composition of lipid materials and surfactant mixture on the particle size, PDI, zeta potential, drug entrapment efficiency, and in vitro drug release behavior were investigated. DSC analysis was performed to characterize the state of drug and lipid modification. Shape and surface morphology were determined by transmission electron microscopy (TEM. SLN and NLC formulations were subjected to stability study over a period of 40 days. Results: The mean particle size, PDI, zeta potential and entrapment efficiency of optimized SLN (SLN1 and NLC were found to be 30.45 nm, 0.156, 12.40 mV, 87.84 % and 32.23 nm, 0.160, 10.47 mV, 90.49 % respectively. DSC studies revealed that DOM was in an amorphous state and triglycerides were in the β prime form in SLN and NLC. Shape and surface morphology was determined by TEM revealed fairly spherical shape of nanoparticles. In vitro release studies demonstrated that both the SLN and NLC formulations possessed a controlled release over a period of 24 hrs. SLN and NLC formulations were subjected to stability over a period of 40 days. There was no significant (P < 0.05 change

  12. Coupling Optical and Electrical Measurements in Artificial Membranes: Lateral Diffusion of Lipids and Channel Forming Peptides in Planar Bilayers

    Directory of Open Access Journals (Sweden)

    Duclohier H

    1998-01-01

    Full Text Available Planar lipid bilayers (PLB were prepared by the Montal-Mueller technique in a FRAP system designed to simultaneously measure conductivity across, and lateral diffusion of, the bilayer. In the first stage of the project the FRAP system was used to characterise the lateral dynamics of bilayer lipids with regards to phospholipid composition (headgroup, chain unsaturation etc., presence of cholesterol and the effect of divalent cations on negatively-charged bilayers. In the second stage of the project, lateral diffusion of two fluorescently-labelled voltage-dependent pore-forming peptides (alamethicin and S4s from Shaker K+ channel was determined at rest and in the conducting state. This study demonstrates the feasibility of such experiments with PLBs, amenable to physical constraints, and thus offers new opportunities for systematic studies of structure-function relationships in membrane-associating molecules.

  13. Characterization of an ancient lepidopteran lateral gene transfer.

    Directory of Open Access Journals (Sweden)

    David Wheeler

    Full Text Available Bacteria to eukaryote lateral gene transfers (LGT are an important potential source of material for the evolution of novel genetic traits. The explosion in the number of newly sequenced genomes provides opportunities to identify and characterize examples of these lateral gene transfer events, and to assess their role in the evolution of new genes. In this paper, we describe an ancient lepidopteran LGT of a glycosyl hydrolase family 31 gene (GH31 from an Enterococcus bacteria. PCR amplification between the LGT and a flanking insect gene confirmed that the GH31 was integrated into the Bombyx mori genome and was not a result of an assembly error. Database searches in combination with degenerate PCR on a panel of 7 lepidopteran families confirmed that the GH31 LGT event occurred deep within the Order approximately 65-145 million years ago. The most basal species in which the LGT was found is Plutella xylostella (superfamily: Yponomeutoidea. Array data from Bombyx mori shows that GH31 is expressed, and low dN/dS ratios indicates the LGT coding sequence is under strong stabilizing selection. These findings provide further support for the proposition that bacterial LGTs are relatively common in insects and likely to be an underappreciated source of adaptive genetic material.

  14. Physicochemical characterization techniques for solid lipid nanoparticles: principles and limitations.

    Science.gov (United States)

    Kathe, Niranjan; Henriksen, Brian; Chauhan, Harsh

    2014-12-01

    Solid lipid nanoparticles (SLNs) are gaining importance due to numerous advantages they offer as a drug delivery system. SLN incorporate poorly soluble drugs, proteins, biologicals, etc. SLN are prepared by techniques like high-pressure homogenization, sonication and employs a wide range of lipids and surfactants. Physicochemical characterization techniques include particle size analysis, zeta potential and determination of crystallinity/polymorphism. Furthermore, drug loading and drug entrapment efficiency are common parameters used to test the efficiency of SLN. Most importantly, the functionality assay of SLN is essential to predict the activity and performance in vivo. The review presented discusses the importance of SLN in drug delivery with emphasis on principles and limitations associated with their physicochemical characterization.

  15. Can pyrene probes be used to measure lateral pressure profiles of lipid membranes? Perspective through atomistic simulations

    DEFF Research Database (Denmark)

    Franova, M. D.; Vattulainen, I.; Ollila, O. H. S.

    2014-01-01

    simulations, since established methods to measure the lateral pressure profile experimentally have not been available. The only experiments that have attempted to gauge the lateral pressure profile have been done by using di-pyrenyl-phosphatidylcholine (di-pyr-PC) probes. In these experiments, the excimer......The lateral pressure profile of lipid bilayers has gained a lot of attention, since changes in the pressure profile have been suggested to shift the membrane protein conformational equilibrium. This relation has been mostly studied with theoretical methods, especially with molecular dynamics....../monomer fluorescence ratio has been assumed to represent the lateral pressure in the location of the pyrene moieties. Here, we consider the validity of this assumption through atomistic molecular dynamics simulations in a DOPC (dioleoylphosphatidylcholine) membrane, which hosts di-pyr-PC probes with different acyl...

  16. Lateral diffusion of PEG-Lipid in magnetically aligned bicelles measured using stimulated echo pulsed field gradient 1H NMR.

    Science.gov (United States)

    Soong, Ronald; Macdonald, Peter M

    2005-01-01

    Lateral diffusion measurements of PEG-lipid incorporated into magnetically aligned bicelles are demonstrated using stimulated echo (STE) pulsed field gradient (PFG) proton (1H) nuclear magnetic resonance (NMR) spectroscopy. Bicelles were composed of dimyristoyl phosphatidylcholine (DMPC) plus dihexanoyl phosphatidylcholine (DHPC) (q = DMPC/DHPC molar ratio = 4.5) plus 1 mol % (relative to DMPC) dimyristoyl phosphatidylethanolamine-N-[methoxy(polyethylene glycol)-2000] (DMPE-PEG 2000) at 25 wt % lipid. 1H NMR STE spectra of perpendicular aligned bicelles contained only resonances assigned to residual HDO and to overlapping contributions from a DMPE-PEG 2000 ethoxy headgroup plus DHPC choline methyl protons. Decay of the latter's STE intensity in the STE PFG 1H NMR experiment (g(z) = 244 G cm(-1)) yielded a DMPE-PEG 2000 (1 mol %, 35 degrees C) lateral diffusion coefficient D = 1.35 x 10(-11) m2 s(-1). Hence, below the "mushroom-to-brush" transition, DMPE-PEG 2000 lateral diffusion is dictated by its DMPE hydrophobic anchor. D was independent of the diffusion time, indicating unrestricted lateral diffusion over root mean-square diffusion distances of microns, supporting the "perforated lamellae" model of bicelle structure under these conditions. Overall, the results demonstrate the feasibility of lateral diffusion measurements in magnetically aligned bicelles using the STE PFG NMR technique.

  17. Subdiffusion and lateral diffusion coefficient of lipid atoms and molecules in phospholipid bilayers

    CERN Document Server

    Flenner, Elijah; Rheinstadter, Maikel C; Kosztin, Ioan

    2008-01-01

    We use a long, all-atom molecular dynamics (MD) simulation combined with theoretical modeling to investigate the dynamics of selected lipid atoms and lipid molecules in a hydrated diyristoyl-phosphatidylcholine (DMPC) lipid bilayer. From the analysis of a 0.1 $\\mu$s MD trajectory we find that the time evolution of the mean square displacement, [\\delta{r}(t)]^2, of lipid atoms and molecules exhibits three well separated dynamical regions: (i) ballistic, with [\\delta{r}(t)]^2 ~ t^2 for t 30 ns. We propose a memory function approach for calculating [\\delta{r}(t)]^2 over the entire time range extending from the ballistic to the Fickian diffusion regimes. The results are in very good agreement with the ones from the MD simulations. We also examine the implications of the presence of the subdiffusive dynamics of lipids on the self-intermediate scattering function and the incoherent dynamics structure factor measured in neutron scattering experiments.

  18. Recent progress on lipid lateral heterogeneity in plasma membranes: From rafts to submicrometric domains.

    Science.gov (United States)

    Carquin, Mélanie; D'Auria, Ludovic; Pollet, Hélène; Bongarzone, Ernesto R; Tyteca, Donatienne

    2016-04-01

    The concept of transient nanometric domains known as lipid rafts has brought interest to reassess the validity of the Singer-Nicolson model of a fluid bilayer for cell membranes. However, this new view is still insufficient to explain the cellular control of surface lipid diversity or membrane deformability. During the past decades, the hypothesis that some lipids form large (submicrometric/mesoscale vs nanometric rafts) and stable (>min vs s) membrane domains has emerged, largely based on indirect methods. Morphological evidence for stable submicrometric lipid domains, well-accepted for artificial and highly specialized biological membranes, was further reported for a variety of living cells from prokaryot es to yeast and mammalian cells. However, results remained questioned based on limitations of available fluorescent tools, use of poor lipid fixatives, and imaging artifacts due to non-resolved membrane projections. In this review, we will discuss recent evidence generated using powerful and innovative approaches such as lipid-specific toxin fragments that support the existence of submicrometric domains. We will integrate documented mechanisms involved in the formation and maintenance of these domains, and provide a perspective on their relevance on membrane deformability and regulation of membrane protein distribution.

  19. Regional differences in the lateral mobility of plasma membrane lipids in a molluscan embryo

    NARCIS (Netherlands)

    Speksnijder, J.E.; Dohmen, M.R.; Tertoolen, L.G.J.; Laat, S.W. de

    1985-01-01

    Regional and temporal differences in plasma membrane lipid mobility have been analyzed during the first three cleavage cycles of the embryo of the polar-lobe-forming mollusc Nassarius reticulatus by the fluorescence photobleaching recovery (FPR) method, using 1,1′-ditetradecyl 3,3,3′,3′-tetramethyli

  20. Lateral mobility of plasma membrane lipids in Xenopus eggs: Regional differences related to animal/vegetal polarity become extreme upon fertilization

    NARCIS (Netherlands)

    Bluemink, J.G.; Dictus, W.J.A.G.; Zoelen, E.J.J. van; Tetteroo, P.A.T.; Tertoolen, L.G.J.; Laat, S.W. de

    1984-01-01

    Regional differences in the lateral mobility properties of plasma membrane lipids have been studied in unfertilized and fertilizedxaqpus eggs by fluorescence photobleaching recovery (FPR) measurements. Out of a variety of commonly used lipid probes only the aminofluorescein-labeled fatty acids HEDAF

  1. Development and characterization of lipidic cochleate containing recombinant factor VIII

    Science.gov (United States)

    Miclea, Razvan D.; Varma, Prashant R.; Peng, Aaron; Balu-Iyer, Sathy V.

    2007-01-01

    Hemophilia A, a life threatening bleeding disorder is caused by deficiency of Factor VIII (FVIII). Replacement therapy using rFVIII is the first line therapy for hemophilia A. However, 15-30% of patients develop neutralizing antibody, mainly against the C2, A3 and A2 domains. It has been reported that PS-FVIII complex reduced total and neutralizing anti-rFVIII antibody titers in hemophilia A murine models. Here, we developed FVIII – containing cochleate cylinders, utilizing PS-Ca2+ interactions and characterized these particles for optimal in vivo properties using biophysical and biochemical techniques. Approximately 75% of the protein was associated with cochleate cylinders. Sandwich ELISA, acrylamide quenching and enzymatic digestion studies established that rFVIII was shielded from the bulk aqueous phase by the lipidic structures, possibly leading to improved in vivo stability. Freeze – thawing and rate limiting diffusion studies revealed that small cochleate cylinders with a particles size of 500 nm or less could be generated. The release kinetics and in vivo experiments suggested that there is slow and sustained release of FVIII from the complex upon systemic exposure. In vivo studies using tail clip method indicated that FVIII-cochleate complex is effective and protects hemophilic mice from bleeding. Based on these studies, we speculate that the molecular interaction between FVIII and PS may provide a basis for the design of novel FVIII lipidic structures for delivery applications. PMID:17936245

  2. Effects of cholesterol on lateral diffusion and vertical fluctuations in lipid bilayers. An electron-electron double resonance (ELDOR) study

    Energy Technology Data Exchange (ETDEWEB)

    Yin, J.J.; Feix, J.B.; Hyde, J.S.

    1987-12-01

    Electron-electron double resonance (ELDOR) and saturation-recovery spectroscopy employing /sup 14/N:/sup 15/N stearic acid spin-label pairs have been used to study the effects of cholesterol on lateral diffusion and vertical fluctuations in lipid bilayers. The /sup 14/N:/sup 15/N continuous wave electron-electron double resonance (CW ELDOR) theory has been developed using rate equations based on the relaxation model. The collision frequency between /sup 14/N-16 doxyl stearate and /sup 15/N-16 doxyl stearate, WHex (16:16), is indicative of lateral diffusion of the spin probes, while the collision frequency between /sup 14/N-16 doxyl stearate and /sup 15/N-5 doxyl stearate, WHex (16:5), provides information on vertical fluctuations of the /sup 14/N-16 doxyl stearate spin probe toward the membrane surface. Our results show that: (a) cholesterol decreases the electron spin-lattice relaxation time Tle of /sup 14/N-16 doxyl stearate spin label in dimyristoylphosphatidylcholine (DMPC) and egg yolk phosphatidylcholine (egg PC). (b) Cholesterol increases the biomolecular collision frequency WHex (16:16) and decreases WHex (16:5), suggesting that incorporation of cholesterol significantly orders the part of the bilayer that it occupies and disorders the interior region of the bilayer. (c) Alkyl chain unsaturation of the host lipid moderates the effect of cholesterol on both vertical fluctuations and lateral diffusion of /sup 14/N-16 doxyl stearate. And (d), there are marked differences in the effects of cholesterol on lateral diffusion and vertical fluctuations between 0-30 mol% and 30-50 mol% of cholesterol that suggest an inhomogeneous distribution of cholesterol in the membrane.

  3. Structural characterization of suppressor lipids by high-resolution mass spectrometry

    DEFF Research Database (Denmark)

    Rovillos, Mary Joy; Pauling, Josch Konstantin; Hannibal-Bach, Hans Kristian;

    2016-01-01

    RATIONALE: Suppressor lipids were originally identified in 1993 and reported to encompass six lipid classes that enable Saccharomyces cerevisiae to live without sphingolipids. Structural characterization, using non-mass spectrometric approaches, revealed that these suppressor lipids are very long...... chain fatty acid (VLCFA)-containing glycerophospholipids with polar head groups that are typically incorporated into sphingolipids. Here we report, for the first time, the structural characterization of the yeast suppressor lipids using high-resolution mass spectrometry. METHODS: Suppressor lipids were...... isolated by preparative chromatography and subjected to structural characterization using hybrid quadrupole time-of-flight and ion trap-orbitrap mass spectrometry. RESULTS: Our investigation recapitulates the overall structural features of the suppressor lipids and provides an in-depth characterization...

  4. Lateral IBIC characterization of single crystal synthetic diamond detectors

    CERN Document Server

    Giudice, A Lo; Manfredotti, C; Marinelli, M; Milani, E; Picollo, F; Prestopino, G; Re, A; Rigato, V; Verona, C; Verona-Rinati, G; Vittone, E

    2016-01-01

    In order to evaluate the charge collection efficiency (CCE) profile of single-crystal diamond devices based on a p type/intrinsic/metal configuration, a lateral Ion Beam Induced Charge (IBIC) analysis was performed over their cleaved cross sections using a 2 MeV proton microbeam. CCE profiles in the depth direction were extracted from the cross-sectional maps at variable bias voltage. IBIC spectra relevant to the depletion region extending beneath the frontal Schottky electrode show a 100% CCE, with a spectral resolution of about 1.5%. The dependence of the width of the high efficiency region from applied bias voltage allows the constant residual doping concentration of the active region to be evaluated. The region where the electric field is absent shows an exponentially decreasing CCE profile, from which it is possible to estimate the diffusion length of the minority carriers by means of a drift-diffusion model.

  5. Membrane potential governs lateral segregation of plasma membrane proteins and lipids in yeast.

    Science.gov (United States)

    Grossmann, Guido; Opekarová, Miroslava; Malinsky, Jan; Weig-Meckl, Ina; Tanner, Widmar

    2007-01-10

    The plasma membrane potential is mainly considered as the driving force for ion and nutrient translocation. Using the yeast Saccharomyces cerevisiae as a model organism, we have discovered a novel role of the membrane potential in the organization of the plasma membrane. Within the yeast plasma membrane, two non-overlapping sub-compartments can be visualized. The first one, represented by a network-like structure, is occupied by the proton ATPase, Pma1, and the second one, forming 300-nm patches, houses a number of proton symporters (Can1, Fur4, Tat2 and HUP1) and Sur7, a component of the recently described eisosomes. Evidence is presented that sterols, the main lipid constituent of the plasma membrane, also accumulate within the patchy compartment. It is documented that this compartmentation is highly dependent on the energization of the membrane. Plasma membrane depolarization causes reversible dispersion of the H(+)-symporters, not however of the Sur7 protein. Mitochondrial mutants, affected in plasma membrane energization, show a significantly lower degree of membrane protein segregation. In accordance with these observations, depolarized membranes also considerably change their physical properties (detergent sensitivity).

  6. Cyclosporine-loaded solid lipid nanoparticles (SLN): drug-lipid physicochemical interactions and characterization of drug incorporation.

    Science.gov (United States)

    Müller, R H; Runge, S A; Ravelli, V; Thünemann, A F; Mehnert, W; Souto, E B

    2008-03-01

    Solid lipid nanoparticles (SLN) were produced loaded with cyclosporine A in order to develop an improved oral formulation. In this study, the particles were characterized with regard to the structure of the lipid particle matrix, being a determining factor for mode of drug incorporation and drug release. Differential scanning calorimetry (DSC) and wide-angle X-ray scattering (WAXS) measurements were employed for the analysis of the polymorphic modifications and mode of drug incorporation. Particles were produced using Imwitor 900 as lipid matrix (the suspension consisted of 10% particles, 8% Imwitor 900, 2% cyclosporine A), 2.5% Tagat S, 0.5% sodium cholate and 87% water. DSC and WAXS were used to analyse bulk lipid, bulk drug, drug incorporated in the bulk and unloaded and drug-loaded SLN dispersions. The processing of the bulk lipid into nanoparticles was accompanied by a polymorphic transformation from the beta to the alpha-modification. After production, the drug-free SLN dispersions converted back to beta-modification, while the drug-loaded SLN stayed primarily in alpha-modification. After incorporation of cyclosporine A into SLN, the peptide lost its crystalline character. Based on WAXS data, it could be concluded that cyclosporine is molecularly dispersed in between the fatty acid chains of the liquid-crystalline alpha-modification fraction of the loaded SLN.

  7. Extraction and Characterization of Lipids from Salicornia virginica and Salicornia europaea

    Science.gov (United States)

    Kulis,Michael J.; Hepp, Aloysius F.; Pham, Phong X.; Ribita, Daniela; Bomani, Bilal M. M.; Duraj, Stan A.

    2010-01-01

    The lipid content from Salicornia virginica and Salicornia europaea is investigated. The plants are leafless halophytes with seeds contained in terminal nodes. The lipids, in the form of cell membranes and oil bodies that come directly from the node cells, are observed using fluorescence microscopy. Two extraction methods as well as the results of extracting from the seeds and from the entire nodes are described. Characterization of the fatty acid components of the lipids using Gas Chromatography in tandem with Mass Spectroscopy is also described. Comparisons are made between the two methods and between the two plant materials as lipid sources.

  8. LIPID BIOMARKER CHARACTERIZATION OF BLOOM-RELATED DINOFLAGELLATES AND OTHER EUKARYOTIC ALGAE

    Science.gov (United States)

    Marine eukaryotic algae synthesize an array of lipids of chemotaxonomic utility that are potentially valuable in characterizing phytoplankton communities. Sterols and photopigments characteristic of dinoflagellates are rarely found in other algal classes. Long chain (C28) highly ...

  9. Solvent Extraction and Characterization of Neutral Lipids in Oocystis sp.

    Directory of Open Access Journals (Sweden)

    Renil eAnthony

    2015-01-01

    Full Text Available Microalgae are a favorable feedstock for bioproducts and biofuels due to their high oil content, fast growth rates and low resource demands. Solvent lipid extraction efficiency from microalgae is dependent on algal strain and the extraction solvent. Four non-polar extraction solvents were evaluated for the recovery of neutral cellular lipids from microalgae Oocystis sp. (UTEX LB2396. Methylene chloride, hexane, diethyl ether, and cyclohexane were selected as the extraction solvents. All solvent extracts contained hexadecanoic acid, linoleic acid and linolenic acid; accounting for 70% of total lipid content with a proportional wt% composition of the three fatty acids, except for the hexane extracts that showed only hexadecanoic acid and linoleic acid. While not statistically differentiated, methylene chloride proved to be the most effective solvent for Oocystis sp. among the four solvents tested with a total average neutral lipid recovery of 0.25% of dry weight followed by diethyl ether (0.18%, cyclohexane (0.14% and hexane (0.11%. This research presents a simple methodology to optimize the selection of lipid specific extraction solvents for the microalgal strain selected.

  10. Influence of the long-chain/short-chain amphiphile ratio on lateral diffusion of PEG-lipid in magnetically aligned lipid bilayers as measured via pulsed-field-gradient NMR.

    Science.gov (United States)

    Soong, Ronald; Macdonald, Peter M

    2005-09-01

    Lateral diffusion measurements of polyethylene glycol(PEG)-lipid incorporated into magnetically aligned lipid bilayers, composed of dimyristoyl phosphatidylcholine (DMPC) plus dihexanoyl phosphatidylcholine (DHPC) plus 1 mol % (relative to DMPC) dimyristoyl phosphatidylethanolamine-n-[methoxy(polyethylene glycol)-2000] (DMPE-PEG 2000), were performed using stimulated-echo pulsed-field-gradient proton ((1)H) nuclear magnetic resonance spectroscopy. The DMPE-PEG 2000 (1 mol %, 35 degrees C) lateral diffusion coefficient D varied directly with the mole fraction of DMPC, X(DMPC) = q/(1+q) where q = DMPC/DHPC molar ratio, decreasing progressively from D = 1.65 x 10(-11) m(2) s(-1) at q approximately 4.7 to D = 0.65 x 10(-11) m(2) s(-1) at q approximately 2.5. Possible sources of this dependence, including orientational disorder, obstruction, and PEG-lipid sequestration, were simulated using, respectively, a diffusion-in-a-cone model, percolation theory, and a two-phase PEG distribution model. Orientational disorder alone was not capable of reproducing the observations, but in combination with either obstruction or PEG-lipid two-phase distribution models did so satisfactorily. A combination of all three models yielded the most reasonable fit to the observed dependence of lateral diffusion on q. These same effects would be expected to influence lateral diffusion of any bilayer-associating species in such systems.

  11. Dysregulation of lipid and amino acid metabolism precedes islet autoimmunity in children who later progress to type 1 diabetes

    Science.gov (United States)

    Orešič, Matej; Simell, Satu; Sysi-Aho, Marko; Näntö-Salonen, Kirsti; Seppänen-Laakso, Tuulikki; Parikka, Vilhelmiina; Katajamaa, Mikko; Hekkala, Anne; Mattila, Ismo; Keskinen, Päivi; Yetukuri, Laxman; Reinikainen, Arja; Lähde, Jyrki; Suortti, Tapani; Hakalax, Jari; Simell, Tuula; Hyöty, Heikki; Veijola, Riitta; Ilonen, Jorma; Lahesmaa, Riitta; Knip, Mikael; Simell, Olli

    2008-01-01

    The risk determinants of type 1 diabetes, initiators of autoimmune response, mechanisms regulating progress toward β cell failure, and factors determining time of presentation of clinical diabetes are poorly understood. We investigated changes in the serum metabolome prospectively in children who later progressed to type 1 diabetes. Serum metabolite profiles were compared between sample series drawn from 56 children who progressed to type 1 diabetes and 73 controls who remained nondiabetic and permanently autoantibody negative. Individuals who developed diabetes had reduced serum levels of succinic acid and phosphatidylcholine (PC) at birth, reduced levels of triglycerides and antioxidant ether phospholipids throughout the follow up, and increased levels of proinflammatory lysoPCs several months before seroconversion to autoantibody positivity. The lipid changes were not attributable to HLA-associated genetic risk. The appearance of insulin and glutamic acid decarboxylase autoantibodies was preceded by diminished ketoleucine and elevated glutamic acid. The metabolic profile was partially normalized after the seroconversion. Autoimmunity may thus be a relatively late response to the early metabolic disturbances. Recognition of these preautoimmune alterations may aid in studies of disease pathogenesis and may open a time window for novel type 1 diabetes prevention strategies. PMID:19075291

  12. Synthesis and Biophysical Characterization of Chlorambucil Anticancer Ether Lipid Prodrugs

    DEFF Research Database (Denmark)

    Pedersen, Palle Jacob; Christensen, Mikkel Stochkendahl; Ruysschaert, Tristan;

    2009-01-01

    to form unilamellar liposomes (86-125 nm) and are hydrolyzed by phospholipase A2, resulting in chlorambucil release. Liposomal formulations of prodrug lipids displayed cytotoxicity toward HT-29, MT-3, and ES-2 cancer cell lines in the presence of phospholipase A2, with IC50 values in the 8-36 μM range....

  13. Enzymatic characterization of lipid-based drug delivery systems

    DEFF Research Database (Denmark)

    Ljusberg-Wahren, Helena; Seier Nielsen, Flemming; Brogård, Mattias

    2005-01-01

    lipids as substrate, was determined. The impact of incorporating two sparingly water soluble model drugs, probucol and halofantrine, into the SMEDDS was studied. It was found that both model drugs reduced the initial rate of lipolysis compared with the vehicle, probucol having a larger effect than...

  14. FORMULATION AND CHARACTERIZATION OF SOLID LIPID NANOPARTICLES FOR TRANSDERMAL DELIVERY OF TESTOSTERONE

    Directory of Open Access Journals (Sweden)

    L. K. Omray

    2014-07-01

    Full Text Available Present study deals with the formulation and characterization of testosterone bearing solid lipid nanoparticles for transdermal drug delivery. Solid lipid nanoparticles of testosterone were prepared by ether injection method. Solid lipid nanoparticles were prepared by testosterone, glyceryl mono stearate, brij 35, propylene glycol and double distilled water. Four different formulations i.e. F1 to F4 were prepared in different quantity of brij 35. All the solid lipid nanoparticles formulations were characterized on the basis of electron microscopy, particle size by zeta sizer, polydispersity index, encapsulation efficiency, viscosity and in vitro drug release study. Average size and polydispersity index of developed formulation F3 found to have 298 nm and 0.328 respectively, determined by zeta sizer. Encapsulation efficiency of formulation F3 was found to have 54.16%. Viscosity of formulation was also enough to handle for transdermal application. All the formulations followed zero order release profile.

  15. Further characterization of theobroma oil-beeswax admixtures as lipid matrices for improved drug delivery systems.

    Science.gov (United States)

    Attama, A A; Schicke, B C; Müller-Goymann, C C

    2006-11-01

    There is an increasing interest in lipid based drug delivery systems due to factors such as better characterization of lipidic excipients and formulation versatility and the choice of different drug delivery systems. It is important to know the thermal characteristics, crystal habit, texture, and appearance of a new lipid matrix when determining its suitability for use in certain pharmaceutical application. It is line with this that this research was embarked upon to characterize mixtures of beeswax and theobroma oil with a view to applying their admixtures in drug delivery systems such as solid lipid nanoparticles and nanostructured lipid carriers. Admixtures of theobroma oil and beeswax were prepared to contain 25% w/w, 50% w/w, and 75% w/w of theobroma oil. The admixtures were analyzed by differential scanning calorimetry (DSC), small angle X-ray diffraction (SAXD), wide angle X-ray diffraction (WAXD), and isothermal heat conduction microcalorimetry (IMC). The melting behavior and microstructures of the lipid admixtures were monitored by polarized light microscopy (PLM). Transmission electron microscopy (TEM) was used to study the internal structures of the lipid bases. DSC traces indicated that the higher melting peaks were roughly constant for the different admixtures, but lower melting peaks significantly increased (p beeswax in all the lipid matrix admixtures at all stages of the study. PLM micrographs revealed differences with regard to the thermal and optical behaviors depending on the composition of the matrix. The lipid matrix consisting of 75% w/w of theobroma oil showed a spherulite texture after 4 weeks of isothermal storage. Crystallization exotherms of lipid matrices containing 50% w/w and 25% w/w of theobroma oil showed change in modification after 30 min with the latter having a greater time-dependent crystallization. Generally, low non-integral Avrami exponents and growth rate constants were obtained for all the lipid matrices, with the admixture

  16. Preparation, characterization, and in vitro and in vivo evaluation of lovastatin solid lipid nanoparticles

    OpenAIRE

    Suresh, Gande; Manjunath, Kopparam; Venkateswarlu, Vobalaboina; Satyanarayana, Vemula

    2007-01-01

    The purpose of this research was to study whether the bioavailability of lovastatin could be improved by administering lovastatin solid lipid nanoparticles (SLN) duodenally to rats. Lovastatin SLN were developed using triglycerides by hot homogenization followed by ultrasonication. Particle size and zeta potential were measured by photon correlation spectroscopy. The solid state of the drug in the SLN and lipid modification were characterized. Bioavailability studies were conducted in male Wi...

  17. Lipidic characterization of Santa Inês lamb shoulder

    Directory of Open Access Journals (Sweden)

    Christian Albert Carvalho da Cruz

    2011-06-01

    Full Text Available The edible portion of the shoulder of 12 castrated and 12 non-castrated Santa Inês lambs slaughtered at different ages (84, 168, 210, 252 days were used. The shoulders were chemically analyzed to determine the quantity of total lipids, cholesterol, and fatty acids composition. Castrated and non-castrated lambs gained body weight (p = 0.0393, p = 0.0017 and half carcass weight (p = 0.0240, p = 0.0017, respectively. The shoulder weight was increased in the carcasses of non-castrated lambs (p = 0.0110. The edible portion of the shoulder of castrated lambs presented higher total lipids (16.09 g.100 g-1. The cholesterol content was influenced by castration (p = 0.0001 reducing with age. Castrated animals presented higher content of C18:1 T11, CLA, and C18:0. The shoulder weight is only increased with increasing age in the carcasses of non-castrated lambs. Castration influences the cholesterol content of the shoulder; however, both castrated and non-castrated lambs had their cholesterol contents reduced with increasing age. Castration and age interfered in the estearic acid concentration of the edible portion of lamb shoulder.

  18. Characterization of a Novel Intestinal Glycerol-3-phosphate Acyltransferase Pathway and Its Role in Lipid Homeostasis.

    Science.gov (United States)

    Khatun, Irani; Clark, Ronald W; Vera, Nicholas B; Kou, Kou; Erion, Derek M; Coskran, Timothy; Bobrowski, Walter F; Okerberg, Carlin; Goodwin, Bryan

    2016-02-01

    Dietary triglycerides (TG) are absorbed by the enterocytes of the small intestine after luminal hydrolysis into monacylglycerol and fatty acids. Before secretion on chylomicrons, these lipids are reesterified into TG, primarily through the monoacylglycerol pathway. However, targeted deletion of the primary murine monoacylglycerol acyltransferase does not quantitatively affect lipid absorption, suggesting the existence of alternative pathways. Therefore, we investigated the role of the glycerol 3-phosphate pathway in dietary lipid absorption. The expression of glycerol-3-phosphate acyltransferase (GPAT3) was examined throughout the small intestine. To evaluate the role for GPAT3 in lipid absorption, mice harboring a disrupted GPAT3 gene (Gpat3(-/-)) were subjected to an oral lipid challenge and fed a Western-type diet to characterize the role in lipid and cholesterol homeostasis. Additional mechanistic studies were performed in primary enterocytes. GPAT3 was abundantly expressed in the apical surface of enterocytes in the small intestine. After an oral lipid bolus, Gpat3(-/-) mice exhibited attenuated plasma TG excursion and accumulated lipid in the enterocytes. Electron microscopy studies revealed a lack of lipids in the lamina propria and intercellular space in Gpat3(-/-) mice. Gpat3(-/-) enterocytes displayed a compensatory increase in the synthesis of phospholipid and cholesteryl ester. When fed a Western-type diet, hepatic TG and cholesteryl ester accumulation was significantly higher in Gpat3(-/-) mice compared with the wild-type mice accompanied by elevated levels of alanine aminotransferase, a marker of liver injury. Dysregulation of bile acid metabolism was also evident in Gpat3-null mice. These studies identify GPAT3 as a novel enzyme involved in intestinal lipid metabolism.

  19. Nanomechanical properties of lipid bilayer: Asymmetric modulation of lateral pressure and surface tension due to protein insertion in one leaflet of a bilayer

    Science.gov (United States)

    Maftouni, Negin; Amininasab, Mehriar; Ejtehadi, Mohammad Reza; Kowsari, Farshad; Dastvan, Reza

    2013-02-01

    The lipid membranes of living cells form an integral part of biological systems, and the mechanical properties of these membranes play an important role in biophysical investigations. One interesting problem to be evaluated is the effect of protein insertion in one leaflet of a bilayer on the physical properties of lipid membrane. In the present study, an all atom (fine-grained) molecular dynamics simulation is used to investigate the binding of cytotoxin A3 (CTX A3), a cytotoxin from snake venom, to a phosphatidylcholine lipid bilayer. Then, a 5-microsecond coarse-grained molecular dynamics simulation is carried out to compute the pressure tensor, lateral pressure, surface tension, and first moment of lateral pressure in each monolayer. Our simulations reveal that the insertion of CTX A3 into one monolayer results in an asymmetrical change in the lateral pressure and corresponding spatial distribution of surface tension of the individual bilayer leaflets. The relative variation in the surface tension of the two monolayers as a result of a change in the contribution of the various intermolecular forces may potentially be expressed morphologically.

  20. Influence of nonequilibrium lipid transport, membrane compartmentalization, and membrane proteins on the lateral organization of the plasma membrane

    Science.gov (United States)

    Fan, Jun; Sammalkorpi, Maria; Haataja, Mikko

    2010-01-01

    Compositional lipid domains (lipid rafts) in plasma membranes are believed to be important components of many cellular processes. The mechanisms by which cells regulate the sizes, lifetimes, and spatial localization of these domains are rather poorly understood at the moment. We propose a robust mechanism for the formation of finite-sized lipid raft domains in plasma membranes, the competition between phase separation in an immiscible lipid system and active cellular lipid transport processes naturally leads to the formation of such domains. Simulations of a continuum model reveal that the raft size distribution is broad and the average raft size is strongly dependent on the rates of cellular and interlayer lipid transport processes. We demonstrate that spatiotemporal variations in the recycling may enable the cell to localize larger raft aggregates at specific parts along the membrane. Moreover, we show that membrane compartmentalization may further facilitate spatial localization of the raft domains. Finally, we demonstrate that local interactions with immobile membrane proteins can spatially localize the rafts and lead to further clustering.

  1. Preparation and characterization of Biochanin A loaded solid lipid nanoparticles

    Directory of Open Access Journals (Sweden)

    Chunlei Tao

    2012-01-01

    Full Text Available Biochanin A, the predominant isoflavones found in plants, had proved its human health benefits. The purpose of this research was to study whether Biochanin A (BCA loaded solid lipid nanoparticles (SLN could improve solution and prolong the half-life of BCA. BCA-SLN was prepared by emulsion evaporation and low temperature solidification technique, and freeze-dried powders were developed to improve stability. The mean particle sizes, zeta potential, entrapment efficiency (EE, and drug loading capacity (DL of BCA was 176.0 nm, −18.7 ± 0.26, 97.15 ± 0.28%, and 6.38 ± 0.04%, respectively. The results of differential scanning calorimetry (DSC and X-ray diffraction analysis (XRD indicated that the BCA was wrapped and absorbed in the nanoparticles. The solution of preparation is much higher than the untreated BCA. Results of stability of SLN showed a relatively short-term stability after storage at 4°C and 25°C for 15 days. Drug release of untreated BCA and BCA-SLN was fit into the Biexponential equations and Weibull equations, respectively, and SLN showed sustained release properties. But after freeze-dried, stability was improved, and the EE and DL had a slightly decrease. The mean particle size was slightly increased, but the structure was not changed. In conclusion, SLN systems can represent an effective strategy to change the poor aqueous solubility and prolong the half-time of BCA.

  2. Phase transition of lipid-like monolayer characterized by second harmonic generation

    Institute of Scientific and Technical Information of China (English)

    于安池; 常青; 赵新生; 周晴中; 李东; 黄岩谊; 程天蓉; 黄春辉

    1999-01-01

    Phase transition of a lipid-like hemicyanine compound characterized by second harmonic generation is studied carefully. The phase transition is assigned as the first order transition between solid state and liquid state. The transition temperature increases with an increase in the surface molecular concentration. A monolayer structure parameter a which is very sensitive to the phase transition is introduced.

  3. Characterization of Different Functionalized Lipidic Nanocapsules as Potential Drug Carriers

    Directory of Open Access Journals (Sweden)

    José Manuel Peula-García

    2012-02-01

    Full Text Available Lipid nanocapsules (LNC based on a core-shell structure consisting of an oil-filled core with a surrounding polymer layer are known to be promising vehicles for the delivery of hydrophobic drugs in the new therapeutic strategies in anti-cancer treatments. The present work has been designed as basic research about different LNC systems. We have synthesized—and physico-chemically characterized—three different LNC systems in which the core was constituted by olive oil and the shell by different phospholipids (phosphatidyl-serine or lecithin and other biocompatible molecules such as Pluronic® F68 or chitosan. It is notable that the olive-oil-phosphatidyl-serine LCN is a novel formulation presented in this work and was designed to generate an enriched carboxylic surface. This carboxylic layer is meant to link specific antibodies, which could facilitate the specific nanocapsule uptake by cancer cells. This is why nanoparticles with phosphatidyl-serine in their shell have also been used in this work to form immuno-nanocapsules containing a polyclonal IgG against a model antigen (C-reactive protein covalently bounded by means of a simple and reproducible carbodiimide method. An immunological study was made to verify that these IgG-LNC complexes showed the expected specific immune response. Finally, a preliminary in vitro study was performed by culturing a breast-carcinoma cell line (MCF-7 with Nile-Red-loaded LNC. We found that these cancer cells take up the fluorescent Nile-Red molecule in a process dependent on the surface properties of the nanocarriers.

  4. Characterization of Floating Surface Layers of Lipids and Lipopolymers by Surface-Sensitive Scattering

    Science.gov (United States)

    Krüger, Peter; Lösche, Mathias

    Nanotechnology and molecular (bio-)engineering are making ever deepening inroads into everybodys daily life. Physicochemical and biotechnological achievements in the design of physiologically active supramolecular assemblies have brought about the quest for their submolecular-level characterization. We employ surface-sensitive scattering techniques for the investigation of planar lipid membranes - floating monolayers on aqueous surfaces - to correlate structural, functional and dynamic aspects of biomembrane models. This chapter surveys recent work on the submolecular structure of floating phospholipid monolayers - where the advent of third-generation synchrotron X-ray sources has driven the development of realistic, submolecular-scale quasi-chemical models - as well as of more complex systems: cation binding to anionic lipid surfaces; conformational changes of lipopolymers undergoing phase transitions; the conformational organization of phosphatidylinositol and phosphatidylinositides, as examples of physiologically important lipids; and the adsorption of peptides (neuropeptide Y, NPY) or solvents (dimethylsulfoxide, DMSO) onto phospholipid surface layers.

  5. Synthesis and characterization of cationic lipid coated magnetic nanoparticles using multiple emulsions as microreactors

    Science.gov (United States)

    Akbaba, Hasan; Karagöz, Uğur; Selamet, Yusuf; Kantarcı, A. Gülten

    2017-03-01

    The aim of this study was to develop a novel iron oxide nanoparticle synthesis method with in-situ surface coating. For this purpose multiple emulsions were used as microreactors for the first time and magnetic iron oxide particles synthesized in the core of cationic solid lipid nanoparticles. DLS, SEM, TEM, VSM, Raman Spectrometer, XRD, and XPS techniques were performed for characterization of the magnetic nanoparticles. Obtained magnetic nanoparticles are superparamagnetic and no additional process was needed for surface adjustments. They are positively charged as a result of cationic lipid coating and has appropriate particle size (drug or nucleic acid delivery. Structure analysis showed that magnetic core material is in the form of magnetite. Saturation magnetization value was measured as 15-17 emu g-1 for lipid coated magnetic nanoparticles obtained by multiple emulsion method which is reasonably sufficient for magnetic targeting.

  6. Characterization of growth and lipid production by Chlorella sp. PCH90, a microalga native to Quebec.

    Science.gov (United States)

    Abdelaziz, Ahmed Elsayed Mohamed; Ghosh, Dipankar; Hallenbeck, Patrick C

    2014-03-01

    Microalgae are being investigated as potential candidates for biodiesel production since they can be grown without competition with food production, have an inherently fast growth rate, and can have a high lipid content under different nutrient limiting conditions. However, large scale production will best be carried out with indigenous strains, well adapted to local conditions. This study reports on the characterization of the novel microalga Chlorella sp. PCH90, isolated in Quebec. Its molecular phylogeny was established and lipid production studies as a function of the initial concentrations of nitrate, phosphate, and sodium chloride were carried out using response surface methodology. Under the appropriate conditions this microalga could produce up to 36% lipid and grew well in both synthetic medium and secondary effluent from a wastewater treatment plant at both 22 and 10°C. Thus, this strain is promising for further development as a potential biofuels producer under local climatic conditions.

  7. Characterization of Lipid A Variants by Energy-Resolved Mass Spectrometry: Impact of Acyl Chains

    Science.gov (United States)

    Crittenden, Christopher M.; Akin, Lucas D.; Morrison, Lindsay J.; Trent, M. Stephen; Brodbelt, Jennifer S.

    2016-12-01

    Lipid A molecules consist of a diglucosamine sugar core with a number of appended acyl chains that vary in their length and connectivity. Because of the challenging nature of characterizing these molecules and differentiating between isomeric species, an energy-resolved MS/MS strategy was undertaken to track the fragmentation trends and map genealogies of product ions originating from consecutive cleavages of acyl chains. Generalizations were developed based on the number and locations of the primary and secondary acyl chains as well as variations in preferential cleavages arising from the location of the phosphate groups. Secondary acyl chain cleavage occurs most readily for lipid A species at the 3' position, followed by primary acyl chain fragmentation at both the 3' and 3 positions. In the instances of bisphosphorylated lipid A variants, phosphate loss occurs readily in conjunction with the most favorable primary and secondary acyl chain cleavages.

  8. Natural lipid nanoparticles containing nimesulide: synthesis, characterization and in vivo antiedematogenic and antinociceptive activities.

    Science.gov (United States)

    Raffin, Renata P; Lima, Amanda; Lorenzoni, Ricardo; Antonow, Michelli B; Turra, Cláudia; Alves, Marta P; Fagan, Solange B

    2012-04-01

    Lipid nanoparticles are drug delivery systems able to increase bioavailability of poorly soluble drugs. They can be prepared with different lipid materials, especially natural lipids. Shea butter is a natural lipid obtained from the Butyrospermum parkii seed and rich in oleic and stearic acids. Nimesulide is a COX 2 selective anti-inflammatory that is poorly soluble in water. The purpose of this study was to develop and characterize shea butter lipid nanoparticles using a new technique and evaluate the in vivo activity of these nanoparticles. Lipid nanoparticles were prepared by melting shea butter and mixing with an aqueous phase using a high shear mixer. The nanoparticles presented pH of 6.9 +/- 0.1, mean particle size of 90 nm and a narrow polydispersity (0.21). Zeta potential was around -20 mV and the encapsulation efficiency was 97.5%. Drug release was evaluated using dialysis bags and presented monoexponential profile with t50% of 4.80 h (free drug t50% was only 2.86 h). Antinociceptive activity was performed by the acetic acid model. Both nimesulide and nimesulide-loaded nanoparticles presented significant activity compared to the control. The in vivo anti-inflammatory activity was evaluated by paw edema and was statistically different for the nanoparticles containing nimesulide compared to free nimesulide, blank nanoparticles and saline. In conclusion, the use of shea butter as encapsulating lipid was very successful and allowed nanoparticles to be prepared with a very simple technique. The nanoparticles presented significant pharmacological effects that were not seen for free drug administration.

  9. Cannabinoid antagonist in nanostructured lipid carriers (NLCs): design, characterization and in vivo study.

    Science.gov (United States)

    Esposito, Elisabetta; Ravani, Laura; Drechsler, Markus; Mariani, Paolo; Contado, Catia; Ruokolainen, Janne; Ratano, Patrizia; Campolongo, Patrizia; Trezza, Viviana; Nastruzzi, Claudio; Cortesi, Rita

    2015-03-01

    This study describes the preparation, characterization, and in vivo evaluation in rats of nanostructured lipid carriers (NLCs) encapsulating rimonabant (RMN) as prototypical cannabinoid antagonist. A study was conducted in order to optimize NLC production by melt and ultrasonication method. NLCs were prepared by alternatively adding the lipid phase into the aqueous one (direct protocol) or the aqueous phase into the lipid one (reverse protocol). RMN-NLCs have been characterized by cryogenic transmission electron microscopy (cryo-TEM), X-ray, photon correlation spectroscopy (PCS) and sedimentation field flow fractionation (SdFFF). Reverse NLCs were treated with polysorbate 80. RMN release kinetics have been determined in vitro by dialysis method. In vivo RMN biodistribution in rats was evaluated after intranasal (i.n.) administration of reverse RMN-NLC. The reverse protocol enabled to prevent the lost of lipid phase and to achieve higher RMN encapsulation efficacy (EE) with respect to the direct protocol (98% w/w versus 67% w/w). The use of different protocols did not affect NLC morphology and dimensional distribution. An in vitro dissolutive release rate of RMN was calculated. The in vivo data indicate that i.n. administration of RMN by reverse NLC treated with polysorbate 80 increased RMN concentration in the brain with respect to the drug in solution. The nanoencapsulation protocol presented here appears as an optimal strategy to improve the low solubility of cannabinoid compounds in an aqueous system suitable for in vivo administration.

  10. Characterizing the boundary lateral to the shear direction of deformation twins in magnesium

    Science.gov (United States)

    Liu, Y.; Li, N.; Shao, S.; Gong, M.; Wang, J.; McCabe, R. J.; Jiang, Y.; Tomé, C. N.

    2016-06-01

    The three-dimensional nature of twins, especially the atomic structures and motion mechanisms of the boundary lateral to the shear direction of the twin, has never been characterized at the atomic level, because such boundary is, in principle, crystallographically unobservable. We thus refer to it here as the dark side of the twin. Here, using high-resolution transmission electron microscopy and atomistic simulations, we characterize the dark side of deformation twins in magnesium. It is found that the dark side is serrated and comprised of coherent twin boundaries and semi-coherent twist prismatic-prismatic boundaries that control twin growth. The conclusions of this work apply to the same twin mode in other hexagonal close-packed materials, and the conceptual ideas discussed here should hold for all twin modes in crystalline materials.

  11. Cannabinoid antagonist in nanostructured lipid carriers (NLCs): design, characterization and in vivo study

    Energy Technology Data Exchange (ETDEWEB)

    Esposito, Elisabetta; Ravani, Laura [Department of Life Sciences and Biotechnology, University of Ferrara, I-44121 Ferrara (Italy); Drechsler, Markus [BIMF/Soft Matter Electron Microscopy, University of Bayreuth (Germany); Mariani, Paolo [Department of Life and Environmental Sciences and CNISM, Università Politecnica delle Marche, I-60100 Ancona (Italy); Contado, Catia [Department of Chemical and Pharmaceutical Sciences, University of Ferrara, I-44121 Ferrara (Italy); Ruokolainen, Janne [Department of Applied Physics, Aalto University, 00076 Aalto (Finland); Ratano, Patrizia; Campolongo, Patrizia [Department of Physiology and Pharmacology, Sapienza University of Rome, 00185 Roma (Italy); Trezza, Viviana [Department of Science, Roma Tre University, 00146 Roma (Italy); Nastruzzi, Claudio, E-mail: nas@unife.it [Department of Life Sciences and Biotechnology, University of Ferrara, I-44121 Ferrara (Italy); Cortesi, Rita [Department of Life Sciences and Biotechnology, University of Ferrara, I-44121 Ferrara (Italy)

    2015-03-01

    This study describes the preparation, characterization, and in vivo evaluation in rats of nanostructured lipid carriers (NLCs) encapsulating rimonabant (RMN) as prototypical cannabinoid antagonist. A study was conducted in order to optimize NLC production by melt and ultrasonication method. NLCs were prepared by alternatively adding the lipid phase into the aqueous one (direct protocol) or the aqueous phase into the lipid one (reverse protocol). RMN-NLCs have been characterized by cryogenic transmission electron microscopy (cryo-TEM), X-ray, photon correlation spectroscopy (PCS) and sedimentation field flow fractionation (SdFFF). Reverse NLCs were treated with polysorbate 80. RMN release kinetics have been determined in vitro by dialysis method. In vivo RMN biodistribution in rats was evaluated after intranasal (i.n.) administration of reverse RMN-NLC. The reverse protocol enabled to prevent the lost of lipid phase and to achieve higher RMN encapsulation efficacy (EE) with respect to the direct protocol (98% w/w versus 67% w/w). The use of different protocols did not affect NLC morphology and dimensional distribution. An in vitro dissolutive release rate of RMN was calculated. The in vivo data indicate that i.n. administration of RMN by reverse NLC treated with polysorbate 80 increased RMN concentration in the brain with respect to the drug in solution. The nanoencapsulation protocol presented here appears as an optimal strategy to improve the low solubility of cannabinoid compounds in an aqueous system suitable for in vivo administration. - Highlights: • Rimonabant (RMN) can be encapsulated in nanostructured lipid carriers (NLCs). • Nanoencapsulation improves RMN solubility in a stable physiologic aqueous formulation. • RMN is released in vitro from NLC by a controlled dissolutive release modality. • I.n. administration leads to higher RMN concentration in the brain with respect to plasma. • NLC increases RMN concentration in the brain with respect to

  12. Structural characterization of ether lipids from the archaeon Sulfolobus islandicus by high-resolution shotgun lipidomics

    DEFF Research Database (Denmark)

    Jensen, Sara Munk; Brandl, Martin; Treusch, Alexander H;

    2015-01-01

    -resolution Fourier transform mass spectrometry using an ion trap-orbitrap mass spectrometer. This analysis identified five clusters of molecular ions that matched ether lipids in the database with sub-ppm mass accuracy. To structurally characterize and validate the identities of the potential lipid species, we...

  13. In vitro characterization and in vivo evaluation of nanostructured lipid curcumin carriers for intragastric administration

    Directory of Open Access Journals (Sweden)

    Fang M

    2012-10-01

    Full Text Available Min Fang, Yilin Jin, Wei Bao, Hui Gao, Mengjin Xu, Di Wang, Xia Wang, Ping Yao, Liegang LiuDepartment of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, and Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, People’s Republic of ChinaBackground: Curcumin has a variety of pharmacological effects. However, poor water solubility and low oral bioavailability limit its clinical utility. A delivery system for nanostructured lipid carriers has been reported to be a promising approach to enhancing the oral absorption of curcumin. The aim of the present study was to investigate the pharmacokinetics, tissue distribution, and relative bioavailability of curcumin in rats after a single intragastric dose of a nanostructured lipid curcumin carrier formulation.Methods: Nanostructured lipid curcumin carriers were prepared using the ethanol dripping method and characterized in terms of the particle size, polydispersity index, zeta potential, differential scanning calorimetry, drug-loading capacity, encapsulation efficiency, and in vitro release. The pharmacokinetics and tissue distribution of nanostructured lipid curcumin carriers and curcumin suspension were compared after intragastric administration.Results: Nanostructured lipid curcumin carriers showed a significantly higher peak plasma concentration (564.94 ± 14.98 ng/mL versus 279.43 ± 7.21 ng/mL, P < 0.01, a shorter time taken to reach peak plasma concentration (0.5 ± 0.01 hour versus 1.0 ± 0.12 hour, P < 0.01, and a greater AUC0–∞ (820.36 ± 25.11 mg × hour/L versus 344.11 ± 10.01 mg × hour/L, P < 0.05 compared with curcumin suspension. In the tissue distribution studies, curcumin could be detected in the spleen, heart, liver, kidneys, lungs, and brain. Following intragastric administration of the nanostructured lipid curcumin

  14. Traumatic brain injury in the rat: characterization of a lateral fluid-percussion model.

    Science.gov (United States)

    McIntosh, T K; Vink, R; Noble, L; Yamakami, I; Fernyak, S; Soares, H; Faden, A L

    1989-01-01

    Experimental fluid-percussion models produce brain injury by rapidly injecting saline into the closed cranium. In the present study we characterize the physiological, histopathological and neurological responses to mechanical brain injury in the rat produced by lateral fluid-percussion injury of graded severity. Physiological experiments (n = 105) demonstrated that all levels of injury produced an acute and transient systemic hypertension and bradycardia. Acute hypertension followed by significant hypotension occurred at higher magnitudes of injury. Post-injury suppression of electroencephalographic amplitude was related to the severity of injury. An increase in slow wave (delta/theta) electroencephalographic activity with a concomitant decrease in alpha/beta electroencephalographic activity were observed only at moderate and high magnitude of injury and were correlated with a worsened neurological outcome (r = 0.84; P less than 0.05) and increased mortality (r = 0.66; P less than 0.05). Alterations in brainstem auditory-evoked potentials were also observed only at the higher levels of injury. Histopathological analysis revealed that the extent of post-injury hemorrhage, cavitation and vascular disruption (as measured by extravasation of Evans Blue dye) was greater at the higher magnitudes of injury. Neurological scoring performed over a 4-week post-injury period demonstrated that lateral fluid-percussion brain injury produces a chronic neurological deficit that is directly related to the severity of injury. Survival was also significantly reduced at the higher magnitudes of injury. These data demonstrate that the lateral model of fluid-percussion injury in the rat reproduces many of the features of head injury observed in other models and species and may therefore be a useful experimental model for the study of the pathophysiology of traumatic brain injury.

  15. Characterization of multi-layered impact damage in polymer matrix composites using lateral thermography

    Science.gov (United States)

    Whitlow, Travis; Sathish, Shamachary

    2017-02-01

    Polymer matrix composites (PMCs) are increasingly being integrated into aircraft structures. However, these components are susceptible to impact related delamination, which, on aircrafts, can occur due to a number of reasons during aircraft use and maintenance. Quantifying impact damage is an important aspect for life-management of aircraft and requires in-depth knowledge of the damage zone on a ply-by-ply level. Traditionally, immersion ultrasound has provided relative high resolution images of impact damage. Ultrasonic time-of-flight data can be used to determine the front surface delamination depth and an approximation of the delaminated area. However, such inspections require the material to be immersed in water and can be time consuming. The objective of this work is to develop a quick and robust methodology to non-destructively characterize multi-layered impact damage using lateral thermography. Initial results suggest lateral heat flow is sensitive to the depth of impact damage. The anticipated outcome of this project is to estimate the extent of through-thickness impact damage. Initial results are shown and future efforts are discussed.

  16. Characterization and Modeling of 4H-SiC Lateral MOSFETs for Integrated Circuit Design

    Energy Technology Data Exchange (ETDEWEB)

    Mudholkar, M; Mantooth, HA

    2013-06-01

    A new process in 4H-SiC is developed that features n-type buried and inversion channel lateral MOSFETs that are fabricated with several different channel lengths (2-8 mu m) and widths (8-32 mu m) and characterized over a wide temperature range (25 degrees C-225 degrees C). It is shown that the on-resistance of enhancement-mode SiC MOSFETs reduces with temperature despite a reduction in inversion mobility because of the interaction of interface states with temperature. To enable integrated circuit development using the developed MOSFETs, their electrical characteristics are modeled over geometry and temperature using the industry standard PSP MOSFET model. A new mathematical formulation to describe the presence of the interface states is also developed and implemented in the PSP model, and excellent agreement is shown between measurement and simulation using the modified PSP model.

  17. Isolation, purification and characterization of a nonspecific lipid transfer protein from Cuminum cyminum.

    Science.gov (United States)

    Zaman, Uzma; Abbasi, Atiya

    2009-05-01

    Cuminum cyminum, an aromatic plant from the family Umbelliferae, is used as a flavoring and seasoning agent in foods. This communication reports the characterization of a nonspecific lipid transfer protein nsLTP1 from its seeds. Plant nsLTPs are small basic proteins involved in transport of lipids between membranes. These proteins are known to participate in plant defense; however, the exact mechanism of their antimicrobial action against fungi or bacteria is still unclear. The cumin nsLTP1 has been purified using a combination of chromatographic procedures and further characterized using mass spectrometry, circular dichroism spectroscopy and Edman degradation. Amino acid sequence has been used to predict homology model of cumin nsLTP1 in complex with myristic acid, and lyso-myristoyl phosphatidyl choline (LMPC). Cumin nsLTP1 is a monomeric protein with a molecular weight of 9.7 kDa as estimated by SDS-PAGE and ESIMS. The protein shows an isoelectric point of 7.8 on 6% PAGE. The primary structure consists of 92 amino acids with eight conserved cysteine residues. The global fold of cumin nsLTP1 includes four alpha-helices stabilized by four disulfide bonds and a C-terminal tail. The role of internal hydrophobic cavity of the protein in lipid transfer is discussed.

  18. Design, characterization, and clinical evaluation of argan oil nanostructured lipid carriers to improve skin hydration.

    Science.gov (United States)

    Tichota, Deise Michele; Silva, Ana Catarina; Sousa Lobo, José Manuel; Amaral, Maria Helena

    2014-01-01

    Given its advantages in skin application (eg, hydration, antiaging, and protection), argan oil could be used in both dermatological and cosmetic formulations. Therefore, the preparation of nanostructured lipid carriers (NLCs) using argan oil as a liquid lipid is a promising technique, since the former constitute well-established systems for dermal delivery. The aim of this work was to develop a topical formulation of argan oil NLCs to improve skin hydration. Firstly an NLC dispersion was developed and characterized, and afterward an NLC-based hydrogel was prepared. The in vivo evaluation of the suitability of the prepared formulation for the proposed application was assessed in volunteers, by measuring different skin-surface parameters for 1 month. An argan oil NLC-based hydrogel formulation was successfully prepared and characterized. Moreover, the entrapment of the NLCs in the hydrogel net did not affect their colloidal sizes. Additionally, it was observed that this formulation precipitated an increase in skin hydration of healthy volunteers. Therefore, we concluded that the preparation of NLC systems using argan oil as the liquid lipid is a promising strategy, since a synergistic effect on the skin hydration was obtained (ie, NLC occlusion plus argan oil hydration).

  19. Physical-Chemical Characterization and Formulation Considerations for Solid Lipid Nanoparticles.

    Science.gov (United States)

    Chauhan, Harsh; Mohapatra, Sarat; Munt, Daniel J; Chandratre, Shantanu; Dash, Alekha

    2016-06-01

    Pure glyceryl mono-oleate (GMO) (lipid) and different batches of GMO commonly used for the preparation of GMO-chitosan nanoparticles were characterized by modulated differential scanning calorimetry (MDSC), cryo-microscopy, and cryo-X-ray powder diffraction techniques. GMO-chitosan nanoparticles containing poloxamer 407 as a stabilizer in the absence and presence of polymers as crystallization inhibitors were prepared by ultrasonication. The effect of polymers (polyvinyl pyrrolidone (PVP), Eudragits, hydroxyl propyl methyl cellulose (HPMC), polyethylene glycol (PEG)), surfactants (poloxamer), and oils (mineral oil and olive oil) on the crystallization of GMO was investigated. GMO showed an exothermic peak at around -10°C while cooling and another exothermic peak at around -12°C while heating. It was followed by two endothermic peaks between 15 and 30 C, indicative of GMO melting. The results are corroborated by cryo-microscopy and cryo-X-ray. Significant differences in exothermic and endothermic transition were observed between different grades of GMO and pure GMO. GMO-chitosan nanoparticles resulted in a significant increase in particle size after lyophilization. MDSC confirmed that nanoparticles showed similar exothermic crystallization behavior of lipid GMO. MDSC experiments showed that PVP inhibits GMO crystallization and addition of PVP showed no significant increase in particle size of solid lipid nanoparticle (SLN) during lyophilization. The research highlights the importance of extensive physical-chemical characterization for successful formulation of SLN.

  20. Formulation, Optimization and In vitro Characterization of Letrozole Loaded Solid Lipid Nanoparticles

    Directory of Open Access Journals (Sweden)

    Archana Nerella

    2014-07-01

    Full Text Available Letrozole (LTZ is an oral non-steroidal aromatase inhibitor for the treatment of hormonally responsive breast cancer after surgery. The objective of the current study is to prepare and evaluate Solid lipid nanoparticles (SLN of LTZ. SLNs were prepared by hot homogenization followed by ultrasonication. Trimyristin was used as solid lipid core, Soyphosphatidyl choline, Tween 80 as surfactant mixture. Process and formulation variables were studied and optimized. LTZ-SLN were characterized for mean particle size, polydispersity index (PDI and zeta potential for all the formulations. The mean particles size, PDI, zeta potential and entrapment efficiency of optimized LTZ-SLN optimized formulation was found to be 28.54 nm, 0.162, 11.80 mV, 85.64 %, respectively. In vitro release profiles are performed in 0.1N HCl using modified franz diffusion cell showed controlled drug release behavior over a period of 24h. LTZ-SLN formulations are subjected to stability study over a period of 1 month in terms of particle size, zeta potential, PDI, entrapment efficiency and are found to be stable. Differential scanning calorimetry (DSC and transmission electron microscopy (TEM analysis was performed to characterize the state of drug, lipid modification, shape and surface morphology of prepared LTZ-SLN formulations.

  1. Characterization of lipid model membranes designed for studying impact of ceramide species on drug diffusion and penetration.

    Science.gov (United States)

    Ochalek, M; Heissler, S; Wohlrab, J; Neubert, R H H

    2012-05-01

    The stratum corneum (SC) intercellular lipid matrix plays a crucial role in the skin barrier function. In the present study, lipid model membranes mimicking its phase behavior were prepared and characterized using different analytical techniques (i.a. SAXD, HPTLC, ESEM, confocal Raman imaging, ATR-FTIR spectroscopy) in order to obtain well-standardized model membranes for diffusion and penetration studies. The lipid model membranes should be used in the future for studying the impact of each ceramide species on the diffusion and penetration of drugs. The SAXD study confirmed that the lipids within artificial lipid systems are arranged similarly to the lipids in the human SC. The polarization microscopic and ESEM images showed the homogenous deposition of lipids on the polycarbonate filter. Both the HPTLC and confocal Raman imaging studies proved the homogenous distribution of individual lipid classes within the lipid model membranes. First in vitro diffusion experiments (performed using an ATR-FTIR diffusion cell) of the hydrophilic compound, urea, revealed that the lipid model membrane represents even stronger diffusion barrier than the human SC.

  2. Design and Characterization of Metformin-Loaded Solid Lipid Nanoparticles for Colon Cancer.

    Science.gov (United States)

    Ngwuluka, Ndidi C; Kotak, Darsheen J; Devarajan, Padma V

    2017-02-01

    Colorectal cancer is a global concern, and its treatment is fraught with non-selective effects including adverse side effects requiring hospital visits and palliative care. A relatively safe drug formulated in a bioavailability enhancing and targeting delivery platform will be of significance. Metformin-loaded solid lipid nanoparticles (SLN) were designed, optimized, and characterized for particle size, zeta potential, drug entrapment, structure, crystallinity, thermal behavior, morphology, and drug release. Optimized SLN were 195.01 ± 6.03 nm in size, -17.08 ± 0.95 mV with regard to surface charge, fibrous in shape, largely amorphous, and release of metformin was controlled. The optimized size, charge, and shape suggest the solid lipid nanoparticles will migrate and accumulate in the colon tumor preventing its proliferation and subsequently leading to tumor shrinkage and cell death.

  3. Effect of fish oil on lateral mobility of prostaglandin F2α (FP) receptors and spatial distribution of lipid microdomains in bovine luteal cell plasma membrane in vitro.

    Science.gov (United States)

    Plewes, M R; Burns, P D; Graham, P E; Hyslop, R M; Barisas, B G

    2017-01-01

    Lipid microdomains are ordered regions on the plasma membrane of cells, rich in cholesterol and sphingolipids, ranging in size from 10 to 200 nm in diameter. These lipid-ordered domains may serve as platforms to facilitate colocalization of intracellular signaling proteins during agonist-induced signal transduction. It is hypothesized that fish oil will disrupt the lipid microdomains, increasing spatial distribution of these lipid-ordered domains and lateral mobility of the prostaglandin (PG) F2α (FP) receptors in bovine luteal cells. The objectives of this study were to examine the effects of fish oil on (1) the spatial distribution of lipid microdomains, (2) lateral mobility of FP receptors, and (3) lateral mobility of FP receptors in the presence of PGF2α on the plasma membrane of bovine luteal cells in vitro. Bovine ovaries were obtained from a local abattoir and corpora lutea were digested using collagenase. In experiment 1, lipid microdomains were labeled using cholera toxin subunit B Alexa Fluor 555. Domains were detected as distinct patches on the plasma membrane of mixed luteal cells. Fish oil treatment decreased fluorescent intensity in a dose-dependent manner (P oil treatment on lateral mobility of FP receptors. Fish oil treatment increased microdiffusion and macrodiffusion coefficients of FP receptors as compared to control cells (P oil-treated cells (P oil treatment. Lateral mobility of receptors was decreased within 5 min following the addition of ligand for control cells (P oil-treated cells (P > 0.10). The data presented provide strong evidence that fish oil causes a disruption in lipid microdomains and affects lateral mobility of FP receptors in the absence and presence of PGF2α.

  4. Design, characterization, and clinical evaluation of argan oil nanostructured lipid carriers to improve skin hydration

    Directory of Open Access Journals (Sweden)

    Tichota DM

    2014-08-01

    Full Text Available Deise Michele Tichota,1 Ana Catarina Silva,2,3 José Manuel Sousa Lobo,2 Maria Helena Amaral2 1Federal University of Rio Grande do Sul, Porto Alegre, 2Laboratory of Pharmaceutical Technology/Centre of Research in Pharmaceutical Sciences, Faculty of Pharmacy, University of Porto, 3Faculty of Health Sciences, Fernando Pessoa University, Porto, Portugal Abstract: Given its advantages in skin application (eg, hydration, antiaging, and protection, argan oil could be used in both dermatological and cosmetic formulations. Therefore, the preparation of nanostructured lipid carriers (NLCs using argan oil as a liquid lipid is a promising technique, since the former constitute well-established systems for dermal delivery. The aim of this work was to develop a topical formulation of argan oil NLCs to improve skin hydration. Firstly an NLC dispersion was developed and characterized, and afterward an NLC-based hydrogel was prepared. The in vivo evaluation of the suitability of the prepared formulation for the proposed application was assessed in volunteers, by measuring different skin-surface parameters for 1 month. An argan oil NLC-based hydrogel formulation was successfully prepared and characterized. Moreover, the entrapment of the NLCs in the hydrogel net did not affect their colloidal sizes. Additionally, it was observed that this formulation precipitated an increase in skin hydration of healthy volunteers. Therefore, we concluded that the preparation of NLC systems using argan oil as the liquid lipid is a promising strategy, since a synergistic effect on the skin hydration was obtained (ie, NLC occlusion plus argan oil hydration. Keywords: argan oil, nanostructured lipid carriers, NLC, hydrogels, skin hydration 

  5. Characterization of a Native Algae Species Chlamydomonas debaryana: Strain Selection, Bioremediation Ability, and Lipid Characterization

    Directory of Open Access Journals (Sweden)

    Bo Zhang

    2014-08-01

    Full Text Available Native microalgal species may offer a favorable combination of both wastewater treatment and biofuel production. In this research, a green microalgae, Chlamydomonas debaryana, was isolated from a local lagoon, screened for its lipid content using flow cytometry, and further identified with microscopic observations and DNA sequence analysis. When using swine wastewater as a medium, the biomass yields were between 0.6 and 1.62 g/L, giving a median value of 1.11 g/L. By increasing mass transfer rates and providing sufficient light intensity, the microalgal growth was intrinsically enhanced. The growth of C. debaryana reduced most nutritional contents of the wastewater except iron. When combining the microalgal growth and nutrient removal, C. debaryana was able to utilize 1.3 to 1.6×103 mg COD (chemical oxygen demand/g biomass, 55 to 90 ppm ammonia/g biomass, and 48 to 89 ppm phosphorous/g biomass, The lipid content of C. debaryana was 19.9 ± 4.3% of cell dry weight. The transesterified microalgal oil mostly consisted of 14 kinds of fatty acids, ranging from C5 to C22, which can be refined into renewable jet fuel or used as sources of omega-3 and omega-6 fatty acids.

  6. Physicochemical characterization of sildenafil-loaded solid lipid nanoparticle dispersions (SLN) for pulmonary application.

    Science.gov (United States)

    Paranjpe, M; Finke, J H; Richter, C; Gothsch, T; Kwade, A; Büttgenbach, S; Müller-Goymann, C C

    2014-12-10

    For the development of any colloidal system, thorough characterization is extremely essential. This article discusses the physicochemical characterization of sildenafil-loaded solid lipid nanoparticle dispersions (SLN) including stability analysis over 6 months time period for possible pulmonary administration for the treatment of pulmonary arterial hypertension (PAH). SLN consisting of phospholipid and triglycerides were manufactured using a novel microchannel homogenization method. These sildenafil-loaded SLN were then subjected to physicochemical characterization namely, particle size and distribution over shelf life, differential scanning calorimetry (DSC), wide angle X-ray diffraction (WAXD) and analysis of nebulization performance of these SLN by the means of next generation impactor (NGI). Additionally, the morphology of nebulized particles was assessed by transmission electron microscopy using negative staining technique. The solubility of sildenafil citrate and base in the lipid matrix was determined and was 0.1% w/w and 1% w/w, respectively. From the particle size measurements, it was observed that SLN without sildenafil demonstrated consistent particle sizes over 6 months. For the sildenafil-loaded SLN, increased particle sizes were found after manufacturing and further increased within weeks. From WAXD studies, after 6 months high intensity reflections corresponding to the stable β modification were observed. From DSC results, the peak minimum temperatures increased upon storage, hinting at a transformation to the stable β modification of triglycerides in the case of sildenafil-loaded SLN. Hence, it can be concluded that even small drug concentration influences particle size and stability.

  7. Development and characterization of 5-FU bearing ferritin appended solid lipid nanoparticles for tumour targeting.

    Science.gov (United States)

    Jain, Sanjay K; Chaurasiya, Akash; Gupta, Yashwant; Jain, Anekant; Dagur, Pradeep; Joshi, Beenu; Katoch, Vishwa M

    2008-08-01

    Ferritin coupled solid lipid nanoparticles were investigated for tumour targeting. Solid lipid nanoparticles were prepared using HSPC, cholesterol, DSPE and triolien. The SLNs without ferritin which has similar lipid composition were used for comparison. SLNs preparations were characterized for shape, size and percentage entrapment. The average size of SLNs was found to be in the range 110-152 nm and maximum drug entrapment was found to be 34.6-39.1%. In vitro drug release from the formulations is obeying fickian release kinetics. Cellular uptake and IC50 values of the formulation were determined in vitro in MDA-MB-468 breast cancer cells. In vitro cell binding of Fr-SLN exhibits 7.7-folds higher binding to MDA-MB-468 breast cancer cells in comparison to plain SLNs. Ex-vivo cytotoxicity assay on targeted nanoparticles gave IC50 of 1.28 microM and non-targeted nanoparticles gave IC50 of 3.56 microM. In therapeutic experiments, 5-FU, SLNs and Fr-SLNs were administered at the dose of 10 mg 5-FU/kg body weight to MDA-MB-468 tumour bearing Balb/c mice. Administration of Fr-SLNs formulation results in effective reduction in tumour growth as compared with free 5-FU and plain SLNs. The result demonstrates that this delivery system possessed an enhanced anti-tumour activity. The results warrant further evaluation of this delivery system.

  8. Formulation and characterization of solid lipid nanoparticles for an anti-retroviral drug darunavir

    Science.gov (United States)

    Bhalekar, Mangesh; Upadhaya, Prashant; Madgulkar, Ashwini

    2017-02-01

    Darunavir, an anti-HIV drug having poor solubility in aqueous and lipid medium, illustrates degradation above its melting point, i.e. 74 °C, thus, posing a challenge to dosage formulation. Despite, the drug suffers from poor oral bioavailability (37%) owing to less permeability and being poly-glycoprotein and cyp3A metabolism substrate. The study aimed formulating a SLN system to overcome the formulation and bioavailability associated problems of the drug. Based on the drug solubility and stable dispersion findings, lipid and surfactant were chosen and nanoparticles were prepared using hot-homogenization technique. Optimization of variables such as lipid concentration, oil-surfactant and homogenization cycle was carried and their effect on particle size and entrapment efficiency was studied. Freeze-dried SLN further characterized using SEM, DSC and PXRD analysis revealed complete entrapment of the drug and amorphous nature of the SLN. In vitro pH release studies in 0.1 N HCl and 6.8 pH buffer demonstrated 84 and 80% release at the end of 12th h. The apparent permeability of the SLN across rat intestine was found to be 24 × 10-6 at 37 °C at the end of 30 min while at 4 °C the same was found to be 5.6 × 10-6 prompting involvement of endocytic processes in the uptake of SLN. Accelerated stability studies revealed no prominent changes upon storage.

  9. Preparation and characterization of tetrandrine-phospholipid complex loaded lipid nanocapsules as potential oral carriers

    Directory of Open Access Journals (Sweden)

    Zhao YQ

    2013-10-01

    Full Text Available Yi-qing Zhao, Li-ping Wang, Chao Ma, Kun Zhao, Ying Liu, Nian-ping FengSchool of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of ChinaBackground: Tetrandrine is an active constituent that is extracted from the root tuber of the Chinese herb Stephania tetrandra S. Moore. It has shown various pharmacological effects, such as antitumor activity, multidrug resistance reversal, and hepatic fibrosis resistance. In clinical applications, it has been used to treat hypertension, pneumosilicosis, and lung cancer. However, the poor water solubility of tetrandrine has limited its application. In this study, a newly emerging oral drug carrier of phospholipid complex loaded lipid nanocapsules was developed to improve the oral bioavailability of tetrandrine.Methods: The phospholipid complex was prepared with the solvent-evaporation method to enhance the liposolubility of tetrandrine. The formation of the phospholipid complex was confirmed with a solubility study, infrared spectroscopy, and a differential scanning calorimetry (DSC analysis. The tetrandrine-phospholipid complex loaded lipid nanocapsules (TPC-LNCs were prepared using the phase inversion method. Lyophilization was performed with mannitol (10% as a cryoprotectant. TPC-LNCs were characterized according to their particle size, zeta potential, encapsulation efficiency, morphology by transmission electron microscopy, and crystallinity by DSC. In addition, the in vitro release of tetrandrine from TPC-LNCs was examined to potentially illustrate the in vivo release behavior. The in vivo bioavailability of TPC-LNCs was studied and compared to tetrandrine tablets in rats.Results: The liposolubility of tetrandrine in n-octanol improved from 8.34 µg/mL to 35.64 µg/mL in the tetrandrine-phospholipid complex. The prepared TPC-LNCs were spherical-shaped particles with a small size of 40 nm and a high encapsulation efficiency of 93.9%. DSC measurements revealed

  10. Characterization of the abnormal lipid profile in Chinese patients with psoriasis.

    Science.gov (United States)

    Pang, Xiaowen; Lin, Kai; Liu, Wen; Zhang, Ping; Zhu, Sainan

    2015-01-01

    Psoriasis is a chronic inflammatory skin disease that has been associated with abnormal lipid metabolism. To characterize the lipid profile in Chinese, 86 patients with psoriasis and 84 healthy control subjects were assessed. Compared with healthy controls, the fasting serum values of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I (ApoA-I) were lower in the patient group. Compared with vulgaris psoriasis, special types of psoriasis had even lower levels of HDL-C and ApoA-I. Considering the severity of psoriasis, the level of ApoA-I and HDL-C were also the only two serum lipid parameters decreased in the mild group compared to those in controls. In the moderate and the severe group, the values of TC, LDL-C, HDL-C and ApoA-I were all decreased compared to healthy control group. Further analysis indicated that the values of HDL-C and ApoA-I were significantly lower in the severe group compared to the moderate group. Correlation analysis indicated that the levels of HDL-C but not ApoA-I was negatively associated with the severity of the disease. Interestingly, when psoriasis was improved by treatment, the serum levels of TG, TC, HDL-C and ApoA-I were increased from the pre-treatment values. We conclude that abnormalities in serum lipid metabolism may play an important role in the pathogenesis of Chinese patients with psoriasis.

  11. Lipid characterization of individual porcine oocytes by dual mode DESI-MS and data fusion

    Energy Technology Data Exchange (ETDEWEB)

    Pirro, Valentina, E-mail: valentina.pirro@unito.it [Department of Chemistry, University of Turin, Via Pietro Giuria 7, Turin 10125 (Italy); Oliveri, Paolo [Department of Pharmacy, University of Genoa, Via Brigata Salerno 13, Genoa 16147 (Italy); Ferreira, Christina Ramires [Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, IN 47907 (United States); González-Serrano, Andrés Felipe [Institute of Farm Animal Genetics, Friedrich-Loeffler-Institut, Hoeltystrasse 10, 31535 Neustadt, Mariensee (Germany); Machaty, Zoltan [Department of Animal Sciences, Purdue University, 915 W. State St., West Lafayette, IN 47907 (United States); Cooks, Robert Graham [Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, IN 47907 (United States)

    2014-10-27

    Highlights: • Repeated analysis by DESI(±)-MS of intact single oocytes for lipid characterization. • Deployment of a data fusion strategy to merge positive and negative ion mode data. • Enhanced interpretation of metabolic changes by more efficient analysis of spectral data. • Discovery of increased fatty acid metabolism and membrane complexity during maturation. • Assistance in the improvement of in vitro embryo production for porcine species. - Abstract: The development of sensitive measurements to analyze individual cells is of relevance to elucidate specialized roles or metabolic functions of each cell under physiological and pathological conditions. Lipids play multiple and critical roles in cellular functions and the application of analytical methods in the lipidomics area is of increasing interest. In this work, in vitro maturation of porcine oocytes was studied. Two independent sources of chemical information (represented by mass spectra in the positive and negative ion modes) from single oocytes (immature oocytes, 24-h and 44-h in vitro matured oocytes) were acquired by using desorption electrospray ionization-mass spectrometry (DESI-MS). Low and mid-level data fusion strategies are presented with the aim of better exploring the large amount of chemical information contained in the two mass spectrometric lipid profiles. Data were explored by principal component analysis (PCA) within the two multi-block approaches to include information on free fatty acids, phospholipids, cholesterol-related molecules, di- and triacylglycerols. After data fusion, clearer differences among immature and in vitro matured porcine oocytes were observed, which provide novel information regarding lipid metabolism throughout oocyte maturation. In particular, changes in TAG composition, as well as increase in fatty acid metabolism and membrane complexity were evidenced during the in vitro maturation process. This information can assist the improvement of in vitro embryo

  12. In-Situ Waviness Characterization of Metal Plates by a Lateral Shearing Interferometric Profilometer

    Directory of Open Access Journals (Sweden)

    Ignacio Álvarez

    2013-04-01

    Full Text Available Characterizing waviness in sheet metal is a key process for quality control in many industries, such as automotive and home appliance manufacturing. However, there is still no known technique able to work in an automated in-floor inspection system. The literature describes many techniques developed in the last three decades, but most of them are either slow, only able to work in laboratory conditions, need very short (unsafe working distances, or are only able to estimate certain waviness parameters. In this article we propose the use of a lateral shearing interferometric profilometer, which is able to obtain a 19 mm profile in a single acquisition, with sub-micron precision, in an uncontrolled environment, and from a working distance greater than 90 mm. This system allows direct measurement of all needed waviness parameters even with objects in movement. We describe a series of experiments over several samples of steel plates to validate the sensor and the processing method, and the results are in close agreement with those obtained with a contact stylus device. The sensor is an ideal candidate for on-line or in-machine fast automatic waviness assessment, reducing delays and costs in many metalworking processes.

  13. Morphological characterization of selectively overgrown GaN via lateral epitaxy

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    @@ Introduction GaN has attracted a lot of research attention because it has lower Ohmic contact resistance, large electron saturation velocity and a large breakdown field, combined with excellent thermal conductivity and stability, making it an excellent material for high-temperature, high-power and high-brightness optoelectronic devices such as field effect transistors (FET), junction (FET), bipolar transistors and photodiodes[1]. Since threading dislocations resulting from large lattice mismatach and the difference between thermal expansion coefficients of epitaxial GaN and substrate severely degrade the optical and electric qualities of the GaN layer, high quality GaN is indeed required for manufacture of high performance optical device[2]. Characterization of the microstructures of selectively lateral overgrowth of epitaxial GaN using SEM is presented in this work with focus on fully understanding evolution of the morphology and dislocation distribution that occurs in the different growth situations in order for establishment of procession-microstructure-properties interrelations.

  14. Formulation and characterization of solid lipid nanoparticles, nanostructured lipid carriers and nanoemulsion of lornoxicam for transdermal delivery

    Directory of Open Access Journals (Sweden)

    Gönüllü Ümit

    2015-03-01

    Full Text Available Solid lipid nanoparticles (SLN, nanostructured lipid carriers (NLC and nanoemulsion (NE of lornoxicam (LRX were prepared for the treatment of painful and inflammatory conditions of the skin. Compritol® 888 ATO, Lanette® O and oleic acid were used as solid and liquid lipids. SLN, NLC and NE were found physically stable at various temperatures for 6 months. Case I diffusional drug release was detected as the dominant mechanism indicating Fickian drug diffusion from nanoparticles and nanoemulsion. The highest rate of drug penetration through rat skin was obtained with NE followed by NLC, SLN and a gel formulation. Nanoformulations significantly increased drug penetration through rat skin compared to the gel (p < 0.05. Thus, SLN, NLC and NE of LRX can be suggested for relieving painful and inflammatory conditions of the skin

  15. Formulation and characterization of solid lipid nanoparticles, nanostructured lipid carriers and nanoemulsion of lornoxicam for transdermal delivery.

    Science.gov (United States)

    Gönüllü, Ümit; Üner, Melike; Yener, Gülgün; Karaman, Ecem Fatma; Aydoğmuş, Zeynep

    2015-03-01

    Solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC) and nanoemulsion (NE) of lornoxicam (LRX) were prepared for the treatment of painful and inflammatory conditions of the skin. Compritol® 888 ATO, Lanette® O and oleic acid were used as solid and liquid lipids. SLN, NLC and NE were found physically stable at various temperatures for 6 months. Case I diffusional drug release was detected as the dominant mechanism indicating Fickian drug diffusion from nanoparticles and nanoemulsion. The highest rate of drug penetration through rat skin was obtained with NE followed by NLC, SLN and a gel formulation. Nanoformulations significantly increased drug penetration through rat skin compared to the gel (pSLN, NLC and NE of LRX can be suggested for relieving painful and inflammatory conditions of the skin.

  16. Zebrafish brain lipid characterization and quantification by ¹H nuclear magnetic resonance spectroscopy and MALDI-TOF mass spectrometry.

    Science.gov (United States)

    van Amerongen, Yvonne F; Roy, Upasana; Spaink, Herman P; de Groot, Huub J M; Huster, Daniel; Schiller, Jürgen; Alia, A

    2014-06-01

    Lipids play an important role in many neurodegenerative diseases, such as Parkinson's disease, Alzheimer's disease, and Huntington's disease. Zebrafish models for these diseases have been recently developed. The detailed brain lipid composition of the adult zebrafish is not known, and therefore, the representativeness of these models cannot be properly evaluated. In this study, we characterized the total lipid composition of healthy adult zebrafish using (1)H nuclear magnetic resonance spectroscopy. A close resemblance of the zebrafish brain composition is shown in comparison to the human brain. Moreover, several lipids involved in the pathogenesis of neurodegenerative diseases (i.e., cholesterol, phosphatidylcholine, docosahexaenoic acid, and further, polyunsaturated fatty acids) are detected and quantified. These lipids might represent useful biomarkers in future research toward human therapies. Matrix-assisted laser desorption-ionization time-of-flight mass spectrometry coupled with high-performance thin-layer chromatography was used for further characterization of zebrafish brain lipids. Our results show that the lipid composition of the zebrafish brain is rather similar to the human brain and thus confirms that zebrafish represents a good model for studying various brain diseases.

  17. Lateral diffusion, function, and expression of the slow channel congenital myasthenia syndrome αC418W nicotinic receptor mutation with changes in lipid raft components.

    Science.gov (United States)

    Oyola-Cintrón, Jessica; Caballero-Rivera, Daniel; Ballester, Leomar; Baéz-Pagán, Carlos A; Martínez, Hernán L; Vélez-Arroyo, Karla P; Quesada, Orestes; Lasalde-Dominicci, José A

    2015-10-30

    Lipid rafts, specialized membrane microdomains in the plasma membrane rich in cholesterol and sphingolipids, are hot spots for a number of important cellular processes. The novel nicotinic acetylcholine receptor (nAChR) mutation αC418W, the first lipid-exposed mutation identified in a patient that causes slow channel congenital myasthenia syndrome was shown to be cholesterol-sensitive and to accumulate in microdomains rich in the membrane raft marker protein caveolin-1. The objective of this study is to gain insight into the mechanism by which lateral segregation into specialized raft membrane microdomains regulates the activable pool of nAChRs. We performed fluorescent recovery after photobleaching (FRAP), quantitative RT-PCR, and whole cell patch clamp recordings of GFP-encoding Mus musculus nAChRs transfected into HEK 293 cells to assess the role of cholesterol and caveolin-1 (CAV-1) in the diffusion, expression, and functionality of the nAChR (WT and αC418W). Our findings support the hypothesis that a cholesterol-sensitive nAChR might reside in specialized membrane microdomains that upon cholesterol depletion become disrupted and release the cholesterol-sensitive nAChRs to the pool of activable receptors. In addition, our results in HEK 293 cells show an interdependence between CAV-1 and αC418W that could confer end plates rich in αC418W nAChRs to a susceptibility to changes in cholesterol levels that could cause adverse drug reactions to cholesterol-lowering drugs such as statins. The current work suggests that the interplay between cholesterol and CAV-1 provides the molecular basis for modulating the function and dynamics of the cholesterol-sensitive αC418W nAChR.

  18. Development, Characterization and Evaluation of Solid Lipid Nanoparticles as a potential Anticancer Drug Delivery System

    Science.gov (United States)

    Patel, Meghavi

    Solid lipid nanoparticles (SLNs) consist of spherical solid lipid particles in the nanometer size range, which are dispersed in water or in an aqueous surfactant solution. SLN technology represents a promising new approach to deliver hydrophilic as well as lipophilic drugs. The commercialization of SLN technology remains limited despite numerous efforts from researchers. The purpose of this research was to advance SLN preparation methodology by investigating the feasibility of preparing glyceryl monostearate (GMS) nanoparticles by using three preparation methods namely microemulsion technique, magnetic stirring technique and temperature modulated solidification technique of which the latter two were developed in our laboratory. An anticancer drug 5-fluorouracil was incorporated in the SLNs prepared via the temperature modulated solidification process. Optimization of the magnetic stirring process was performed to evaluate how the physicochemical properties of the SLN was influenced by systematically varying process parameters including concentration of the lipid, concentration of the surfactant, type of surfactant, time of stirring and temperature of storage. The results demonstrated 1:2 GMS to tween 80 ratio, 150 ml dispersion medium and 45 min stirring at 4000 RPM speed provided an optimum formulation via the temperature modulated solidification process. SLN dispersions were lyophilized to stabilize the solid lipid nanoparticles and the lyophilizates exhibited good redispersibility. The SLNs were characterized by particle size analysis via dynamic light scattering (DLS), zeta potential, transmission electron microscopy (TEM), differential scanning calorimetry (DSC), drug encapsulation efficiency and in vitro drug release studies. Particle size of SLN dispersion prepared via the three preparation techniques was approximately 66 nm and that of redispersed lyophilizates was below 500 nm. TEM images showed spherical to oval particles that were less dense in the core

  19. Lipids Characterization and Industrial Potentials of Pumpkin Seeds (Telfairia occidentalis and Cashew Nuts (Anacardium occidentale

    Directory of Open Access Journals (Sweden)

    E. O. Eddy

    2011-01-01

    Full Text Available Oil from Telfaria occidentalis and Anarcardium occidentale has been extracted and characterized. The lipid content of the Telfaria occidentalis and Anarcardium occidentalis were 58.41% and 42.15% respectively. The physicochemical parameters of Telfaria occidentalis and Anarcardium occidentale seeds were; boiling point; (58.90, 62.60 °C, melting point; (18.50, 21.80 °C, refractive index; (1.462, 1.498, specific gravity; (0.87, 0.69 saponification value; (91.16, 92.57 iodine value; (51.52, 47.20, acid value; (0.76, 3.74 ester value; (90.40, 88.87, % free fatty acid; (.38, 1.88 and peroxide value; (11.75, 15.23 respectively. Oils from these seeds were found to exhibit the needed potentials for utilization in paint and food industries and as biofuel.

  20. A simple and rapid method to characterize lipid fate in skeletal muscle

    OpenAIRE

    Massart, Julie; Juleen R Zierath; Chibalin, Alexander V.

    2014-01-01

    Background Elevated fatty acids contribute to the development of type 2 diabetes and affect skeletal muscle insulin sensitivity. Since elevated intramuscular lipids and insulin resistance is strongly correlated, aberrant lipid storage or lipid intermediates may be involved in diabetes pathogenesis. The aim of this study was to develop a method to determine the dynamic metabolic fate of lipids in primary human skeletal muscle cells and in intact mouse skeletal muscle. We report a simple and fa...

  1. Identification and characterization of major lipid particle proteins of the yeast Saccharomyces cerevisiae.

    Science.gov (United States)

    Athenstaedt, K; Zweytick, D; Jandrositz, A; Kohlwein, S D; Daum, G

    1999-10-01

    Lipid particles of the yeast Saccharomyces cerevisiae were isolated at high purity, and their proteins were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Major lipid particle proteins were identified by mass spectrometric analysis, and the corresponding open reading frames (ORFs) were deduced. In silicio analysis revealed that all lipid particle proteins contain several hydrophobic domains but none or only few (hypothetical) transmembrane spanning regions. All lipid particle proteins identified by function so far, such as Erg1p, Erg6p, and Erg7p (ergosterol biosynthesis) and Faa1p, Faa4p, and Fat1p (fatty acid metabolism), are involved in lipid metabolism. Based on sequence homology, another group of three lipid particle proteins may be involved in lipid degradation. To examine whether lipid particle proteins of unknown function are also involved in lipid synthesis, mutants with deletions of the respective ORFs were constructed and subjected to systematic lipid analysis. Deletion of YDL193w resulted in a lethal phenotype which could not be suppressed by supplementation with ergosterol or fatty acids. Other deletion mutants were viable under standard conditions. Strains with YBR177c, YMR313c, and YKL140w deleted exhibited phospholipid and/or neutral lipid patterns that were different from the wild-type strain and thus may be further candidate ORFs involved in yeast lipid metabolism.

  2. Effect of liquid-to-solid lipid ratio on characterizations of flurbiprofen-loaded solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) for transdermal administration.

    Science.gov (United States)

    Song, Aihua; Zhang, Xiaoshu; Li, Yanting; Mao, Xinjuan; Han, Fei

    2016-08-01

    The aim of this study is to evaluate the effect of liquid-to-solid lipid ratio on properties of flurbiprofen-loaded solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs), and to clarify the superiority of NLCs over SLNs for transdermal administration. Particle size, zeta potential, drug encapsulation efficiency, in vitro occlusion factor, differential scanning calorimetry, X-ray diffractometry, in vitro percutaneous permeation profile, and stability of SLNs and NLCs were compared. Particle size, zeta potential, drug encapsulation efficiency, in vitro occlusion factor, and in vitro percutaneous permeation amount of the developed NLCs were all 78%, >35, and >240 μg/cm(2), respectively, however, for SLNs were 280 nm, -29.11 mV, 63.2%, 32.54, and 225.9 μg/cm(2), respectively. After 3 months storage at 4 °C and 25 °C, almost no significant differences between the evaluated parameters of NLCs were observed. However, for SLNs, particle size was increased to higher than 300 nm (4 °C and 25 °C), drug encapsulation efficiency was decreased to 51.2 (25 °C), in vitro occlusion factor was also decreased to lower than 25 (4 °C and 25 °C), and the cumulative amount was decreased to 148.9 μg/cm(2) (25 °C) and 184.4 μg/cm(2) (4 °C), respectively. And DSC and XRD studies indicated that not only the crystalline peaks of the encapsulated flurbiprofen disappeared but also obvious difference between samples and bulk Compritol® ATO 888 was seen. It could be concluded that liquid-to-solid lipid ratio has significant impact on the properties of SLNs and NLCs, and NLCs showed better stability than SLNs. Therefore, NLCs might be a better option than SLNs for transdermal administration.

  3. Physicochemical characterization and in vivo bioluminescence imaging of nanostructured lipid carriers for targeting the brain: apomorphine as a model drug

    Energy Technology Data Exchange (ETDEWEB)

    Hsu, Shu-Hui [Department of Pharmacy, Chia Nan University of Pharmacy and Science, Tainan 717, Taiwan (China); Wen, Chih-Jen; Yen, Tzu-Chen [Animal Molecular Imaging Center, Chang Gung Memorial Hospital, Kweishan, Taoyuan 333, Taiwan (China); Al-Suwayeh, S A; Fang, Jia-You [Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh (Saudi Arabia); Chang, Hui-Wen, E-mail: fajy@mail.cgu.edu.tw [Pharmaceutics Laboratory, Graduate Institute of Natural Products, Chang Gung University, Kweishan, Taoyuan 333, Taiwan (China)

    2010-10-08

    Nanostructured lipid carriers (NLCs) were prepared to investigate whether the duration of brain targeting and accumulation of drugs in the brain can be improved by intravenous delivery. NLCs were developed using cetyl palmitate as the lipid matrix, squalene as the cationic surfactant, and Pluronic F68, polysorbate 80 and polyethylene glycol as the interfacial additives. Solid lipid nanoparticles (SLNs) and lipid emulsions (LEs) were also prepared for comparison. An anti-Parkinson's drug, apomorphine, was used as the model drug. Nuclear magnetic resonance and differential scanning calorimetry showed possible interactions between the solid and liquid lipids in the inner core. The lipid nanoparticles with different compositions were characterized by mean size, zeta potential, apomorphine encapsulation and in vitro drug release. NLCs were 370-430 nm in size, which was between the sizes of the SLNs and LEs. A cationic surfactant was used to produce a positive surface charge of 42-50 mV. The base form of apomorphine was successfully entrapped by NLCs with an entrapment percentage of > 60%. The loading of apomorphine in nanoparticles resulted in a slower release behavior compared to the aqueous solution, with LEs showing the lowest release. In vivo real-time bioluminescence imaging of the rat brain revealed that NLCs could be targeted, through certain vessels, to selected brain regions. This effect was further confirmed by imaging the entire brain and brain slices. The results indicated that NLCs with moderate additives are a promising controlled-release and drug-targeting system.

  4. A generic protocol for the purification and characterization of water-soluble complexes of affinity-tagged proteins and lipids.

    Science.gov (United States)

    Maeda, Kenji; Poletto, Mattia; Chiapparino, Antonella; Gavin, Anne-Claude

    2014-09-01

    Interactions between lipids and proteins in the aqueous phases of cells contribute to many aspects of cell physiology. Here we describe a detailed protocol to systematically characterize in vivo-assembled complexes of soluble proteins and lipids. Saccharomyces cerevisiae strains expressing physiological amounts of a protein of interest fused to the tandem-affinity purification (TAP) tag are first lysed in the absence of detergent to capture intact protein-lipid complexes. The affinity-purified complexes (typically 30-50 kDa) are subjected to analytical size-exclusion chromatography (SEC) to remove contaminating lipids that elute at the void volume (>600 kDa), in order to achieve sufficient signal-to-background lipid ratios. Proteins in the SEC fractions are then analyzed by denaturing gel electrophoresis. Lipidomics techniques such as high-performance thin-layer chromatography or gas or liquid chromatography-mass spectrometry can then be applied to measure the elution profiles of lipids and to pinpoint the true interactors co-eluting with the TAP fusions. The procedure (starting from cell lysis) requires 2 d, and it can easily be adapted to other organisms.

  5. Solid-State Characterization of Novel Propylene Glycol Ester Solvates Isolated from Lipid Formulations.

    Science.gov (United States)

    Chakravarty, Paroma; Kothari, Sanjeev; Deese, Alan; Lubach, Joseph W

    2015-07-06

    The purpose of this study was to identify and characterize precipitates obtained from a liquid formulation of GNE068.HCl, a Genentech developmental compound, and lipophilic excipients, such as propylene glycol monocaprylate, and monolaurate. Precipitates were characterized using powder X-ray diffractometry (PXRD), differential scanning calorimetry, thermogravimetry, microscopy, nuclear magnetic resonance spectroscopy (NMR; solution and solid-state) and water sorption analysis. PXRD and NMR revealed the precipitates to be crystalline solvates of propylene glycol esters. The solvates (capryolate and lauroglycolate) were isomorphic and stable up to 70 °C, beyond which melting of the lattice occurred with subsequent dissolution of the active ingredient in the melt (microscopy and variable temperature PXRD). They were found to be mechanically stable (no change in PXRD pattern upon compression) and were nonhygroscopic up to ∼70% RH (25 °C). Our results highlight the outcome of inadvertent drug-excipient interactions in two separate lipid solution formulations with good solid-state properties and, thus, potential for further development.

  6. Design and characterization of a membrane protein unfolding platform in lipid bilayers.

    Directory of Open Access Journals (Sweden)

    Vincent G Nadeau

    Full Text Available Accurate measurement of membrane protein stability--and particularly how it may vary as a result of disease-phenotypic mutations--ideally requires a denaturant that can unfold a membrane-embedded structure while leaving the solubilizing environment unaffected. The steric trap method fulfills this requirement by using monovalent streptavidin (mSA molecules to unfold membrane proteins engineered with two spatially close biotin tags. Here we adapted this method to an 87-residue helix-loop-helix (hairpin construct derived from helices 3 and 4 in the transmembrane domain of the human cystic fibrosis transmembrane conductance regulator (CFTR, wherein helix-helix tertiary interactions are anticipated to confer a portion of construct stability. The wild type CFTR TM3/4 hairpin construct was modified with two accessible biotin tags for mSA-induced unfolding, along with two helix-terminal pyrene labels to monitor loss of inter-helical contacts by pyrene excimer fluorescence. A series of eight constructs with biotin tags at varying distances from the helix-terminal pyrene labels were expressed, purified and labeled appropriately; all constructs exhibited largely helical circular dichroism spectra. We found that addition of mSA to an optimized construct in lipid vesicles led to a complete and reversible loss in pyrene excimer fluorescence and mSA binding, and hence hairpin unfolding--results further supported by SDS-PAGE visualization of mSA bound and unbound species. While some dimeric/oligomeric populations persist that may affect quantitation of the unfolding step, our characterization of the design yields a promising prototype of a future platform for the systematic study of membrane protein folding in a lipid bilayer environment.

  7. Characterization of fatty acids, bioactive lipids, and radical scavenging activity of Canterbury bells seed oil

    Directory of Open Access Journals (Sweden)

    Hassanien, M. F.R.

    2014-06-01

    Full Text Available The aim of this study was to characterize the chemical composition and radical scavenging activity of Canterbury bells (Campanula medium seed oil. C. medium seeds contained 9.2% extractable oil. The lipid classes, fatty acids, phytosterol and tocopherol composition of C. medium seed oil were determined. The amount of neutral lipids in the oil was the highest, followed by glycolipids and phospholipids. Linoleic and oleic were the main fatty acids. C. medium oil is characterized by high levels of phytosterols and β-sitosterol was the main compound. β-Tocopherol constituted 42.5% of the total tocopherol content followed by γ-tocopherol. The radical scavenging activity (RSA toward 1,1-diphenyl-2-picrylhydrazyl (DPPH radicals and galvinoxyl radicals of C. medium oil were higher than those of extra virgin olive oil. The diverse potential uses of C. medium oil may make this plant industrially important.El objetivo de este estudio fue caracterizar la composición química y la actividad de captación de radicales de aceites de semillas de campanillas de Canterbury (Campanula medium. Las semillas de C. medium contenían 9,2 % de aceite extraíble. Se determinó la composición de las diferentes clases de lípidos, ácidos grasos, fitoesteroles y tocoferoles. La cantidad de lípidos neutros en el aceite fue mayoritario, seguido de glicolípidos y fosfolípidos. Linoleico y oleico fueron los ácidos grasos principales. El aceite de C. medium se caracteriza por altos niveles de fitoesteroles y β-sitosterol fue el compuesto principal. β-tocoferol constituía 42,5 % del contenido total de tocoferol seguido de γ-tocoferol. La actividad de captación de radicales (RSA a 1,1-difenil-2- picrilhidrazil (DPPH y radicales galvinoxil de C. medium fueron superiores a las de aceite de oliva virgen extra. Los diversos usos potenciales de los aceites de C. medium pueden hacer que esta planta pueda ser importante industrialmente.

  8. Importance of the hexagonal lipid phase in biological membrane organisation

    Directory of Open Access Journals (Sweden)

    Juliette eJouhet

    2013-12-01

    Full Text Available Abstract:Domains are present in every natural membrane. They are characterised by a distinctive protein and/or lipid composition. Their size is highly variable from the nano- to the micrometer scale. The domains confer specific properties to the membrane leading to original structure and function. The determinants leading to domain organisation are therefore important but remain obscure. This review presents how the ability of lipids to organize into hexagonal II or lamellar phases can promote particular local structures within membranes. Since biological membranes are composed of a mixture of lipids, each with distinctive biophysical properties, lateral and transversal sorting of lipids can promote creation of domains inside the membrane through local modulation of the lipid phase. Lipid biophysical properties have been characterized for long based on in vitro analyses using non-natural lipid molecules; their re-examinations using natural lipids might open interesting perspectives on membrane architecture occurring in vivo in various cellular and physiological contexts.

  9. Platelet lipidomics: a modern day perspective on lipid discovery and characterization in platelets

    OpenAIRE

    O’Donnell, Valerie B.; Murphy, Robert C.; Watson, Steve P.

    2014-01-01

    Lipids are diverse families of biomolecules that perform essential structural and signaling roles in platelets. Their formation and metabolism is tightly controlled by enzymes and signal transduction pathways, and their dysregulation leads to significant defects in platelet function and disease. Platelet activation is associated with significant changes to membrane lipids, and formation of diverse bioactive lipids that play essential roles in hemostasis. In recent years, new generation mass s...

  10. Characterization of myrtle seed (Myrtus communis var. baetica as a source of lipids, phenolics, and antioxidant activities

    Directory of Open Access Journals (Sweden)

    Wissem Aidi Wannes

    2016-04-01

    Full Text Available This study aimed to characterize the chemical composition and antioxidant activity of the oil and the methanolic extract of Myrtus communis var. baetica seed. The oil yield of myrtle seed was 8.90%, with the amount of neutral lipid, especially triacylglycerol, being the highest, followed by phospholipids and glycolipids. Total lipids and all lipid classes were rich in linoleic acid. The content of total phenols, flavonoids, tannins, and proanthocyanidins of the methanolic extract and the oil from myrtle seed was determined using spectrophotometric methods. Antioxidant activities of the oil and the methanolic extract from myrtle seed were evaluated using 1,1-diphenyl-2-picrylhydrazyl radical scavenging, β-carotene–linoleic acid bleaching, and reducing power and metal chelating activity assays. In all tests, the methanolic extract of myrtle seed showed better antioxidant activity than oil. This investigation could suggest the use of myrtle seed in food, industrial, and biomedical applications for its potential metabolites and antioxidant abilities.

  11. In Situ Characterizing Membrane Lipid Phenotype of Human Lung Cancer Cell Lines Using Mass Spectrometry Profiling

    OpenAIRE

    2016-01-01

    Abnormal lipid metabolisms are closely associated with cancers. In this study, mass spectrometry was employed to in situ investigate the associations of membrane lipid phenotypes of six human lung cancer cell lines (i.e., A549, H1650, H1975 from adenocarcinoma, H157 and H1703 from squamous cell carcinomas, and H460 from a large cell carcinoma) with cancer cell types and finally total 230 lipids were detected. Based these 230 lipids, partial least-square discriminant analysis indicated that fi...

  12. Application of image cytometry to characterize heterologous lipid flippases in yeast

    DEFF Research Database (Denmark)

    Jensen, Maria Stumph; Costa, Sara; Theorin, Lisa

    2016-01-01

    is typically monitored by flow cytometry, a costly and maintenance-intensive method. Here, we have optimized a protocol to use an automated image-based cell counter to accurately measure lipid uptake by heterologous lipid flippases expressed in yeast. The method was validated by comparison with the classical...... flow cytometric evaluation of lipid-labeled cells. In addition, we demonstrated that expression of fluorescently tagged flippase complexes can be directly co-related with fluorescent lipid uptake using the image-based cell counter system. The method extends the number of techniques available...

  13. Docetaxel-loaded solid lipid nanoparticles: preparation, characterization, in vitro, and in vivo evaluations.

    Science.gov (United States)

    Mosallaei, Navid; Jaafari, Mahmoud Reza; Hanafi-Bojd, Mohammad Yahya; Golmohammadzadeh, Shiva; Malaekeh-Nikouei, Bizhan

    2013-06-01

    The aim of the present study was to prepare, characterize, and evaluate solid lipid nanoparticles (SLNs) containing docetaxel (DTX) to improve the efficacy of this chemotherapeutic agent. SLNs containing DTX (SLN-DTX) were prepared by microemulsion and probe sonication techniques. In vitro cytotoxicity of SLN-DTX compared with Taxotere® (TXT) was evaluated on colorectal (C-26) and malignant melanoma (A-375) cell lines. Cellular uptake experiment was also carried out on C-26 cells. In in vivo tests, tumor inhibitory efficacy and survival were compared with TXT on C-26-implanted BALB/c mice. SLN-DTX particle size was 180 nm and PDI of 0.2 with spherical shape. Encapsulation efficacy was more than 98%. SLN-DTX at concentration of 100 μM caused 100% and 99.9% viability reduction in C-26 and A-375 after 48 and 72 h, respectively. The half maximal inhibitory concentration (IC50 ) of SLN-DTX on C-26 and A-375 was respectively 0.769 and 28.132 μM after 24 h. DTX cell uptake from SLN-DTX was remarkably higher than TXT. SLN-DTX showed better tumor inhibitory efficacy and survival at a dose of 10 mg/kg versus 10 and 20 mg/kg TXT. In conclusion, the results of the present study showed that the efficacy of SLN-DTX was better than TXT in cell-uptake and in vivo experiments.

  14. Preparation and characterization of decyl-terminated silicon nanoparticles encapsulated in lipid nanocapsules.

    Science.gov (United States)

    Pan, Guo-Hui; Barras, Alexandre; Boussekey, Luc; Qu, Xuesong; Addad, Ahmed; Boukherroub, Rabah

    2013-10-15

    In this Article, we report on the encapsulation of decyl-modified silicon nanoparticles (decyl-SiNPs) into ∼80 nm lipid nanocapsules (LNCs). The decyl-SiNPs were produced by thermal hydrosilylation of hydride-terminated SiNPs (H-SiNPs) liberated from porous silicon. Various techniques, including Fourier transform infrared spectroscopy (FT-IR), transmission electron microscopy (TEM), UV-vis absorption, dynamic light scattering (DLS), and photoluminescence (PL), were used to characterize their size, shape, colloidal, and optical properties. The results indicate that these nanocapsules feature controllable size, good dispersity, high loading rate of SiNPs, colloidal stability in various media, and bright PL. The PL of decyl-SiNPs loaded LNCs was stable upon heating to 80 °C, but was sensitive to basic solutions due to proton-gated emission of the SiNPs arranged at the LNCs interface between the oil phase and the hydrophilic polyethylene glycol moieties of the surfactant. These luminescent nanocapsules are therefore promising candidates as cellular probes for fluorescence imaging. In addition, it was found that TEM imaging of small-sized decyl-SiNPs could be greatly improved by preliminary negative staining of TEM grids with phosphotungstic acid.

  15. Development of lycopene-loaded lipid-core nanocapsules: physicochemical characterization and stability study

    Science.gov (United States)

    dos Santos, Priscilla Pereira; Paese, Karina; Guterres, Silvia Stanisçuaski; Pohlmann, Adriana Raffin; Costa, Tania Hass; Jablonski, André; Flôres, Simone Hickmann; Rios, Alessandro de Oliveira

    2015-02-01

    The objective of this study was to develop lycopene-loaded lipid-core nanocapsules (Lyc-LNCs) by the interfacial deposition of preformed poly(ɛ-caprolactone) (PCL). Lyc extract (93.9 %) was obtained from tomatoes, and the organic phase was prepared with polymer (PCL), caprylic/capric triglycerides, sorbitan monostearate, and Lyc in a mixture of acetone and ethanol under magnetic stirring at 40 °C. The organic phase was injected into an aqueous phase containing polysorbate 80, and the suspension was concentrated under reduced pressure. The formulation with a Lyc concentration of 85 µg/mL was characterized in terms of size distribution, zeta potential, encapsulation efficiency, pH, viscosity, and color. The Lyc-LNC formulation presented stable values for the z-average (193 ± 4.7 nm) and zeta potential (-11.5 ± 0.40 mV). Despite the lower pH, Lyc content, and color change of the suspension, the nanocapsules showed satisfactory stability, presenting around 50 % Lyc content after 14 days of storage at room temperature (25 °C).

  16. Development of lycopene-loaded lipid-core nanocapsules: physicochemical characterization and stability study

    Energy Technology Data Exchange (ETDEWEB)

    Santos, Priscilla Pereira dos [Universidade Federal do Rio Grande do Sul (UFRGS), Instituto de Ciência e Tecnologia de Alimentos (Brazil); Paese, Karina; Guterres, Silvia Stanisçuaski [Universidade Federal do Rio Grande do Sul, Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia (Brazil); Pohlmann, Adriana Raffin [Universidade Federal do Rio Grande do Sul (UFRGS), Departamento de Química Orgânica, Instituto de Química (Brazil); Costa, Tania Hass [Universidade Federal do Rio Grande do Sul (UFRGS), Departamento de Química, Instituto de Química (Brazil); Jablonski, André [Universidade Federal do Rio Grande do Sul (UFRGS), Departamento de Engenharia de Minas (Brazil); Flôres, Simone Hickmann; Rios, Alessandro de Oliveira, E-mail: alessandro.rios@ufrgs.br [Universidade Federal do Rio Grande do Sul (UFRGS), Instituto de Ciência e Tecnologia de Alimentos (Brazil)

    2015-02-15

    The objective of this study was to develop lycopene-loaded lipid-core nanocapsules (Lyc-LNCs) by the interfacial deposition of preformed poly(ε-caprolactone) (PCL). Lyc extract (93.9 %) was obtained from tomatoes, and the organic phase was prepared with polymer (PCL), caprylic/capric triglycerides, sorbitan monostearate, and Lyc in a mixture of acetone and ethanol under magnetic stirring at 40 °C. The organic phase was injected into an aqueous phase containing polysorbate 80, and the suspension was concentrated under reduced pressure. The formulation with a Lyc concentration of 85 µg/mL was characterized in terms of size distribution, zeta potential, encapsulation efficiency, pH, viscosity, and color. The Lyc-LNC formulation presented stable values for the z-average (193 ± 4.7 nm) and zeta potential (−11.5 ± 0.40 mV). Despite the lower pH, Lyc content, and color change of the suspension, the nanocapsules showed satisfactory stability, presenting around 50 % Lyc content after 14 days of storage at room temperature (25 °C)

  17. Radiobiological characterization of post-lumpectomy focal brachytherapy with lipid nanoparticle-carried radionuclides

    Science.gov (United States)

    Hrycushko, Brian A.; Gutierrez, Alonso N.; Goins, Beth; Yan, Weiqiang; Phillips, William T.; Otto, Pamela M.; Bao, Ande

    2011-02-01

    Post-operative radiotherapy has commonly been used for early stage breast cancer to treat residual disease. The primary objective of this work was to characterize, through dosimetric and radiobiological modeling, a novel focal brachytherapy technique which uses direct intracavitary infusion of β-emitting radionuclides (186Re/188Re) carried by lipid nanoparticles (liposomes). Absorbed dose calculations were performed for a spherical lumpectomy cavity with a uniformly injected activity distribution using a dose point kernel convolution technique. Radiobiological indices were used to relate predicted therapy outcome and normal tissue complication of this technique with equivalent external beam radiotherapy treatment regimens. Modeled stromal damage was used as a measure of the inhibition of the stimulatory effect on tumor growth driven by the wound healing response. A sample treatment plan delivering 50 Gy at a therapeutic range of 2.0 mm for 186Re-liposomes and 5.0 mm for 188Re-liposomes takes advantage of the dose delivery characteristics of the β-emissions, providing significant EUD (58.2 Gy and 72.5 Gy for 186Re and 188Re, respectively) with a minimal NTCP (0.046%) of the healthy ipsilateral breast. Modeling of kidney BED and ipsilateral breast NTCP showed that large injected activity concentrations of both radionuclides could be safely administered without significant complications.

  18. Methods to create thermally oxidized lipids and comparison of analytical procedures to characterize peroxidation.

    Science.gov (United States)

    Liu, P; Kerr, B J; Chen, C; Weber, T E; Johnston, L J; Shurson, G C

    2014-07-01

    The objective of this experiment was to evaluate peroxidation in 4 lipids, each with 3 levels of peroxidation. Lipid sources were corn oil (CN), canola oil (CA), poultry fat, and tallow. Peroxidation levels were original lipids (OL), slow-oxidized lipids (SO), and rapid-oxidized lipids (RO). To produce peroxidized lipids, OL were either heated at 95°C for 72 h to produce SO or heated at 185°C for 7 h to produce RO. Five indicative measurements (peroxide value [PV], p-anisidine value [AnV], thiobarbituric acid reactive substances [TBARS] concentration, hexanal concentration, 4-hydroxynonenal [HNE] concentration, and 2,4-decadienal [DDE]) and 2 predictive tests (active oxygen method [AOM] stability and oxidative stability index [OSI]) were performed to quantify the level of oxidation of the subsequent 12 lipids with varying levels of peroxidation. Analysis showed that a high PV accurately indicated the high level of lipid peroxidation, but a moderate or low PV may be misleading due to the unstable characteristics of hydroperoxides as indicated by the unchanged PV of rapidly oxidized CN and CA compared to their original state (OL). However, additional tests, which measure secondary peroxidation products such as AnV, TBARS, hexanal, HNE, and DDE, may provide a better indication of lipid peroxidation than PV for lipids subjected to a high level of peroxidation. Similar to PV analysis, these tests may also not provide irrefutable information regarding the extent of peroxidation because of the volatile characteristics of secondary peroxidation products and the changing stage of lipid peroxidation. For the predictive tests, AOM accurately reflected the increased lipid peroxidation caused by SO and RO as indicated by the increased AOM value in CN and CA but not in poultry fat and tallow, which indicated a potential disadvantage of the AOM test. Oxidative stability index successfully showed the increased lipid peroxidation caused by SO and RO in all lipids, but it too may

  19. Characterization of underivatized lipid biomarkers from microorganisms with pyrolysis short-column gas chromatography/ion trap mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Snyder, A.P. (Army Chemical Research, Aberdeen Proving Ground, MD (USA)); McClennen, W.H.; Dworzanski, J.P.; Meuzelaar, H.L.C. (Univ. of Utah, Salt Lake City (USA))

    1990-12-01

    A microvolume Curie-point pyrolysis short-column (5 m) gas chromatography/mass spectrometry (Py-Gc/MS) procedure was developed for the characterization of various lipid moieties in microorganisms. High linear flow rates (approximately 175 cm/s) characterized the GC conditions in order to effect an efficient chromatographic transfer and elution of the underivatized diglycerides and monoglycerides, and small modifications were necessary to the ion trap MS system in order for it to accommodate the relatively high gas load. During a typical analysis run anhydrodiacylglycerides eluted within a 5-6-min time frame. Gram-positive bacilli and Gram-negative species were differentiated from each other by the pyrolysis patterns of their lipid components. In spite of the complexity of the analyte, a straightforward visual analysis was achieved with the aid of simple computerized data display procedures. These procedures included examination of (1) total ion current (TIC) profiles of the lipid region of the reconstructed chromatogram, (2) the integrated mass spectrum of this region, (3) selected reconstructed ion chromatograms (RICs), (4) RIC intensity distributions, and (5) corresponding mass spectra. An appealing aspect of the lipid data reduction procedure is that most of it can be accomplished visually without requiring computerized pattern recognition techniques.

  20. Amsacrine analog-loaded solid lipid nanoparticle to resolve insolubility for injection delivery: characterization and pharmacokinetics

    Directory of Open Access Journals (Sweden)

    Fang YP

    2016-03-01

    Full Text Available Yi-Ping Fang,1 Chih-Hung Chuang,2 Pao-Chu Wu,1 Yaw-Bin Huang,1 Cherng-Chyi Tzeng,3 Yeh-Long Chen,3 Ya-Ting Liu,1 Yi-Hung Tsai,1 Ming-Jun Tsai4–6 1School of Pharmacy, College of Pharmacy, 2Department of Biomedical and Environment Biology, College of Life Science, 3School of Medicinal and Applied Chemistry, College of Life Science, Kaohsiung Medical University, Kaohsiung, 4Department of Neurology, China Medical University Hospital, 5School of Medicine, Medical College, China Medical University, Taichung, 6Department of Neurology, China Medical University An-Nan Hospital, Tainan, Taiwan Abstract: Amsacrine analog is a novel chemotherapeutic agent that provides potentially broad antitumor activity when compared to traditional amsacrine. However, the major limitation of amsacrine analog is that it is highly lipophilic, making it nonconductive to intravenous administration. The aim of this study was to utilize solid lipid nanoparticles (SLN to resolve the delivery problem and to investigate the biodistribution of amsacrine analog-loaded SLN. Physicochemical characterizations of SLN, including particle size, zeta potential, entrapment efficiency, and stability, were evaluated. In vitro release behavior was also measured by the dialysis method. In vivo pharmacokinetics and biodistribution behavior of amsacrine analog were investigated and incorporated with a non invasion in vivo imaging system to confirm the localization of SLN. The results showed that amsacrine analog-loaded SLN was 36.7 nm in particle size, 0.37 in polydispersity index, and 34.5±0.047 mV in zeta potential. More than 99% of amsacrine analog was successfully entrapped in the SLN. There were no significant differences in the physicochemical properties after storage at room temperature (25°C for 1 month. Amsacrine analog-loaded SLN maintained good stability. An in vitro release study showed that amsacrine analog-loaded SLN sustained a release pattern and followed the zero equation. An

  1. Structure characterization of phospholipids and lipid A of Pseudomonas putida KT2442.

    Science.gov (United States)

    Wang, Yuqian; Wang, Jianli; Li, Ye; Wang, Biwen; Tao, Guanjun; Wang, Xiaoyuan

    2015-01-01

    Pseudomonas putida KT2442 is an important bacterium for producing various types of polyhydroxyalkanoate polymers. Phospholipids and lipid A in membranes of P. putida play important roles in stress responses, but detailed structural information of these lipids is not known. In this study, phospholipids and lipid A were isolated from P. putida KT2442, and their structures were analyzed using thin layer chromatography, high performance liquid chromatography, and electrospray ionization/mass spectrometry. Major phospholipids in P. putida KT2442 were phosphatidylethanolamine (79.9%), phosphatidylglycero1 (12.7%), and cardiolipin (7.4%), with C16:1 and/or C18:1 acyl chains. Four lipid A species were found in P. putida KT2442: two are hexa-acylated, and the other two are penta-acylated. Compared with lipid A of P. aeruginosa, P. putida lipid A has less hydroxylation on the secondary acyl chains and less modification. Therefore, P. putida lipid A could be used as a base structure to investigate lipid A modification of P. aeruginosa for understanding its pathogenesis.

  2. Characterization of spin pumping effect in Permalloy/Cu/Pt microfabricated lateral devices

    Energy Technology Data Exchange (ETDEWEB)

    Yamamoto, Tatsuya, E-mail: tyamamoto@imr.tohoku.ac.jp; Seki, Takeshi; Takanashi, Koki [Institute for Materials Research, Tohoku University, Sendai 980-8577 (Japan); Ono, Shimpei [Central Research Institute of Electric Power Industry, Tokyo 201-8511 (Japan)

    2014-05-07

    We studied ferromagnetic resonance (FMR) for microfabricated lateral devices consisting of a Permalloy (Py) rectangular element and a Pt nano-element bridged by a Cu wire, which were located on a coplanar waveguide. A change in the resonance linewidth (Δf) was observed in the FMR spectra when the distance between Py and Pt (d) was varied. For devices with d < 400 nm, Δf definitely increased, suggesting the enhancement of the Gilbert damping constant (α). We discussed a possible reason for the this enhancement taking into account the increase in the efficiency of spin pumping into Cu due to the spin absorption of the attached Pt.

  3. Lipid characterization of an arachidonic acid-rich oil producing fungus Mortierella alpina

    Institute of Scientific and Technical Information of China (English)

    Wenjia Wu; Jiacheng Yan; Xiaojun Ji; Xin Zhang; Jingsheng Shang; Lina Sun; Lujing Ren; He Huang

    2015-01-01

    Mortierel a alpina has been considered as the most effective producer of arachidonic acid (ARA)-rich oil. It was found that several methods could improve the percentage of ARA in total lipids successful y, as they activated the desaturation system on the endoplasmic reticulum. Additionally, in M. alpina the ARA exists in several forms, such as triacylglycerol (TAG), and diacylglycerol (DAG). These forms are caused by different acyltransferases and they determine the nutrient value of the microbial oil. However, few works revealed de-tailed fatty acid distribution among lipid classes, which to some extent impeded the accurate regulation in ARA accumulation. Herein, this paper gives information on the accumulation process of main lipid classes and the changes of fatty acid composition in these lipids during ARA accumulation period in M. alpina. The result dem-onstrates that TAG was the dominant component of the total lipids, and it is the main form for ARA storage. The ARA enrichment stage occurred during 168–192 h when the amount of total lipids maintained steady. Further analysis indicated that the newly formed ARA-TAG might come from the incorporation and modification of sat-urated and monounsaturated fatty acids in other lipid classes. This work could be helpful for further optimization of ARA-rich TAG production.

  4. Characterization of Membrane Protein-Lipid Interactions by Mass Spectrometry Ion Mobility Mass Spectrometry

    Science.gov (United States)

    Liu, Yang; Cong, Xiao; Liu, Wen; Laganowsky, Arthur

    2016-12-01

    Lipids in the biological membrane can modulate the structure and function of integral and peripheral membrane proteins. Distinguishing individual lipids that bind selectively to membrane protein complexes from an ensemble of lipid-bound species remains a daunting task. Recently, ion mobility mass spectrometry (IM-MS) has proven to be invaluable for interrogating the interactions between protein and individual lipids, where the complex undergoes collision induced unfolding followed by quantification of the unfolding pathway to assess the effect of these interactions. However, gas-phase unfolding experiments for membrane proteins are typically performed on the entire ensemble (apo and lipid bound species), raising uncertainty to the contribution of individual lipids and the species that are ejected in the unfolding process. Here, we describe the application of mass spectrometry ion mobility mass spectrometry (MS-IM-MS) for isolating ions corresponding to lipid-bound states of a model integral membrane protein, ammonia channel (AmtB) from Escherichia coli. Free of ensemble effects, MS-IM-MS reveals that bound lipids are ejected as neutral species; however, no correlation was found between the lipid-induced stabilization of complex and their equilibrium binding constants. In comparison to data obtained by IM-MS, there are surprisingly limited differences in stability measurements from IM-MS and MS-IM-MS. The approach described here to isolate ions of membrane protein complexes will be useful for other MS methods, such as surface induced dissociation or collision induced dissociation to determine the stoichiometry of hetero-oligomeric membrane protein complexes.

  5. Candesartan cilexetil loaded solid lipid nanoparticles for oral delivery: characterization, pharmacokinetic and pharmacodynamic evaluation.

    Science.gov (United States)

    Dudhipala, Narendar; Veerabrahma, Kishan

    2016-01-01

    Candesartan cilexetil (CC) is used in the treatment of hypertension and heart failure. It has poor aqueous solubility and low oral bioavailability. In this work, CC loaded solid lipid nanoparticles (CC-SLNs) were developed to improve the oral bioavailability. Components of the SLNs include either of trimyristin/tripalmitin/tristearin, and surfactants (Poloxamer 188 and egg lecithin E80). The CC loaded nanoparticles were prepared by hot homogenization followed by ultrasonication method. The physicochemical properties, morphology of CC-SLNs were characterized, the pharmacokinetic and pharmacodynamic behaviour of CC-SLNs were evaluated in rats. Stable CC-SLNs having a mean particle size of 180-220 nm with entrapment efficiency varying in between 91-96% were developed. The physical stability of optimized formulation was studied at refrigerated and room temperature for 3 months. Further, freeze drying was tried for improving the physical stability. DSC and XRD analyses indicated that the drug incorporated into SLN was in amorphous form but not in crystalline state. The SLN-morphology was found to be nearly spherical by electron microscopic studies. Pharmacokinetic results indicated that the oral bioavailability of CC was improved over 2.75-fold after incorporation into SLNs. Pharmacodynamic study of SLNs in hypertensive rats showed a decrease in systolic blood pressure for 48 h, while suspension showed a decrease in systolic blood pressure for only 2 h. Taken together, these effects are due to enhanced bioavailability coupled with sustained action of CC in SLN formulation. Thus, the results conclusively demonstrated the role of CC-SLNs for a significant enhancement in oral bioavailability along with improved pharmacodynamic effect.

  6. Physicochemical characterization of wet microalgal cells disrupted with instant catapult steam explosion for lipid extraction.

    Science.gov (United States)

    Cheng, Jun; Huang, Rui; Li, Tao; Zhou, Junhu; Cen, Kefa

    2015-09-01

    Instant catapult steam explosion (ICSE) was employed to disrupt wet microalgal cells for efficient lipid extraction. Physicochemical properties of exploded cells were investigated through SEM, TEM, FTIR, and TGA. The exploded cells increased in fractal dimension (1.53-1.65) when preheat time was prolonged from 0 min to 5 min and in surface pore area when steam pressure was increased. Meanwhile, the exploded cells decreased in mean size (1.69-1.44 μm) when the filling ratio of wet microalgal biomass in the preheat chamber decreased (75-12.5%). Flash evaporation and volume expansion exploded the cell walls and released the cytoplasm of the microalgal cells. These phenomena decreased the carbohydrate content and increased the lipid content in the exploded biomass. However, ICSE treatment did not change the lipid compositions in the microalgal cells. Using isopropanol as a cosolvent significantly increased the yield of lipids extracted with hexane from the exploded wet microalgal biomass.

  7. Advanced shotgun lipidomics for characterization of altered lipid patterns in neurodegenerative diseases and brain injury

    Science.gov (United States)

    Wang, Miao; Han, Xianlin

    2016-01-01

    Summary Multi-dimensional mass spectrometry-based shotgun lipidomics (MDMS-SL) is a powerful technology platform among current lipidomics practices due to its high efficiency, sensitivity, and reproducibility, as well as its broad coverage. This platform has been broadly used to determine the altered lipid profiles induced by diseases, injury, genetic manipulations, drug treatments, and aging, among others. Herein, we summarized the principles underlying this platform and presented a protocol for analysis of many of the lipid classes and subclasses covered by MDMS-SL directly from lipid extracts of brain samples. We believe that this protocol could aid the researchers in the field to determine the altered lipid patterns in neurodegenerative diseases and brain injury. PMID:26235081

  8. Preparation and characterization of n-dodecyl-ferulate-loaded solid lipid nanoparticles (SLN).

    Science.gov (United States)

    Souto, E B; Anselmi, C; Centini, M; Müller, R H

    2005-05-13

    Solid lipid nanoparticles (SLN) containing a novel potential sunscreen n-dodecyl-ferulate (ester of ferulic acid) were developed. The preparation and stability parameters of n-dodecyl-ferulate-loaded SLN have been investigated concerning particle size, surface electrical charge (zeta potential) and matrix crystallinity. The chemical stability of n-dodecyl-ferulate at high temperatures was also assessed by thermal gravimetry analysis. For the selection of the appropriated lipid matrix, chemically different lipids were melted with 4% (m/m) of active and lipid nanoparticles were prepared by the so-called high pressure homogenization technique. n-Dodecyl-ferulate-loaded SLN prepared with cetyl palmitate showed the lowest mean particle size and polydispersity index, as well as the highest physical stability during storage time of 21 days at 4, 20 and 40 degrees C. These colloidal dispersions containing the sunscreen also exhibited the common melting behaviour of aqueous SLN dispersions.

  9. Assessing the nature of lipid raft membranes.

    Directory of Open Access Journals (Sweden)

    Perttu S Niemelä

    2007-02-01

    Full Text Available The paradigm of biological membranes has recently gone through a major update. Instead of being fluid and homogeneous, recent studies suggest that membranes are characterized by transient domains with varying fluidity. In particular, a number of experimental studies have revealed the existence of highly ordered lateral domains rich in sphingomyelin and cholesterol (CHOL. These domains, called functional lipid rafts, have been suggested to take part in a variety of dynamic cellular processes such as membrane trafficking, signal transduction, and regulation of the activity of membrane proteins. However, despite the proposed importance of these domains, their properties, and even the precise nature of the lipid phases, have remained open issues mainly because the associated short time and length scales have posed a major challenge to experiments. In this work, we employ extensive atom-scale simulations to elucidate the properties of ternary raft mixtures with CHOL, palmitoylsphingomyelin (PSM, and palmitoyloleoylphosphatidylcholine. We simulate two bilayers of 1,024 lipids for 100 ns in the liquid-ordered phase and one system of the same size in the liquid-disordered phase. The studies provide evidence that the presence of PSM and CHOL in raft-like membranes leads to strongly packed and rigid bilayers. We also find that the simulated raft bilayers are characterized by nanoscale lateral heterogeneity, though the slow lateral diffusion renders the interpretation of the observed lateral heterogeneity more difficult. The findings reveal aspects of the role of favored (specific lipid-lipid interactions within rafts and clarify the prominent role of CHOL in altering the properties of the membrane locally in its neighborhood. Also, we show that the presence of PSM and CHOL in rafts leads to intriguing lateral pressure profiles that are distinctly different from corresponding profiles in nonraft-like membranes. The results propose that the functioning of

  10. Optical method and system for the characterization of laterally-patterned samples in integrated circuits

    Science.gov (United States)

    Maris, Humphrey J.

    2008-03-04

    Disclosed is a method for characterizing a sample having a structure disposed on or within the sample, comprising the steps of applying a first pulse of light to a surface of the sample for creating a propagating strain pulse in the sample, applying a second pulse of light to the surface so that the second pulse of light interacts with the propagating strain pulse in the sample, sensing from a reflection of the second pulse a change in optical response of the sample, and relating a time of occurrence of the change in optical response to at least one dimension of the structure.

  11. Molecular characterization of cadmium resistance in Streptococcus thermophilus strain 4134: an example of lateral gene transfer.

    Science.gov (United States)

    Schirawski, Jan; Hagens, Werner; Fitzgerald, Gerald F; Van Sinderen, Douwe

    2002-11-01

    Two genes (cadC(St) and cadA(St) [subscript St represents Streptococcus thermophilus]), located on the chromosome of S. thermophilus 4134, were shown to constitute a cadmium/zinc resistance cassette. The genes seem to be organized in an operon, and their transcription is cadmium dependent in vivo. The proposed product of the cadA open reading frame (CadA(St)) is highly similar to P-type cadmium efflux ATPases, whereas the predicted protein encoded by cadC(St) (CadC(St)) shows high similarity to ArsR-type regulatory proteins. The observed homologies and G+C content of this cassette and surrounding regions suggest that this DNA was derived from Lactococcus lactis and may have been introduced relatively recently into the S. thermophilus 4134 genome by a lateral gene transfer event. The complete cassette confers cadmium and zinc resistance to both S. thermophilus and L. lactis, but expression of cadA(St) alone is sufficient to give resistance. By using electrophoretic mobility shift assays it was shown that the CadC(St) protein is a DNA binding protein that binds specifically to its own promoter region, possibly to two copies of an inverted repeat, and that this CadC(St)-DNA interaction is lost in the presence of cadmium. Using lacZ fusion constructs it was shown that the cadmium-dependent expression of CadA(St) is mediated by the negative regulator CadC(St). A model for the regulation of the expression of cadmium resistance in S. thermophilus is discussed.

  12. Lateral diffusion of peripheral membrane proteins on supported lipid bilayers is controlled by the additive frictional drags of (1) bound lipids and (2) protein domains penetrating into the bilayer hydrocarbon core.

    Science.gov (United States)

    Ziemba, Brian P; Falke, Joseph J

    2013-01-01

    Peripheral membrane proteins bound to lipids on bilayer surfaces play central roles in a wide array of cellular processes, including many signaling pathways. These proteins diffuse in the plane of the bilayer and often undergo complex reactions involving the binding of regulatory and substrate lipids and proteins they encounter during their 2D diffusion. Some peripheral proteins, for example pleckstrin homology (PH) domains, dock to the bilayer in a relatively shallow position with little penetration into the bilayer. Other peripheral proteins exhibit more complex bilayer contacts, for example classical protein kinase C isoforms (PKCs) bind as many as six lipids in stepwise fashion, resulting in the penetration of three PKC domains (C1A, C1B, C2) into the bilayer headgroup and hydrocarbon regions. A molecular understanding of the molecular features that control the diffusion speeds of proteins bound to supported bilayers would enable key molecular information to be extracted from experimental diffusion constants, revealing protein-lipid and protein-bilayer interactions difficult to study by other methods. The present study investigates a range of 11 different peripheral protein constructs comprised by 1-3 distinct domains (PH, C1A, C1B, C2, anti-lipid antibody). By combining these constructs with various combinations of target lipids, the study measures 2D diffusion constants on supported bilayers for 17 different protein-lipid complexes. The resulting experimental diffusion constants, together with the known membrane interaction parameters of each complex, are used to analyze the molecular features correlated with diffusional slowing and bilayer friction. The findings show that both (1) individual bound lipids and (2) individual protein domains that penetrate into the hydrocarbon core make additive contributions to the friction against the bilayer, thereby defining the 2D diffusion constant. An empirical formula is developed that accurately estimates the diffusion

  13. Formulation and characterization of solid lipid nanoparticles loaded Neem oil for topical treatment of acne

    Institute of Scientific and Technical Information of China (English)

    V. Vijayan; Shaik Aafreen; S. Sakthivel; K. Ravindra Reddy

    2013-01-01

    Objective:To investigate the treatment of acne and pimples as well as improves skin elasticity by solid lipid nanoparticles(SLNs) loadedNeem oil.Method:Neem oil as a natural agent was incorporated intoSLNs prepared by double emulsification method using different concentration of lecithin andTween80.The characteristics ofSLNs with different concentration of lipid were investigated.Result:The average particlesize ofNeem oil loadedSLNs decreased with increasing concentration of surfactant.SLNs of(221.6±2.0) nm with aPolydispersity index of (0.948±0.040) were obtained at higher concentration of lipid and surfactant.High entrapment efficiency of82.10% revealed the ability of solid lipid nanoparticles to incorporate a high quantity ofNeem oil.Furthermore the stability ofSLNs indicated with negligible drug leakage after3 weeks.Conclusion:The result concluded thatNeem oil loaded solid lipid nanoparticles with more lecithin content in their colloid exhibit sustained effect which satisfactorily produced the antibacterial action onAcne microbes.ThereforeNeem oil loadedSLN was used successfully for prolonged treatment ofAcne.

  14. Preparation, characterization and pharmacokinetic studies of linalool-loaded nanostructured lipid carriers.

    Science.gov (United States)

    Shi, Feng; Zhao, Yingying; Firempong, Caleb Kesse; Xu, Ximing

    2016-10-01

    Context Linalool (LL) is associated with numerous pharmacological activities. However, its poor solubility usually results in poor bioavailability, and further limited its applications. Objective To reduce volatilization and improve bioavailability of LL, linalool-loaded nanostructured lipid carriers (LL-NLCs) were prepared. Materials and methods LL-NLCs were prepared using high-pressure homogenization method and optimized via response surface methodology-central composite design, followed by characterization, including particle size (PS), zeta potential (ZP), transmission electron microscope (TEM), X-ray diffraction (XRD), differential scanning calorimetry (DSC) and in vitro release study. Rats were administered 300 mg × kg (-) (1) LL with each preparation (LL-NLCs or LL) via oral gavage. Results LL-NLCs had a PS of 52.72 nm with polydispersity index of 0.172, and ZP of -16.0 mV. The encapsulation efficiency and drug loading gave 79.563 and 7.555%, respectively. The cumulative release of LL from free LL reached 51.414% at 180 min, while LL from LL-NLCs was 15.564%. All the pharmacokinetics parameters of LL-NLCs were better than those of LL, including Cmax (from 1915.45 to 2182.45 ng × mL (-) (1)), AUC0-t (from 76003.40 to 298948.46 ng × min × mL (-) (1)) and relative bioavailability (393.34%). The t1/2, MRT and tmax of LL-NLCs (110.50, 146.66 and 60 min) were also longer than that of LL (44.72, 45.66 and 40 min). Discussion and conclusion LL-NLCs were for the first time prepared and its oral administration in rats thoroughly investigated. LL-NLCs exhibited sustained release effect and increased absorption of LL. Therefore, these findings might provide a potential possibility for clinical application of LL.

  15. Preparation, characterization, and optimization of primaquine-loaded solid lipid nanoparticles

    Directory of Open Access Journals (Sweden)

    Omwoyo WN

    2014-08-01

    Full Text Available Wesley Nyaigoti Omwoyo,1,2 Bernhards Ogutu,3,4 Florence Oloo,3,5 Hulda Swai,6 Lonji Kalombo,6 Paula Melariri,6 Geoffrey Maroa Mahanga,2 Jeremiah Waweru Gathirwa3,4 1Department of Chemistry, Maasai Mara University, Narok, Kenya; 2Department of Chemistry, Jaramogi Oginga Odinga University of Science and Technology, Bondo, Kenya; 3Center for Research in Therapeutic Sciences, Strathmore University, Nairobi, Kenya; 4Kenya Medical Research Institute, Nairobi, Kenya; 5Department of Chemical Sciences and Technology, Technical University of Kenya, Nairobi, Kenya; 6Department of Polymers and Composites, Council for Scientific and Industrial Research, Pretoria, South Africa Abstract: Primaquine (PQ is one of the most widely used antimalarial drugs and is the only available drug that combats the relapsing form of malaria. PQ use in higher doses is limited by severe tissue toxicity including hematological- and gastrointestinal-related side effects. Nanoformulation of drugs in an appropriate drug carrier system has been extensively studied and shown to have the potential to improve bioavailability, thereby enhancing activity, reducing dose frequency, and subsequently reducing toxicity. The aim of this work was to design, synthesize, and characterize PQ-loaded solid lipid nanoparticles (SLNs (PQ-SLNs as a potential drug-delivery system. SLNs were prepared by a modified solvent emulsification evaporation method based on a water-in-oil-in-water (w/o/w double emulsion. The mean particle size, zeta potential, drug loading, and encapsulation efficiency of the PQ-SLNs were 236 nm, +23 mV, 14%, and 75%, respectively. The zeta potential of the SLNs changed dramatically, from -6.54 mV to +23.0 mV, by binding positively charged chitosan as surface modifier. A spherical morphology of PQ-SLNs was seen by scanning electron microscope. In vitro, release profile depicted a steady drug release over 72 hours. Differential scanning calorimeter thermograms demonstrated presence

  16. Temporal and spatial characterization of neuronal injury following lateral fluid-percussion brain injury in the rat.

    Science.gov (United States)

    Hicks, R; Soares, H; Smith, D; McIntosh, T

    1996-01-01

    The pattern of neuronal injury following lateral fluid-percussion (FP) brain injury in the rat was systematically characterized at sequential time points to identify selectively vulnerable regions and to determine the temporal contribution of primary and delayed neuropathological events. Male Sprague-Dawley rats (n = 28) were killed 10 min, 2 h, 12 h, 24 h, 4 days, and 7 days following a lateral FP brain injury of moderate severity (2.2 atm), or 24 h after a sham injury. Brain sections were stained and analyzed using Nissl, acid fuchsin, and silver staining methods to identify regions with injured neurons or with visible lesions. Extensive numbers of acid fuchsin or silver-stained neurons were observed as early as 10 min after the FP brain injury in regions extending from the caudate/putamen to the pons. The frequency of injured neurons was greatest in the ipsilateral cortex, hippocampus, and thalamus, and a visible loss of Nissl-stained neurons was observed in these regions beginning at 12 h after the FP brain injury. Acid fuchsin-stained neurons were restricted to the same brain regions for all of the survival periods and gradually decreased in numbers between 24 h and 7 days after injury. These findings suggest that lateral FP brain injury in the rat produces a combination of focal cortical contusion and diffuse subcortical neuronal injury, which is present within minutes of the impact, progresses to a loss of neurons by 12 h, and does not markedly expand into other brain regions with survival periods up to 7 days. Furthermore, the acute onset and rapid evolution of the neuronal injury process may have important implications when considering a window of opportunity for pharmacological intervention.

  17. Isolation and genetic characterization of mother-of-snow-white, a maternal effect allele affecting laterality and lateralized behaviors in zebrafish.

    Directory of Open Access Journals (Sweden)

    Alice Domenichini

    Full Text Available In the present work we report evidence compatible with a maternal effect allele affecting left-right development and functional lateralization in vertebrates. Our study demonstrates that the increased frequency of reversed brain asymmetries in a zebrafish line isolated through a behavioral assay is due to selection of mother-of-snow-white (msw, a maternal effect allele involved in early stages of left-right development in zebrafish. msw homozygous females could be identified by screening of their progeny for the position of the parapineal organ because in about 50% of their offspring we found an altered, either bilateral or right-sided, expression of lefty1 and spaw. Deeper investigations at earlier stages of development revealed that msw is involved in the specification and differentiation of precursors of the Kupffer's vesicle, a structure homologous to the mammalian node. To test the hypothesis that msw, by controlling Kupffer's vesicle morphogenesis, controls lateralized behaviors related to diencephalic asymmetries, we analyzed left- and right-parapineal offspring in a "viewing test". As a result, left- and right-parapineal individuals showed opposite and complementary eye preference when scrutinizing a model predator, and a different degree of lateralization when scrutinizing a virtual companion. As maternal effect genes are expected to evolve more rapidly when compared to zygotic ones, our results highlight the driving force of maternal effect alleles in the evolution of vertebrates behaviors.

  18. Preparation, characterization and evaluation of breviscapine lipid emulsions coated with monooleate-PEG-COOH.

    Science.gov (United States)

    Xiong, Fei; Xiong, Chen; Yao, Juan; Chen, Xinmei; Gu, Ning

    2011-12-15

    Series of monooleate-modified PEG with active carboxylic terminus on the other end (MO-PEG-COOH) were used to modify the lipid emulsions surface to prepare a sterically stabilized lipid emulsions for carrying Traditional Chinese Medicine - breviscapine. Based on the research of relationship between polymer structure and prolonged circulation activity, we developed an optimized formulation and a technological method to prepare the sterile and stable MO-PEG(10,000)-COOH (Bre-LE-PEG(10,000)) coated breviscapine lipid emulsions (Bre-LE) for intravenous administration. Follow the optimum preparation, the average particle size, polydispersity index, zeta potential, Ke value and content of final product were determined to be (207.1±8.5)nm, 0.197±0.005, (-33.6±2.0)mV, (21.1±2.3)% and (95.0±1.8)% respectively (n=3). The characteristics, stability and safety of Bre-LE-PEG(10,000) were also studied with Bre-LE as a control. Increased plasma concentration by surface modification of the lipid emulsions may enhance the pharmacological activity of breviscapine to promote blood circulation.

  19. Formulation and characterization of solid lipid nanoparticles loaded Neem oil for topical treatment of acne

    Directory of Open Access Journals (Sweden)

    V. Vijayan

    2013-01-01

    Conclusion: The result concluded that Neem oil loaded solid lipid nanoparticles with more lecithin content in their colloid exhibit sustained effect which satisfactorily produced the antibacterial action on Acne microbes. Therefore Neem oil loaded SLN was used successfully for prolonged treatment of Acne.

  20. Fabrication and characterization of an integrated ionic device from suspended polypyrrole and alamethicin-reconstituted lipid bilayer membranes

    Science.gov (United States)

    Northcutt, Robert; Sundaresan, Vishnu-Baba

    2012-09-01

    Conducting polymers are electroactive materials that undergo conformal relaxation of the polymer backbone in the presence of an electrical field through ion exchange with solid or aqueous electrolytes. This conformal relaxation and the associated morphological changes make conducting polymers highly suitable for actuation and sensing applications. Among smart materials, bioderived active materials also use ion transport for sensing and actuation functions via selective ion transport. The transporter proteins extracted from biological cell membranes and reconstituted into a bilayer lipid membrane in bioderived active materials regulate ion transport for engineering functions. The protein transporter reconstituted in the bilayer lipid membrane is referred to as the bioderived membrane and serves as the active component in bioderived active materials. Inspired by the similarities in the physics of transduction in conducting polymers and bioderived active materials, an integrated ionic device is formed from the bioderived membrane and the conducting polymer membrane. This ionic device is fabricated into a laminated thin-film membrane and a common ion that can be processed by the bioderived and the conducting polymer membranes couple the ionic function of these two membranes. An integrated ionic device, fabricated from polypyrrole (PPy) doped with sodium dodecylbenzenesulfonate (NaDBS) and an alamethicin-reconstituted DPhPC bilayer lipid membrane, is presented in this paper. A voltage-gated sodium current regulates the electrochemical response in the PPy(DBS) layer. The integrated device is fabricated on silicon-based substrates through microfabrication, electropolymerization, and vesicle fusion, and ionic activity is characterized through electrochemical measurements.

  1. Lipid nanocarriers (GeluPearl) containing amphiphilic lipid Gelucire 50/13 as a novel stabilizer: fabrication, characterization and evaluation for oral drug delivery

    Energy Technology Data Exchange (ETDEWEB)

    Date, Abhijit A; Nagarsenker, Mangal S [Department of Pharmaceutics, Bombay College of Pharmacy, Kalina, Santacruz (E.), Mumbai (India); Vador, Nimish; Jagtap, Aarti, E-mail: mangal_nag511@yahoo.co.in, E-mail: mangal@bcp.edu.in [Department of Pharmacology, Bombay College of Pharmacy, Kalina, Santacruz (E.), Mumbai (India)

    2011-07-08

    Purpose. To evaluate the ability of Gelucire 50/13 (an amphiphilic lipid excipient) to act as a stabilizer for lipid nanocarriers such as solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) and to establish the ability of Gelucire 50/13 based lipid nanocarriers to improve oral delivery of hydrophobic drugs using repaglinide (RPG) as a model drug. Methods. The ability of Gelucire 50/13 to nanosize various solid lipids was evaluated. The ability of Gelucire 50/13 to yield NLC was evaluated by using Precirol ATO 5 as a model solid lipid and various liquid lipids (oils). Gelucire 50/13 based NLC (GeluPearl) were evaluated for their ability to improve the efficacy of RPG on oral administration in comparison to RPG tablets. The short term stability of RPG-GeluPearl was evaluated at 25 deg. C/60% RH. Results. Gelucire 50/13 could successfully yield SLN and NLC of various solid lipids, demonstrating its potential to act as a novel stabilizer. DSC studies indicated that Gelucire 50/13 interacts with Precirol ATO 5 and this interaction suppresses polymorphic transitions of both the components. RPG-GeluPearl exhibited significantly higher anti-diabetic activity compared to marketed RPG tablets. RPG-GeluPearl demonstrated good colloidal and chemical stability at the end of 1 month.

  2. Lipid nanocarriers (GeluPearl) containing amphiphilic lipid Gelucire 50/13 as a novel stabilizer: fabrication, characterization and evaluation for oral drug delivery

    Science.gov (United States)

    Date, Abhijit A.; Vador, Nimish; Jagtap, Aarti; Nagarsenker, Mangal S.

    2011-07-01

    Purpose. To evaluate the ability of Gelucire 50/13 (an amphiphilic lipid excipient) to act as a stabilizer for lipid nanocarriers such as solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) and to establish the ability of Gelucire 50/13 based lipid nanocarriers to improve oral delivery of hydrophobic drugs using repaglinide (RPG) as a model drug. Methods. The ability of Gelucire 50/13 to nanosize various solid lipids was evaluated. The ability of Gelucire 50/13 to yield NLC was evaluated by using Precirol ATO 5 as a model solid lipid and various liquid lipids (oils). Gelucire 50/13 based NLC (GeluPearl) were evaluated for their ability to improve the efficacy of RPG on oral administration in comparison to RPG tablets. The short term stability of RPG-GeluPearl was evaluated at 25 °C/60% RH. Results. Gelucire 50/13 could successfully yield SLN and NLC of various solid lipids, demonstrating its potential to act as a novel stabilizer. DSC studies indicated that Gelucire 50/13 interacts with Precirol ATO 5 and this interaction suppresses polymorphic transitions of both the components. RPG-GeluPearl exhibited significantly higher anti-diabetic activity compared to marketed RPG tablets. RPG-GeluPearl demonstrated good colloidal and chemical stability at the end of 1 month. Indian patent application number 2167/MUM/2008.

  3. Surface modified solid lipid microparticles based on homolipids and Softisan® 142:preliminary characterization

    Institute of Scientific and Technical Information of China (English)

    Nnamani PO; Ibezim EC; Attama AA; Adikwu MU

    2010-01-01

    Objective:To preliminarily investigate three different lipid matrices consisting of two natural homolipids fromCapra hircus (goat fat) andBovine Spp.(tallow fat) and one semi-synthetic lipid (Softisan® 142) separately structured with Phospholipon® 90G (P90G) as potential delivery systems for poorly water soluble drugs.Methods:The structured lipid matrices were characterized by differential scanning calorimetry (DSC) and employed to prepare solid lipid microparticles(SLMs) by the melt homogenization method using gradient concentrations of polysorbate 80 and at different emulsification times of 2, 5 and 10 min using a Silverson mixer. TheSLMs were analyzed for morphology and particle size, thermal properties, stability studies and determination of injectability.Results: The results showed that SLM production was optimum at 5 % of lipid matrices, 1.5 % of polysorbate 80 and emulsification time of 5 min. Increase in polysorbate 80 concentrations decreased the particle size of the SLMs. TheSLMs were well formed, spherical, smooth and non-porous with particle sizes in the ranges of (13.90± 2.10) μm– (0.09 ± 0.01) μm for SLMs produced from the structured - tallow fat; (13.40± 1.30)μm– (0.10 ± 0.01) μm for the structured– goat fat and (13.40±2.00) μm– (2.10± 1.00)μm for the structured Softisan® 142 lipid matrices. DSC traces showed that Softisan® 142 was the most crystalline of all three bulk matrices due to its high enthalpy (-7.962 mW/mg) while tallow fat was the least (-5.067 mW/mg) but addition of P90G to the matrices lowered their enthalpies mostly in the structured goat fat matrices. The SLMs when stored at 4-6 ℃ were most stable and syringeable with 27 G needle.Conclusions:This suggests that structured goat fat matrices with the enthalpy of -2.813 mW/mg will mostly favour drug loading of some poorly soluble drugs more than tallow fat (-4.892 mW/mg) and Softisan® 142 (-5.501 mW/mg).

  4. Characterization of lipid oxidation in plant oils by micro-calorimetry.

    Science.gov (United States)

    Dridi, Wafa; Toutain, Jean; Sommier, Alain; Essafi, Wafa; Gargouri, Mohamed; Leal-Calderon, Fernando; Cansell, Maud

    2016-04-15

    A new experimental device was developed, based on the measurement of the heat flux dissipated during chemical reactions. The technique was exploited for real time monitoring of lipid oxidation in plant oils. The thermopiles were used in adiabatic configuration in order to measure the entire heat flux and improve sensitivity. Measurements were operated with a resolution of few μW as required to follow low exothermic reactions like oxidation. The validation of the device was performed by correlating conjugated diene concentrations measured by spectrophotometry and the heat flux dissipated by oxidation reactions. Our experimental approach involved several plant oils analyzed in isothermal conditions. This novel technique provides a versatile, sensitive, solvent-free and yet low-cost method to assess lipid oxidation stability, particularly suitable for the fast screening of plant oils.

  5. Characterization of Lipids and Fatty Acid Methyl Ester Contents in Leaves and Roots of Crocus vallicola

    OpenAIRE

    YAYLI, Nurettin; KIRAN, Zerrin; SEYMEN, Hasan; GENÇ, Hasan

    2001-01-01

    The chemical composition of the fatty acids methyl esters (FAMEs) and other lipids in leaves and roots of Crocusvallicola were analyzed by gas chromatography-mass spectrometry(GC-MS). In this work, twenty-eight compounds, including 22 FAMEs, 1 aldehyde, 3 hydrocarbons (substitute alkane and alkene), 2 alcohols in the leaves and twenty-one compounds (17 FAMEs, 1 anhydride, 1 substitute alcohol, 1 ketone, 1 substitute amide) in the roots were identified by GC-MS from C. vallicola. Th...

  6. Vitamin C conjugates of genotoxic lipid peroxidation products: Structural characterization and detection in human plasma

    OpenAIRE

    Sowell, John; Frei, Balz; Stevens, Jan F.

    2004-01-01

    α,β-Unsaturated aldehydes such as 4-hydroxy-2-nonenal (HNE) and other electrophilic lipid peroxidation (LPO) products may contribute to the pathogenesis of cancer, cardiovascular diseases, and other age-related diseases by cytotoxic, genotoxic, and proinflammatory mechanisms. The notion that vitamin C (ascorbic acid) acts as a biological antioxidant has been challenged recently by an in vitro study showing that ascorbic acid promotes, rather than inhibits, the formation of genotoxic LPO produ...

  7. Formulation and Physicochemical Characterization of Lycopene-Loaded Solid Lipid Nanoparticles

    OpenAIRE

    Elham Nazemiyeh; Morteza Eskandani; Hossein Sheikhloie; Hossein Nazemiyeh

    2016-01-01

    Purpose: Lycopene belongs to the carotenoids that shows good pharmacological properties including antioxidant, anti-inflammatory and anticancer. However, as a result of very low aqueous solubility, it has a limited systemic absorption, following oral administration. Methods: Here, we prepared a stable lycopene-loaded solid lipid nanoparticles using Precirol® ATO5, Compritol 888 ATO and myristic acid by hot homogenization method with some modification. The size and morph...

  8. Fractal microstructure characterization of wet microalgal cells disrupted with ultrasonic cavitation for lipid extraction.

    Science.gov (United States)

    Cheng, Jun; Sun, Jing; Huang, Yun; Zhou, Junhu; Cen, Kefa

    2014-10-01

    The effects of ultrasonic treatment on fractal microstructures of wet microalgal cells were investigated for lipid extraction. Fractal dimension of cells with distorted surfaces increased with power and ultrasonication time. Microalgal cells shrank owing to dehydration and cytomembranes were reduced to debris, but cell walls were not fragmented. When ultrasonication power increased from 0 to 500W for 30min, the fractal dimension of cells increased from 1.21 to 1.51, cell sizes decreased from 2.78 to 1.68μm and cell wall thickness decreased from 0.08 to 0.05μm. When ultrasonication time increased from 5 to 30min with a power of 150W, the fractal dimension of cells increased from 1.24 to 1.37, cell sizes decreased from 2.72 to 2.38μm and cell wall thickness first increased to a peak of 0.22μm and then decreased. Long-chain and unsaturated lipids were degraded into short-chain and saturated lipids with ultrasonic cavitation.

  9. Preparation, Characterization and Evaluation of Quetiapine Fumarate Solid Lipid Nanoparticles to Improve the Oral Bioavailability

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    Arjun Narala

    2013-01-01

    Full Text Available Quetiapine fumarate is an antipsychotic drug with poor oral bioavailability (9% due to first-pass metabolism. Present work is an attempt to improve oral bioavailability of quetiapine fumarate by incorporating in solid lipid nanoparticles (SLN. Six quetiapine fumarate SLN formulations were developed using three different lipids by hot homogenisation followed by ultrasonication. The drug excipient compatibility was studied by differential scanning calorimetry (DSC. Stable quetiapine fumarate SLNs having a mean particle size of 200–250 nm with entrapment efficiency varying in between 80% and 92% were developed. The physical stability of optimized formulation F3 was checked at room temperature for 2 months. Comparative bioavailability studies were conducted in male Wistar rats after oral administration of quetiapine fumarate suspension and SLN formulation. The relative bioavailability of quetiapine fumarate from optimized SLN preparation was increased by 3.71 times when compared with the reference quetiapine fumarate suspension. The obtained results are indicative of SLNs as potential lipid carriers for improving the bioavailability of quetiapine fumarate by minimizing first-pass metabolism.

  10. Lipid characterization of individual porcine oocytes by dual mode DESI-MS and data fusion.

    Science.gov (United States)

    Pirro, Valentina; Oliveri, Paolo; Ferreira, Christina Ramires; González-Serrano, Andrés Felipe; Machaty, Zoltan; Cooks, Robert Graham

    2014-10-27

    The development of sensitive measurements to analyze individual cells is of relevance to elucidate specialized roles or metabolic functions of each cell under physiological and pathological conditions. Lipids play multiple and critical roles in cellular functions and the application of analytical methods in the lipidomics area is of increasing interest. In this work, in vitro maturation of porcine oocytes was studied. Two independent sources of chemical information (represented by mass spectra in the positive and negative ion modes) from single oocytes (immature oocytes, 24-h and 44-h in vitro matured oocytes) were acquired by using desorption electrospray ionization-mass spectrometry (DESI-MS). Low and mid-level data fusion strategies are presented with the aim of better exploring the large amount of chemical information contained in the two mass spectrometric lipid profiles. Data were explored by principal component analysis (PCA) within the two multi-block approaches to include information on free fatty acids, phospholipids, cholesterol-related molecules, di- and triacylglycerols. After data fusion, clearer differences among immature and in vitro matured porcine oocytes were observed, which provide novel information regarding lipid metabolism throughout oocyte maturation. In particular, changes in TAG composition, as well as increase in fatty acid metabolism and membrane complexity were evidenced during the in vitro maturation process. This information can assist the improvement of in vitro embryo production for porcine species.

  11. Ciprofloxacin Controlled-Solid Lipid Nanoparticles: Characterization, In Vitro Release, and Antibacterial Activity Assessment

    Science.gov (United States)

    2017-01-01

    The objective of this research was to formulate ciprofloxacin (CIP) in solid lipid nanoparticles (SLNs) in an attempt to develop a controlled drug delivery system. An ultrasonic melt-emulsification method was used for preparing CIP-loaded SLNs. Key findings included that SLNs were successfully produced with average particle sizes ranging from 165 to 320 nm and polydispersity index in the range of 0.18–0.33. High entrapment efficiency values were reported in all formulations. The atomic force scanning microscopic images showed spherical shape with the size range closer to those found by the particle size analyzer. CIP release exhibited controlled-release behavior with various lipids. Ciprofloxacin solid lipid nanoparticles formula containing stearic acid (CIPSTE) displayed the strongest burst effect and the most rapid release rate. The release data revealed a better fit to the Higuchi diffusion model. After storing the CIPSTE formula at room temperature for 120 days, no significant difference in particle size and zeta potential was found. CIP-loaded SLNs exhibited superior antibacterial activity. Incorporation of CIP into SLNs leads to controlled release and a superior antibacterial effect of CIP. PMID:28194408

  12. Characterization, pharmacokinetics, and hypoglycemic effect of berberine loaded solid lipid nanoparticles

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    Xue M

    2013-12-01

    Full Text Available Mei Xue, Ming-xing Yang, Wei Zhang, Xiu-min Li, De-hong Gao, Zhi-min Ou, Zhi-peng Li, Su-huan Liu, Xue-jun Li, Shu-yu Yang Xiamen Diabetes Institute, The First Affiliated Hospital of Xiamen University, Xiamen, People’s Republic of China Abstract: The high aqueous solubility, poor permeability, and absorption of berberine (BBR result in its low plasma level after oral administration, which greatly limits its clinical application. BBR solid lipid nanoparticles (SLNs were prepared to achieve improved bioavailability and prolonged effect. Developed SLNs showed homogeneous spherical shapes, small size (76.8 nm, zeta potential (7.87 mV, encapsulation efficiency (58%, and drug loading (4.2%. The power of X-ray diffraction combined with 1H nuclear magnetic resonance spectroscopy was employed to analyze chemical functional groups and the microstructure of BBR-SLNs, and indicated that the drug was wrapped in a lipid carrier. Single dose (50 mg/kg oral pharmacokinetic studies in rats showed significant improvement (P<0.05 in the peak plasma concentration, area under the curve, and variance of mean residence time of BBR-SLNs when compared to BBR alone (P<0.05, suggesting improved bioavailability. Furthermore, oral administration of both BBR and BBR-SLNs significantly suppressed body weight gain, fasting blood glucose levels, and homeostasis assessment of insulin resistance, and ameliorated impaired glucose tolerance and insulin tolerance in db/db diabetic mice. BBR-SLNs at high dose (100 mg/kg showed more potent effects when compared to an equivalent dose of BBR. Morphologic analysis demonstrated that BBR-SLNs potentially promoted islet function and protected the islet from regeneration. In conclusion, our study demonstrates that by entrapping BBR into SLNs the absorption of BBR and its anti-diabetic action were effectively enhanced. Keywords: berberine, solid lipid nanoparticles, pharmacokinetic, hypoglycemic effect

  13. Preparation and characterization of solid lipid nanoparticles loaded with frankincense and myrrh oil

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    Shi F

    2012-04-01

    Full Text Available Feng Shi, Ji-Hui Zhao, Ying Liu, Zhi Wang, Yong-Tai Zhang, Nian-Ping FengSchool of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of ChinaAbstract: The aim of the present study was to prepare solid lipid nanoparticles (SLNs for the oral delivery of frankincense and myrrh essential oils (FMO. Aqueous dispersions of SLNs were successfully prepared by a high-pressure homogenization method using Compritol 888 ATO as the solid lipid and soybean lecithin and Tween 80 as the surfactants. The properties of the SLNs such as particle size, zeta potential (ZP, and drug encapsulation efficiency (EE were investigated. The morphology of SLNs was observed by transmission electron microscopy (TEM. The crystallinity of the formulation was analyzed by differential scanning calorimetry (DSC and X-ray diffraction (XRD. In addition, drug evaporation release and antitumor activity were also studied. Round SLNs with a mean size of 113.3 ± 3.6 nm, a ZP of -16.8 ± 0.4 mV, and an EE of 80.60% ± 1.11% were obtained. DSC and XRD measurements revealed that less ordered structures were formed in the inner cores of the SLN particles. Evaporation loss of the active components in FMO could be reduced in the SLNs. Furthermore, the SLN formulation increased the antitumor efficacy of FMO in H22-bearing Kunming mice. Hence, the presented SLNs can be used as drug carriers for hydrophobic oil drugs extracted from traditional Chinese medicines.Keywords: solid lipid nanoparticles, frankincense oil, myrrh oil, evaporation release, antitumor activity, traditional Chinese medicine

  14. FORMULATION, CHARACTERIZATION AND IN VITRO EVALUATION OF NOVEL THIENOPYRIMIDINES AND TRIAZOLOTHIENOPYRIMIDINES LOADED SOLID LIPID NANOPARTICLES

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    Mulla Jameel Ahmed S.

    2010-09-01

    Full Text Available Thienopyrimidines and triazolothienopyrimidines loaded solid lipid nanoparticles (SLNs were produced by microemulsion method. All the formulations were subjected to particle size analysis, zeta potential, compound entrapment efficiency and in vitro release studies. The SLNs formed were in nano-size range with maximum entrapment efficiency. Formulation with 195 nm in particle size and 84.20% of compound entrapment was subjected to scanning electron microscopy (SEM for surface morphology, differential scanning calorimetry (DSC for thermal analysis and short term stability studies. SEM confirms that the SLNs are circular in shape. The compound release behavior from SLN suspension exhibited biphasic pattern with an initial burst and prolonged release over 24 h.

  15. Characterization of the proteome of cytoplasmic lipid droplets in mouse enterocytes after a dietary fat challenge.

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    Theresa D'Aquila

    Full Text Available Dietary fat absorption by the small intestine is a multistep process that regulates the uptake and delivery of essential nutrients and energy. One step of this process is the temporary storage of dietary fat in cytoplasmic lipid droplets (CLDs. The storage and mobilization of dietary fat is thought to be regulated by proteins that associate with the CLD; however, mechanistic details of this process are currently unknown. In this study we analyzed the proteome of CLDs isolated from enterocytes harvested from the small intestine of mice following a dietary fat challenge. In this analysis we identified 181 proteins associated with the CLD fraction, of which 37 are associated with known lipid related metabolic pathways. We confirmed the localization of several of these proteins on or around the CLD through confocal and electron microscopy, including perilipin 3, apolipoprotein A-IV, and acyl-CoA synthetase long-chain family member 5. The identification of the enterocyte CLD proteome provides new insight into potential regulators of CLD metabolism and the process of dietary fat absorption.

  16. Carvedilol nano lipid carriers: formulation, characterization and in-vivo evaluation.

    Science.gov (United States)

    Mishra, Akansha; Imam, Syed Sarim; Aqil, Mohammed; Ahad, Abdul; Sultana, Yasmin; Ameeduzzafar; Ali, Asgar

    2016-05-01

    The purpose of this study was to develop Carvedilol nanostructured lipid carriers (CAR-NLCs) using stearic acid and oleic acid as lipid, and to estimate the potential as oral delivery system for poorly water soluble drug. The particle-size analysis revealed that all the developed formulations were within the nanometer range. The EE and loading were found to be between 69.45-88.56% and 9.58-12.56%, respectively. The CAR-NLCopt showed spherical morphology with smooth surface under transmission electron microscope (TEM). The crystallization of the drug in NLC was investigated by powder X-ray diffraction and differential scanning calorimetry (DSC) and revealed that the drug was in an amorphous state in the NLC matrix. The ex vivo gut permeation study showed many folds increment in the permeation of CAR-NLCs compared to Carvedilol suspension (CAR-S). The oral bioavailability study of CAR was carried out using Wistar rats and relative bioavailability of CAR-NLCopt was found to be 3.95 fold increased in comparison with CAR-S. In vivo antihypertensive study in Wistar rats showed significant reduction in mean systolic BP by CAR-NLCopt vis-à-vis CAR-S (p CAR and demonstrated a promising perspective for oral delivery of poorly water-soluble drugs. The promising findings in this investigation suggest the practicability of these systems for the enhancement of bioavailability of CAR.

  17. Preparation and characterization of ketoprofen-loaded solid lipid nanoparticles made from beeswax and carnauba wax.

    Science.gov (United States)

    Kheradmandnia, Soheila; Vasheghani-Farahani, Ebrahim; Nosrati, Mohsen; Atyabi, Fatemeh

    2010-12-01

    Solid lipid nanoparticles (SLNs) have been proposed as suitable colloidal carriers for delivery of drugs with limited solubility. Ketoprofen as a model drug was incorporated into SLNs prepared from a mixture of beeswax and carnauba wax using Tween 80 and egg lecithin as emulsifiers. The characteristics of the SLNs with various lipid and surfactant composition were investigated. The mean particle size of drug-loaded SLNs decreased upon mixing with Tween 80 and egg lecithin as well as upon increasing total surfactant concentration. SLNs of 75 ± 4 nm with a polydispersity index of 0.2 ± 0.02 were obtained using 1% (vol/vol) mixed surfactant at a ratio of 60:40 Tween 80 to egg lecithin. The zeta potential of these SLNs varied in the range of -15 to -17 (mV), suggesting the presence of similar interface properties. High drug entrapment efficiency of 97% revealed the ability of SLNs to incorporate a poorly water-soluble drug such as ketoprofen. Differential scanning calorimetry thermograms and high-performance liquid chromatographic analysis indicated the stability of nanoparticles with negligible drug leakage after 45 days of storage. It was also found that nanoparticles with more beeswax content in their core exhibited faster drug release as compared with those containing more carnauba wax in their structure.

  18. Preparation and Characterization of Catalase-Loaded Solid Lipid Nanoparticles Protecting Enzyme against Proteolysis

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    Ce Qi

    2011-07-01

    Full Text Available Catalase-loaded solid lipid nanoparticles (SLNs were prepared by the double emulsion method (w/o/w and solvent evaporation techniques, using acetone/methylene chloride (1:1 as an organic solvent, lecithin and triglyceride as oil phase and Poloxmer 188 as a surfactant. The optimized SLN was prepared by lecithin: triglyceride ratio (5%, 20-second + 30-second sonication, and 2% Poloxmer 188. The mean particle size of SLN was 296.0 ± 7.0 nm, polydispersity index range and zeta potential were 0.322–0.354 and −36.4 ± 0.6, respectively, and the encapsulation efficiency reached its maximum of 77.9 ± 1.56. Catalase distributed between the solid lipid and inner aqueous phase and gradually released from Poloxmer coated SLNs up to 20% within 20 h. Catalase-loaded SLN remained at 30% of H2O2-degrading activity after being incubated with Proteinase K for 24 h, while free catalase lost activity within 1 h.

  19. Preparation, characterization and scale-up of sesamol loaded solid lipid nanoparticles

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    Vandita Kakkar

    2012-01-01

    Full Text Available Sesamol loaded solid lipid nanoparticles (SSLNs were prepared with the aim of minimizing its distribution to tissues and achieving its targeting to the brain. Three scale-up batches (100x1 L of S-SLNs were prepared using a microemulsification technique and all parameters were statistically compared with the small batch (1x;10 mL. S-SLNs with a particle size of less than 106 nm with a spherical shape (transmission electron microscopy were successfully prepared with a total drug content and entrapment efficiency of 94.26±2.71% and 72.57±5.20%, respectively. Differential scanning calorimetry and infrared spectroscopy confirmed the formation of lipidic nanoparticles while powder X-ray diffraction revealed their amorphous profile. S-SLNs were found to be stable for three months at 5±3°C in accordance with International Conference on Harmonisation guidelines. The SLN preparation process was successfully scaled-up to a 100x batch on a laboratory scale. The procedure was easy to perform and allowed reproducible SLN dispersions to be obtained.

  20. Identification and characterization of a symbiotic alga from soil bryophyte for lipid profiles

    Science.gov (United States)

    Feng, Jia; Guo, Yuning; Zhang, Xiujuan; Wang, Guihua; Lv, Junping; Liu, Qi; Xie, Shulian

    2016-01-01

    ABSTRACT A symbiotic alga was successfully isolated from the soil moss Entodon obtusatus found in the Guandi Mountains, Shanxi Province, China, and cultivated under axenic conditions. Morphological observations showed that the symbiotic alga was similar to Chlorococcum. Based on phylogenetic analysis of 18S rRNA and rbcL genes and internal transcribed spacer (ITS) regions, Chlorococcum sp. GD was identified as Chlorococcum sphacosum. The three data sets were congruent for those aspects of the topologies that were relatively robust, and differed for those parts of the topologies that were not. This strain was cultured in BG11 medium to test its growth and biodiesel properties. It produced a lipid content of nearly 40%, and achieved biomass concentration of 410 mg l−1 and lipid productivity of 6.76 mg l−1 day−1, with favorable C16:0 (23.10%) and C18:1 (21.62%) fatty acid content. This alga appears to have potential for use in biodiesel production. PMID:27543061

  1. Identification and characterization of a symbiotic alga from soil bryophyte for lipid profiles

    Directory of Open Access Journals (Sweden)

    Jia Feng

    2016-09-01

    Full Text Available A symbiotic alga was successfully isolated from the soil moss Entodon obtusatus found in the Guandi Mountains, Shanxi Province, China, and cultivated under axenic conditions. Morphological observations showed that the symbiotic alga was similar to Chlorococcum. Based on phylogenetic analysis of 18S rRNA and rbcL genes and internal transcribed spacer (ITS regions, Chlorococcum sp. GD was identified as Chlorococcum sphacosum. The three data sets were congruent for those aspects of the topologies that were relatively robust, and differed for those parts of the topologies that were not. This strain was cultured in BG11 medium to test its growth and biodiesel properties. It produced a lipid content of nearly 40%, and achieved biomass concentration of 410 mg l−1 and lipid productivity of 6.76 mg l−1 day−1, with favorable C16:0 (23.10% and C18:1 (21.62% fatty acid content. This alga appears to have potential for use in biodiesel production.

  2. Lipid droplet biology and evolution illuminated by the characterization of a novel perilipin in teleost fish

    Science.gov (United States)

    Granneman, James G; Kimler, Vickie A; Zhang, Huamei; Ye, Xiangqun; Luo, Xixia; Postlethwait, John H; Thummel, Ryan

    2017-01-01

    Perilipin (PLIN) proteins constitute an ancient family important in lipid droplet (LD) formation and triglyceride metabolism. We identified an additional PLIN clade (plin6) that is unique to teleosts and can be traced to the two whole genome duplications that occurred early in vertebrate evolution. Plin6 is highly expressed in skin xanthophores, which mediate red/yellow pigmentation and trafficking, but not in tissues associated with lipid metabolism. Biochemical and immunochemical analyses demonstrate that zebrafish Plin6 protein targets the surface of pigment-containing carotenoid droplets (CD). Protein kinase A (PKA) activation, which mediates CD dispersion in xanthophores, phosphorylates Plin6 on conserved residues. Knockout of plin6 in zebrafish severely impairs the ability of CD to concentrate carotenoids and prevents tight clustering of CD within carotenoid bodies. Ultrastructural and functional analyses indicate that LD and CD are homologous structures, and that Plin6 was functionalized early in vertebrate evolution for concentrating and trafficking pigment. DOI: http://dx.doi.org/10.7554/eLife.21771.001 PMID:28244868

  3. Lipid Characterization of White, Dark, and Milk Chocolates by FT-Raman Spectroscopy and Capillary Zone Electrophoresis.

    Science.gov (United States)

    de Oliveira, Leandra Natália; de Jesus Coelho Castro, Renata; de Oliveira, Marcone Augusto Leal; de Oliveira, Luiz Fernando C

    2015-01-01

    There are few studies about different types of chocolate and their chemical characterization by Fourier transform (FT)-Raman spectroscopy and capillary zone electrophoresis (CZE). The aim of this study was to evaluate the lipid profile of different types of Brazilian chocolate through characterization by FT-Raman spectroscopy and identification and quantification of major fatty acids (FAs) by CZE to confirm FT-Raman spectrometry results. It was found that the main spectroscopic profile difference of the chocolate samples analyzed was related to the presence of saturated or unsaturated FAs. Well defined bands at approximately 1660, 1267, and 1274 cm(-1) corresponding to vibrational modes of unsaturated FAs (UnFAs) were found only in the spectra of samples with cocoa butter in their composition according to label specifications, mainly in dark chocolate samples. The FA identification and quantification by CZE found the presence of stearic (18:0) and palmitic (16:0) acids as the major saturated FAs in all chocolate samples. Dark chocolate samples showed the highest levels of oleic (cis-9 18:1) and linoleic (cis, cis -9,12 18:2) UnFAs monitored and the lowest levels of 14:0 in their chemical composition. Samples coded as 02 (with not only cocoa butter in their composition according to label) had the highest levels of 14:0 (FA not present in cocoa butter composition) corresponding to label information and inferring the presence of other fat sources, called cocoa butter substitutes, mainly for milk and white chocolate samples. This study suggests FT-Raman spectroscopy is a powerful technique that can be used to chemically characterize the chocolate lipid fraction, and CZE is a tool able to confirm Raman spectroscopy results and identify and quantify the major FAs in chocolate samples.

  4. Rapamycin Loaded Solid Lipid Nanoparticles as a New Tool to Deliver mTOR Inhibitors: Formulation and in Vitro Characterization

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    Alice Polchi

    2016-05-01

    Full Text Available Recently, the use of mammalian target of rapamycin (mTOR inhibitors, in particular rapamycin (Rp, has been suggested to improve the treatment of neurodegenerative diseases. However, as Rp is a strong immunosuppressant, specific delivery to the brain has been postulated to avoid systemic exposure. In this work, we fabricated new Rp loaded solid lipid nanoparticles (Rp-SLN stabilized with polysorbate 80 (PS80, comparing two different methods and lipids. The formulations were characterized by differential scanning calorimetry (DSC, nuclear magnetic resonance (NMR, wide angle X-ray scattering (WAXS, cryo-transmission electron microscopy (cryo-TEM, dynamic light scattering (DLS and particle tracking. In vitro release and short-term stability were assessed. Biological behavior of Rp-SLN was tested in SH-SY5Y neuroblastoma cells. The inhibition of mTOR complex 1 (mTORC1 was evaluated over time by a pulse-chase study compared to free Rp and Rp nanocrystals. Compritol Rp-SLN resulted more stable and possessing proper size and surface properties with respect to cetyl palmitate Rp-SLN. Rapamycin was entrapped in an amorphous form in the solid lipid matrix that showed partial crystallinity with stable Lβ, sub-Lα and Lβ′ arrangements. PS80 was stably anchored on particle surface. No drug release was observed over 24 h and Rp-SLN had a higher cell uptake and a more sustained effect over a week. The mTORC1 inhibition was higher with Rp-SLN. Overall, compritol Rp-SLN show suitable characteristics and stability to be considered for further investigation as Rp brain delivery system.

  5. Lateral intermolecular forces between biomembrane lipids in two dimensions: 1,2-dipalmitin at the heptane/water interface compared with phospholipids.

    Science.gov (United States)

    Pallas, Norman R; Pethica, Brian A

    2007-01-11

    The lateral interaction forces between phospholipids in two-dimensional arrays are fundamental to understanding membrane biophysics. In previous studies the related thermodynamic functions have been measured for spread phospholipid monolayers at the oil/water interface over a range of temperatures and densities, and the two-dimensional virial coefficients obtained. These coefficients have been computed from a model that emphasizes the head group zwitterion interactions. In this study we examine the contribution of the diglyceride portion of phospholipid molecules to the lateral intermolecular forces. Measurements of the heptane/water interfacial tension as a function of the concentration of 1,2-dipalmitoyl glycerol (DP) in the heptane were made over a range of low surface pressures at 25 degrees C. Infrared measurements on the DP solutions show that the solutions are ideal. The results are interpreted to give two-dimensional virial coefficients for the adsorbed monolayer. The second virial coefficient B2(T) for DP is +0.31 nm2/molecule, in marked contrast to the much larger positive values found for the corresponding phospholipids at the same interface and temperature, and clearly indicating an attractive component to the lateral potentials of mean force between pairs of DP molecules. The contribution of the diglyceride moiety to the pair potentials of the phospholipids thus appears to be minor but not negligible. The differences in the second virial coefficients for DP and the phospholipids are interpreted primarily in terms of the orientation of the ester carbonyl dipoles, also drawing on spectroscopic and diffraction evidence from related structures.

  6. Characterization and evaluation of sensory acceptability of ice creams incorporated with beta-carotene encapsulated in solid lipid microparticles

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    Juliana Gobbi de LIMA

    Full Text Available Abstract The feasibility of incorporating beta-carotene-loaded solid lipid microparticles (BCSLM into vanilla ice creams was investigated, through the physico-chemical characterization and evaluation of sensory acceptability of the products products. The BCSLM were produced with palm stearin as the lipid phase, hydrolyzed soy protein isolate as the surfactant, and xanthan gum as the thickener. The results showed similar values of proximate composition, total soluble solids, pH, and overrun for all formulations. On the other hand, colorimetric evaluations showed that the ice cream produced with partial substitution of artificial additives by BCSLM containing alpha-tocopherol presented a more intense color, while in the product with non-encapsulated beta-carotene, a fast degradation of carotenoid was confirmed, highlighting the importance of the encapsulation techniques. The results of the sensorial analysis of the products were highly satisfactory and showed that the panelists preferred the ice creams produced with BCSLM containing alpha-tocopherol and with partial substitution of artificial additives by BCSLM containing alpha-tocopherol, confirming the feasibility of incorporating BCSLM into ice creams to reduce the application of artificial dyes to the product.

  7. Characterization of rheology and release profiles of olanzapine-loaded lipid-core nanocapsules in thermosensitive hydrogel.

    Science.gov (United States)

    Dimer, F A; Pohlmann, A R; Guterres, S S

    2013-12-01

    In this study we developed a new drug delivery system for olanzanpine comprised of drug-loaded lipid-core nanocapsules incorporated in a thermosensitive hydrogel, intended to sustain the drug release. Firstly, olanzapine, a hydrophobic drug, was loaded in poly(epsilon-caprolactone) lipid core nanocapsules prepared by interfacial deposition of preformed polymer. The effects of the presence of ethanol and the amounts of sorbitan monostearate and medium-chain triglycerides on the particle size, zeta potential, polydispersity index, presence of microparticles and encapsulation efficiency were investigated using a 2(3) factorial design. The optimized nanocapsules were incorporated into a hydrophilic polymer (Poloxamer 407) dispersion in order to obtain a thermosensitive gel. The formulation containing 0.077 g of sorbitan monostearate, 0.22 ml of medium-chain triglycerides, 3 ml of ethanol and 18% of the thermosensitive polymer was selected according to the physicochemical properties. The rheology and release profiles of the mixed hydrophobic and hydrophilic delivery system were successfully characterized and revealed its great potential for the administration of hydrophobic drugs such as olanzapine with sustained in situ drug release.

  8. Characterization of five typical agave plants used to produce mezcal through their simple lipid composition analysis by gas chromatography.

    Science.gov (United States)

    Martínez-Aguilar, Juan Fco; Peña-Alvarez, Araceli

    2009-03-11

    Five agave plants typically used in Mexico for making mezcal in places included in the Denomination of Origin (Mexican federal law that establishes the territory within which mezcal can be produced) of this spirit were analyzed: Agave salmiana ssp. crassispina, A. salmiana var. salmiana, Agave angustifolia, Agave cupreata, and Agave karwinskii. Fatty acid and total simple lipid profiles of the mature heads of each plant were determined by means of a modified Bligh-Dyer extraction and gas chromatography. Sixteen fatty acids were identified, from capric to lignoceric, ranging from 0.40 to 459 microg/g of agave. Identified lipids include free fatty acids, beta-sitosterol, and groups of mono-, di-, and triacylglycerols, their total concentration ranging from 459 to 992 microg/g of agave. Multivariate analyses performed on the fatty acid profiles showed a close similarity between A. cupreata and A. angustifolia. This fact can be ascribed to the taxa themselves or differences in growing conditions, an issue that is still to be explored. These results help to characterize the agaves chemically and can serve to relate the composition of mezcals from various states of Mexico with the corresponding raw material.

  9. Development, characterization, and in vitro and in vivo evaluation of benzocaine- and lidocaine-loaded nanostructrured lipid carriers.

    Science.gov (United States)

    Puglia, Carmelo; Sarpietro, Maria Grazia; Bonina, Francesco; Castelli, Francesco; Zammataro, Magda; Chiechio, Santina

    2011-05-01

    The present study concerns the in vitro and in vivo evaluation of benzocaine (BENZO) and lidocaine (LIDO) topical delivery from nanostructured lipid carriers (NLCs). Morphology and dimensional distribution of NLCs have been, respectively, characterized by differential scanning calorimetry (DSC) and photon correlation spectroscopy. The release pattern of BENZO and LIDO from NLCs was evaluated in vitro determining drug percutaneous absorption through excised human skin. Radiant heat tail-flick test was carried out in mice to determine the antinociceptive effect of BENZO and LIDO from NLC. DSC studies revealed that the inner oil phase of NLC plays a significant role in stabilizing the particle architecture and increasing the drug solubility. In vitro evidences show that BENZO and LIDO, when incorporated in viscosized NLC dispersions, exhibited a lower flux with respect to formulations containing the free drugs in the aqueous phase. In vivo study enabled to demonstrate that BENZO and LIDO can be released in a prolonged fashion when incorporated into lipid carriers. The results obtained pointed out NLC capability to act as an effective drug reservoir, thus prolonging the anesthetic effect of BENZO and LIDO.

  10. Preparation, characterization and biocompatibility studies on risperidone-loaded solid lipid nanoparticles (SLN): high pressure homogenization versus ultrasound.

    Science.gov (United States)

    Silva, A C; González-Mira, E; García, M L; Egea, M A; Fonseca, J; Silva, R; Santos, D; Souto, E B; Ferreira, D

    2011-08-01

    The suitability of solid lipid nanoparticles (SLN) for the encapsulation of risperidone (RISP), an antipsychotic lipophilic drug, was assessed for oral administration. The hot high pressure homogenization (HPH) and the ultrasound (US) technique were used as production methods for SLN. All the studies on the SLN formulations were done in parallel, in order to compare the results and conclude about the advantages and limitations of both techniques. The particle sizes were in the nanometer range for all prepared SLN formulations and the zeta potential absolute values were high, predicting good long-term stability. Optical analyses demonstrated the achievement of stable colloidal dispersions. Physicochemical characterization of dispersions and bulk lipids, performed by differential scanning calorimetry (DSC) and X-ray assays, support prediction of occurrence of drug incorporation in the SLN and good long term stability of the systems. The toxicity of SLN with Caco-2 cells and the existence of contaminations derived from the production equipments were assessed by the (4,5-dimethylthiazol-2-yl)2,5-diphenyl-tetrazolium bromide (MTT) assay. The results showed 90% of cell viability after SLN exposure, with no significant differences within all prepared formulations (p > 0.05). From this study, we conclude that SLN can be considered as efficient carriers for RISP encapsulation. Moreover, HPH and US revealed to be both effective methods for SLN production.

  11. Development of olmesartan medoxomil lipid-based nanoparticles and nanosuspension: preparation, characterization and comparative pharmacokinetic evaluation.

    Science.gov (United States)

    B, Arun; D, Narendar; Veerabrahma, Kishan

    2017-03-14

    The aim was to enhance the oral bioavailability of olmesartan medoxomil (OM) by preparing solid lipid nanoparticles (SLNs) and comparing with nanosuspension (OM-NS). OM-SLNs and OM-NS were prepared by known methods. Prepared SLNs were evaluated for physical characters and in vivo pharmacokinetic (PK) performance in rats. OM-NS showed more than four-fold increase in the solubility. During DSC and XRD studies, drug incorporated in SLNs was found to be in amorphous form. The relative bioavailability of OM-SLN and OM-NS was 7.21- and 3.52-fold when compared with that of coarse suspension. Further, OM-SLNs also increased the oral bioavailability by two-fold over that of OM-NS.

  12. Characterization of lipid metabolism in insulin-sensitive adipocytes differentiated from immortalized human mesenchymal stem cells

    DEFF Research Database (Denmark)

    Prawitt, Janne; Niemeier, Andreas; Kassem, Moustapha

    2008-01-01

    There is a great demand for cell models to study human adipocyte function. Here we describe the adipogenic differentiation of a telomerase-immortalized human mesenchymal stem cell line (hMSC-Tert) that maintains numerous features of terminally differentiated adipocytes even after prolonged......, the presence of the PPARgamma agonist rosiglitazone was not required for the stable expression of lipoprotein lipase, adipocyte fatty acid binding protein and perilipin on mRNA and protein levels. Adiponectin expression was post-transcriptionally down-regulated in the absence of rosiglitazone. Insulin...... sensitivity as measured by insulin-induced phosphorylation of Akt and S6 ribosomal protein was also independent of rosiglitazone. In addition to commonly used adipogenic markers, we investigated further PPARgamma-stimulated proteins with a role in lipid metabolism. We observed an increase of lipoprotein...

  13. Characterization of polysaccharides with marked inhibitory effect on lipid accumulation in Pleurotus eryngii.

    Science.gov (United States)

    Chen, Jingjing; Yong, Yangyang; Xing, Meichun; Gu, Yifan; Zhang, Zhao; Zhang, Shizhu; Lu, Ling

    2013-09-12

    Mushrooms have a great potential for the production of useful bioactive metabolites. To explore the bioactive compounds from edible mushrooms for interfering with the development of macrophage-derived foam cells, which is recognized as the hallmark of early atherosclerosis, eight types of mushrooms polysaccharides had been selected to be tested. Consequently, different mushrooms polysaccharides displayed diverse component profiles. Of polysaccharides that we tested, the Pleurotus eryngii polysaccharide had the strongest inhibitory effect on lipid accumulation. Furthermore, through fractionation of DEAE-52 and Sephadex G-100, the polysaccharide from P. eryngii had been successfully purified and identified. By the analysis of IR, GC, and HPLC, the purified polysaccharide was estimated to be 30-38 kDa for the average molecular weight with the monosaccharide composition mainly composed of D-types of mannose, glucose and galactose. Findings presented in this report firstly provide direct evidence, which links the purified polysaccharide moiety with the biological function in foam-cell model.

  14. Kinetics characterization of c-Src binding to lipid membranes: Switching from labile to persistent binding.

    Science.gov (United States)

    Le Roux, Anabel-Lise; Busquets, Maria Antònia; Sagués, Francesc; Pons, Miquel

    2016-02-01

    Cell signaling by the c-Src proto-oncogen requires the attachment of the protein to the inner side of the plasma membrane through the myristoylated N-terminal region, known as the SH4 domain. Additional binding regions of lower affinity are located in the neighbor intrinsically disordered Unique domain and the structured SH3 domain. Here we present a surface plasmon resonance study of the binding of a myristoylated protein including the SH4, Unique and SH3 domains of c-Src to immobilized liposomes. Two distinct binding processes were observed: a fast and a slow one. The second process lead to a persistently bound form (PB) with a slower binding and a much slower dissociation rate than the first one. The association and dissociation of the PB form could be detected using an anti-SH4 antibody. The kinetic analysis revealed that binding of the PB form follows a second order rate law suggesting that it involves the formation of c-Src dimers on the membrane surface. A kinetically equivalent PB form is observed in a myristoylated peptide containing only the SH4 domain but not in a construct including the three domains but with a 12-carbon lauroyl substituent instead of the 14-carbon myristoyl group. The PB form is observed with neutral lipids but its population increases when the immobilized liposomes contain negatively charged lipids. We suggest that the PB form may represent the active signaling form of c-Src while the labile form provides the capacity for fast 2D search of the target signaling site on the membrane surface.

  15. Preparation and characterization of vinculin-targeted polymer–lipid nanoparticle as intracellular delivery vehicle

    Directory of Open Access Journals (Sweden)

    Wang J

    2012-12-01

    Full Text Available Junping Wang,* Ceren Örnek-Ballanco,* Jiahua Xu, Weiguo Yang, Xiaojun YuDepartment of Chemistry, Chemical Biology, and Biomedical Engineering, Stevens Institute of Technology, Hoboken, NJ, USA*These authors contributed equally to this workAbstract: Intracellular delivery vehicles have been extensively investigated as these can serve as an effective tool in studying the cellular mechanism, by delivering functional protein to specific locations of the cells. In the current study, a polymer–lipid nanoparticle (PLN system was developed as an intracellular delivery vehicle specifically targeting vinculin, a focal adhesion protein associated with cellular adhesive structures, such as focal adhesions and adherens junctions. The PLNs possessed an average size of 106 nm and had a positively charged surface. With a lower encapsulation efficiency 32% compared with poly(lactic-co-glycolic acid (PLGA nanoparticles (46%, the PLNs showed the sustained release profile of model drug BSA, while PLGA nanoparticles demonstrated an initial burst-release property. Cell-uptake experiments using mouse embryonic fibroblasts cultured in fibrin–fibronectin gels observed, under confocal microscope, that the anti-vinculin conjugated PLNs could successfully ship the cargo to the cytoplasm of fibroblasts, adhered to fibronectin–fibrin. With the use of cationic lipid, the unconjugated PLNs were shown to have high gene transfection efficiency. Furthermore, the unconjugated PLNs had nuclear-targeting capability in the absence of nuclear-localization signals. Therefore, the PLNs could be manipulated easily via different type of targeting ligands and could potentially be used as a powerful tool for cellular mechanism study, by delivering drugs to specific cellular organelles.Keywords: 3D gel, PLGA, targeting

  16. Physiological characterization of lipid accumulation and in vivo ester formation in Gordonia sp. KTR9.

    Science.gov (United States)

    Eberly, Jed O; Ringelberg, David B; Indest, Karl J

    2013-02-01

    Previous work has demonstrated the feasibility of in vivo biodiesel synthesis in Escherichia coli, however, ethyl ester formation was dependent on an external fatty acid feedstock. In contrast to E. coli, actinomycetes may be ideal organisms for direct biodiesel synthesis because of their capacity to synthesize high levels of triacylglcerides (TAGs). In this study, we investigated the physiology and associated TAG accumulation along with the in vivo ability to catalyze ester formation from exogenous short chain alcohol sources in Gordonia sp. KTR9, a strain that possesses a large number of genes dedicated to fatty acid and lipid biosynthesis. Total lipid fatty acids content increased by 75 % and TAG content increased by 50 % under nitrogen starvation conditions in strain KTR9. Strain KTR9 tolerated the exogenous addition of up to 4 % methanol, 4 % ethanol and 2 % propanol in the media. Increasing alcohol concentrations resulted in a decrease in the degree of saturation of recovered fatty acid alcohol esters and a slight increase in the fatty acid chain length. A linear dose dependency in fatty alcohol ester synthesis was observed in the presence of 0.5-2 % methanol and ethanol compared to control KTR9 strains grown in the absence of alcohols. An inspection of the KTR9 genome revealed the presence of several putative wax ester synthase/acyl-coenzyme A : diacylglycerol acyltransferase (WS/DGAT) enzymes, encoded by atf gene homologs, that may catalyze the in vivo synthesis of fatty acid esters from short chain alcohols. Collectively, these results indicate that Gordonia sp. KTR9 may be a suitable actinomycete host strain for in vivo biodiesel synthesis.

  17. Lyophilized sponges loaded with curcumin solid lipid nanoparticles for buccal delivery: Development and characterization.

    Science.gov (United States)

    Hazzah, Heba A; Farid, Ragwa M; Nasra, Maha M A; El-Massik, Magda A; Abdallah, Ossama Y

    2015-08-15

    This study aimed to prepare and evaluate mucoadhesive sponges as dosage forms for delivering solid lipid nanoparticles. For this purpose curcumin (Cur) was formulated as solid nanoparticles (SLN) using Gelucire 50/13, and polaxomer 407. The prepared CurSLN dispersion was thickened with different mucoadhesive polymers. Different concentrations of glycerol, and mannitol of range (0.25-20%), and (0-1%), respectively were also examined. The formed gel was poured into oblong molds and freeze dried to form mucoadhesive sponge to be applied to the buccal mucosa. The prepared sponges were evaluated for their, in-vivo residence time, in-vitro and in-vivo drug release, and hydration capacity. Surface morphology for the different sponges were examined using SEM. TEM was also carried out for sponge fragments previously dispersed into water. Infrared spectroscopy was conducted to investigate interaction between used ingredients. The results showed that the CurSLN loaded HPMC, and Polycarbophil sponges showed 4, and 15 h in-vivo residence time, respectively, providing a considerable amount of curcumin into saliva. The incorporation of glycerol and mannitol at concentration of 1% provided elegant and flexible sponges. The SEM showed that the deposition of CurSLN differed according to the type of polymer used. TEM confirmed the integrity of liberated CurSLN from sponges. IR spectra showed an interaction between HPMC and poloxamer 407, which affected its behavior as a gelling agent. The obtained results provide an efficient approach for delivering solid lipid nanoparticles in a solid dosage form keeping the nanoparticle characters and integrity.

  18. Preparation, characterization and evaluation of moisturizing and UV protecting effects of topical solid lipid nanoparticles

    Directory of Open Access Journals (Sweden)

    Shiva Golmohammadzadeh

    2012-12-01

    Full Text Available Solid lipid nanoparticles (SLN were recently proposed as carriers for various pharmaceutical and cosmetic actives. These lipid nanoparticles can act as moisturizers and physical sunscreens on their own. Therefore, the full potential of these carriers has yet to be determined. The present study was aimed to determine and compare moisturizing and UV-protecting effects of different solid lipid nanoparticles (SLN prepared by different solid lipids including Glyceryl monostearate (GMS, Precirol® (P and cetyl palmitate (CP as carrier systems of moisturizers and sunscreens. The influence of the size and matrix crystallinity of the solid lipids on the occlusive factor, skin hydration and UV-protection were evaluated by in vitro and in vivo methods. The SLN were prepared by high-shear homogenization and ultrasound methods. Size, zeta potential and morphological characteristics of the samples were assessed by transmission electron microscopy (TEM and thermotropic properties with differential scanning calorimetry (DSC technique. Results of the assessments showed that SLN-CP significantly increases skin hydration and UV-protection, compared to SLN-GMS and SLN-P. It was demonstrated that the size of SLN, crystallinity index of solid lipid in SLN and probably other mechanisms besides the occlusive factor can influence skin hydration and UV-protection indices. Furthermore, findings of the assessments demonstrated significant difference between in vitro and in vivo assessments regarding occlusive factor and moisturizing effects. Findings of the present study indicate that the SLN-CP could be a promising carrier for sunscreens and moisturizers.Nanopartículas lipídicas sólidas (NLS foram, recentemente, propostas como carreadores de vários ativos cosméticos e farmacêuticos. Essas nanopartículas lipídicas podem atuar como hidratantes e protetores solares físicos por si só. Assim sendo, determinou-se o potencial desses carreadores. Os objetivos do

  19. Ultrastructural characterization of noradrenergic- and beta-adrenergic receptor-containing profiles in the lateral nucleus of the amygdala

    Directory of Open Access Journals (Sweden)

    Claudia Farb

    2010-10-01

    Full Text Available Norepinephrine (NE is thought to play a key role in fear and anxiety, but its role in amygdala-dependent Pavlovian fear conditioning, a major model for understanding the neural basis of fear, is poorly understood. The lateral nucleus of the amygdala (LA is a critical brain region for fear learning and regulating the effects of stress on memory. To understand better the cellular mechanisms of NE and its adrenergic receptors in the LA, we used antibodies directed against dopamine beta-hydroxylase (DβH, the synthetic enzyme for NE, or against two different isoforms of the beta-adrenergic receptors (βARs, one that predominately recognizes neurons (βAR 248 and the other astrocytes (βAR 404, to characterize the microenvironments of DβH and βAR. By electron microscopy, most DβH terminals did not make synapses, but when they did, they formed both asymmetric and symmetric synapses. By light microscopy, βARs were present in both neurons and astrocytes. Confocal microscopy revealed that both excitatory and inhibitory neurons express βAR248. By electron microscopy, βAR 248 was present in neuronal cell bodies, dendritic shafts and spines, and some axon terminals and astrocytes. When in dendrites and spines, βAR 248 was frequently concentrated along plasma membranes and at post-synaptic densities of asymmetric (excitatory synapses. βAR 404 was expressed predominately in astrocytic cell bodies and processes. These astrocytic processes were frequently interposed between unlabeled terminals or ensheathed asymmetric synapses. Our findings provide a morphological basis for understanding ways in which NE may modulate transmission by acting via synaptic or non-synaptic mechanisms in the LA.

  20. Preparation and characterization of insulin-surfactant complexes for loading into lipid-based drug delivery systems

    DEFF Research Database (Denmark)

    Li, Ping; Nielsen, Hanne Mørck; Fano, Mathias

    2013-01-01

    as complexing surfactant and dimethyl sulfoxide (DMSO) as solvent. Significant change in secondary structure of insulin freeze dried from DMSO was observed using Fourier transform infrared spectroscopy. Changes were quantitatively smaller in the presence of surfactants, demonstrating both a stabilizing effect...... and preservation of native structure. The aim of the present study was to characterize insulin after complexation with biocompatible surfactants to improve loading into lipid-based DDS. Insulin-surfactant complexes were prepared by freeze-drying with distearyldimethylammonium bromide or soybean phospholipid...... of surfactants, but also a nonnative secondary structure in the solid state. Finally, circular dichroism analysis of rehydrated complexes showed that the processing did not irreversibly alter the secondary structure of insulin. In short, the present study demonstrates changes in the secondary structure...

  1. Development and characterization of lipid microparticles as a drug carrier for somatostatin.

    Science.gov (United States)

    Reithmeier, H; Herrmann, J; Göpferich, A

    2001-05-07

    Somatostatin, a therapeutic peptide with a high therapeutical potential but a very short biological half-live was encapsulated within microparticles by a modified solvent evaporation method and a melt dispersion method without the use of organic solvent. As the use of synthetic polymer matrix materials often goes along with detrimental effects on incorporated peptides, we investigated the potential of physiological lipids such as glyceryl tripalmitate (Dynasan 116) as an alternative matrix material. The two preparation methods were evaluated with respect to surface topography, particle size distribution, encapsulation efficiency, in-vitro release behavior and modification of the resulting microparticles. Microparticles with a suitable particle size distribution for i.m. or s.c. injection could be prepared with both methods. The encapsulation efficiency of the peptide into glyceryl tripalmitate microparticles was substantially influenced by the preparation method and the physical state of the peptide to be incorporated. The melt dispersion technique and the incorporation of the drug as an aqueous solution gave the best results with actual drug loadings up to 9% and an encapsulation efficiency of approximately 90%. Microparticles prepared by the melt dispersion technique crystallized in the unstable alpha-modification. The peptide was released almost continuously over 10 days with no burst effect, 20-30% of the incorporated somatostatin was not released in the monitored time period.

  2. Characterization of lipid metabolism in insulin-sensitive adipocytes differentiated from immortalized human mesenchymal stem cells.

    Science.gov (United States)

    Prawitt, Janne; Niemeier, Andreas; Kassem, Moustapha; Beisiegel, Ulrike; Heeren, Joerg

    2008-02-15

    There is a great demand for cell models to study human adipocyte function. Here we describe the adipogenic differentiation of a telomerase-immortalized human mesenchymal stem cell line (hMSC-Tert) that maintains numerous features of terminally differentiated adipocytes even after prolonged withdrawal of the peroxisome proliferator activated receptor gamma (PPARgamma) agonist rosiglitazone. Differentiated hMSC-Tert developed the characteristic monolocular phenotype of mature adipocytes. The expression of adipocyte specific markers was highly increased during differentiation. Most importantly, the presence of the PPARgamma agonist rosiglitazone was not required for the stable expression of lipoprotein lipase, adipocyte fatty acid binding protein and perilipin on mRNA and protein levels. Adiponectin expression was post-transcriptionally down-regulated in the absence of rosiglitazone. Insulin sensitivity as measured by insulin-induced phosphorylation of Akt and S6 ribosomal protein was also independent of rosiglitazone. In addition to commonly used adipogenic markers, we investigated further PPARgamma-stimulated proteins with a role in lipid metabolism. We observed an increase of lipoprotein receptor (VLDLR, LRP1) and apolipoprotein E expression during differentiation. Despite this increased expression, the receptor-mediated endocytosis of lipoproteins was decreased in differentiated adipocytes, suggesting that these proteins may have an additional function in adipose tissue beyond lipoprotein uptake.

  3. Characterization of microalgae-bacteria consortium cultured in landfill leachate for carbon fixation and lipid production.

    Science.gov (United States)

    Zhao, Xin; Zhou, Yan; Huang, Sheng; Qiu, Duanyang; Schideman, Lance; Chai, Xiaoli; Zhao, Youcai

    2014-03-01

    The characteristics of cultivating high-density microalgae-bacteria consortium with landfill leachate was tested in this study. Landfill leachate was collected from Laogang landfill operated for over 10 years in Shanghai, China. The maximum biomass concentration of 1.58g L(-1) and chlorophyll a level of 22mg L(-1) were obtained in 10% leachate spike ratio. Meanwhile, up to 90% of the total nitrogen in landfill leachate was removed in culture with 10% leachate spike ratio with a total nitrogen concentration of 221.6mg L(-1). The fluorescence peak of humic-like organic matters red shifted to longer wavelengths by the end of culture, indicating that microalgae-bacteria consortium was effective for treating landfill leachate contaminants. Furthermore, with the leachate spike ratio of 10%, the maximum lipid productivity and carbon fixation were 24.1 and 65.8mg L(-1)d(-1), respectively. Results of this research provide valuable information for optimizing microalgae culture in landfill leachate.

  4. Characterization and Inducing Melanoma Cell Apoptosis Activity of Mannosylerythritol Lipids-A Produced from Pseudozyma aphidis.

    Directory of Open Access Journals (Sweden)

    Linlin Fan

    Full Text Available Mannosylerythritol lipids (MELs are natural glycolipid biosurfactants which have potential applications in the fields of food, cosmetic and medicine. In this study, MELs were produced from vegetable oil by Pseudozyma aphidis. Their structural data through LC/MS, GC/MS and NMR analysis revealed that MEL-A with two acetyls was the major compound and the identified homologs of MEL-A contained a length of C8 to C14 fatty acid chains. This glycolipid exhibited a surface tension of 27.69 mN/m at a critical micelle concentration (CMC, self-assembling into particles in the water solution. It was observed to induce cell growth-inhibition and apoptosis of B16 melanoma cells in a dose-dependent manner, as well as cause cell cycle arrest at the S phase. Further quantitative RT-PCR analysis and western blotting revealed an increasing tendency of both mRNA and protein expressions of Caspase-12, CHOP, GRP78 and Caspase-3, and a down-regulation of protein Bcl-2. Combined with the up regulation of signaling IRE1 and ATF6, it can be speculated that MEL-A-induced B16 melanoma cell apoptosis was associated with the endoplasmic reticulum stress (ERS.

  5. Omental Lipid-Coated Mesh

    Science.gov (United States)

    2011-06-16

    civilian medicine. REFERENCES: 1. Takada T, Kamei Y, Iwata T, et al. Effect of Omental Lipid Fraction on Enhancement of Skin Flap Survival. Annals of...Characterization of Feline Omentum Lipids. Lipids, 1987; 22:229-235. 7. Nottebaert M, Lane J, Juhn A, et al. Omental Angiogenic Lipid Fraction and

  6. Molecular characterization of Api g 2, a novel allergenic member of the lipid-transfer protein 1 family from celery stalks

    NARCIS (Netherlands)

    G. Gadermaier; M. Egger; T. Girbl; A. Erler; A. Harrer; E. Vejvar; M. Liso; K. Richter; L. Zuidmeer; A. Mari; F. Ferreira

    2011-01-01

    Scope: Celery represents a relevant cross-reactive food allergen source in the adult population. As the currently known allergens are not typical elicitors of severe symptoms, we aimed to identify and characterize a non-specific lipid transfer protein (nsLTP). Methods and results: MS and cDNA clonin

  7. Physiological and molecular characterization of atypical lipid-dependent Malassezia yeasts from a dog with skin lesions: adaptation to a new host?

    NARCIS (Netherlands)

    Cafarchia, C.; Latrofa, M.S.; Figueredo, L.A.; da Silva Machado, M.L.; Ferreiro, L.; Guillot, J.; Boekhout, T.; Otranto, D.

    2011-01-01

    Three lipid-dependent Malassezia isolates (here named 114A, 114B and 114C) recovered from a dog with skin lesions were phenotypically and genotypically characterized. All presented ovoid cells and buds formed on a narrow base. Most of the results from physiological tests were consistent with those o

  8. Volumetric characterization of ester- and ether-linked lipid bilayers by pressure perturbation calorimetry and densitometry.

    Science.gov (United States)

    Tamai, Nobutake; Nambu, Yuko; Tanaka, Saeko; Goto, Masaki; Matsuki, Hitoshi; Kaneshina, Shoji

    2012-04-01

    We investigated the thermotropic volume behavior of dimyristoylphosphatidylcholine (DMPC), dipalmitoylphosphatidylcholine (DPPC) and dihexadecylphosphatidylcholine (DHPC) membranes using pressure perturbation calorimetry (PPC) and densitometry. The ln φ(2) vs temperature curves (φ(2): apparent molar volume of phospholipid) obtained from the PPC data using an analysis method that we developed agreed with the results from the density measurements for these lipids within the relative difference of about 0.62%. From those curves, the volume changes with the main transition were estimated at 18.0±0.49, 23.5±2.33 and 23.0±0.33 cm(3) mol(-1) for DMPC, DPPC and DHPC, respectively. For DPPC and DMPC, the average volume per methylene group of the hydrocarbon chains v(CH2) calculated by referring to the procedure by Nagle and Wilkinson was consistent with the previous result, which indicates that the DPPC bilayer in the gel state has denser hydrophobic bilayer core than the DMPC bilayer. For DHPC, the volume of the headgroup region v(H) was calculated to be 244 Å(3) by assuming that v(CH2) of DHPC equals that of DPPC above 45°C. This value was comparable to that of DPPC when the volume of the carbonyl groups was considered, which may signify that there is no significant conformational difference in the polar headgroups of both phospholipids. However, it was suggested from the consideration on v(H) of DHPC at 20°C that expansion of the headgroup region should occur as the interdigitated structure is formed, which means some conformational change of the headgroup region is induced by the interdigitation.

  9. Physicochemical characterization of lycopene-loaded nanostructured lipid carrier formulations for topical administration.

    Science.gov (United States)

    Okonogi, Siriporn; Riangjanapatee, Pornthida

    2015-01-30

    Nanostructured lipid carriers (NLC) are interesting delivery systems for enhancing the penetration of an active substance through the skin after topical administration. In the present study, lycopene was loaded into NLC, composed of Eumulgin(®) SG, orange wax and rice bran oil, using high pressure homogenization (HPH). Photon correlation spectroscopy analysis showed that the lycopene-loaded NLC had a size of 150-160nm with a relatively small size distribution (PdIlycopene was found to be 100±0% for all formulations. An in vitro release study of lycopene showed a biphasic release profile: a relatively fast release during the first 6h followed by a sustained release during the next 18h. An in vitro occlusion test showed that the occlusive properties of NLC increased with increasing lycopene loading. A free radical scavenging activity test of the NLC loaded with 50mg% lycopene showed a Trolox equivalent antioxidant capacity value of 36.6±0.4μM Trolox/mg NLC which is higher than that of the NLC base (26.6±0.1μM Trolox/mg NLC). The concentration of 50% antioxidant activity (IC50) of the lycopene-loaded NLC was 14.1±0.6mg/mL, and lower than that of the formulation without lycopene (17.7±0.4mg/mL). The particle size, size distribution, and zeta potential of lycopene-loaded NLC stored at different temperatures of 4, 30, 40°C for 120 days did not change in time, demonstrating an excellent colloidal stability of the systems. Chemical stability data indicated that the utilization of NLC increased the stability of lycopene and it was found that the degradation of lycopene was retarded when stored at low temperatures. In conclusion, NLC are attractive systems for the cutaneous delivery of lycopene.

  10. In vitro characterization of 6-Coumarin loaded solid lipid nanoparticles and their uptake by immunocompetent fish cells.

    Science.gov (United States)

    Trapani, Adriana; Mandracchia, Delia; Di Franco, Cinzia; Cordero, Héctor; Morcillo, Patricia; Comparelli, Roberto; Cuesta, Alberto; Esteban, Maria Angeles

    2015-03-01

    The primary aim of the present work was to evaluate the in vitro uptake of 6-Coumarin (6COUM) loaded solid lipid nanoparticles (SLN) by two gilthead seabream (Sparus aurata L.) cell types: an established cell line (SAF-1 cells) and the primary cultures of head-kidney (HK)-the main haemopoietic organ in fish, equivalent to mammalian bone marrow-leucocytes. For this purpose, after the physicochemical characterization of SLN, the uptake by those immunocompetent fish cells was evaluated using flow cytometry and confocal microscopy. Concomitantly, the uptake of 6-COUM loaded SLN was compared with that achieved with 6-COUM loaded pectin microparticles (MPs), which were selected as a competitor of the delivery carriers. After SLN and MP physicochemical characterization, the results demonstrated that SAF-1 cells were able to internalize high percentages of 6-COUM SLNs when incubated for 4, 8 and 24h, with the highest SLN concentration tested (10 μg/ml). The ability of HK leucocytes to internalize SLN was also found to vary depending on both incubation time and SLN concentration. The highest values of HK leucocytes internalizing SLN particles (around 16%) were detected at the maximum SLN concentration (20 μg/ml) at incubation times of 4 or 8h. Conversely, HK leucocytes were unable to internalize MPs at any tested concentration and incubation time. A possible mechanism explaining the uptake into cells is proposed. The present work constitutes the first approximation to consider SLN as nanocarriers for delivering biologically active substances to fish.

  11. A plural role for lipids in motor neuron diseases: energy, signaling and structure.

    Directory of Open Access Journals (Sweden)

    Florent eSCHMITT

    2014-02-01

    Full Text Available Motor neuron diseases (MNDs are characterized by selective death of motor neurons and include mainly adult-onset amyotrophic lateral sclerosis (ALS and spinal muscular atrophy (SMA. Neurodegeneration is not the single pathogenic event occurring during disease progression. There are multiple lines of evidence for the existence of defects in lipid metabolism at peripheral level. For instance, hypermetabolism is well characterized in ALS, and dyslipidemia correlates with better prognosis in patients. Lipid metabolism plays also a role in other MNDs. In SMA, misuse of lipids as energetic nutrients is described in patients and in related animal models. The composition of structural lipids in the central nervous system is modified, with repercussion on membrane fluidity and on cell signaling mediated by bioactive lipids. Here, we review the main epidemiologic and mechanistic findings that link alterations of lipid metabolism and motor neuron degeneration, and we discuss the rationale of targeting these modifications for therapeutic management of MNDs.

  12. Binding of oligoarginine to membrane lipids and heparan sulfate: structural and thermodynamic characterization of a cell-penetrating peptide.

    Science.gov (United States)

    Gonçalves, Elisabete; Kitas, Eric; Seelig, Joachim

    2005-02-22

    Cell-penetrating peptides (CPPs) comprise a group of arginine-rich oligopeptides that are able to deliver exogenous cargo into cells. A first step in the internalization of CPPs is their binding to the cell surface, a reaction likely to involve membrane phospholipids and/or heparan sulfate proteoglycans (HSPGs). The present work characterizes the interaction of R(9), one of the most efficient CPPs, with either heparan sulfate (HS) or lipid vesicles composed of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine (POPC) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylglycerol (POPG). Isothermal titration calorimetry shows that R(9) binds to HS with high affinity. Assuming that HS has n independent and equivalent binding sites for R(9), we find an association constant of 3.1 x 10(6) M(-1) at 28 degrees C. At this temperature, the reaction enthalpy is DeltaH(degrees)pep = - 5.5 kcal/mol and approximately 7 R(9) molecules bind per HS chain, which is equivalent to approximately 0.95 cationic/anionic charge ratio. Delta decreases in magnitude upon an increase in temperature, and the reaction becomes entropy-driven at higher temperatures (>or=37 degrees C). The positive heat-capacity change entailed by this reaction (DeltaC(degrees)P = +167 cal mol(-1) K(-1)) indicates the loss of polar residues on R(9)-HS binding, suggesting that hydrophobic forces play no major role on binding. Calorimetric analysis of the interaction of R(9) with POPC/POPG (75:25) vesicles reveals an association constant of 8.2 x 10(4) M(-1) at 28 degrees C. Using a surface partition equilibrium model to correct for electrostatic effects, we find an intrinsic partition constant of approximately 900 M(-1), a value that is also confirmed by electrophoretic mobility measurements. This corresponds to an electrostatic contribution of approximately 33% to the total free energy of binding. Deuterium nuclear magnetic resonance (NMR) shows no change in the headgroup conformation of POPC and POPG, suggesting

  13. Characterization of renal cell carcinoma, oncocytoma, and lipid-poor angiomyolipoma by unenhanced, nephrographic, and delayed phase contrast-enhanced computed tomography.

    Science.gov (United States)

    Ishigami, Kousei; Pakalniskis, Marius G; Leite, Leandro V; Lee, Daniel K; Holanda, Danniele G; Rajput, Maheen

    2015-01-01

    The purpose of this study was to assess the characterization of renal cell carcinoma (RCC) and benign renal tumors by unenhanced, nephrographic, and delayed phase computed tomography (CT). The study group consisted of 129 renal tumors including 79 clear cell RCCs, 17 papillary RCCs, 6 chromophobe RCCs, 21 oncocytoma, and 6 lipid-poor angiomyolipomas (AMLs). CT studies were retrospectively reviewed. Our results suggested that it was possible to discriminate clear cell RCC from papillary RCC, chromophobe RCC, and lipid-poor AML. CT findings of oncocytoma overlapped with both clear cell and non-clear cell RCCs, although oncocytoma more commonly became homogeneous in the delayed phase.

  14. Bone Scan "Hot Spot" at the Superior Lateral Orbital Margin Fronto-zygomatic Suture Uptake Characterized with Tc-99m MDP SPECT/CT.

    Science.gov (United States)

    Thang, S P; Tan, A E H; Goh, A S W

    2011-07-01

    Findings of a solitary "hot spot" at the superior lateral orbital margin on bone scan scintigraphy is not uncommonly seen, and is often dismissed as a benign lesion. However, the exact etiology is indeterminate. We present two cases in which hybrid single photon emission computed tomography/computed tomography imaging was able to characterize and localize this uptake, demonstrating correlation to the right fronto-zygomatic suture.

  15. Functional organization of the HIV lipid envelope

    Science.gov (United States)

    Huarte, Nerea; Carravilla, Pablo; Cruz, Antonio; Lorizate, Maier; Nieto-Garai, Jon A.; Kräusslich, Hans-Georg; Pérez-Gil, Jesús; Requejo-Isidro, Jose; Nieva, José L.

    2016-01-01

    The chemical composition of the human immunodeficiency virus type 1 (HIV-1) membrane is critical for fusion and entry into target cells, suggesting that preservation of a functional lipid bilayer organization may be required for efficient infection. HIV-1 acquires its envelope from the host cell plasma membrane at sites enriched in raft-type lipids. Furthermore, infectious particles display aminophospholipids on their surface, indicative of dissipation of the inter-leaflet lipid asymmetry metabolically generated at cellular membranes. By combining two-photon excited Laurdan fluorescence imaging and atomic force microscopy, we have obtained unprecedented insights into the phase state of membranes reconstituted from viral lipids (i.e., extracted from infectious HIV-1 particles), established the role played by the different specimens in the mixtures, and characterized the effects of membrane-active virucidal agents on membrane organization. In determining the molecular basis underlying lipid packing and lateral heterogeneity of the HIV-1 membrane, our results may help develop compounds with antiviral activity acting by perturbing the functional organization of the lipid envelope. PMID:27678107

  16. Solid lipid nanoparticles co-loaded with simazine and atrazine: preparation, characterization, and evaluation of herbicidal activity.

    Science.gov (United States)

    de Oliveira, Jhones Luiz; Campos, Estefânia Vangelie Ramos; Gonçalves da Silva, Camila Morais; Pasquoto, Tatiane; Lima, Renata; Fraceto, Leonardo Fernandes

    2015-01-21

    Solid lipid nanoparticles (SLN) containing the herbicides atrazine and simazine were prepared and characterized, and in vitro evaluation was made of the release kinetics, herbicidal activity, and cytotoxicity. The stability of the nanoparticles was investigated over a period of 120 days, via analyses of particle size, ζ potential, polydispersion, pH, and encapsulation efficiency. SLN showed good physicochemical stability and high encapsulation efficiencies. Release kinetics tests showed that use of SLN modified the release profiles of the herbicides in water. Herbicidal activity assays performed with pre- and postemergence treatment of the target species Raphanus raphanistrum showed the effectiveness of the formulations of nanoparticles containing herbicides. Assays with nontarget organisms (Zea mays) showed that the formulations did not affect plant growth. The results of cytotoxicity assays indicated that the presence of SLN acted to reduce the toxicity of the herbicides. The new nanoparticle formulations enable the use of smaller quantities of herbicide and therefore offer a more environmentally friendly method of controlling weeds in agriculture.

  17. Lipid exchange by ultracentrifugation

    DEFF Research Database (Denmark)

    Drachmann, Nikolaj Düring; Olesen, Claus

    2014-01-01

    Lipids play an important role in maintaining P-type ATPase structure and function, and often they are crucial for ATPase activity. When the P-type ATPases are in the membrane, they are surrounded by a mix of different lipids species with varying aliphatic chain lengths and saturation......, and the complex interplay between the lipids and the P-type ATPases are still not well understood. We here describe a robust method to exchange the majority of the lipids surrounding the ATPase after solubilisation and/or purification with a target lipid of interest. The method is based on an ultracentrifugation...... step, where the protein sample is spun through a dense buffer containing large excess of the target lipid, which results in an approximately 80-85 % lipid exchange. The method is a very gently technique that maintains protein folding during the process, hence allowing further characterization...

  18. IgG from Amyotrophic Lateral Sclerosis Patients Increases Current Through P-Type Calcium Channels in Mammalian Cerebellar Purkinje Cells and in Isolated Channel Protein in Lipid Bilayer

    Science.gov (United States)

    Llinas, R.; Sugimori, M.; Cherksey, B. D.; Smith, R. Glenn; Delbono, O.; Stefani, E.; Appel, S.

    1993-12-01

    The effect of the IgG from amyotrophic lateral sclerosis (ALS) patients was tested on the voltage-dependent barium currents (IBa) in mammalian dissociated Purkinje cells and in isolated P-type calcium channels in lipid bilayers. Whole cell clamp of Purkinje cells demonstrates that ALS IgG increases the amplitude of IBa without modifying their voltage kinetics. This increased IBa could be blocked by a purified nonpeptide toxin from Agelenopsis aperta venom (purified funnel-web spider toxin) or by a synthetic polyamine analog (synthetic funnel-web spider toxin) and by a peptide toxin from the same spider venom, ω-Aga-IVA. Similar results were obtained on single-channel recordings from purified P channel protein. The addition of ALS IgG increased single-channel IBa open time without affecting slope conductance. The results described above were not seen with normal human IgG nor with boiled ALS IgG. It is concluded that ALS IgG enhances inward current through P-type calcium channels. Since P-type Ca2+ channels are present in motoneuron axon terminals, we propose that the enhanced calcium current triggered by ALS IgG may contribute to neuronal damage in ALS.

  19. Characterization of the deep-sea microbial community and investigation of their carbon sources using lipid biomarkers

    Science.gov (United States)

    Rampen, S. W.; Sinninghe Damsté, J. S.; Schouten, S.; Middelburg, J. J.

    2012-12-01

    Most marine microbiology studies so far have been devoted to the photic zone, as this is the area where most of the primary production occurs. However, recently several groups of autotrophic organisms belonging to the Thaumarchaeota have been identified in the deep-sea. Thaumarchaeota belong to the Archaea, which form one of the three Domains of life, next to the Eukarya and the Bacteria. While until the 1990s the Archaea were viewed as extremophilic organisms, results obtained over the last twenty years indicate that Thaumarchaeota are an ubiquitous component of marine plankton, being among the most widely distributed and most abundant groups of microorganisms on the planet; Thaumarchaeota even exceed Bacteria in abundance below 1000 m water depth. Despite these findings, our understanding on their physiology and their biogeochemical function remains mostly speculative because only very few of these organisms could be cultivated. The aim of our project is 1) to characterize the microbial community in the deep-sea using lipid biomarkers for Bacteria, Archaea and Eukarya, 2) to investigate the carbon sources for these organisms using compound specific 13C and 14C analyses and 3) to elucidate the flow of carbon in deep-sea microbial communities using 13C labeling studies. To this end, organic matter has been collected from several locations in the Mediterranean Sea and from the Iceland Basin. Water volumes up to 160 liters were sampled using Niskin bottles which were then filtered on board, while larger volumes, up to 5000 liters, were sampled by deployment of two McLane in-situ pumps at depth. Additional water samples were filtered from the subsurface to distinguish in-situ production from settling organic biomass produced in the upper water column. In addition, 13C labeled glucose, amino acids and sodium bicarbonate were each added to deep-sea water kept in separate 20 liter Nalgene bottles. Incubated water samples and control samples were kept at deep

  20. Kinetic characterization of on-chip DNA ligation on dendron-coated surfaces with nanoscaled lateral spacings

    Science.gov (United States)

    Kim, Eung-Sam; Lee, Namgyu; Park, Joon Won; Choi, Kwan Yong

    2013-10-01

    We analyzed the enzymatic profiles of on-chip DNA ligation as we controlled the lateral spacing of surface-immobilized DNA substrates using dendron molecules with different sizes at the nanoscale. Enzymatic on-chip DNA ligation was performed on the dendron-coated surface within 20 min with no need for post-ligation gel electrophoresis. The enzymatic DNA repair was assessed by the fluorescence intensity at the repaired DNA duplex after thermally dissociating the unligated Cy3-labeled DNA from the DNA duplex, in which the Cy3-labeled DNA was hybridized prior to the on-chip DNA ligation. The rate of the nick-sealing reaction on the 27-acid dendron surface was 3-fold higher than that on the 9-acid dendron surface, suggesting that the wider lateral spacing determined by the larger dendron molecule could facilitate the access of DNA ligase to the nick site. The performance of on-chip DNA ligation was dropped to 10% and 3% when the nick was replaced by one- and two-nucleotide-long gaps, respectively. The 5‧ terminal phosphorylation of DNA strands by polynucleotide kinase and the on-chip DNA cleavage by endonucleases were also quantitatively monitored throughout the on-chip DNA ligation on the dendron-coated surface. A better understanding of the enzymatic kinetics of on-chip DNA ligation will contribute to a more reliable performance of various on-chip DNA ligation-based assays.

  1. Solid lipid nanoparticles containing 7-ethyl-10-hydroxycamptothecin (SN38): Preparation, characterization, in vitro, and in vivo evaluations.

    Science.gov (United States)

    Mosallaei, Navid; Mahmoudi, Asma; Ghandehari, Hamidreza; Yellepeddi, Venkata Kashyap; Jaafari, Mahmoud Reza; Malaekeh-Nikouei, Bizhan

    2016-07-01

    7-Ethyl-10-hydroxycamptothecin (SN38) is a biologically active metabolite of irinotecan. Due to the variability of irinotecan metabolism rate to SN38, and poor solubility of this compound in pharmaceutically acceptable solvents, SN38 has not been successfully used in the clinic. In the present study, we prepared solid lipid nanoparticle (SLN) formulations containing SN38 and evaluated the in vitro and in vivo efficacy of these nanoparticles. SLNs and PEGylated SLNs containing SN38 (SLN-SN38 and PEG-SLN-SN38) were prepared using ultrasonication technique. Nanoparticles were characterized for size, zeta potential, and drug encapsulation efficiency. In vitro cytotoxicity of these compounds was evaluated in two colorectal carcinoma cell lines, namely C-26 and HT-116. In vivo antitumor efficacy of the formulations was evaluated in C-26 xenograft tumor mice models. Mice survival was also explored through 60days post IV injection. Mean size of SLN-SN38 and PEG-SLN-SN38 was around 103 and 131nm, respectively. Polydispersity index (PDI) for all the formulations was around 0.2 and zeta potential was negative (-5 to -15mV). Nearly 90% of the drug was encapsulated in SLNs. SLN-SN38 and PEG-SLN-SN38 compared to irinotecan were significantly more toxic to C-26 and HT-116 cell lines after 48h of exposure. Calculation of IC50 suggests higher sensitivity of HT-116 cells than C-26 cells to SLN-SN38 and PEG-SLN-SN38. Tumor inhibitory efficacy presented the highest efficacy in SLN-SN38. However, both SLN-SN38 and PEG-SLN-SN38 carriers showed higher efficiency to inhibit tumors compared to irinotecan (25mg/kg).

  2. 15d-PGJ2-Loaded Solid Lipid Nanoparticles: Physicochemical Characterization and Evaluation of Pharmacological Effects on Inflammation

    Science.gov (United States)

    da Silva, Camila Morais Gonçalves; Pasquoto, Tatiane; de Lima, Renata; Fraceto, Leonardo Fernandes

    2016-01-01

    15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2), a peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist, has physiological properties including pronounced anti-inflammatory activity, though it binds strongly to serum albumin. The use of solid lipid nanoparticles (SLN) can improve therapeutic properties increasing drug efficiency and availability. 15d-PGJ2-SLN was therefore developed and investigated in terms of its immunomodulatory potential. 15d-PGJ2-SLN and unloaded SLN were physicochemically characterized and experiments in vivo were performed. Animals were pretreated with 15d-PGJ2-SLN at concentrations of 3, 10 or 30 μg·kg-1 before inflammatory stimulus with carrageenan (Cg), lipopolysaccharide (LPS) or mBSA (immune response). Interleukins (IL-1β, IL-10 and IL-17) levels were also evaluated in exudates. The 15d-PGJ2-SLN system showed good colloidal parameters and encapsulation efficiency of 96%. The results showed that the formulation was stable for up to 120 days with low hemolytic effects. The 15d-PGJ2-SLN formulation was able to reduce neutrophil migration in three inflammation models tested using low concentrations of 15d-PGJ2. Additionally, 15d-PGJ2-SLN increased IL-10 levels and reduced IL-1β as well as IL-17 in peritoneal fluid. The new 15d-PGJ2-SLN formulation highlights perspectives of a potent anti-inflammatory system using low concentrations of 15d-PGJ2. PMID:27575486

  3. Characterization of M-laurdan, a versatile probe to explore order in lipid membranes [v2; ref status: indexed, http://f1000r.es/4on

    Directory of Open Access Journals (Sweden)

    Serge Mazeres

    2014-11-01

    Full Text Available Microdomains corresponding to localized partition of lipids between ordered and less ordered environments are the subject of intensive investigations, because of their putative participation in modulating cellular responses. One popular approach in the field consists in labelling membranes with solvatochromic fluorescent probes such as laurdan and C-laurdan. In this report, we describe a high-yield procedure for the synthesis of laurdan, C-laurdan and two new fluorophores, called MoC-laurdan and M-laurdan, as well as their extensive photophysical characterization. We find that the latter probe, M-laurdan, is particularly suited to discriminate lipid phases independently of the chemical nature of the lipids, as measured by both fluorescence Generalized Polarization (GP and anisotropy in large unilamellar vesicles made of various lipid compositions. In addition, staining of live cells with M-laurdan shows a good stability over time without any apparent toxicity, as well as a wider distribution in the various cell compartments than the other probes.

  4. Lipid colloidal carriers for improvement of anticancer activity of orally delivered quercetin: formulation, characterization and establishing in vitro-in vivo advantage.

    Science.gov (United States)

    Jain, Ankitkumar S; Shah, Sanket M; Nagarsenker, Mangal S; Nikam, Yuvraj; Gude, Rajiv P; Steiniger, Frank; Thamm, Jana; Fahr, Alfred

    2013-07-01

    Novel lipid nanocarriers, GeluPearl (GP) comprising of Precirol ATO 5 lipid nanoparticles with (GPNLC) or without oil (GPSLN), loaded with Quercetin (QR), were successfully fabricated to improve therapeutic efficacy. QR loaded GP nanoparticles were optimized to yield adequate colloidal stability, mean particle size in range of 350-380 nm and entrapment efficiency of more than 90%. GPSLN and GPNLC were characterized for morphological evaluation by virtue of cryo-TEM, surface charge, protection offered to QR against alkali mediated degradation and fluorescence studies to evaluate QR-lipid interaction. DSC analysis was performed to get insight into physical state of QR loaded in nanosystems. The in vitro release studies demonstrated sustained drug release potential of QR loaded GP. In vitro lipolysis studies confirmed that lipidic nanocarriers can improve QR solubilization. QR loaded GP nanosystems significantly (P < 0.05) reduced flank tumor volumes in C57BL/6 mice over a 22 day study period compared to QR suspension. GPSLN significantly reduced lung colonization and enhanced antimetastatic activity (P < 0.05) of drug against B16F10 melanoma cells in C57BL/6 mice as compared to QR suspension. QR loaded GPSLN and GPNLC could be effectively lyophilized without much change in particle size and drug content using 15% w/v mannitol as cryoprotectant.

  5. Characterization of late acyltransferase genes of Yersinia pestis and their role in temperature-dependent lipid A variation.

    Science.gov (United States)

    Rebeil, Roberto; Ernst, Robert K; Jarrett, Clayton O; Adams, Kristin N; Miller, Samuel I; Hinnebusch, B Joseph

    2006-02-01

    Yersinia pestis is an important human pathogen that is maintained in flea-rodent enzootic cycles in many parts of the world. During its life cycle, Y. pestis senses host-specific environmental cues such as temperature and regulates gene expression appropriately to adapt to the insect or mammalian host. For example, Y. pestis synthesizes different forms of lipid A when grown at temperatures corresponding to the in vivo environments of the mammalian host and the flea vector. At 37 degrees C, tetra-acylated lipid A is the major form; but at 26 degrees C or below, hexa-acylated lipid A predominates. In this study, we show that the Y. pestis msbB (lpxM) and lpxP homologs encode the acyltransferases that add C12 and C(16:1) groups, respectively, to lipid IV(A) to generate the hexa-acylated form, and that their expression is upregulated at 21 degrees C in vitro and in the flea midgut. A Y. pestis deltamsbB deltalpxP double mutant that did not produce hexa-acylated lipid A was more sensitive to cecropin A, but not to polymyxin B. This mutant was able to infect and block fleas as well as the parental wild-type strain, indicating that the low-temperature-dependent change to hexa-acylated lipid A synthesis is not required for survival in the flea gut.

  6. Comparison of pharmacokinetic profiles of PM02734 loaded lipid nanoparticles and cyclodextrins: in vitro and in vivo characterization.

    Science.gov (United States)

    Estella-Hermoso de Mendoza, A; Calvo, P; Bishop, A; Avilés, P; Blanco-Prieto, M J

    2012-08-01

    PM02734 is a chemically synthesized depsipeptide derived from the marine kahalalides family with a broad spectrum of activity against solid tumors in vitro and in vivo, but presenting low bioavailability. In this work, solid lipid nanoparticles made of Precirol ATO 5 have been developed using a hot homogenization method followed by high shear homogenization and ultrasonication. These solid lipid nanoparticles show suitable size (around 150 nm) and encapsulation efficiency (nearly 70%) for the oral administration of the compound PM02734. A physical-chemical stability study was performed after 6 months of storage at different thermical conditions, concluding that solid lipid nanoparticles stored at 4 degrees C were more stable than solid lipid nanoparticles stored at 25 degrees C. The pharmacokinetic profile of drug-loaded solid lipid nanoparticles was also evaluated in Beagle dogs and compared with that of a cyclodextrin-based delivery system by means of AUC, C(max) and T(max) parameter estimation. Solid lipid nanoparticle based formulation provided a sustained release of the drug for a longer period of time than the cyclodextrins.

  7. Effect of solar radiation on the lipid characterization of biomass cultivated in high-rate algal ponds using domestic sewage.

    Science.gov (United States)

    Assemany, Paula Peixoto; Calijuri, Maria Lúcia; Santiago, Anibal da Fonseca; do Couto, Eduardo de Aguiar; Leite, Mauricio de Oliveira; Sierra, Jose Jovanny Bermudez

    2014-01-01

    The objective of this paper is to compare the lipid content and composition ofbiomass produced by a consortium of microalgae and bacteria, cultivated under different solar radiation intensities and tropical conditions in pilot-scale high-rate ponds (HRPs) using domestic sewage as culture medium. The treatment system consisted of an upflow anaerobic sludge blanket reactor followed by UV disinfection and six HRPs covered with shading screens that blocked 9%, 18%, 30%, 60% and 80% of the solar radiation. The total lipid content does not vary significantly among the units, showing a medium value of 9.5%. The results show that blocking over 30% of the solar radiation has a negative effect on the lipid productivity. The units with no shading and with 30% and 60% of solar radiation blocking have statistically significant lipid productivities, varying from 0.92 to 0.96 gm(-2) day(-1). Besides radiation, other variables such as volatile suspended solids and chlorophyll-a are able to explain the lipid accumulation. The lipid profile has a predominance of C16, C18:1 and C18:3 acids. The unsaturation of fatty acids increases with the reduction in solar radiation. On the other hand, the effect of polyunsaturation is not observed, which is probably due to the presence of a complex and diverse biomass.

  8. Lateral Concepts

    Directory of Open Access Journals (Sweden)

    Christopher Gad

    2016-06-01

    Full Text Available This essay discusses the complex relation between the knowledges and practices of the researcher and his/her informants in terms of lateral concepts. The starting point is that it is not the prerogative of the (STS scholar to conceptualize the world; all our “informants” do it too. This creates the possibility of enriching our own conceptual repertoires by letting them be inflected by the concepts of those we study. In a broad sense, the lateral means that there is a many-to-many relation between domains of knowledge and practice. However, each specific case of the lateral is necessarily immanent to a particular empirical setting and form of inquiry. In this sense lateral concepts are radically empirical since it locates concepts within the field. To clarify the meaning and stakes of lateral concepts, we first make a contrast between lateral anthropology and Latour’s notion of infra-reflexivity. We end with a brief illustration and discussion of how lateral conceptualization can re-orient STS modes of inquiry, and why this matters.

  9. Structural Characterization of Lateral-grown 6H-SiC am-plane Seed Crystals by Hot Wall CVD Epitaxy

    Science.gov (United States)

    Goue, Ouloide Yannick; Raghothamachar, Balaji; Dudley, Michael; Trunek, Andrew J.; Neudeck, Philip G.; Woodworth, Andrew A.; Spry, David J.

    2014-01-01

    The performance of commercially available silicon carbide (SiC) power devices is limited due to inherently high density of screw dislocations (SD), which are necessary for maintaining polytype during boule growth and commercially viable growth rates. The NASA Glenn Research Center (GRC) has recently proposed a new bulk growth process based on axial fiber growth (parallel to the c-axis) followed by lateral expansion (perpendicular to the c-axis) for producing multi-faceted m-plane SiC boules that can potentially produce wafers with as few as one SD per wafer. In order to implement this novel growth technique, the lateral homoepitaxial growth expansion of a SiC fiber without introducing a significant number of additional defects is critical. Lateral expansion is being investigated by hot wall chemical vapor deposition (HWCVD) growth of 6H-SiC am-plane seed crystals (0.8mm x 0.5mm x 15mm) designed to replicate axially grown SiC single crystal fibers. The post-growth crystals exhibit hexagonal morphology with approximately 1500 m (1.5 mm) of total lateral expansion. Preliminary analysis by synchrotron white beam x-ray topography (SWBXT) confirms that the growth was homoepitaxial, matching the polytype of the respective underlying region of the seed crystal. Axial and transverse sections from the as grown crystal samples were characterized in detail by a combination of SWBXT, transmission electron microscopy (TEM) and Raman spectroscopy to map defect types and distribution. X-ray diffraction analysis indicates the seed crystal contained stacking disorders and this appears to have been reproduced in the lateral growth sections. Analysis of the relative intensity for folded transverse acoustic (FTA) and optical (FTO) modes on the Raman spectra indicate the existence of stacking faults. Further, the density of stacking faults is higher in the seed than in the grown crystal. Bundles of dislocations are observed propagating from the seed in m-axis lateral directions

  10. Texture of lipid bilayer domains

    DEFF Research Database (Denmark)

    Jensen, Uffe Bernchou; Brewer, Jonathan R.; Midtiby, Henrik Skov;

    2009-01-01

    We investigate the texture of gel (g) domains in binary lipid membranes composed of the phospholipids DPPC and DOPC. Lateral organization of lipid bilayer membranes is a topic of fundamental and biological importance. Whereas questions related to size and composition of fluid membrane domain...... are well studied, the possibility of texture in gel domains has so far not been examined. When using polarized light for two-photon excitation of the fluorescent lipid probe Laurdan, the emission intensity is highly sensitive to the angle between the polarization and the tilt orientation of lipid acyl...... chains. By imaging the intensity variations as a function of the polarization angle, we map the lateral variations of the lipid tilt within domains. Results reveal that gel domains are composed of subdomains with different lipid tilt directions. We have applied a Fourier decomposition method...

  11. Characterization of cell wall lipids from the pathogenic phase of Paracoccidioides brasiliensis cultivated in the presence or absence of human plasma.

    Directory of Open Access Journals (Sweden)

    Larissa V G Longo

    Full Text Available BACKGROUND: The fungal cell wall is a complex and dynamic outer structure. In pathogenic fungi its components interact with the host, determining the infection fate. The present work aimed to characterize cell wall lipids from P. brasiliensis grown in the presence and absence of human plasma. We compared the results from isolates Pb3 and Pb18, which represent different phylogenetic species that evoke distinct patterns of experimental paracoccidioidomycosis. METHODOLOGY/PRINCIPAL FINDINGS: We comparatively characterized cell wall phospholipids, fatty acids, sterols, and neutral glycolipids by using both electrospray ionization- and gas chromatography-mass spectrometry analyses of lipids extracted with organic solvents followed by fractionation in silica-gel-60. We detected 49 phospholipid species in Pb3 and 38 in Pb18, including phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylglycerol, phosphatidylinositol, and phosphatidic acid. In both Pb3 and Pb18, PC and PE had the most numerous species. Among the fatty acids, C18:1 and C18:2 were the most abundant species in both isolates, although C18:2 was more abundant in Pb18. There was a different effect of plasma supplementation on fatty acids depending on the fungal isolate. The prevalent glycolipid species was Hex-C18:0-OH/d19:2-Cer, although other four minor species were also detected. The most abundant sterol in all samples was brassicasterol. Distinct profiles of cell wall and total yeast sterols suggested that the preparations were enriched for cell wall components. The presence of plasma in the culture medium specially increased cell wall brassicasterol abundance and also other lipids. CONCLUSIONS/SIGNIFICANCE: We here report an original comparative lipidomic analysis of P. brasiliensis cell wall. Our results open doors to understanding the role of cell wall lipids in fungal biology, and interaction with anti-fungal drugs and the host.

  12. Isolation, characterization and lipid-binding properties of the recalcitrant FtsA division protein from Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Ariadna Martos

    Full Text Available We have obtained milligram amounts of highly pure Escherichia coli division protein FtsA from inclusion bodies with an optimized purification method that, by overcoming the reluctance of FtsA to be purified, surmounts a bottleneck for the analysis of the molecular basis of FtsA function. Purified FtsA is folded, mostly monomeric and interacts with lipids. The apparent affinity of FtsA binding to the inner membrane is ten-fold higher than to phospholipids, suggesting that inner membrane proteins could modulate FtsA-membrane interactions. Binding of FtsA to lipids and membranes is insensitive to ionic strength, indicating that a net contribution of hydrophobic interactions is involved in the association of FtsA to lipid/membrane structures.

  13. Characterization of the P4-ATPase ATP8A2: Identification of Key Residues Involved in Catalysis and Lipid Transport

    DEFF Research Database (Denmark)

    Coleman, Jonathan Allan; Vestergaard, Anna Lindeløv; Molday, Robert S.;

    ATP8A2 is a P4-ATPase ("lipid flippase") highly expressed in the retina, brain, and testes. Previous studies in our laboratory have shown that ATP8A2 exists as a complex with its β-subunit CDC50A in retinal rod and cone photoreceptor cells and this complex preferentially transports phosphatidylse......ATP8A2 is a P4-ATPase ("lipid flippase") highly expressed in the retina, brain, and testes. Previous studies in our laboratory have shown that ATP8A2 exists as a complex with its β-subunit CDC50A in retinal rod and cone photoreceptor cells and this complex preferentially transports...... are likely the only species which are transported by P4-ATPases. These studies form a basis for further understanding lipid transport by this critical yet poorly understood class of P-type ATPases....

  14. Isolation, characterization and lipid-binding properties of the recalcitrant FtsA division protein from Escherichia coli.

    Science.gov (United States)

    Martos, Ariadna; Monterroso, Begoña; Zorrilla, Silvia; Reija, Belén; Alfonso, Carlos; Mingorance, Jesús; Rivas, Germán; Jiménez, Mercedes

    2012-01-01

    We have obtained milligram amounts of highly pure Escherichia coli division protein FtsA from inclusion bodies with an optimized purification method that, by overcoming the reluctance of FtsA to be purified, surmounts a bottleneck for the analysis of the molecular basis of FtsA function. Purified FtsA is folded, mostly monomeric and interacts with lipids. The apparent affinity of FtsA binding to the inner membrane is ten-fold higher than to phospholipids, suggesting that inner membrane proteins could modulate FtsA-membrane interactions. Binding of FtsA to lipids and membranes is insensitive to ionic strength, indicating that a net contribution of hydrophobic interactions is involved in the association of FtsA to lipid/membrane structures.

  15. Coarse-grained modeling of interactions of lipid bilayers with supports

    Science.gov (United States)

    Hoopes, Matthew I.; Deserno, Markus; Longo, Margie L.; Faller, Roland

    2008-11-01

    We characterize the differences between supported and unsupported lipid bilayer membranes using a mesoscopic simulation model and a simple particle-based realization for a flat support on to which the lipids are adsorbed. We show that the nanometer roughness of the support affects membrane binding strength very little. We then compare the lipid distributions and pressure profiles of free and supported membranes. The surface localization of the proximal leaflet breaks the symmetry seen in a free bilayer, and we quantify the entropic penalty for binding and the increased lateral compression modulus.

  16. Bridging the gap between single molecule and ensemble methods for measuring lateral dynamics in the plasma membrane

    DEFF Research Database (Denmark)

    Christensen, Eva Arnspang; Schwartzentruber, J.; Clausen, M. P.;

    2013-01-01

    The lateral dynamics of proteins and lipids in the mammalian plasma membrane are heterogeneous likely reflecting both a complex molecular organization and interactions with other macromolecules that reside outside the plane of the membrane. Several methods are commonly used for characterizing...... the lateral dynamics of lipids and proteins. These experimental and data analysis methods differ in equipment requirements, labeling complexities, and further oftentimes give different results. It would therefore be very convenient to have a single method that is flexible in the choice of fluorescent label...... for analyzing lateral dynamics in samples that are labeled at high densities, can also be used for fast and accurate analysis of single molecule density data of lipids and proteins labeled with quantum dots (QDs). We have further used kICS to investigate the effect of the label size and by comparing the results...

  17. Exploring the in meso crystallization mechanism by characterizing the lipid mesophase microenvironment during the growth of single transmembrane α-helical peptide crystals.

    Science.gov (United States)

    van 't Hag, Leonie; Knoblich, Konstantin; Seabrook, Shane A; Kirby, Nigel M; Mudie, Stephen T; Lau, Deborah; Li, Xu; Gras, Sally L; Mulet, Xavier; Call, Matthew E; Call, Melissa J; Drummond, Calum J; Conn, Charlotte E

    2016-07-28

    The proposed mechanism for in meso crystallization of transmembrane proteins suggests that a protein or peptide is initially uniformly dispersed in the lipid self-assembly cubic phase but that crystals grow from a local lamellar phase, which acts as a conduit between the crystal and the bulk cubic phase. However, there is very limited experimental evidence for this theory. We have developed protocols to investigate the lipid mesophase microenvironment during crystal growth using standard procedures readily available in crystallography laboratories. This technique was used to characterize the microenvironment during crystal growth of the DAP12-TM peptide using synchrotron small angle X-ray scattering (SAXS) with a micro-sized X-ray beam. Crystal growth was found to occur from the gyroid cubic mesophase. For one in four crystals, a highly oriented local lamellar phase was observed, providing supporting evidence for the proposed mechanism for in meso crystallization. A new observation of this study was that we can differentiate diffraction peaks from crystals grown in meso, from peaks originating from the surrounding lipid matrix, potentially opening up the possibility of high-throughput SAXS analysis of in meso grown crystals.This article is part of the themed issue 'Soft interfacial materials: from fundamentals to formulation'.

  18. Characterization and storage stability of astaxanthin esters, fatty acid profile and α-tocopherol of lipid extract from shrimp (L. vannamei) waste with potential applications as food ingredient.

    Science.gov (United States)

    Gómez-Estaca, J; Calvo, M M; Álvarez-Acero, I; Montero, P; Gómez-Guillén, M C

    2017-02-01

    In this work a lipid extract from shrimp waste was obtained and characterized. The most abundant fatty acids found were C16:0, C18:2n6c, C18:1n9c, C22:6n3, and C20:5n3. The extract contained all-trans-astaxanthin, two cis-astaxanthin isomers, 5 astaxanthin monoesters, and 10 astaxanthin diesters (7±1mg astaxanthin/g). C22:6n3 and C20:5n3 were the most frequent fatty acids in the esterified forms. Appreciable amounts of α-tocopherol and cholesterol were also found (126±11mg/g and 65±1mg/g, respectively). Little lipid oxidation was observed after 120days of storage at room temperature, revealed by a slight reduction of ω-3 fatty acids, but neither accumulation of TBARS nor formation of oxidized cholesterol forms was found. This is attributed to the antioxidant effect of astaxanthin and α-tocopherol, as their concentrations decreased as storage continued. The lipid extract obtained has interesting applications as food ingredient, owing to the coloring capacity and the presence of healthy components.

  19. The Structure of Cholesterol in Lipid Rafts

    CERN Document Server

    Toppozini, Laura; Armstrong, Clare L; Yamani, Zahra; Kucerka, Norbert; Schmid, Friederike; Rheinstaedter, Maikel C

    2014-01-01

    Rafts, or functional domains, are transient nano- or mesoscopic structures in the plasma membrane and are thought to be essential for many cellular processes such as signal transduction, adhesion, trafficking and lipid/protein sorting. Observations of these membrane heterogeneities have proven challenging, as they are thought to be both small and short-lived. With a combination of coarse-grained molecular dynamics simulations and neutron diffraction using deuterium labeled cholesterol molecules we observe raft-like structures and determine the ordering of the cholesterol molecules in binary cholesterol-containing lipid membranes. From coarse-grained computer simulations, heterogenous membranes structures were observed and characterized as small, ordered domains. Neutron diffraction was used to study the lateral structure of the cholesterol molecules. We find pairs of strongly bound cholesterol molecules in the liquid-disordered phase, in accordance with the umbrella model. Bragg peaks corresponding to orderin...

  20. Lipid nanoparticles for topical and transdermal application for alopecia treatment: development, physicochemical characterization, and in vitro release and penetration studies

    Directory of Open Access Journals (Sweden)

    Gomes MJ

    2014-03-01

    Full Text Available Maria João Gomes,1 Susana Martins,2,3 Domingos Ferreira,2 Marcela A Segundo,1 Salette Reis1 1REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, 2Laboratory of Pharmaceutical Technology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal; 3Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Odense, Denmark Abstract: Alopecia is a dermatological disorder, commonly known as hair loss, which affects up to half of the Caucasian male population by middle age, and almost all (95% Caucasian men by old age. Considering that alopecia affects so many people and that there is currently no scientifically proven treatment with few side effects, new drug-delivery systems able to improve alopecia therapy are urgently required. With this purpose in mind, the present study aimed to develop lipid nanoparticles (nanostructured lipid carriers with the ability to incorporate and deliver anti-alopecia active compounds (minoxidil and finasteride into the dermis and hair follicles. Lipid nanoparticles, prepared by ultrasonication method, showed mean particle sizes around 200 nm, which is sufficient for reaching the dermis and hair follicles, and zeta potential values around -30 mV, which indicates good physical stability. Over 28 days of storage, no significant variations in these parameters were observed, which indicates that all nanoformulations are stable in storage over that period. Cryo-scanning electron microscope measurements showed that all the lipid nanoparticles exhibited a spherical shape and a smooth surface regardless of their composition. Differential scanning calorimetry studies allowed the determination of phase transition temperatures and confirmed the recrystallization of the lipid nanoparticles (recrystallization index between 11% and 86%. A high loading efficiency was achieved for finasteride (between 70% and 90%, while less than 30% was

  1. Structural characterization of the polar lipids of Clostridium novyi NT. Further evidence for a novel anaerobic biosynthetic pathway to plasmalogens.

    Science.gov (United States)

    Guan, Ziqiang; Johnston, Norah C; Aygun-Sunar, Semra; Daldal, Fevzi; Raetz, Christian R H; Goldfine, Howard

    2011-03-01

    A study of the polar lipids of Clostridium novyi NT has revealed the presence of phosphatidylethanolamine (PE) and cardiolipin as major phospholipids with smaller amounts of phosphatidylglycerol (PG), lysyl-PG and alanyl-PG. Other minor phospholipids included phosphatidic acid, CDP-diacylglycerol, phosphatidylserine (PS) and phosphatidylthreonine (PT). PE, PG and amino acyl PG were present in both the diacyl and alk-1'-enyl acyl (plasmalogen) forms and cardiolipin plasmalogens were found to contain one or two alk-1'-enyl chains. In contrast, the precursor lipids phosphatidic acid, CDP-diacylglycerol and PS were present almost exclusively as diacyl phospholipids. These findings are consistent with the hypothesis that plasmalogens are formed from diacylated phospholipids at a late stage of phospholipid formation in Clostridium species. This novel pathway contrasts with the route in animals in which a saturated ether bond is formed at an early stage of plasmalogen biosynthesis and the alk-1-enyl bond is formed by an aerobic mechanism.

  2. Lipid nanoparticles for topical and transdermal application for alopecia treatment: development, physicochemical characterization, and in vitro release and penetration studies

    DEFF Research Database (Denmark)

    Gomes, M. J.; Martins, S.; Ferreira, D.

    2014-01-01

    less than 30% was achieved for minoxidil nanoparticles, over 28 days. Controlled release assays in physiological conditions demonstrated that nanoparticles loaded with minoxidil yielded a prolonged release, as desired. Penetration assays through pig ear skin demonstrated that nanoparticles loaded...... and finasteride) into the dermis and hair follicles. Lipid nanoparticles, prepared by ultrasonication method, showed mean particle sizes around 200 nm, which is sufficient for reaching the dermis and hair follicles, and zeta potential values around -30 mV, which indicates good physical stability. Over 28 days...... of storage, no significant variations in these parameters were observed, which indicates that all nanoformulations are stable in storage over that period. Cryo-scanning electron microscope measurements showed that all the lipid nanoparticles exhibited a spherical shape and a smooth surface regardless...

  3. Structural Characterization of the Polar Lipids of Clostridium novyi NT. Further Evidence for a Novel Anaerobic Biosynthetic Pathway to Plasmalogens

    OpenAIRE

    Guan, Ziqiang; Johnston, Norah C.; Aygun-Sunar, Semra; Daldal, Fevzi; Raetz, Christian R. H.; Goldfine, Howard

    2010-01-01

    A study of the polar lipids of Clostridium novyi NT has revealed the presence of phosphatidylethanolamine (PE) and cardiolipin as major phospholipids with smaller amounts of phosphatidylglycerol (PG), lysyl-PG and alanyl-PG. Other minor phospholipids included phosphatidic acid, CDP-diacylglycerol, phosphatidylserine (PS) and phosphatidylthreonine (PT). PE, PG and amino acyl PG were present in both the diacyl and alk-1’-enyl acyl (plasmalogen) forms and cardiolipin plasmalogens were found to c...

  4. Formulation design, preparation, and in vitro and in vivo characterizations of β-Elemene- loaded nanostructured lipid carriers

    Directory of Open Access Journals (Sweden)

    Shi F

    2013-07-01

    Full Text Available Feng Shi,1 Gang Yang,1 Juan Ren,2 Teng Guo,1 Yan Du,1 Nianping Feng1 1Department of Pharmaceutics, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China; 2Department of Traditional Chinese Medicine, Changhai Hospital, Shanghai, People's Republic of China Abstract: In the present study, nanostructured lipid carriers (NLCs were prepared and optimized for the intravenous delivery of β-Elemene (β-E. Aqueous dispersions of NLCs were successfully prepared by high-pressure homogenization method using glycerol monostearate as the solid lipid and a mixture of Maisine 35-1 and Labrafil M1944 CS as the liquid lipid. The results revealed that the morphology of the NLCs was spheroidal. The particle size, zeta potential, and entrapment efficiency (EE for the optimized formulation were observed as 138.9 nm, –20.2 mV, and 82.11%, respectively. X-ray diffraction analysis revealed the formation of less ordered structures in the inner core of the NLC particles. Moreover, the β-E-loaded NLCs were also less irritating and less toxic compared to Elemene injection. In addition, β-E-NLCs showed a significantly higher bioavailability and anti-tumor efficacy than Elemene injection. Taken together, our data indicate that the β-E-NLCs described in this study are well-suited for the intravenous delivery of β-E. Keywords: nanostructured lipid carriers, high-pressure homogenization, β-Elemene, venous irritation, anti-tumor efficacy

  5. Analysis of neutral lipid biosynthesis in Streptomyces avermitilis MA-4680 and characterization of an acyltransferase involved herein.

    Science.gov (United States)

    Kaddor, Chlud; Biermann, Karolin; Kalscheuer, Rainer; Steinbüchel, Alexander

    2009-08-01

    The physiology of lipid production in Streptomyces avermitilis MA-4680 with regard to the fatty acid composition of the accumulated lipids and their cellular distribution was analyzed. Cells were able to accumulate about ten to 30 lipid granules with diameters between 100 and 500 nm filling about 70-80% of the cell cytoplasm. Gas chromatography/mass spectrometry analyses of total cellular lipids and from isolated triacylglycerols (TAG) confirmed a similar fatty acid composition with a large portion of iso- and anteiso-methyl-branched fatty acids. De novo biosynthesis of wax esters (WE) appeared only during cocultivation on glucose and hexadecanol as carbon source. Homology alignments with the wax ester synthase/acyl-CoA:diacylglycerol acyltransferase (WS/DGAT; AtfA) from Acinetobacter baylyi strain ADP1 yielded one open reading frame in the genome databases of S. avermitilis MA-4680 referred to as SAV7256 with 25.3% homology. The highly conserved HHAxxDG active site motif found in AtfA, which is present in SAV7256, as well as the similar hydrophobicity profiles of AtfA and SAV7256 indicate a similar structure and function of both proteins. High acyl-CoA:diacylglycerol acyltransferase activity (DGAT; 143 pmol (mg min)(-1)) but low wax ester synthase activity (WS; 1.3 pmol (mg min)(-1)) were detected in crude extracts of S. avermitilis, which were consistent with the high TAG and negligible WE content of the cells. This indicates that TAG accumulation in S. avermitilis MA-4680 is mediated by the classical acyl-CoA-dependent DGAT pathway. Heterologous expression experiments in recombinant Escherichia coli BL21(DE3) demonstrated both WS and DGAT enzyme activity of SAV7256. Furthermore, substrate specificities of the acyltransferase SAV7256 will be discussed.

  6. Lateral Mixing

    Science.gov (United States)

    2012-11-08

    being made on their analysis. A process we became very curious about was the separation of tendrils of warm salty water from the north wall figure 7...structure, and to remove the effect of internal waves by mapping this structure onto isopycnals. This has been very successful in elucidating lateral...we passed through the same water on multiple passes, and that changes in the horizontal structure of the water mas should be readily apparent from

  7. Design, development, and characterization of lipid nanocarriers-based epigallocatechin gallate delivery system for preventive and therapeutic supplementation

    Directory of Open Access Journals (Sweden)

    Frias I

    2016-10-01

    Full Text Available Iúri Frias, Ana Rute Neves, Marina Pinheiro, Salette Reis Research Unit on Applied Molecular Biosciences, Rede de Química e Tecnologia, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal Abstract: Green tea is manufactured from the leaves of Camellia sinensis and has been shown to possess, among other properties, anticancer, antiobesity, antiatherosclerotic, antidiabetic, antibacterial, and antiviral effects. The beneficial effects of green tea are related to the activities of (--epigallocatechin gallate (EGCG. This catechin is very unstable, undergoing degradation and epimerization, which is responsible for the loss of its health benefits. Encapsulation in nanoparticles (NPs is an effective method to protect EGCG from adverse environmental conditions. In this work, solid lipid NPs (SLN and nanostructured lipid carriers (NLC were successfully developed to be used as biocompatible nanocarriers, enhancing the stability of EGCG. The mean diameter of the NPs was found to be around 300–400 nm, which is suitable for oral administration. Moreover, EGCG was effectively encapsulated with a remarkable efficiency of encapsulation of 80% and 90% for SLN and NLC, respectively. In addition, high storage stability of the formulations is expected as they maintain the initial characteristics for 3 months. Limited release of EGCG from the NPs was observed in simulated gastric and intestinal fluids. MTT and lactate dehydrogenase (LDH assays demonstrated that NPs possess low toxicity, and so have potential to be used for preventive and therapeutic EGCG supplementation. Keywords: EGCG, lipid nanoparticles, nanoparticles, nutraceuticals, supplementation

  8. Structural and functional characterization of human apolipoprotein E 72-166 peptides in both aqueous and lipid environments

    Directory of Open Access Journals (Sweden)

    Chou Chi-Yuan

    2011-01-01

    Full Text Available Abstract Backgrounds There are three apolipoprotein E (apoE isoforms involved in human lipid homeostasis. In the present study, truncated apoE2-, apoE3- and apoE4-(72-166 peptides that are tailored to lack domain interactions are expressed and elucidated the structural and functional consequences. Methods & Results Circular dichroism analyses indicated that their secondary structure is still well organized. Analytical ultracentrifugation analyses demonstrated that apoE-(72-166 produces more complicated species in PBS. All three isoforms were significantly dissociated in the presence of dihexanoylphosphatidylcholine. Dimyristoylphosphatidylcholine turbidity clearance assay showed that apoE4-(72-166 maintains the highest lipid-binding capacity. Finally, only apoE4-(72-166 still maintained significant LDL receptor binding ability. Conclusions Overall, apoE4-(72-166 peptides displayed a higher lipid-binding and comparable receptor-binding ability as to full-length apoE. These findings provide the explanation of diverged functionality of truncated apoE isoforms.

  9. Molecular characterization of carnitine palmitoyltransferase IA in Megalobrama amblycephala and effects on its expression of feeding status and dietary lipid and berberine.

    Science.gov (United States)

    Lu, Kang-Le; Zhang, Ding-Dong; Wang, Li-Na; Xu, Wei-Na; Liu, Wen-Bin

    2016-01-01

    Carnitine palmitoyltransferase I (CPT I, EC 2.3.1.21) controls the main regulatory step of fatty acid oxidation, and hence studies of its molecular characterization are useful to understand lipid metabolism in cultured fish. Here, a full-length cDNA coding CPT I was cloned from liver of blunt snout bream Megalobrama amblycephala. This cDNA obtained covered 2499bp with an open reading frame of 2181bp encoding 726 amino acids. This CPT I mRNA predominantly expressed in heart and white muscle, while little in eye and spleen. The phylogenetic tree constructed on the basis of sequence alignments among several vertebrate species suggests that this blunt snout bream CPT I sequence belongs to the CPT IA family. In order to investigate the characterization of CPT IA mRNA expression, post-prandial experiment and feeding trial were conducted. The results showed that CPT IA mRNA expression was unchanged from 2 to 12h, and then significantly increased at 24h post-feeding in liver and heart. Berberine, an alkaloid, was identified as a promising lipid-lowering drug. In order to elucidate the effect of berberine on CPT I expression, fish were fed for 8 weeks with three diets (low-fat diet (LFD, 5% fat), high-fat diet (HFD, 15% fat), and berberine-supplemented diet (BSD, 15% fat). The results showed that HFD could decrease the expression of CPT IA and PPARα, while BSD increased those expressions.

  10. Bioorthogonal chemical reporters for analyzing protein lipidation and lipid trafficking.

    Science.gov (United States)

    Hang, Howard C; Wilson, John P; Charron, Guillaume

    2011-09-20

    Protein lipidation and lipid trafficking control many key biological functions in all kingdoms of life. The discovery of diverse lipid species and their covalent attachment to many proteins has revealed a complex and regulated network of membranes and lipidated proteins that are central to fundamental aspects of physiology and human disease. Given the complexity of lipid trafficking and the protein targeting mechanisms involved with membrane lipids, precise and sensitive methods are needed to monitor and identify these hydrophobic molecules in bacteria, yeast, and higher eukaryotes. Although many analytical methods have been developed for characterizing membrane lipids and covalently modified proteins, traditional reagents and approaches have limited sensitivity, do not faithfully report on the lipids of interest, or are not readily accessible. The invention of bioorthogonal ligation reactions, such as the Staudinger ligation and azide-alkyne cycloadditions, has provided new tools to address these limitations, and their use has begun to yield fresh insight into the biology of protein lipidation and lipid trafficking. In this Account, we discuss how these new bioorthogonal ligation reactions and lipid chemical reporters afford new opportunities for exploring the biology of lipid-modified proteins and lipid trafficking. Lipid chemical reporters from our laboratory and several other research groups have enabled improved detection and large-scale proteomic analysis of fatty-acylated and prenylated proteins. For example, fatty acid and isoprenoid chemical reporters in conjunction with bioorthogonal ligation methods have circumvented the limited sensitivity and hazards of radioactive analogues, allowing rapid and robust fluorescent detection of lipidated proteins in all organisms tested. These chemical tools have revealed alterations in protein lipidation in different cellular states and are beginning to provide unique insights in mechanisms of regulation. Notably, the

  11. Generation and characterization of transgenic mice expressing mitochondrial targeted red fluorescent protein selectively in neurons: modeling mitochondriopathy in excitotoxicity and amyotrophic lateral sclerosis

    Directory of Open Access Journals (Sweden)

    Wang Yi

    2011-11-01

    Full Text Available Abstract Background Mitochondria have roles or appear to have roles in the pathogenesis of several chronic age-related and acute neurological disorders, including Charcot-Marie-Tooth disease, amyotrophic lateral sclerosis, Parkinson's disease, and cerebral ischemia, and could be critical targets for development of rational mechanism-based, disease-modifying therapeutics for treating these disorders effectively. A deeper understanding of neural tissue mitochondria pathobiologies as definitive mediators of neural injury, disease, and cell death merits further study, and the development of additional tools to study neural mitochondria will help achieve this unmet need. Results We created transgenic mice that express the coral (Discosoma sp. red fluorescent protein DsRed2 specifically in mitochondria of neurons using a construct engineered with a Thy1 promoter, specific for neuron expression, to drive expression of a fusion protein of DsRed2 with a mitochondrial targeting sequence. The biochemical and histological characterization of these mice shows the expression of mitochondrial-targeted DsRed2 to be specific for mitochondria and concentrated in distinct CNS regions, including cerebral cortex, hippocampus, thalamus, brainstem, and spinal cord. Red fluorescent mitochondria were visualized in cerebral cortical and hippocampal pyramidal neurons, ventrobasal thalamic neurons, subthalamic neurons, and spinal motor neurons. For the purpose of proof of principle application, these mice were used in excitotoxicity paradigms and double transgenic mice were generated by crossing Thy1-mitoDsRed2 mice with transgenic mice expressing enhanced-GFP (eGFP under the control of the Hlxb9 promoter that drives eGFP expression specifically in motor neurons and by crossing Thy1-mitoDsRed2 mice to amyotrophic lateral sclerosis (ALS mice expressing human mutant superoxide dismutase-1. Conclusions These novel transgenic mice will be a useful tool for better understanding

  12. Separation and characterization of the aldehydic products of lipid peroxidation stimulated by ADP-Fe2+ in rat liver microsomes.

    Science.gov (United States)

    Esterbauer, H; Cheeseman, K H; Dianzani, M U; Poli, G; Slater, T F

    1982-01-01

    1. Methods using t.l.c. and high-pressure liquid chromatography (h.p.l.c.) have been used to separate the complex variety of substances possessing a carbonyl function that are produced during lipid peroxidation. 2. The major type of lipid peroxidation studied was the ADP-Fe2+-stimulated peroxidation of rat liver microsomal phospholipids. Preliminary separation of the polar and non-polar products was achieved by t.l.c.: further separation and identification of individual components was performed by h.p.l.c. Estimations were performed on microsomal pellets and the supernatant mixture after incubation of microsomes for 30 min at 37 degrees C. 3. The polar fraction was larger than the non-polar fraction when expressed as nmol of carbonyl groups/g of liver. In the non-polar supernatant fraction the major contributors were n-alkanals (31% of the total), alpha-dicarbonyl compounds (22%) and 4-hydroxyalkenals (37%) with the extraction method used. 4. Major individual contributors to the non-polar fraction were found to be propanal, 4-hydroxynonenal, hexanal and oct-2-enal. Other components identified include butanal, pent-2-enal, hex-2-enal, hept-2-enal, 4-hydroxyoctenal and 4-hydroxyundecenal. The polar carbonyl fraction was less complex than the non-polar fraction, although the identities of the individual components have not yet been established. 5. Since these carbonyl compounds do not react significantly in the thiobarbituric acid reaction, which largely demonstrates the presence of malonaldehyde, it is concluded that considerable amounts of biologically reactive carbonyl derivatives are released in lipid peroxidation and yet may not be picked up by the thiobarbituric acid reaction. PMID:7159389

  13. Characterization of a new antifungal non-specific lipid transfer protein (nsLTP) from sugar beet leaves

    DEFF Research Database (Denmark)

    Kristensen, A K; Brunstedt, J; Madsen, M T;

    2000-01-01

    A novel protein (IWF5) comprising 92 amino acids has been purified from the intercellular washing fluid of sugar beet leaves using cation exchange chromatography and reversed phase high performance liquid chromatography. Based on amino acid sequence homology, including the presence of eight...... cysteines at conserved positions, the protein can be classified as a member of the plant family of non-specific lipid transfer proteins (nsLTPs). The protein is 47% identical to IWF1, an antifungal nsLTP previously isolated from leaves of sugar beet. A potential site for N-linked glycosylation present...

  14. Formulation, characterization and in vitro-in vivo evaluation of flurbiprofen-loaded nanostructured lipid carriers for transdermal delivery.

    Science.gov (United States)

    Kawadkar, Jitendra; Pathak, Ashwinkumar; Kishore, Raj; Chauhan, Meenakshi Kanwar

    2013-04-01

    Flurbiprofen is used in the treatment of arthritis. However, its multiple dosing due to short elimination half life is a concern for such treatment. This work aims to develop nanostructured lipid carriers (NLCs) of flurbiprofen and evaluate their potential for transdermal delivery. The NLCs were prepared by the optimized o/w emulsification-homogenization-sonication technique using coconut oil (liquid lipid). The NLCs were found to be spherical with uniform size (214 nm). The entrapment efficiency and zeta potential were 92.58% and -30.70 mV, respectively. Differential scanning calorimetry (DSC) showed the amorphous state of flurbiprofen encapsulated in NLCs. The percentage cumulative drug release through the excised rat skin from NLCs was biphasic and significantly prolonged compared with the commercial gel. DSC of the treated skin indicated that the NLCs penetrate into follicles of the skin and accumulate in the dermis. The bioavailability of flurbiprofen from NLCs was more than 1.7-fold that of the commercial gel. The NLCs showed a quick onset and sustained anti-inflammatory effect over period of 24 h for carrageenan-induced rat paw edema than the commercial gel. The stability data revealed that the NLCs were more stable when stored at 5°C. In conclusion, prepared NLCs have potential for skin targeting and sustained drug release.

  15. Design, development, and characterization of lipid nanocarriers-based epigallocatechin gallate delivery system for preventive and therapeutic supplementation

    Science.gov (United States)

    Frias, Iúri; Neves, Ana Rute; Pinheiro, Marina; Reis, Salette

    2016-01-01

    Green tea is manufactured from the leaves of Camellia sinensis and has been shown to possess, among other properties, anticancer, antiobesity, antiatherosclerotic, antidiabetic, antibacterial, and antiviral effects. The beneficial effects of green tea are related to the activities of (−)-epigallocatechin gallate (EGCG). This catechin is very unstable, undergoing degradation and epimerization, which is responsible for the loss of its health benefits. Encapsulation in nanoparticles (NPs) is an effective method to protect EGCG from adverse environmental conditions. In this work, solid lipid NPs (SLN) and nanostructured lipid carriers (NLC) were successfully developed to be used as biocompatible nanocarriers, enhancing the stability of EGCG. The mean diameter of the NPs was found to be around 300–400 nm, which is suitable for oral administration. Moreover, EGCG was effectively encapsulated with a remarkable efficiency of encapsulation of 80% and 90% for SLN and NLC, respectively. In addition, high storage stability of the formulations is expected as they maintain the initial characteristics for 3 months. Limited release of EGCG from the NPs was observed in simulated gastric and intestinal fluids. MTT and lactate dehydrogenase (LDH) assays demonstrated that NPs possess low toxicity, and so have potential to be used for preventive and therapeutic EGCG supplementation. PMID:27826184

  16. Characterization of pegylated liposomal mitomycin C lipid-based prodrug (Promitil®) by high sensitivity differential scanning calorimetry and cryogenic transmission electron microscopy.

    Science.gov (United States)

    Wei, Xiaohui; Patil, Yogita; Ohana, Patricia; Amitay, Yasmine; Shmeeda, Hilary; Gabizon, Alberto; Barenholz, Yechezkel

    2017-01-03

    The effect of a lipidated prodrug of mitomycin C (MLP) on the membrane of a pegylated liposome formulation (PL-MLP), also known as Promitil®, was characterized through high-sensitivity differential scanning calorimetry (DSC), and cryo-TEM. The thermodynamic analysis demonstrated that MLP led to the formation of heterogeneous domains in the membrane plane of PL-MLP. MLP concentrated in prodrug-rich domains, arranged in high-ordered crystal-like structures, as suggested by the sharp and high enthalpy endotherm in the 1st heating scanning. After thiolytic cleavage of mitomycin C from MLP by dithiotreitol (DTT) treatment, the crystal-like prodrug domain disappears and a homogeneous membrane with stronger lipid interactions and higher phase transition temperature compared with the blank (MLP-free) liposomes is observed by DSC. In parallel, the rod-like discoid liposomes and the "kissing liposomes" seen by cryo-TEM in the PL-MLP formulation disappear, and liposome mean size and polydispersity increase after DTT treatment. Both MLP and the residual post-cleavage lipophilic moiety of the prodrug increased rigidity of the liposome membrane as indicated by DSC. These results confirm that MLP is inserted in the PL-MLP liposome membrane via its lipophilic anchor, and its mitomycin C moiety located mainly at the region of the phospholipid glycerol backbone and polar head-group. We hypothesize that Π-Π stacking between the planar aromatic rings of the mitomycin C moieties leads to the formation of prodrug-rich domains with highly ordered structure on the PL-MLP liposome membrane. This thermodynamically stable conformation may explain the high stability of the PL-MLP formulation. These results also provide us with an interesting example of the application of high sensitivity DSC in understanding the composition-structure-behavior dynamics of liposomal nanocarriers having a lipid-based drug as pharmaceutical ingredient.

  17. Characterization of thoracic motor and sensory neurons and spinal nerve roots in canine degenerative myelopathy, a potential disease model of amyotrophic lateral sclerosis.

    Science.gov (United States)

    Morgan, Brandie R; Coates, Joan R; Johnson, Gayle C; Shelton, G Diane; Katz, Martin L

    2014-04-01

    Canine degenerative myelopathy (DM) is a progressive, adult-onset, multisystem degenerative disease with many features in common with amyotrophic lateral sclerosis (ALS). As with some forms of ALS, DM is associated with mutations in superoxide dismutase 1 (SOD1). Clinical signs include general proprioceptive ataxia and spastic upper motor neuron paresis in pelvic limbs, which progress to flaccid tetraplegia and dysphagia. The purpose of this study was to characterize DM as a potential disease model for ALS. We previously reported that intercostal muscle atrophy develops in dogs with advanced-stage DM. To determine whether other components of the thoracic motor unit (MU) also demonstrated morphological changes consistent with dysfunction, histopathologic and morphometric analyses were conducted on thoracic spinal motor neurons (MNs) and dorsal root ganglia (DRG) and in motor and sensory nerve root axons from DM-affected boxers and Pembroke Welsh corgis (PWCs). No alterations in MNs or motor root axons were observed in either breed. However, advanced-stage PWCs exhibited significant losses of sensory root axons, and numerous DRG sensory neurons displayed evidence of degeneration. These results indicate that intercostal muscle atrophy in DM is not preceded by physical loss of the motor neurons innervating these muscles, nor of their axons. Axonal loss in thoracic sensory roots and sensory neuron death suggest that sensory involvement may play an important role in DM disease progression. Further analysis of the mechanisms responsible for these morphological findings would aid in the development of therapeutic intervention for DM and some forms of ALS.

  18. Formulation and characterization of lipid-based drug delivery system of raloxifene-microemulsion and self-microemulsifying drug delivery system

    Directory of Open Access Journals (Sweden)

    Hetal Thakkar

    2011-01-01

    Full Text Available Background : Raloxifene, a second-generation selective estrogen receptor modulator (SERM used to prevent osteoporosis in postmenopausal women is administered orally in the form of a tablet. The absolute bioavailability of the drug is only 2% because of extensive hepatic first-pass metabolism. Lipid-based formulations are reported to reduce the first-pass metabolism by promoting its lymphatic uptake. Materials and Methods : In the present investigation, microemulsion and Self-Microemulsifying Drug Delivery System (SMEDDS formulations of Raloxifene were prepared. The prepared formulations were characterized for drug loading, size, transparency, zeta potential, Transmission Electron Microscopy (TEM and in vitro intestinal permeability. Results : The results indicated that high drug loading, optimum size and desired zeta potential and transparency could be achieved with both SMEDDS and microemulsion. The TEM studies indicated the absence of aggregation with both the systems. The in vitro intestinal permeability results showed that the permeation of the drug from the microemulsion and SMEDDs was significantly higher than that obtained from the drug dispersion and marketed formulation. Conclusion : Lipid based formulations such as microemulsion and Self Microemulsifying drug delivery systems are expected to increase the oral bioavailability as evidenced by the increased intestinal permeation.

  19. Solid lipid nanoparticles (SLN)--based hydrogels as potential carriers for oral transmucosal delivery of risperidone: preparation and characterization studies.

    Science.gov (United States)

    Silva, A C; Amaral, M H; González-Mira, E; Santos, D; Ferreira, D

    2012-05-01

    Two different solid lipid nanoparticles (SLN)-based hydrogels (HGs) formulations were developed as potential mucoadhesive systems for risperidone (RISP) oral transmucosal delivery. The suitability of the prepared semi-solid formulations for application on oral mucosa was assessed by means of rheological and textural analysis, during 30 days. Plastic flows with thixotropy and high adhesiveness were obtained for all the tested systems, which predict their success for the oral transmucosal application proposed. The SLN remained within the colloidal range after HGs preparation. However, after 30 days of storage, a particle size increase was detected in one type of the HGs formulations. In vitro drug release studies revealed a more pronounced RISP release after SLN hydrogel entrapment, when compared to the dispersions alone. In addition, a pH-dependent release was observed as well. The predicted in vivo RISP release mechanism was Fickian diffusion alone or combined with erosion.

  20. Stability of lipid excipients in solid lipid nanoparticles.

    Science.gov (United States)

    Radomska-Soukharev, Anna

    2007-07-10

    The paper is devoted to the investigation of chemical stability of lipids used as excipients in the production of Solid Lipid Nanoparticles (SLN). Different lipids and amounts of surfactants were considered. Most of the formulations were produced using identical binary surfactant mixtures and concentrations to analyze the effect of the chemical nature of the lipids on their stability in SLN. In some formulations, surfactants were exchanged or their concentration was increased to assess the contribution of surfactants on stability of lipids particles. Solid Lipid Nanoparticles were characterized by photon correlation spectroscopy, laser diffractometry, zeta potential determination and differential scanning calorimetry. Potential effects of lipid crystallinity and modifications were assessed. A gas chromatography (GC) analysis in combination with a method for lipid extraction from aqueous SLN dispersions was used to investigate the chemical stability of the lipid excipients forming the particle matrix. All formulations were produced by the hot homogenization technique. The production process of SLN itself did not affect the chemical stability of lipid excipient forming the particle matrix. The formulations where lipids consisted of trigylicerides showed a negligible decomposition of the structure during incubation at 25 degrees C. Dynasan 118 showed the highest chemical stability (loss<4%) within two years.

  1. Comparative physical-chemical characterization of encapsulated lipid-based isotretinoin products assessed by particle size distribution and thermal behavior analyses

    Energy Technology Data Exchange (ETDEWEB)

    Guimaraes, Carla Aiolfi, E-mail: carlaaiolfi@usp.br [Department of Pharmacy, Faculty of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, SP 05508-000 (Brazil); Menaa, Farid [Department of Dermatology, School of Medicine Wuerzburg, Wuerzburg 97080 (Germany); Fluorotronics, Inc., 1425 Russ Bvld, San Diego Technology Incubator, San Diego, CA 92101 (United States); Menaa, Bouzid, E-mail: bouzid.menaa@gmail.com [Fluorotronics, Inc., 1425 Russ Bvld, San Diego Technology Incubator, San Diego, CA 92101 (United States); Quenca-Guillen, Joyce S. [Department of Pharmacy, Faculty of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, SP 05508-000 (Brazil); Matos, Jivaldo do Rosario [Department of Fundamental Chemistry, Institute of Chemistry, University of Sao Paulo, Sao Paulo, SP 05508-000 (Brazil); Mercuri, Lucildes Pita [Department of Exact and Earth Sciences, Federal University of Sao Paulo, Diadema, SP 09972-270 (Brazil); Braz, Andre Borges [Department of Engineering of Mines and Oil, Polytechnical School, University of Sao Paulo, SP 05508-900 (Brazil); Rossetti, Fabia Cristina [Department of Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, SP 14015-120 (Brazil); Kedor-Hackmann, Erika Rosa Maria; Santoro, Maria Ines Rocha Miritello [Department of Pharmacy, Faculty of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, SP 05508-000 (Brazil)

    2010-06-10

    Isotretinoin is the drug of choice for the management of severe recalcitrant nodular acne. Nevertheless, some of its physical-chemical properties are still poorly known. Hence, the aim of our study consisted to comparatively evaluate the particle size distribution (PSD) and characterize the thermal behavior of the three encapsulated isotretinoin products in oil suspension (one reference and two generics) commercialized in Brazil. Here, we show that the PSD, estimated by laser diffraction and by polarized light microscopy, differed between the generics and the reference product. However, the thermal behavior of the three products, determined by thermogravimetry (TGA), differential thermal (DTA) analyses and differential scanning calorimetry (DSC), displayed no significant changes and were more thermostable than the isotretinoin standard used as internal control. Thus, our study suggests that PSD analyses in isotretinoin lipid-based formulations should be routinely performed in order to improve their quality and bioavailability.

  2. Cationic Dimyristoylphosphatidylcholine and Dioleoyloxytrimethylammonium Propane Lipid Bilayers: Atomistic Insight for Structure and Dynamics

    DEFF Research Database (Denmark)

    Zhao, W.; Gurtovenko, A. A.; Vattulainen, I.

    2012-01-01

    of 0.4, that is, at lower TAP fractions compared with saturated PC/TAP bilayers. Adding unsaturated DOTAP lipids into DMPC bilayers was found to promote lipid chain interdigitation and to fluidize lipid bilayers, as seen through enhanced lateral lipid diffusion. The speed-up in lateral diffusion...

  3. Corrugation of Phase-Separated Lipid Bilayers Supported by Nanoporous Silica Xerogel Surfaces

    Energy Technology Data Exchange (ETDEWEB)

    Goksu, E I; Nellis, B A; Lin, W; Satcher Jr., J H; Groves, J T; Risbud, S H; Longo, M L

    2008-10-30

    Lipid bilayers supported by substrates with nanometer-scale surface corrugations holds interest in understanding both nanoparticle-membrane interactions and the challenges of constructing models of cell membranes on surfaces with desirable properties, e.g. porosity. Here, we successfully form a two-phase (gel-fluid) lipid bilayer supported by nanoporous silica xerogel. Surface topology, diffusion, and lipid density in comparison to mica-supported lipid bilayers were characterized by AFM, FRAP, FCS, and quantitative fluorescence microscopy, respectively. We found that the two-phase lipid bilayer follows the xerogel surface contours. The corrugation imparted on the lipid bilayer results in a lipid density that is twice that on a flat mica surface. In direct agreement with the doubling of actual bilayer area in a projected area, we find that the lateral diffusion coefficient (D) of lipids on xerogel ({approx}1.7 {micro}m{sup 2}/s) is predictably lower than on mica ({approx}4.1 {micro}m{sup 2}/s) by both FRAP and FCS techniques. Furthermore, the gel-phase domains on xerogel compared to mica were larger and less numerous. Overall, our results suggest the presence of a relatively defect-free continuous two-phase bilayer that penetrates approximately midway into the first layer of {approx}50 nm xerogel beads.

  4. Characterization of GABAergic neurons in the mouse lateral septum: a double fluorescence in situ hybridization and immunohistochemical study using tyramide signal amplification.

    Directory of Open Access Journals (Sweden)

    Changjiu Zhao

    Full Text Available Gamma-aminobutyric acid (GABA neurotransmission in the lateral septum (LS is implicated in modulating various behavioral processes, including emotional reactivity and maternal behavior. However, identifying the phenotype of GABAergic neurons in the CNS has been hampered by the longstanding inability to reliably detect somal immunoreactivity for GABA or glutamic acid decarboxylase (GAD, the enzyme that produces GABA. In this study, we designed unique probes for both GAD65 (GAD2 and GAD67 (GAD1, and used fluorescence in Situ hybridization (FISH with tyramide signal amplification (TSA to achieve unequivocal detection of cell bodies of GABAergic neurons by GAD mRNAs. We quantitatively characterized the expression and chemical phenotype of GABAergic neurons across each subdivision of LS and in cingulate cortex (Cg and medial preoptic area (MPOA in female mice. Across LS, almost all GAD65 mRNA-expressing neurons were found to contain GAD67 mRNA (approximately 95-98%, while a small proportion of GAD67 mRNA-containing neurons did not express GAD65 mRNA (5-14%. Using the neuronal marker NeuN, almost every neuron in LS (> 90% was also found to be GABA-positive. Interneuron markers using calcium-binding proteins showed that LS GABAergic neurons displayed immunoreactivity for calbindin (CB or calretinin (CR, but not parvalbumin (PV; almost all CB- or CR-immunoreactive neurons (98-100% were GABAergic. The proportion of GABAergic neurons immunoreactive for CB or CR varied depending on the subdivisions examined, with the highest percentage of colocalization in the caudal intermediate LS (LSI (approximately 58% for CB and 35% for CR. These findings suggest that the vast majority of GABAergic neurons within the LS have the potential for synthesizing GABA via the dual enzyme systems GAD65 and GAD67, and each subtype of GABAergic neurons identified by distinct calcium-binding proteins may exert unique roles in the physiological function and neuronal circuitry of

  5. Electrodiffusion of lipids on membrane surfaces

    Science.gov (United States)

    Zhou, Y. C.

    2012-05-01

    Lateral translocation of lipids and proteins is a universal process on membrane surfaces. Local aggregation or organization of lipids and proteins can be induced when the random lateral motion is mediated by the electrostatic interactions and membrane curvature. Although the lateral diffusion rates of lipids on membranes of various compositions are measured and the electrostatic free energies of predetermined protein-membrane-lipid systems can be computed, the process of the aggregation and the evolution to the electrostatically favorable states remain largely undetermined. Here we propose an electrodiffusion model, based on the variational principle of the free energy functional, for the self-consistent lateral drift-diffusion of multiple species of charged lipids on membrane surfaces. Finite sizes of lipids are modeled to enforce the geometrical constraint of the lipid concentration on membrane surfaces. A surface finite element method is developed to appropriate the Laplace-Beltrami operators in the partial differential equations of the model. Our model properly describes the saturation of lipids on membrane surfaces, and correctly predicts that the MARCKS peptide can consistently sequester three multivalent phosphatidylinositol 4,5-bisphosphate lipids through its basic amino acid residues, regardless of a wide range of the percentage of monovalent phosphatidylserine in the membrane.

  6. The fusion of lipid droplets is involved in fat loss during cooking of duck "foie gras".

    Science.gov (United States)

    Théron, L; Astruc, T; Bouillier-Oudot, M; Molette, C; Vénien, A; Peyrin, F; Vitezica, Z G; Fernandez, X

    2011-12-01

    Fat loss during cooking of duck "foie gras" is the main quality issue in processing plants. To better understand this phenomenon, a histological and ultrastructural study was conducted. The aim was to characterize changes in lipid droplets of duck "foie gras" related to fat loss during cooking. Ten fatty livers were sampled before and after cooking and prepared for optical and transmission electron microscopy. In raw livers, the lipid droplets were nearly spherical while after cooking, they were larger and lost their spherical shape. We also observed a decrease in the number of droplets after cooking, probably due to droplet fusion caused by the heat treatment. Before cooking, there were fewer lipid droplets and a higher osmium tetroxyde staining intensity in the fatty liver, which later gave a lower technological yield. Fat loss during cooking was higher when there was more fusion of lipid droplets before cooking.

  7. Decoupling of crystalline and conformational degrees of freedom in lipid monolayers

    DEFF Research Database (Denmark)

    Ipsen, John Hjorth; Mouritsen, Ole G.; Zuckermann, Martin J.

    1989-01-01

    by a liquid-conformationally ordered phase. This prediction is consistent with synchrotron x-ray experiments which show that the chain-ordering transition and the crystallization process need not take place at the same lateral pressure. A characterization is provided of the nonequilibrium effects and pattern-formation...... of the experimentally observed isotherms of lipid monolayer phase behavior. It is pointed out that cholesterol, which promotes lipid-chain conformational order, has a unique capacity of acting as a `crystal breaker' in the solid monolayer phases and therefore provides a molecular mechanism for decoupling crystalline...... and conformational order in lipid monolayers containing cholesterol. The phase diagram of mixed cholesterol–lipid monolayers is derived and discussed in relation to monolayer experiments. The Journal of Chemical Physics is copyrighted by The American Institute of Physics....

  8. Enhancing biopharmaceutical attributes of phospholipid complex-loaded nanostructured lipidic carriers of mangiferin: Systematic development, characterization and evaluation.

    Science.gov (United States)

    Khurana, Rajneet Kaur; Bansal, Arvind K; Beg, Sarwar; Burrow, Andrea Julie; Katare, O P; Singh, Kamalinder K; Singh, Bhupinder

    2017-02-25

    Mangiferin (Mgf), largely expressed out from the leaves and stem bark of Mango, is a potent antioxidant. However, its in vivo activity gets tremendously reduced owing to poor aqueous solubility and inconsistent gastrointestinal absorption, high hepatic first-pass metabolism and high P-gp efflux. The current research work, therefore, was undertaken to overcome the biopharmaceutical hiccups by developing the Mgf-phospholipid complex (PLCs) loaded in nanostructured lipidic carriers (NLCs). The PLCs and NLCs were prepared using refluxing, solvent evaporation and hot emulsification technique, respectively with three molar ratios of Mgf and Phospholipon 90G, i.e., 1:1; 1:2; and 1:3. The complex was evaluated for various physicochemical parameters like drug content (96.57%), aqueous solubility (25-fold improved) and oil-water partition coefficient (10-fold enhanced). Diverse studies on the prepared complex using FTIR, DSC, PXRD and SEM studies ratified the formation of PLCs at 1:1 ratio. The PLCs were further incorporated onto NLCs, which were systematically optimized employing a face centered cubic design (FCCD), while evaluating for particle size, zeta potential, encapsulation efficiency and in vitro drug release as the CQAs. Caco-2 cell line studies indicated insignificant cytotoxicity, and P-gp efflux, while bi-directional permeability model and in situ perfusion studies specified enhanced intestinal permeation parameters. In vivo pharmacokinetic studies revealed notable increase in the values of Cmax (4.7-fold) and AUC (2.1-fold), respectively, from PLCs-loaded NLCs vis-à-vis Mgf solution. In a nutshell, the promising results observed from the present research work signify enhanced biopharmaceutical attributes of the novel PLCs-loaded NLCs for potentially augmenting the therapeutic efficacy of Mgf.

  9. Cloning and expression characterization of peroxisome proliferator-activated receptors (PPARs) with their agonists, dietary lipids, and ambient salinity in rabbitfish Siganus canaliculatus.

    Science.gov (United States)

    You, Cuihong; Jiang, Danli; Zhang, Qinghao; Xie, Dizhi; Wang, Shuqi; Dong, Yewei; Li, Yuanyou

    2017-04-01

    Rabbitfish Siganus canaliculatus is the first marine teleost reported to have the ability of biosynthesizing C20-22 long-chain polyunsaturated fatty acids (LC-PUFA) from C18 precursors, and thus provides a model for studying the regulatory mechanisms of LC-PUFA biosynthesis in teleosts. To investigate the possible roles of peroxisome proliferator-activated receptors (PPARs), critical transcription factors involved in the regulation of lipid metabolism, in the regulation of LC-PUFA biosynthesis in rabbitfish, the PPAR genes were cloned and their expression characterization with PPAR agonists, dietary lipid resource, and ambient salinity were examined. Three cDNA sequences respectively encoding 477, 516 and 519 amino acids of PPARα, PPARβ, and PPARγ isoforms were obtained. PPARα exhibited a wide tissue expression with its highest levels in the heart and brain; PPARβ was predominantly expressed in the gills, while PPARγ was highly expressed in the intestine and gills. In rabbitfish primary hepatocytes, both the PPAR agonists 2-bromopalmitate (2-Bro) and fenofibrate (FF) increased the expression of PPARγ, SREBP1c and Elovl5, whereas FF depressed the expression of Δ6/Δ5 Fad. Moreover, a higher hepatic PPARβ expression was observed in fish fed diets with vegetable oils (VO) than that with fish oil (FO), in the former the expression of PPARα, PPARβ, and PPARγ were increased at the low ambient salinity (10ppt), where an increasing expression of Δ5/Δ6 Fad, Δ4 Fad and Elovl5 genes was previously reported. These results suggest that PPARs might be involved in the upregulation of LC-PUFA biosynthesis with dietary VO and low ambient salinity in rabbitfish.

  10. A supercritical fluid-based coating technology. 3: preparation and characterization of bovine serum albumin particles coated with lipids.

    Science.gov (United States)

    Ribeiro Dos Santos, I; Richard, J; Thies, C; Pech, B; Benoit, J-P

    2003-01-01

    Solvent-free microparticles, loaded with bovine serum albumin as a model protein, were produced using a novel supercritical (SC) fluid-based coating technology. Coating material consists either of trimyristin (Dynasan 114) or of Gelucire 50-02. Microparticles obtained were characterized as regards their morphology, protein content and in vitro release profile. A discontinuous coating made of micro-needles of trimyristin led to an initial burst release of approximately 70% in 30 min. However, a prolonged release of the BSA could be achieved in a phosphate buffer solution at 37 degrees C over a 24 h period from particles coated with Gelucire 50-02. Furthermore, it was shown that BSA does not undergo any degradation after SC CO(2) treatment under the conditions used in the coating process.

  11. Characterization of Oilseed Lipids from “DHA-Producing Camelina sativa”: A New Transformed Land Plant Containing Long-Chain Omega-3 Oils

    OpenAIRE

    Maged P. Mansour; Pushkar Shrestha; Srinivas Belide; Petrie, James R.; Peter D Nichols; Surinder P. Singh

    2014-01-01

    New and sustainable sources of long-chain (LC, ≥C20) omega-3 oils containing DHA (docosahexaenoic acid, 22:6ω3) are required to meet increasing demands. The lipid content of the oilseed of a novel transgenic, DHA-producing land plant, Camelina sativa, containing microalgal genes able to produce LC omega-3 oils, contained 36% lipid by weight with triacylglycerols (TAG) as the major lipid class in hexane extracts (96% of total lipid). Subsequent chloroform-methanol (CM) extraction recovered fur...

  12. Characterization of RNA-Like Oligomers from Lipid-Assisted Nonenzymatic Synthesis: Implications for Origin of Informational Molecules on Early Earth

    Directory of Open Access Journals (Sweden)

    Chaitanya V. Mungi

    2015-01-01

    Full Text Available Prebiotic polymerization had to be a nonenzymatic, chemically driven process. These processes would have been particularly favored in scenarios which push reaction regimes far from equilibrium. Dehydration-rehydration (DH-RH cycles are one such regime thought to have been prevalent on prebiotic Earth in niches like volcanic geothermal pools. The present study defines the optimum DH-RH reaction conditions for lipid-assisted polymerization of nucleotides. The resultant products were characterized to understand their chemical makeup. Primarily, our study demonstrates that the resultant RNA-like oligomers have abasic sites, which means these oligomers lack information-carrying capability because of losing most of their bases during the reaction process. This results from low pH and high temperature conditions, which, importantly, also allows the formation of sugar-phosphate oligomers when ribose 5'-monophosphates are used as the starting monomers instead. Formation of such oligomers would have permitted sampling of a large variety of bases on a preformed polymer backbone, resulting in “prebiotic phosphodiester polymers” prior to the emergence of modern RNA-like molecules. This suggests that primitive genetic polymers could have utilized bases that conferred greater N-glycosyl bond stability, a feature crucial for information propagation in low pH and high temperature regimes of early Earth.

  13. Characterization of RNA-Like Oligomers from Lipid-Assisted Nonenzymatic Synthesis: Implications for Origin of Informational Molecules on Early Earth.

    Science.gov (United States)

    Mungi, Chaitanya V; Rajamani, Sudha

    2015-01-05

    Prebiotic polymerization had to be a nonenzymatic, chemically driven process. These processes would have been particularly favored in scenarios which push reaction regimes far from equilibrium. Dehydration-rehydration (DH-RH) cycles are one such regime thought to have been prevalent on prebiotic Earth in niches like volcanic geothermal pools. The present study defines the optimum DH-RH reaction conditions for lipid-assisted polymerization of nucleotides. The resultant products were characterized to understand their chemical makeup. Primarily, our study demonstrates that the resultant RNA-like oligomers have abasic sites, which means these oligomers lack information-carrying capability because of losing most of their bases during the reaction process. This results from low pH and high temperature conditions, which, importantly, also allows the formation of sugar-phosphate oligomers when ribose 5'-monophosphates are used as the starting monomers instead. Formation of such oligomers would have permitted sampling of a large variety of bases on a preformed polymer backbone, resulting in "prebiotic phosphodiester polymers" prior to the emergence of modern RNA-like molecules. This suggests that primitive genetic polymers could have utilized bases that conferred greater N-glycosyl bond stability, a feature crucial for information propagation in low pH and high temperature regimes of early Earth.

  14. Lipid characterization of seed oils from high-palmitic, low-palmitoleic, and very high-stearic acid sunflower lines.

    Science.gov (United States)

    Serrano-Vega, María J; Martínez-Force, Enrique; Garcés, Rafael

    2005-04-01

    Information obtained in recent years regarding the enzymes involved in FA synthesis can now be applied to develop novel sunflower lines by incorporating enzymes with specific characteristics into lines with a defined background. We have generated three highly saturated mutant lines in this way and characterized their FA content. The new high-palmitic, low-palmitoleic lines CAS-18 and CAS-25, the latter on a high-oleic background, have been selected from the high-stearic mutant CAS-3 by introducing a deficient stearic acid desaturase in a high-palmitic background from the previously developed mutant lines CAS-5 and CAS-12, respectively. As such, the desaturation of palmitic acid and the synthesis of palmitoleic acid and its derivatives (asclepic and palmitolinoleic acids) were reduced in these high-palmitic lines, increasing the stearic acid content. Likewise, introducing a FA thioesterase from a high-palmitic line (e.g., CAS-5) into the high-stearic CAS-3 increased the stearic acid content from 27 to 32% in the new high-stearic line CAS-31. As previously described in high-palmitic lines, high growth temperatures did not reduce the linoleic acid content of the oil. Furthermore, the FA composition of TAG, DAG, and phospholipids was modified in these lines. Besides a high degree of saturation, the TAG from these new vegetable oils have a low content of saturated FA in the sn-2 position. The alpha asymmetric coefficient obtained also indicates that the saturated FA are asymmetrically distributed within the TAG molecules. Indeed, the disaturated TAG content rose from 31.8 to 48.2%. These values of disaturated TAG are the highest to date in a temperate oilseed.

  15. Lipid functionalized biopolymers: A review.

    Science.gov (United States)

    Qurat-Ul-Ain; Zia, Khalid Mahmood; Zia, Fatima; Ali, Muhammad; Rehman, Saima; Zuber, Mohammad

    2016-12-01

    Lipids are the main source of energy and widely used for various applications. In this review, the modification of lipids by using them in combination with other biomaterials like natural and synthetic polymers is elaborated. These new blends have characteristic features of both polymers and are characterized by different techniques (NMR, DSC, TGA, IR and Raman spectroscopy etc.) to understand their structure, properties and functional behavior. Lipids are hydrophobic, have anti-oxidant and anti-bacterial properties and thus impart hydrophobicity and flexibility to the polymers. While the polymers, on the other hand, make the lipids tougher. Properties of few polymers such as starch, polyethylene protein and chitosan that have brittleness, low combustion rate and hydrophobicity, are improved by incorporation of lipids ultimately increased their flexibility, combustion rate and hydrophobicity respectively. This review article is also focused on emerging fields for the applications of these composite materials. The most notable application of composite materials are in the field of paint industry.

  16. Pollute first, clean up later?

    NARCIS (Netherlands)

    Azadi, Hossein; Verheijke, Gijs; Witlox, Frank

    2011-01-01

    There is a growing concern with regard to sustainability in emerging economies like China. The Chinese growth is characterized by a strategy which is known as "pollute first, clean up later". Here we show that based on this strategy, the pollution alarm can often be postponed by a tremendous economi

  17. Interaction of carbonylcyanide p-trifluoromethoxyphenylhydrazone (FCCP) with lipid membrane systems: a biophysical approach with relevance to mitochondrial uncoupling.

    Science.gov (United States)

    Monteiro, João P; Martins, André F; Lúcio, Marlene; Reis, Salette; Geraldes, Carlos F G C; Oliveira, Paulo J; Jurado, Amália S

    2011-06-01

    FCCP (carbonylcyanide p-trifluoromethoxyphenylhydrazone), a classical uncoupler of mitochondrial oxidative phosphorylation, is used in this study as a model to clarify how interactions of uncouplers with membrane lipid bilayers may influence membrane biophysics and their protonophoric activity itself. In order to disclose putative effects that may be important when considering using uncouplers for pharmacological purposes, an extensive characterization of FCCP membrane lipid interactions using accurate biophysical approaches and simple model lipid systems was carried out. Differential scanning calorimetry studies showed that FCCP molecules disturb lipid bilayers and favor lateral phase separation in mixed lipid systems. (31)P NMR assays indicated that FCCP alters the curvature elastic properties of membrane models containing non-bilayer lipids, favoring lamellar/H(II) transition, probably by alleviation of hydrocarbon-packing constraints in the inverted hexagonal phase. Taking advantage of FCCP quenching effects on the fluorescent probes DPH (1,6-diphenyl-1,3,5-hexatriene) and DPH-PA (3-(p-(6-phenyl)-1,3,5-hexatrienyl)phenylpropionic acid), it is demonstrated that FCCP distributes across the bilayer thickness in both a single and a ternary lipid system mimicking the inner mitochondrial membrane. This behavior is consistent with the ability of the compound to migrate through the thickness of the inner mitochondrial membrane, an event required for its protonophoric activity. Finally, the study of the membrane fluidity in different lipid systems, as reported by the rotational correlation time (θ) of DPH or DPH-PA, showed that the extension at which FCCP disturbs membrane properties associated with the dynamics and the order of lipid molecules depends on the lipid composition of the model lipid system assayed.

  18. Structure and distribution of the Bacillus thuringiensis Cry4Ba toxin in lipid membranes

    Energy Technology Data Exchange (ETDEWEB)

    Puntheeranurak, Theeraporn [Institute for Biophysics, Johannes Kepler University of Linz, Altenbergerstr. 69, A-4040 Linz (Austria); Laboratory of Molecular Biophysics, Institute of Molecular Biology and Genetics, Mahidol University, Salaya Campus, Nakornpathom 73170 (Thailand); Stroh, Cordula [Institute for Biophysics, Johannes Kepler University of Linz, Altenbergerstr. 69, A-4040 Linz (Austria); Zhu Rong [Institute for Biophysics, Johannes Kepler University of Linz, Altenbergerstr. 69, A-4040 Linz (Austria); Angsuthanasombat, Chanan [Laboratory of Molecular Biophysics, Institute of Molecular Biology and Genetics, Mahidol University, Salaya Campus, Nakornpathom 73170 (Thailand); Hinterdorfer, Peter [Institute for Biophysics, Johannes Kepler University of Linz, Altenbergerstr. 69, A-4040 Linz (Austria)]. E-mail: peter.hinterdorfer@jku.at

    2005-11-15

    Bacillus thuringiensis Cry {delta}-endotoxins cause death of susceptible insect larvae by forming lytic pores in the midgut epithelial cell membranes. The 65 kDa trypsin activated Cry4Ba toxin was previously shown to be capable of permeabilizing liposomes and forming ionic channels in receptor-free planar lipid bilayers. Here, magnetic ACmode (MACmode) atomic force microscopy (AFM) was used to characterize the lateral distribution and the native molecular structure of the Cry4Ba toxin in the membrane. Liposome fusion and the Langmuir-Blodgett technique were employed for supported lipid bilayer preparations. The toxin preferentially inserted in a self-assembled structure, rather than as a single monomeric molecule. In addition, the spontaneous insertion into receptor-free lipid bilayers lead to formation of characteristic pore-like structures with four-fold symmetry, suggesting that tetramers are the preferred oligomerization state of this toxin.

  19. Structure of Cholesterol in Lipid Rafts

    Science.gov (United States)

    Toppozini, Laura; Meinhardt, Sebastian; Armstrong, Clare L.; Yamani, Zahra; Kučerka, Norbert; Schmid, Friederike; Rheinstädter, Maikel C.

    2014-11-01

    Rafts, or functional domains, are transient nano-or mesoscopic structures in the plasma membrane and are thought to be essential for many cellular processes such as signal transduction, adhesion, trafficking, and lipid or protein sorting. Observations of these membrane heterogeneities have proven challenging, as they are thought to be both small and short lived. With a combination of coarse-grained molecular dynamics simulations and neutron diffraction using deuterium labeled cholesterol molecules, we observe raftlike structures and determine the ordering of the cholesterol molecules in binary cholesterol-containing lipid membranes. From coarse-grained computer simulations, heterogenous membranes structures were observed and characterized as small, ordered domains. Neutron diffraction was used to study the lateral structure of the cholesterol molecules. We find pairs of strongly bound cholesterol molecules in the liquid-disordered phase, in accordance with the umbrella model. Bragg peaks corresponding to ordering of the cholesterol molecules in the raftlike structures were observed and indexed by two different structures: a monoclinic structure of ordered cholesterol pairs of alternating direction in equilibrium with cholesterol plaques, i.e., triclinic cholesterol bilayers.

  20. Interactions between HIV-1 Neutralizing Antibodies and Model Lipid Membranes imaged with AFM

    Science.gov (United States)

    Zauscher, Stefan; Hardy, Gregory; Alam, Munir; Shapter, Joseph

    2012-02-01

    Lipid membrane interactions with rare, broadly neutralizing antibodies (NAbs), 2F5 and 4E10, play a critical role in HIV-1 neutralization. Our research is motivated by recent immunization studies that have shown that induction of antibodies that avidly bind the gp41-MPER antigen is not sufficient for neutralization. Rather, it is required that antigen designs induce polyreactive antibodies that recognize MPER antigens as well as the viral lipid membrane. However, the mechanistic details of how membrane properties influence NAb-lipid and NAb-antigen interactions remain unknown. Furthermore, it is well established that the native viral membrane is heterogeneous, representing a mosaic of lipid rafts and protein clustering. However, the size, physical properties, and dynamics of these regions are poorly characterized and their potential roles in HIV-1 neutralization are also unknown. To understand how membrane properties contribute to 2F5/4E10 membrane interactions, we have engineered biomimetic supported lipid bilayers (SLBs) and use atomic force microscopy to visualize membrane domains, antigen clustering, and antibody-membrane interactions at sub-nanometer z-resolution. Our results show that localized binding of HIV-1 antigens and NAbs occur preferentially with the most fluid membrane domain. This supports the theory that NAbs may interact with regions of low lateral lipid forces that allow antibody insertion into the bilayer.

  1. Characterization of Oilseed Lipids from “DHA-Producing Camelina sativa”: A New Transformed Land Plant Containing Long-Chain Omega-3 Oils

    Directory of Open Access Journals (Sweden)

    Maged P. Mansour

    2014-02-01

    Full Text Available New and sustainable sources of long-chain (LC, ≥C20 omega-3 oils containing DHA (docosahexaenoic acid, 22:6ω3 are required to meet increasing demands. The lipid content of the oilseed of a novel transgenic, DHA-producing land plant, Camelina sativa, containing microalgal genes able to produce LC omega-3 oils, contained 36% lipid by weight with triacylglycerols (TAG as the major lipid class in hexane extracts (96% of total lipid. Subsequent chloroform-methanol (CM extraction recovered further lipid (~50% polar lipid, comprising glycolipids and phospholipids and residual TAG. The main phospholipid species were phosphatidyl choline and phosphatidyl ethanolamine. The % DHA was: 6.8% (of total fatty acids in the TAG-rich hexane extract and 4.2% in the polar lipid-rich CM extract. The relative level of ALA (α-linolenic acid, 18:3ω3 in DHA-camelina seed was higher than the control. Major sterols in both DHA- and control camelina seeds were: sitosterol, campesterol, cholesterol, brassicasterol and isofucosterol. C16–C22 fatty alcohols, including iso-branched and odd-chain alcohols were present, including high levels of iso-17:0, 17:0 and 19:0. Other alcohols present were: 16:0, iso-18:0, 18:0 and 18:1 and the proportions varied between the hexane and CM extracts. These iso-branched odd-chain fatty alcohols, to our knowledge, have not been previously reported. These components may be derived from wax esters, or free fatty alcohols.

  2. Characterization of oilseed lipids from "DHA-producing Camelina sativa": a new transformed land plant containing long-chain omega-3 oils.

    Science.gov (United States)

    Mansour, Maged P; Shrestha, Pushkar; Belide, Srinivas; Petrie, James R; Nichols, Peter D; Singh, Surinder P

    2014-02-21

    New and sustainable sources of long-chain (LC, ≥C₂₀) omega-3 oils containing DHA (docosahexaenoic acid, 22:6ω3) are required to meet increasing demands. The lipid content of the oilseed of a novel transgenic, DHA-producing land plant, Camelina sativa, containing microalgal genes able to produce LC omega-3 oils, contained 36% lipid by weight with triacylglycerols (TAG) as the major lipid class in hexane extracts (96% of total lipid). Subsequent chloroform-methanol (CM) extraction recovered further lipid (~50% polar lipid, comprising glycolipids and phospholipids) and residual TAG. The main phospholipid species were phosphatidyl choline and phosphatidyl ethanolamine. The % DHA was: 6.8% (of total fatty acids) in the TAG-rich hexane extract and 4.2% in the polar lipid-rich CM extract. The relative level of ALA (α-linolenic acid, 18:3ω3) in DHA-camelina seed was higher than the control. Major sterols in both DHA- and control camelina seeds were: sitosterol, campesterol, cholesterol, brassicasterol and isofucosterol. C₁₆-C₂₂ fatty alcohols, including iso-branched and odd-chain alcohols were present, including high levels of iso-17:0, 17:0 and 19:0. Other alcohols present were: 16:0, iso-18:0, 18:0 and 18:1 and the proportions varied between the hexane and CM extracts. These iso-branched odd-chain fatty alcohols, to our knowledge, have not been previously reported. These components may be derived from wax esters, or free fatty alcohols.

  3. Cell wall lipids from Mycobacterium bovis BCG are inflammatory when inoculated within a gel matrix: characterization of a new model of the granulomatous response to mycobacterial components.

    Science.gov (United States)

    Rhoades, Elizabeth R; Geisel, Rachel E; Butcher, Barbara A; McDonough, Sean; Russell, David G

    2005-05-01

    The chronic inflammatory response to Mycobacterium generates complex granulomatous lesions that balance containment with destruction of infected tissues. To study the contributing factors from host and pathogen, we developed a model wherein defined mycobacterial components and leukocytes are delivered in a gel, eliciting a localized response that can be retrieved and analysed. We validated the model by comparing responses to the cell wall lipids from Mycobacterium bovis bacillus Calmette-Guerin (BCG) to reported activities in other models. BCG lipid-coated beads and bone marrow-derived macrophages (input macrophages) were injected intraperitoneally into BALB/c mice. Input macrophages and recruited peritoneal exudate cells took up fluorescently tagged BCG lipids, and matrix-associated macrophages and neutrophils produced tumor necrosis factor, interleukin-1alpha, and interleukin-6. Leukocyte numbers and cytokine levels were greater in BCG lipid-bearing matrices than matrices containing non-coated or phosphatidylglycerol-coated beads. Leukocytes arrived in successive waves of neutrophils, macrophages and eosinophils, followed by NK and T cells (CD4(+), CD8(+), or gammadelta) at 7 days and B cells within 12 days. BCG lipids also predisposed matrices for adherence and vascularization, enhancing cellular recruitment. We submit that the matrix model presents pertinent features of the murine granulomatous response that will prove to be an adaptable method for study of this complex response.

  4. Multiscale Modeling of Supported Lipid Bilayers

    Science.gov (United States)

    Hoopes, Matthew I.; Xing, Chenyue; Faller, Roland

    Cell membranes consist of a multitude of lipid molecules that serve as a framework for the even greater variety of membrane associated proteins [1-4]. As this highly complex (nonequilibrium) system cannot easily be understood and studied in a controlled way, a wide variety of model systems have been devised to understand the dynamics, structure, and thermodynamics in biological membranes. One such model system is a supported lipid bilayer (SLB), a two-dimensional membrane suspended on a surface. SLBs have been realized to be manageable experimentally while reproducing many of the key features of real biological membranes [5,6]. One of the main advantages of supported bilayers is the physical stability due to the solid support that enables a wide range of surface characterization techniques not available to free or unsupported membranes. As SLBs maintain some of the crucial structural and dynamic properties of biological membranes, they provide an important bridge to natural systems. In order to mimic cell membranes reliably, certain structural and dynamic features have to be reliably reproduced in the artificially constructed lipid bilayers. SLBs should display lateral mobility as in living cells, because many membrane activities involve transport, recruitment, or assembly of specific components. It is also critical for membranes to exhibit the correct thermodynamic phase, namely, a fluid lipid bilayer, to respond to environmental stress such as temperature and pressure changes [7]. There are several ways to fabricate supported lipid bilayers (SLBs) on planar substrates. One can use vesicle fusion on solid substrates [5,8-10] as well as Langmuir-Blodgett deposition [11,12]. Proteoliposome adsorption and subsequent membrane formation on a mica surface was first demonstrated by Brian and McConnell [13]. Because of its simplicity and reproducibility, this is one of the most common approaches to prepare supported membranes. A diverse range of different solid substrates

  5. SOLID LIPID NANOPARTICLES: A REVIEW

    Directory of Open Access Journals (Sweden)

    Mudavath Hanumanaik*, Sandeep Kumar Patel and K. Ramya Sree

    2013-03-01

    Full Text Available ABSTRACT: Solid lipid nanoparticles (SLN are at the forefront of the rapidly developing field of nanotechnology with several potential applications in drug delivery and research. Due to their unique size dependent properties, lipid nanoparticles offer possibility to develop new therapeutics. The ability to incorporate drugs into nanocarriers offers a new prototype in drug delivery that could use for drug targeting. Hence solid lipid nanoparticles hold great promise for reaching the goal of controlled and site specific drug delivery and hence attracted wide attention of researchers. This review presents a broad treatment of solid lipid nanoparticles discussing their aims, production procedures, advantages, limitations and their possible remedies. Appropriate analytical techniques for the characterization of SLN like Photon Correlation Spectroscopy (PCS, Scanning Electron Microscopy (SEM, and Differential Scanning Calorimetry are highlighted. Aspects of SLN route of administration and the in vivo fate of the carriers are also discussed.

  6. Lipid dynamics at dendritic spines.

    Science.gov (United States)

    Dotti, Carlos Gerardo; Esteban, Jose Antonio; Ledesma, María Dolores

    2014-01-01

    Dynamic changes in the structure and composition of the membrane protrusions forming dendritic spines underlie memory and learning processes. In recent years a great effort has been made to characterize in detail the protein machinery that controls spine plasticity. However, we know much less about the involvement of lipids, despite being major membrane components and structure determinants. Moreover, protein complexes that regulate spine plasticity depend on specific interactions with membrane lipids for proper function and accurate intracellular signaling. In this review we gather information available on the lipid composition at dendritic spine membranes and on its dynamics. We pay particular attention to the influence that spine lipid dynamism has on glutamate receptors, which are key regulators of synaptic plasticity.

  7. How does the spacer length of cationic gemini lipids influence the lipoplex formation with plasmid DNA? Physicochemical and biochemical characterizations and their relevance in gene therapy.

    Science.gov (United States)

    Muñoz-Úbeda, Mónica; Misra, Santosh K; Barrán-Berdón, Ana L; Datta, Sougata; Aicart-Ramos, Clara; Castro-Hartmann, Pablo; Kondaiah, Paturu; Junquera, Elena; Bhattacharya, Santanu; Aicart, Emilio

    2012-12-10

    Lipoplexes formed by the pEGFP-C3 plasmid DNA (pDNA) and lipid mixtures containing cationic gemini surfactant of the 1,2-bis(hexadecyl dimethyl ammonium) alkanes family referred to as C16CnC16, where n=2, 3, 5, or 12, and the zwitterionic helper lipid, 1,2-dioleoyl-sn-glycero-3-phosphatidylethanolamine (DOPE) have been studied from a wide variety of physical, chemical, and biological standpoints. The study has been carried out using several experimental methods, such as zeta potential, gel electrophoresis, small-angle X-ray scattering (SAXS), cryo-TEM, gene transfection, cell viability/cytotoxicity, and confocal fluorescence microscopy. As reported recently in a communication (J. Am. Chem. Soc. 2011, 133, 18014), the detailed physicochemical and biological studies confirm that, in the presence of the studied series lipid mixtures, plasmid DNA is compacted with a large number of its associated Na+ counterions. This in turn yields a much lower effective negative charge, qpDNA−, a value that has been experimentally obtained for each mixed lipid mixture. Consequently, the cationic lipid (CL) complexes prepared with pDNA and CL/DOPE mixtures to be used in gene transfection require significantly less amount of CL than the one estimated assuming a value of qDNA−=−2. This drives to a considerably lower cytotoxicity of the gene vector. Depending on the CL molar composition, α, of the lipid mixture, and the effective charge ratio of the lipoplex, ρeff, the reported SAXS data indicate the presence of two or three structures in the same lipoplex, one in the DOPE-rich region, other in the CL-rich region, and another one present at any CL composition. Cryo-TEMand SAXS studies with C16CnC16/DOPE-pDNA lipoplexes indicate that pDNA is localized between the mixed lipid bilayers of lamellar structures within a monolayer of ∼2 nm. This is consistent with a highly compacted supercoiled pDNA conformation compared with that of linear DNA. Transfection studies were carried out

  8. Cold induces micro- and nano-scale reorganization of lipid raft markers at mounds of T-cell membrane fluctuations.

    Directory of Open Access Journals (Sweden)

    Yong Chen

    Full Text Available Whether and how cold causes changes in cell-membrane or lipid rafts remain poorly characterized. Using the NSOM/QD and confocal imaging systems, we found that cold caused microscale redistribution of lipid raft markers, GM1 for lipid and CD59 for protein, from the peripheral part of microdomains to the central part on Jurkat T cells, and that cold also induced the nanoscale size-enlargement (1/3- to 2/3-fold of the nanoclusters of lipid raft markers and even the colocalization of GM1 and CD59 nanoclusters. These findings indicate cold-induced lateral rearrangement/coalescence of raft-related membrane heterogeneity. The cold-induced re-distribution of lipid raft markers under a nearly-natural condition provide clues for their alternations, and help to propose a model in which raft lipids associate themselves or interact with protein components to generate functional membrane heterogeneity in response to stimulus. The data also underscore the possible cold-induced artifacts in early-described cold-related experiments and the detergent-resistance-based analyses of lipid rafts at 4 degrees C, and provide a biophysical explanation for recently-reported cold-induced activation of signaling pathways in T cells. Importantly, our fluorescence-topographic NSOM imaging demonstrated that GM1/CD59 raft markers distributed and re-distributed at mounds but not depressions of T-cell membrane fluctuations. Such mound-top distribution of lipid raft markers or lipid rafts provides spatial advantage for lipid rafts or contact molecules interacting readily with neighboring cells or free molecules.

  9. Tennis Elbow (Lateral Epicondylitis)

    Science.gov (United States)

    .org Tennis Elbow (Lateral Epicondylitis) Page ( 1 ) Tennis elbow, or lateral epicondyliti s, is a painful condition of the elbow caused by overuse. Not surprisingly, playing tennis or other racquet sports can cause ...

  10. Primary Lateral Sclerosis

    Science.gov (United States)

    ... mistaken for amyotrophic lateral sclerosis (ALS) or spastic paraplegia. Most neurologists follow an affected individual's clinical course ... mistaken for amyotrophic lateral sclerosis (ALS) or spastic paraplegia. Most neurologists follow an affected individual's clinical course ...

  11. Characterization and fatty acid profiling in two fresh water microalgae for biodiesel production: Lipid enhancement methods and media optimization using response surface methodology.

    Science.gov (United States)

    Karpagam, Rathinasamy; Raj, Kalimuthu Jawahar; Ashokkumar, Balasubramaniem; Varalakshmi, Perumal

    2015-01-01

    Two fresh water microalgae, Coelastrella sp. M-60 and Micractinium sp. M-13 were investigated in this study for their potential of biodiesel production. For increasing biomass and lipid production, these microalgae were subjected to nutrient starvation (nitrogen, phosphorous, iron), salinity stress and nutrient supplementation with sugarcane industry effluent, citric acid, glucose and vitamin B12. The lipid productivity obtained from the isolates Coelastrella sp. M-60 (13.9 ± 0.4 mg/L/day) and Micractinium sp. M-13 (11.1 ± 0.2 mg/L/day) was maximum in salinity stress. The media supplemented with all the four nutrients yielded higher lipid productivity than the control. The response surface methodology (RSM) was employed to evaluate the effect of sugarcane industry effluent and citric acid on growth and lipid yield. Fatty acid profile of Coelastrella sp. M-60 and Micractinium sp. M-13 were composed of C-14, C-16:0, C-18:0, C-18:1 and C-18:2 and their fuel properties were also in accordance with international standards.

  12. Application of quality by design approach for intranasal delivery of rivastigmine loaded solid lipid nanoparticles: Effect on formulation and characterization parameters.

    Science.gov (United States)

    Shah, Brijesh; Khunt, Dignesh; Bhatt, Himanshu; Misra, Manju; Padh, Harish

    2015-10-12

    In the present investigation, Quality by Design (QbD) approach was applied on the development and optimization of solid lipid nanoparticle (SLN) formulation of hydrophilic drug rivastigmine (RHT). RHT SLN were formulated by homogenization and ultrasonication method using Compritol 888 ATO, tween-80 and poloxamer-188 as lipid, surfactant and stabilizer respectively. The effect of independent variables (X1 - drug: lipid ratio, X2 - surfactant concentration and X3 - homogenization time) on quality attributes of SLN i.e. dependent variables (Y1 - size, Y2 - PDI and Y3 - %entrapment efficiency (%EE)) were investigated using 3(3) factorial design. Multiple linear regression analysis and ANOVA were employed to indentify and estimate the main effect, 2FI, quadratic and cubic effect. Optimized RHT SLN formula was derived from an overlay plot on which further effect of probe sonication was evaluated. Final RHT SLN showed narrow size distribution (PDI- 0.132±0.016) with particle size of 82.5±4.07 nm and %EE of 66.84±2.49. DSC and XRD study showed incorporation of RHT into imperfect crystal lattice of Compritol 888 ATO. In comparison to RHT solution, RHT SLN showed higher in-vitro and ex-vivo diffusion. The diffusion followed Higuchi model indicating drug diffusion from the lipid matrix due to erosion. Histopathology study showed intact nasal mucosa with RHT SLN indicating safety of RHT SLN for intranasal administration.

  13. Exploration of polar lipid accumulation profiles in Euglena gracilis using LipidBlast, an MS/MS spectral library constructed in silico.

    Science.gov (United States)

    Ogawa, Takumi; Furuhashi, Takeshi; Okazawa, Atsushi; Nakai, Rai; Nakazawa, Masami; Kind, Tobias; Fiehn, Oliver; Kanaya, Shigehiko; Arita, Masanori; Ohta, Daisaku

    2014-01-01

    A rapid protocol for polar lipid profiling was applied to Euglena gracilis lipid metabolism by LipidBlast, an MS/MS spectral similarity search tool. The similarity search results suggested anoxia-induced polar lipid metabolism in Euglena characterized by the accumulation of differential lipid classes, carbon chain lengths, and unsaturated bond numbers. The informatics-supported MS spectral search provides an alternative option for global lipid profiling studies.

  14. Lipid signaling in plants

    NARCIS (Netherlands)

    Munnik, T.

    2010-01-01

    This book highlights the current status of plant lipid signaling. Written by leading researchers in the field, the chapters include detailed information on the measurement, regulation and function of phospholipases, lipid kinases, lipid phosphatases, inositolpolyphosphates, polyphosphoinositides, ph

  15. Lipid Metabolism Disorders

    Science.gov (United States)

    ... metabolic disorder, something goes wrong with this process. Lipid metabolism disorders, such as Gaucher disease and Tay-Sachs disease, involve lipids. Lipids are fats or fat-like substances. They ...

  16. Primary lateral sclerosis mimicking atypical parkinsonism

    DEFF Research Database (Denmark)

    Norlinah, Ibrahim M; Bhatia, Kailash P; Østergaard, Karen;

    2007-01-01

    Primary lateral sclerosis (PLS), the upper motor neurone variant of motor neurone disease, is characterized by progressive spinal or bulbar spasticity with minimal motor weakness. Rarely, PLS may present with clinical features resembling parkinsonism resulting in occasional misdiagnosis as one...

  17. Bridging the gap between single molecule and ensemble methods for measuring lateral dynamics in the plasma membrane.

    Directory of Open Access Journals (Sweden)

    Eva C Arnspang

    Full Text Available The lateral dynamics of proteins and lipids in the mammalian plasma membrane are heterogeneous likely reflecting both a complex molecular organization and interactions with other macromolecules that reside outside the plane of the membrane. Several methods are commonly used for characterizing the lateral dynamics of lipids and proteins. These experimental and data analysis methods differ in equipment requirements, labeling complexities, and further oftentimes give different results. It would therefore be very convenient to have a single method that is flexible in the choice of fluorescent label and labeling densities from single molecules to ensemble measurements, that can be performed on a conventional wide-field microscope, and that is suitable for fast and accurate analysis. In this work we show that k-space image correlation spectroscopy (kICS analysis, a technique which was originally developed for analyzing lateral dynamics in samples that are labeled at high densities, can also be used for fast and accurate analysis of single molecule density data of lipids and proteins labeled with quantum dots (QDs. We have further used kICS to investigate the effect of the label size and by comparing the results for a biotinylated lipid labeled at high densities with Atto647N-strepatvidin (sAv or sparse densities with sAv-QDs. In this latter case, we see that the recovered diffusion rate is two-fold greater for the same lipid and in the same cell-type when labeled with Atto647N-sAv as compared to sAv-QDs. This data demonstrates that kICS can be used for analysis of single molecule data and furthermore can bridge between samples with a labeling densities ranging from single molecule to ensemble level measurements.

  18. Comparative Genomics Analysis and Phenotypic Characterization of Shewanella putrefaciens W3-18-1: Anaerobic Respiration, Bacterial Microcompartments, and Lateral Flagella

    Energy Technology Data Exchange (ETDEWEB)

    Qiu, D.; Tu, Q.; He, Zhili; Zhou, Jizhong

    2010-05-17

    Respiratory versatility and psychrophily are the hallmarks of Shewanella. The ability to utilize a wide range of electron acceptors for respiration is due to the large number of c-type cytochrome genes present in the genome of Shewanella strains. More recently the dissimilatory metal reduction of Shewanella species has been extensively and intensively studied for potential applications in the bioremediation of radioactive wastes of groundwater and subsurface environments. Multiple Shewanella genome sequences are now available in the public databases (Fredrickson et al., 2008). Most of the sequenced Shewanella strains were isolated from marine environments and this genus was believed to be of marine origin (Hau and Gralnick, 2007). However, the well-characterized model strain, S. oneidensis MR-1, was isolated from the freshwater lake sediment of Lake Oneida, New York (Myers and Nealson, 1988) and similar bacteria have also been isolated from other freshwater environments (Venkateswaran et al., 1999). Here we comparatively analyzed the genome sequence and physiological characteristics of S. putrefaciens W3-18-1 and S. oneidensis MR-1, isolated from the marine and freshwater lake sediments, respectively. The anaerobic respirations, carbon source utilization, and cell motility have been experimentally investigated. Large scale horizontal gene transfers have been revealed and the genetic divergence between these two strains was considered to be critical to the bacterial adaptation to specific habitats, freshwater or marine sediments.

  19. Characterization of surface oxides on water-atomized steel powder by XPS/AES depth profiling and nano-scale lateral surface analysis

    Science.gov (United States)

    Chasoglou, D.; Hryha, E.; Norell, M.; Nyborg, L.

    2013-03-01

    Characterization of oxide products on the surface of water-atomized steel powder is essential in order to determine the reducing conditions required for their removal during the sintering stage which in turn will result in improved mechanical properties. Pre-alloyed powder with 3 wt% Cr and 0.5 wt% Mo was chosen as the model material. Investigation of the powder surface characteristics with regard to composition, morphology, size and distribution of surface oxides was performed using X-ray photoelectron spectroscopy, Auger electron spectroscopy and high resolution scanning electron microscopy combined with X-ray microanalysis. The analysis revealed that the powder is covered by a homogeneous (˜6 nm thick) Fe-oxide layer to ˜94% whereas the rest is covered by fine particulate features with the size below 500 nm. These particulates were further analyzed and were divided into three main categories (i) Cr-based oxides with simultaneous presence of nitrogen, (ii) Si-based oxides of "hemispherical" shape and (iii) agglomerates of the afore mentioned oxides.

  20. Characterization of the Aroma-Active, Phenolic, and Lipid Profiles of the Pistachio (Pistacia vera L.) Nut as Affected by the Single and Double Roasting Process.

    Science.gov (United States)

    Rodríguez-Bencomo, Juan José; Kelebek, Hasim; Sonmezdag, Ahmet Salih; Rodríguez-Alcalá, Luis Miguel; Fontecha, Javier; Selli, Serkan

    2015-09-01

    The pistachio (Pistacia vera L.) nut is one of the most widely consumed edible nuts in the world. However, it is the roasting process that makes the pistachio commercially viable and valuable as it serves as the key step to improving the nut's hallmark sensory characteristics including flavor, color, and texture. Consequently, the present study explores the effects of the single-roasting and double-roasting process on the pistachio's chemical composition, specifically aroma-active compounds, polyphenols, and lipids. Results showed the total polyphenol content of increased with the roasting treatment; however, not all phenolic compounds demonstrated this behavior. With regard to the aroma and aroma-active compounds, the results indicated that roasting process results in the development of characteristics and pleasant aroma of pistachio samples due to the Maillard reaction. With regard to lipids, the pistachio roasting treatment reduced the concentration of CN38 diacylglycerides while increasing the amount of elaidic acid.

  1. Hybrid lipid-based nanostructures

    Science.gov (United States)

    Dayani, Yasaman

    Biological membranes serve several important roles, such as structural support of cells and organelles, regulation of ionic and molecular transport, barriers to non-mediated transport, contact between cells within tissues, and accommodation of membrane proteins. Membrane proteins and other vital biomolecules incorporated into the membrane need a lipid membrane to function. Due to importance of lipid bilayers and their vital function in governing many processes in the cell, the development of various models as artificial lipid membranes that can mimic cell membranes has become a subject of great interest. Using different models of artificial lipid membranes, such as liposomes, planar lipid bilayers and supported or tethered lipid bilayers, we are able to study many biophysical processes in biological membranes. The ability of different molecules to interact with and change the structure of lipid membranes can be also investigated in artificial lipid membranes. An important application of lipid bilayer-containing interfaces is characterization of novel membrane proteins for high throughput drug screening studies to investigate receptor-drug interactions and develop biosensor systems. Membrane proteins need a lipid bilayer environment to preserve their stability and functionality. Fabrication of materials that can interact with biomolecules like proteins necessitates the use of lipid bilayers as a mimic of cell membranes. The objective of this research is to develop novel hybrid lipid-based nanostructures mimicking biological membranes. Toward this aim, two hybrid biocompatible structures are introduced: lipid bilayer-coated multi-walled carbon nanotubes (MWCNTs) and hydrogel-anchored liposomes with double-stranded DNA anchors. These structures have potential applications in biosensing, drug targeting, drug delivery, and biophysical studies of cell membranes. In the first developed nanostructure, lipid molecules are covalently attached to the surfaces of MWCNTs, and

  2. Preparation and Characterization of Loperamide-Loaded Dynasan 114 Solid Lipid Nanoparticles for Increased Oral Absorption In the Treatment of Diarrhea

    Science.gov (United States)

    Wei, Lili; Yang, Yunfang; Shi, Kun; Wu, Jun; Zhao, Wei; Mo, Jingxin

    2016-01-01

    The aim of the project was to assemble two optimum solid lipid nanoparticle (SLN) formulations for oral delivery of loperamide (LPM) to treat different types of diarrhea, and to evaluate their release profiles in vitro and pharmacokinetic properties in vivo. In this work, glyceryl trimyristate (Dynasan 114) nanoparticles containing the drug LPM and sodium cholate as a stabilizer were prepared using a modified solvent evaporation technique. Two LPM-loaded SLNs, namely LPM-SLN-1 (LPM-SLN with a high ratio rate of lipid to drug) and LPM-SLN-2 (LPM-SLN with a low ratio rate of lipid to drug), were prepared by the solvent evaporation method. A change in the lipid concentration affects the characteristics of LPM-SLNs. The average sizes of the LPM-SLNs were 303 ± 18 nm and 519 ± 36 nm, separately, as analyzed by dynamic light scattering. The LPM-SLNs were found to be round with a smooth surface, as observed using a transmission electron microscope and a scanning electron microscope. The average encapsulation efficiencies were 87 ± 3.78% w/w and 84 ± 5.17%, accordingly. In the in vitro release experiments, LPM-SLNs showed a continuous release profile of LPM without any burst release. The oral bioavailability of LPM-SLNs was analyzed using Wistar rats. The relative bioavailabilities of LPM-SLNs were 227 and 153%, respectively, as compared that of the LPM tablet. There was no difference in the Tmax between LPM-SLN-2 and the LPM tablet. In conclusion, LPM-SLN-1 significantly improved the oral bioavailability of LPM, while LPM-SLN-2 having the same swift action as the LPM tablet. These results demonstrate the potential of LPM-SLNs in the oral delivery of LPM to treat different types of diarrhea. PMID:27708583

  3. Preparation and characterization of loperamide-loaded Dynasan 114 solid lipid nanoparticles for increased oral absorption in the treatment of diarrhea

    Directory of Open Access Journals (Sweden)

    Lili Wei

    2016-09-01

    Full Text Available The aim of the project was to assemble two optimum solid lipid nanoparticle (SLN formulations for oral delivery of loperamide (LPM to treat different types of diarrhea, and to evaluate their release profiles in vitro and pharmacokinetic properties in vivo. In this work, glyceryl trimyristate (Dynasan 114 nanoparticles containing the drug LPM and sodium cholate as a stabilizer were prepared using a modified solvent evaporation technique. Two LPM-loaded SLNs, namely LPM-SLN-1 (LPM-SLN with a high ratio rate of lipid to drug and LPM-SLN-2 (LPM-SLN with a low ratio rate of lipid to drug, were prepared by the solvent evaporation method. A change in the lipid concentration affects the characteristics of LPM-SLNs. The average sizes of the LPM-SLNs were 303 ± 18 nm and 519 ± 36 nm, separately, as analyzed by dynamic light scattering (DLS. The LPM-SLNs were found to be round with a smooth surface, as observed using a transmission electron microscope (TEM and a scanning electron microscope (SEM. The average encapsulation efficiencies were 87 ± 3.78% w/w and 84 ± 5.17%, accordingly. In the in vitro release experiments, LPM-SLNs showed a continuous release profile of LPM without any burst release. The oral bioavailability of LPM-SLNs was analyzed using Wistar rats. The relative bioavailabilities of LPM-SLNs were 227% and 153%, respectively, as compared that of the LPM tablet. There was no difference in the Tmax between LPM-SLN-2 and the LPM tablet. In conclusion, LPM-SLN-1 significantly improved the oral bioavailability of LPM, while LPM-SLN-2 having the same swift action as the LPM tablet. These results demonstrate the potential of LPM-SLNs in the oral delivery of LPM to treat different types of diarrhea.

  4. Preparation and Characterization of Loperamide-Loaded Dynasan 114 Solid Lipid Nanoparticles for Increased Oral Absorption In the Treatment of Diarrhea

    OpenAIRE

    Wei, Lili; Yang, Yunfang; Shi, Kun; Wu, Jun; Zhao, Wei; Mo, Jingxin

    2016-01-01

    The aim of the project was to assemble two optimum solid lipid nanoparticle (SLN) formulations for oral delivery of loperamide (LPM) to treat different types of diarrhea, and to evaluate their release profiles in vitro and pharmacokinetic properties in vivo. In this work, glyceryl trimyristate (Dynasan 114) nanoparticles containing the drug LPM and sodium cholate as a stabilizer were prepared using a modified solvent evaporation technique. Two LPM-loaded SLNs, namely LPM-SLN-1 (LPM-SLN with a...

  5. Preparation and characterization of loperamide-loaded Dynasan 114 solid lipid nanoparticles for increased oral absorption in the treatment of diarrhea

    OpenAIRE

    Lili Wei; Yunfang Yang; Kun Shi; Jun Wu; Wei Zhao; Jingxin Mo

    2016-01-01

    The aim of the project was to assemble two optimum solid lipid nanoparticle (SLN) formulations for oral delivery of loperamide (LPM) to treat different types of diarrhea, and to evaluate their release profiles in vitro and pharmacokinetic properties in vivo. In this work, glyceryl trimyristate (Dynasan 114) nanoparticles containing the drug LPM and sodium cholate as a stabilizer were prepared using a modified solvent evaporation technique. Two LPM-loaded SLNs, namely LPM-SLN-1 (LPM-SLN with a...

  6. Lamellar gel (lβ) phases of ternary lipid composition containing ceramide and cholesterol.

    Science.gov (United States)

    Busto, Jon V; García-Arribas, Aritz B; Sot, Jesús; Torrecillas, Alejandro; Gómez-Fernández, Juan C; Goñi, Félix M; Alonso, Alicia

    2014-02-04

    Lipid lateral segregation into specific domains in cellular membranes is associated with cell signaling and metabolic regulation. This phenomenon partially arises as a consequence of the very distinct bilayer-associated lipid physico-chemical properties that give rise to defined phase states at a given temperature. Until now lamellar gel (Lβ) phases have been described in detail in single or two-lipid systems. Using x-ray scattering, differential scanning calorimetry, confocal fluorescence microscopy, and atomic force microscopy, we have characterized phases of ternary lipid compositions in the presence of saturated phospholipids, cholesterol, and palmitoyl ceramide mixtures. These phases stabilized by direct cholesterol-ceramide interaction can exist either with palmitoyl sphingomyelin or with dipalmitoyl phosphatidylcholine and present intermediate properties between raft-associated phospholipid-cholesterol liquid-ordered and phospholipid-ceramide Lβ phases. The present data provide novel, to our knowledge, evidence of a chemically defined, multicomponent lipid system that could cooperate in building heterogeneous segregated platforms in cell membranes.

  7. An unusual lipid in the human pathogenic fungus Epidermophyton floccosum.

    Science.gov (United States)

    Yamada, T A; Nozawa, Y

    1979-09-28

    The dermatophyte Epidermophyton floccosum contains an unusual lipid characterized as 1(3),2-diacylglyceryl-3(1)-O-4'-(N,N,N-trimethyl)homoserine. Its concentration in E. floccosum is approx. 15% of the polar lipids. The role of this lipid in the biosynthesis of polar lipids and fatty acids is not yet known. However, it is interesting from a chemotaxonomic viewpoint that the lipids from two other genera of dermatophyte, Microsporum cookei and Trichophyton rubrum do not contain this novel lipid.

  8. Comparative lipid composition of heterotrophically and autotrophically grown Sulfolobus acidocaldarius.

    Science.gov (United States)

    Langworthy, T A

    1977-06-01

    Complex lipids from the thermoacidophilic facultative autotroph Sulfolobus acidocaldarius, as well as a strictly autotrophic isolate, were compared between cells grown on yeast extract and elemental sulfur. Lipids from both organisms grown autotrophically were nearly identical. Each contained about 15% neutral lipids, 35% glycolipids, and 50% acidic lipids. Glycolipids and acidic lipids contained C40H82-76-derived glycerol ether residues. Major glycolipids included the glycerol ether analogues of glucosyl galactosyl diglyceride (5%) and glucosyl polyol diglyceride (75%). Acidic lipids were comprised mainly of the glycerol ether analogues of phosphatidyl inositol (7%), inositolphosphoryl glucosyl polyol diglyceride (72%), and a partially characterized sulfate- and phosphate-containing derivative of glucosyl polyol diglyceride (13%). The lipids from cells grown heterotrophically were similar to those from autotrophically grown cells, except that the partially characterized acidic lipid was absent. In addition, the two glycolipids as well as the respective inositolphosphoryl derivatives were each present in nearly equal proportions.

  9. Atomistic study of lipid membranes containing chloroform: looking for a lipid-mediated mechanism of anesthesia.

    Directory of Open Access Journals (Sweden)

    Ramon Reigada

    Full Text Available The molecular mechanism of general anesthesia is still a controversial issue. Direct effect by linking of anesthetics to proteins and indirect action on the lipid membrane properties are the two hypotheses in conflict. Atomistic simulations of different lipid membranes subjected to the effect of small volatile organohalogen compounds are used to explore plausible lipid-mediated mechanisms. Simulations of homogeneous membranes reveal that electrostatic potential and lateral pressure transversal profiles are affected differently by chloroform (anesthetic and carbon tetrachloride (non-anesthetic. Simulations of structured membranes that combine ordered and disordered regions show that chloroform molecules accumulate preferentially in highly disordered lipid domains, suggesting that the combination of both lateral and transversal partitioning of chloroform in the cell membrane could be responsible of its anesthetic action.

  10. Temperature dependent heterogeneous rotational correlation in lipids

    Science.gov (United States)

    Dadashvand, Neda; Othon, Christina M.

    2016-12-01

    Lipid structures exhibit complex and highly dynamic lateral structure; and changes in lipid density and fluidity are believed to play an essential role in membrane targeting and function. The dynamic structure of liquids on the molecular scale can exhibit complex transient density fluctuations. Here the lateral heterogeneity of lipid dynamics is explored in free standing lipid monolayers. As the temperature is lowered the probes exhibit increasingly broad and heterogeneous rotational correlation. This increase in heterogeneity appears to exhibit a critical onset, similar to those observed for glass forming fluids. We explore heterogeneous relaxation in in a single constituent lipid monolayer of 1, 2-dimyristoyl-sn-glycero-3-phosphocholine by measuring the rotational diffusion of a fluorescent probe (1-palmitoyl-2-[1]-sn-glycero-3-phosphocholine), which is embedded in the lipid monolayer at low labeling density. Dynamic distributions are measured using wide-field time-resolved fluorescence anisotropy. The observed relaxation exhibits a narrow, liquid-like distribution at high temperatures (τ ˜ 2.4 ns), consistent with previous experimental measures (Dadashvand et al 2014 Struct. Dyn. 1 054701, Loura and Ramalho 2007 Biochim. Biophys. Acta 1768 467-478). However, as the temperature is quenched, the distribution broadens, and we observe the appearance of a long relaxation population (τ ˜ 16.5 ns). This supports the heterogeneity observed for lipids at high packing densities, and demonstrates that the nanoscale diffusion and reorganization in lipid structures can be significantly complex, even in the simplest amorphous architectures. Dynamical heterogeneity of this form can have a significant impact on the organization, permeability and energetics of lipid membrane structures.

  11. Development and characterization of siRNA lipoplexes: Effect of different lipids, in vitro evaluation in cancerous cell lines and in vivo toxicity study.

    Science.gov (United States)

    Khatri, Nirav; Baradia, Dipesh; Vhora, Imran; Rathi, Mohan; Misra, Ambikanandan

    2014-12-01

    Cationic liposomes have long been used as non-viral vectors for small interfering RNA (siRNA) delivery but are associated with high toxicity, less transfection efficiency, and in vivo instability. In this investigation, we have developed siRNA targeted to RRM1 that is responsible for development of resistance to gemcitabine in cancer cells. Effect of different lipid compositions has been evaluated on formation of stable and less toxic lipoplexes. Optimized cationic lipoplex (D2CH) system was comprised of dioleoyl-trimethylammoniumpropane (DOTAP), dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), hydrogenated soya phosphocholine (HSPC), cholesterol, and methoxy(polyethyleneglycol)2000-1,2-distearoyl-sn-glycero-3-phosphoethanolamine (mPEG2000-DSPE). D2CH lipoplexes have shown particle size (147.5 ± 2.89 nm) and zeta potential (12.26 ± 0.54 mV) characteristics essential for their in vivo use. In vitro cytotoxicity study has shown low toxicity of developed lipoplexes as compared with lipofectamine-2000 up to N/P ratio as high as 7.5. Cell uptake studies and gene expression studies have confirmed intracellular availability of siRNA. In addition, developed lipoplexes also showed ~3 times less hemolytic potential as compared with DOTAP/DOPE lipoplexes at lipid concentration of 5 mg/mL. Lipoplexes also maintained particle size less than 200 nm on exposure to high electrolyte concentration and showed >70% siRNA retention in presence of serum showing siRNA protection conferred by lipoplexes. Furthermore, in vivo acute toxicity studies in mice showed that formulation was non-toxic up to a dosage of 0.75 mg of siRNA/kg as lipoplexes and 300 mg lipid/kg as blank liposomes indicating tolerability of lipoplexes at a dose much higher than required for therapeutic use. Promising results of this study warrant further investigation of developed siRNA lipoplexes for cancer treatment.

  12. Mechanical Properties of Nanoscopic Lipid Domains.

    Science.gov (United States)

    Nickels, Jonathan D; Cheng, Xiaolin; Mostofian, Barmak; Stanley, Christopher; Lindner, Benjamin; Heberle, Frederick A; Perticaroli, Stefania; Feygenson, Mikhail; Egami, Takeshi; Standaert, Robert F; Smith, Jeremy C; Myles, Dean A A; Ohl, Michael; Katsaras, John

    2015-12-23

    The lipid raft hypothesis presents insights into how the cell membrane organizes proteins and lipids to accomplish its many vital functions. Yet basic questions remain about the physical mechanisms that lead to the formation, stability, and size of lipid rafts. As a result, much interest has been generated in the study of systems that contain similar lateral heterogeneities, or domains. In the current work we present an experimental approach that is capable of isolating the bending moduli of lipid domains. This is accomplished using neutron scattering and its unique sensitivity to the isotopes of hydrogen. Combining contrast matching approaches with inelastic neutron scattering, we isolate the bending modulus of ∼13 nm diameter domains residing in 60 nm unilamellar vesicles, whose lipid composition mimics the mammalian plasma membrane outer leaflet. Importantly, the bending modulus of the nanoscopic domains differs from the modulus of the continuous phase surrounding them. From additional structural measurements and all-atom simulations, we also determine that nanoscopic domains are in-register across the bilayer leaflets. Taken together, these results inform a number of theoretical models of domain/raft formation and highlight the fact that mismatches in bending modulus must be accounted for when explaining the emergence of lateral heterogeneities in lipid systems and biological membranes.

  13. Development of ibuprofen-loaded nanostructured lipid carrier-based gels: characterization and investigation of in vitro and in vivo penetration through the skin

    Science.gov (United States)

    Sütő, Blanka; Berkó, Szilvia; Kozma, Gábor; Kukovecz, Ákos; Budai-Szűcs, Mária; Erős, Gábor; Kemény, Lajos; Sztojkov-Ivanov, Anita; Gáspár, Róbert; Csányi, Erzsébet

    2016-01-01

    An ibuprofen-loaded nanostructured lipid carrier (IBU-NLC) was developed for enhanced skin penetration to improve the treatment of osteoarthritis and other musculoskeletal diseases. The mean particle size was 106 nm, with a spherical morphology, a smooth surface, and a zeta potential of −18.4 mV. X-ray diffraction studies revealed the amorphous state of the lipid matrix. Both Raman spectroscopy and Fourier transformation infrared analysis indicated no major shifts in the spectra of the formulations, which suggest rapid drug dissolution from the nanoparticles. The drug loading was 9.85%, and the entrapment efficiency was 98.51%. In vitro release of the NLC dispersion, in vitro permeation, and in vivo animal studies of IBU-NLC gel all confirmed that the permeation of IBU was significantly better than that of a reference after 6 hours. In conclusion, IBU-NLC gel is of great potential to enhance drug permeation through the skin and hence the efficacy of the treatment of chronic joint inflammation. PMID:27099487

  14. Purification and characterization of a novel cholesterol esterase from Pseudomonas aeruginosa, with its application to cleaning lipid-stained contact lenses.

    Science.gov (United States)

    Sugihara, Akio; Shimada, Yuji; Nomura, Atsuo; Terai, Tadamasa; Imayasu, Masaki; Nagai, Yusuke; Nagao, Toshihiro; Watanabe, Yomi; Tominaga, Yoshio

    2002-11-01

    With the aim of developing a new cholesterol esterase for eliminating lipids on used contact lenses, microorganisms were screened for the enzyme activity. A Pseudomonas aeruginosa isolated from soil was found to produce a desirable enzyme. The enzyme had an isoelectric point of 3.2, and molecular mass of 58 kDa. The optimal temperature was around 53 degrees C at pH 7.0, and the optimal pH was from 5.5 to 9.5. The enzyme was stable between pH 5 and 10 for 19 h at 25 degrees C, and retained its activity up to 53 degrees C on 30 min of incubation at pH 7.0. The rates of hydrolysis of cholesteryl esters of different fatty acids were in the following order: linoleate > oleate > stearate > palmitate > caprylate > myristate > laurate, caprate > caproate > butyrate, acetate. Addition of (tauro)cholate to a final concentration of 100 mM markedly promoted the hydrolysis of triglycerides of short-, medium-, and long-chain fatty acids. When used with taurocholate, the enzyme acted as an effective cleaner for contact lenses stained with lipids consisting of cholesteryl oleate, tripalmitin, and stearyl stearate.

  15. Purification and characterization of a lipid thiobis ester from human neutrophil cytosol that reversibly deactivates the O2- -generating NADPH oxidase.

    Science.gov (United States)

    Eklund, E A; Gabig, T G

    1990-05-25

    Intact neutrophils possess a cellular mechanism that efficiently deactivates the microbicidal O2-generating NADPH oxidase during the respiratory burst (Akard, L. P., English, D., and Gabig, T. G. (1988) Blood 72, 322-327). The present studies directed at identifying the molecular mechanism(s) involved in NADPH oxidase deactivation showed that a heat- and trypsin-insensitive species in the cytosolic fraction from normal unstimulated neutrophils was capable of deactivating the membrane-associated NADPH oxidase isolated from opsonized zymosan- or phorbol 12-myristate 13-acetate-stimulated neutrophils. This cytosolic species also deactivated the cell-free-activated oxidase. Deactivation by this cytosolic species occurred in the absence of NADPH-dependent catalytic turnover and was reversible, since NADPH oxidase activity could be subsequently reactivated in the cell-free system. The sedimentable particulate fraction from unstimulated neutrophils did not demonstrate deactivator activity. Deactivator activity was demonstrated in the neutral lipid fraction of neutrophil cytosol extracted with chloroform:methanol. Following complete purification of cytosolic deactivator activity by thin layer chromatography and reversed phase high performance liquid chromatography, the deactivator species was shown to be a lipid thiobis ester compound by mass spectroscopy. Cellular metabolism of this compound in human neutrophils may reveal a unique mechanism for enzymatic control of the NADPH oxidase system and thereby play an important role in regulation of the inflammatory response.

  16. Direct visualization of lipid domains in human skin stratum corneum's lipid membranes

    DEFF Research Database (Denmark)

    Plasencia, I; Norlen, Lars; Bagatolli, Luis

    2007-01-01

    The main function of skin is to serve as a physical barrier between the body and the environment. This barrier capacity is in turn a function of the physical state and structural organization of the stratum corneum extracellular lipid matrix. This lipid matrix is essentially composed of very long...... chain saturated ceramides, cholesterol, and free fatty acids. Three unsolved key questions are i), whether the stratum corneum extracellular lipid matrix is constituted by a single gel phase or by coexisting crystalline (solid) domains; ii), whether a separate liquid crystalline phase is present......; and iii), whether pH has a direct effect on the lipid matrix phase behavior. In this work the lateral structure of membranes composed of lipids extracted from human skin stratum corneum was studied in a broad temperature range (10 degrees C-90 degrees C) using different techniques such as differential...

  17. Phase behavior of skin lipid mixtures: the effect of cholesterol on lipid organization.

    Science.gov (United States)

    Mojumdar, E H; Gooris, G S; Bouwstra, J A

    2015-06-07

    The lipid matrix in the stratum corneum (SC), the upper layer of the skin, plays a critical role in the skin barrier. The matrix consists of ceramides (CERs), cholesterol (CHOL) and free fatty acids (FFAs). In human SC, these lipids form two coexisting crystalline lamellar phases with periodicities of approximately 6 and 13 nm. In the studies reported here, we investigated the effect of CHOL on lipid organization in each of these lamellar phases separately. For this purpose, we used lipid model mixtures. Our studies revealed that CHOL is imperative for the formation of each of the lamellar phases. At low CHOL levels, the formation of the lamellar phases was dramatically changed: a minimum 0.2 CHOL level in the CER/CHOL/FFA (1 : 0.2 : 1) mixture is required for the formation of each of the lamellar phases. Furthermore, CHOL enhances the formation of the highly dense orthorhombic lateral packing. The gradual increment of CHOL increases the fraction of lipids forming the very dense orthorhombic lateral packing. Therefore, these studies demonstrate that CHOL is an indispensable component of the SC lipid matrix and is of fundamental importance for appropriate dense lipid organization and thus important for the skin barrier function.

  18. Immobilization, Regiospecificity Characterization and Application of Aspergillus oryzae Lipase in the Enzymatic Synthesis of the Structured Lipid 1,3-Dioleoyl-2-Palmitoylglycerol.

    Directory of Open Access Journals (Sweden)

    Haiying Cai

    Full Text Available The enzymatic synthesis of 1,3-dioleoyl-2-palmitoylglycerol (OPO, one of the main components of human milk fats, has been hindered by the relatively high cost of sn-1,3-specific lipases and the deficiency in biocatalyst stability. The sn-1,3-specific lipase from Aspergillus oryzae (AOL is highly and efficiently immobilized with the polystyrene-based hydrophobic resin D3520, with a significant 49.54-fold increase in specific lipase activity compared with the AOL powder in catalyzing the synthesis of OPO through the acidolysis between palm stearin and oleic acid (OA. The optimal immobilization conditions were investigated, including time course, initial protein concentration and solution pH. The sn-1,3 specificity of lipases under different immobilization conditions was evaluated and identified as positively associated with the lipase activity, and the pH of the immobilization solution influenced the regiospecificity and synthetic activity of these lipases. Immobilized AOL D3520, as the biocatalyst, was used for the enzymatic synthesis of the structured lipid OPO through the acidolysis between palm stearin and OA. The following conditions were optimized for the synthesis of structured lipid OPO: 65 °C temperature; 1:8 substrate molar ratio between palm stearin and OA; 8% (w/w enzyme load; 3.5% water content of the immobilized lipase; and 1 h reaction time. Under these conditions, highly efficient C52 production (45.65% was achieved, with a tripalmitin content of 2.75% and a sn-2 palmitic acid (PA proportion of 55.08% in the system.

  19. Amyotrophic Lateral Sclerosis (ALS)

    Science.gov (United States)

    ... ALS Neurons' broken machinery piles up in ALS Esclerosis Lateral Amiotrófica Dormant viral genes may awaken to ... Dementia Information Page Multifocal Motor Neuropathy Information Page Multiple Sclerosis Information Page Muscular Dystrophy Information Page Myasthenia ...

  20. Amyotrophic lateral sclerosis (ALS)

    Science.gov (United States)

    Lou Gehrig disease; ALS; Upper and lower motor neuron disease; Motor neuron disease ... 98. Shaw PJ. Amyotrophic lateral sclerosis and other motor neuron diseases. In: Goldman L, Schafer AI, eds. Goldman's Cecil ...

  1. A Molecular Dynamics Study of the Structural and Dynamical Properties of Putative Arsenic Substituted Lipid Bilayers

    Directory of Open Access Journals (Sweden)

    Ratna Juwita

    2013-04-01

    Full Text Available Cell membranes are composed mainly of phospholipids which are in turn, composed of five major chemical elements: carbon, hydrogen, nitrogen, oxygen, and phosphorus. Recent studies have suggested the possibility of sustaining life if the phosphorus is substituted by arsenic. Although this issue is still controversial, it is of interest to investigate the properties of arsenated-lipid bilayers to evaluate this possibility. In this study, we simulated arsenated-lipid, 1-palmitoyl-2-oleoyl-sn-glycero-3-arsenocholine (POAC, lipid bilayers using all-atom molecular dynamics to understand basic structural and dynamical properties, in particular, the differences from analogous 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine, (POPC lipid bilayers. Our simulations showed that POAC lipid bilayers have distinct structural and dynamical properties from those of native POPC lipid bilayers. Relative to POPC lipid bilayers, POAC lipid bilayers have a more compact structure with smaller lateral areas and greater order. The compact structure of POAC lipid bilayers is due to the fact that more inter-lipid salt bridges are formed with arsenate-choline compared to the phosphate-choline of POPC lipid bilayers. These inter-lipid salt bridges bind POAC lipids together and also slow down the head group rotation and lateral diffusion of POAC lipids. Thus, it would be anticipated that POAC and POPC lipid bilayers would have different biological implications.

  2. Do Lipids Retard the Evaporation of the Tear Fluid?

    DEFF Research Database (Denmark)

    Rantamaki, A. H.; Javanainen, M.; Vattulainen, I.

    2012-01-01

    . Lipids were applied to an air-water interface, and the evaporation rate through the lipid layer was defined as water loss from the interface. A thick layer of olive oil and a monolayer of long-chain alcohol were used as controls. The artificial TFLLs were composed of 1 to 4 lipid species: polar...... phosphatidylcholine (PC), nonpolar cholesteryl ester, triglycerides, and wax ester (WE). Brewster angle microscopy (BAM) and interfacial shear rheometry (ISR) were used to assess the lateral structure and shear stress response of the lipid layers, respectively. RESULTS. Olive oil and long-chain alcohol decreased...

  3. Irinotecan Lipid Complex Injection

    Science.gov (United States)

    Irinotecan lipid complex is used in combination with other medications to treat pancreatic cancer that has spread to other ... worsened after treatment with other chemotherapy medications. Irinotecan lipid complex is in a class of antineoplastic medications ...

  4. Doxorubicin Lipid Complex Injection

    Science.gov (United States)

    Doxorubicin lipid complex is used to treat ovarian cancer that has not improved or that has worsened after treatment with other medications. Doxorubicin lipid complex is also used to treat Kaposi's sarcoma ( ...

  5. Daunorubicin Lipid Complex Injection

    Science.gov (United States)

    Daunorubicin lipid complex is used to treat advanced Kaposi's sarcoma (a type of cancer that causes abnormal tissue to ... body) related to acquired immunodeficiency syndrome (AIDS). Daunorubicin lipid complex is in a class of medications called ...

  6. Vincristine Lipid Complex Injection

    Science.gov (United States)

    Vincristine lipid complex is used to treat a certain type of acute lymphoblastic leukemia (ALL; a type of cancer ... least two different treatments with other medications. Vincristine lipid complex is in a class of medications called ...

  7. Computational Modeling of Lipid Metabolism in Yeast

    Directory of Open Access Journals (Sweden)

    Vera Schützhold

    2016-09-01

    Full Text Available Lipid metabolism is essential for all major cell functions and has recently gained increasing attention in research and health studies. However, mathematical modeling by means of classical approaches such as stoichiometric networks and ordinary differential equation systems has not yet provided satisfactory insights, due to the complexity of lipid metabolism characterized by many different species with only slight differences and by promiscuous multifunctional enzymes.Here, we present a object-oriented stochastic model approach as a way to cope with the complex lipid metabolic network. While all lipid species are treated objects in the model, they can be modified by the respective converting reactions based on reaction rules, a hybrid method that integrates benefits of agent-based and classical stochastic simulation. This approach allows to follow the dynamics of all lipid species with different fatty acids, different degrees of saturation and different headgroups over time and to analyze the effect of parameter changes, potential mutations in the catalyzing enzymes or provision of different precursors. Applied to yeast metabolism during one cell cycle period, we could analyze the distribution of all lipids to the various membranes in time-dependent manner.The presented approach allows to efficiently treat the complexity of cellular lipid metabolism and to derive conclusions on the time- and location-dependent distributions of lipid species and their properties such as saturation. It is widely applicable, easily extendable and will provide further insights in healthy and diseased states of cell metabolism.

  8. Evaluation of nanostructured lipid carriers (NLC) and nanoemulsions as carriers for UV-filters: characterization, in vitro penetration and photostability studies.

    Science.gov (United States)

    Puglia, Carmelo; Damiani, Elisabetta; Offerta, Alessia; Rizza, Luisa; Tirendi, Giorgia Giusy; Tarico, Maria Stella; Curreri, Sergio; Bonina, Francesco; Perrotta, Rosario Emanuele

    2014-01-23

    The increased awareness of protection against UV radiation damages has led to a rise in the use of topically applied chemical sunscreen agents and to an increased need of innovative carriers designed to achieve the highest protective effect and reduce the toxicological risk resulting from the percutaneous absorption of these substances. In this paper, nanostructured lipid carriers (NLC) and nanoemulsions (NE) were formulated to optimize the topical application of different and widespread UVA or UVB sun filters (ethyl hexyltriazone (EHT), diethylamino hydroxybenzoyl hexyl benzoate (DHHB), bemotrizinol (Tinosorb S), octylmethoxycinnamate (OMC) and avobenzone (AVO)). The preparation and stability parameters of these nanocarriers have been investigated concerning particle size and zeta potential. The release pattern of the sunscreens from NLC and NE was evaluated in vitro, determining their percutaneous absorption through excised human skin. Additional in vitro studies were performed in order to evaluate, after UVA radiation treatment, the spectral stability of the sunfilters once formulated in NLC or NE. From the results obtained, when incorporated in NLC, the skin permeation abilities of the sun filter were drastically reduced, remaining mainly on the surface of the skin. The photostability studies showed that EHT, DHHB and Tinosorb S still retain their photostability when incorporated in these carriers, while OMC and AVO were not photostable as expected. However, no significant differences in terms of photoprotective efficacy between the two carriers were observed.

  9. Characterization of shikonin derivative secretion in Lithospermum eryrhirorizon hairy roots as a model of lipid-soluble metabolite secretion from plants.

    Directory of Open Access Journals (Sweden)

    Kanade Tatsumi

    2016-07-01

    Full Text Available Shikonin derivatives are specialized lipophilic metabolites, secreted in abundant amounts from the root epidermal cells of Lithospermum erythrorhizon. Because they have anti-microbial activities, these compounds, which are derivatives of red naphthoquinone, are thought to serve as a chemical barrier for plant roots. The mechanism by which they are secreted from cells is, however, largely unknown. The shikonin production system in L. erythrorhizon is an excellent model for studying the mechanism by which lipophilic compounds are secreted from plant cells, because of the abundant amounts of these compounds produced by L. erythrorhizon, the 0 to 100% inducibility of their production, the light-specific inhibition of production, and the visibility of these products as red pigments. To date, many factors regulating shikonin biosynthesis have been identified, but no mechanism that regulates shikonin secretion without inhibiting biosynthesis has been detected. This study showed that inhibitors of membrane traffic strongly inhibit shikonin secretion without inhibiting shikonin production, suggesting that the secretion of shikonin derivatives into the apoplast utilizes pathways common to the ADP-ribosylation factor/GTPase-activating protein (ARF/GAP system and actin filament polymerization, at least in part. These findings provide clues about the machinery involved in secreting lipid-soluble metabolites from cells.

  10. Characterization of Shikonin Derivative Secretion in Lithospermum erythrorhizon Hairy Roots as a Model of Lipid-Soluble Metabolite Secretion from Plants.

    Science.gov (United States)

    Tatsumi, Kanade; Yano, Mariko; Kaminade, Kenta; Sugiyama, Akifumi; Sato, Mayuko; Toyooka, Kiminori; Aoyama, Takashi; Sato, Fumihiko; Yazaki, Kazufumi

    2016-01-01

    Shikonin derivatives are specialized lipophilic metabolites, secreted in abundant amounts from the root epidermal cells of Lithospermum erythrorhizon. Because they have anti-microbial activities, these compounds, which are derivatives of red naphthoquinone, are thought to serve as a chemical barrier for plant roots. The mechanism by which they are secreted from cells is, however, largely unknown. The shikonin production system in L. erythrorhizon is an excellent model for studying the mechanism by which lipophilic compounds are secreted from plant cells, because of the abundant amounts of these compounds produced by L. erythrorhizon, the 0 to 100% inducibility of their production, the light-specific inhibition of production, and the visibility of these products as red pigments. To date, many factors regulating shikonin biosynthesis have been identified, but no mechanism that regulates shikonin secretion without inhibiting biosynthesis has been detected. This study showed that inhibitors of membrane traffic strongly inhibit shikonin secretion without inhibiting shikonin production, suggesting that the secretion of shikonin derivatives into the apoplast utilizes pathways common to the ADP-ribosylation factor/guanine nucleotide exchange factor (ARF/GEF) system and actin filament polymerization, at least in part. These findings provide clues about the machinery involved in secreting lipid-soluble metabolites from cells.

  11. Roles of Interleaflet Coupling and Hydrophobic Mismatch in Lipid Membrane Phase-Separation Kinetics

    Science.gov (United States)

    2016-01-01

    Characterizing the nanoscale dynamic organization within lipid bilayer membranes is central to our understanding of cell membranes at a molecular level. We investigate phase separation and communication across leaflets in ternary lipid bilayers, including saturated lipids with between 12 and 20 carbons per tail. Coarse-grained molecular dynamics simulations reveal a novel two-step kinetics due to hydrophobic mismatch, in which the initial response of the apposed leaflets upon quenching is to increase local asymmetry (antiregistration), followed by dominance of symmetry (registration) as the bilayer equilibrates. Antiregistration can become thermodynamically preferred if domain size is restricted below ∼20 nm, with implications for the symmetry of rafts and nanoclusters in cell membranes, which have similar reported sizes. We relate our findings to theory derived from a semimicroscopic model in which the leaflets experience a “direct” area-dependent coupling, and an “indirect” coupling that arises from hydrophobic mismatch and is most important at domain boundaries. Registered phases differ in composition from antiregistered phases, consistent with a direct coupling between the leaflets. Increased hydrophobic mismatch purifies the phases, suggesting that it contributes to the molecule-level lipid immiscibility. Our results demonstrate an interplay of competing interleaflet couplings that affect phase compositions and kinetics, and lead to a length scale that can influence lateral and transverse bilayer organization within cells. PMID:27574865

  12. Lipid membranes on nanostructured silicon.

    Energy Technology Data Exchange (ETDEWEB)

    Slade, Andrea Lynn; Lopez, Gabriel P. (University of New Mexico, Albuquerque, NM); Ista, Linnea K. (University of New Mexico, Albuquerque, NM); O' Brien, Michael J. (University of New Mexico, Albuquerque, NM); Sasaki, Darryl Yoshio; Bisong, Paul (University of New Mexico, Albuquerque, NM); Zeineldin, Reema R. (University of New Mexico, Albuquerque, NM); Last, Julie A.; Brueck, Stephen R. J. (University of New Mexico, Albuquerque, NM)

    2004-12-01

    A unique composite nanoscale architecture that combines the self-organization and molecular dynamics of lipid membranes with a corrugated nanotextured silicon wafer was prepared and characterized with fluorescence microscopy and scanning probe microscopy. The goal of this project was to understand how such structures can be assembled for supported membrane research and how the interfacial interactions between the solid substrate and the soft, self-assembled material create unique physical and mechanical behavior through the confinement of phases in the membrane. The nanometer scale structure of the silicon wafer was produced through interference lithography followed by anisotropic wet etching. For the present study, a line pattern with 100 nm line widths, 200 nm depth and a pitch of 360 nm pitch was fabricated. Lipid membranes were successfully adsorbed on the structured silicon surface via membrane fusion techniques. The surface topology of the bilayer-Si structure was imaged using in situ tapping mode atomic force microscopy (AFM). The membrane was observed to drape over the silicon structure producing an undulated topology with amplitude of 40 nm that matched the 360 nm pitch of the silicon structure. Fluorescence recovery after photobleaching (FRAP) experiments found that on the microscale those same structures exhibit anisotropic lipid mobility that was coincident with the silicon substructure. The results showed that while the lipid membrane maintains much of its self-assembled structure in the composite architecture, the silicon substructure indeed influences the dynamics of the molecular motion within the membrane.

  13. Laterally loaded masonry

    DEFF Research Database (Denmark)

    Raun Gottfredsen, F.

    In this thesis results from experiments on mortar joints and masonry as well as methods of calculation of strength and deformation of laterally loaded masonry are presented. The strength and deformation capacity of mortar joints have been determined from experiments involving a constant compressive...... stress and increasing shear. The results show a transition to pure friction as the cohesion is gradually destroyed. An interface model of a mortar joint that can take into account this aspect has been developed. Laterally loaded masonry panels have also been tested and it is found to be characteristic...

  14. Lateral Thinking of Prospective Teachers

    Science.gov (United States)

    Lawrence, A. S. Arul; Xavier, S. Amaladoss

    2013-01-01

    Edward de Bono who invented the term "lateral thinking" in 1967 is the pioneer of lateral thinking. Lateral thinking is concerned with the generation of new ideas. Liberation from old ideas and the stimulation of new ones are twin aspects of lateral thinking. Lateral thinking is a creative skills from which all people can benefit…

  15. Nutrients and neurodevelopment: lipids.

    Science.gov (United States)

    González, Horacio F; Visentin, Silvana

    2016-10-01

    Nutrients, lipids in particular, make up the central nervous system structure and play major functional roles: they stimulate development, migration, and nerve cell differentiation. They are part of gray matter, white matter, nerve nuclei, and synaptogenesis. Breast milk contains lipids which are crucial for infant brain development. The lipid profile of breast milk was used as a guideline for the development of breast milk substitutes. However, to date, no substitute has matched it. Complementary feeding should include docosahexaenoic acid, arachidonic acid, other polyunsaturated fatty acids, saturated fatty acids, and complex lipids found in milk fat. The lipid composition of breast milk depends on maternal intake and nutritional status during pregnancy and breast-feeding. It has a great impact on development. Our goal is to review scientific literature regarding the role of lipids on infant brain development and the importance of breast milk lipid composition, maternal diet, and complementary feeding.

  16. Preparation and Characterization of Liranaftate Solid Lipid Nanoparticles%利拉萘酯固体脂质纳米粒的构建及表征

    Institute of Scientific and Technical Information of China (English)

    张海龙; 刘海乐; 兰天; 丁劲松

    2012-01-01

    Solid lipid nanoparticles (SLN) loaded with liranaftate were prepared by emulsion solvent diffusion method with glyceryl monostearate and cholesterin as matrix material. The formulation was optimized through orthogonal design. The mean particle size of the liranaftate SLN was (145.3±6.1)nm with the entrapment efficiency of (75.8±0.7) % and drug loading of (4.82±0.03) %. The results of differential scanning calorimetry (DSC) showed that liranaftate was entrapped in the SLN as amorphous form. The results of preliminary stability test showed that the liranaftate SLN stored at 4℃ for 30 d could maintain stable. The results of in vitro transdermal test showed that the skin deposition ratio of liranaftate SLN gel was about 100 times of the commercial cream (Zefnart).%以单硬脂酸甘油酯和胆固醇为脂质材料,采用乳化溶剂扩散法制备利拉萘酯固体脂质纳米粒,并采用正交设计优化处方.结果表明,所得优化制品平均粒径为(145.3±6.1)nm,包封率为(75.8±0.7)%,载药量为(4.82±0.03)%,DSC分析提示药物可能以无定形状态存在于载体中.稳定性初步研究显示制品在4℃条件放置30 d可维持稳定.体外透皮试验表明,利拉萘酯固体脂质纳米粒凝胶的皮肤滞留比约为市售乳膏(Zefnart)的100倍.

  17. Gas chromatography coupled with mass spectrometric characterization of Curcuma longa: Protection against pathogenic microbes and lipid peroxidation in rat's tissue homogenate.

    Science.gov (United States)

    Hassan, Waseem; Gul, Shehnaz; Rehman, Shakilla; Kanwal, Farina; Afridi, Muhammad Siddique; Fazal, Hina; Shah, Ziarat; Rahman, Ataur; da Rocha, Joao B T

    2016-03-01

    The present study was designed to investigate the mineral content and antimicrobial activity of Curcuma Longa extracts and its essential oil. We also determined the lipid peroxidation inhibition activity of the ethanolic extract against sodium nitroprusside (SNP) induced thiobarbituric acid reactive species (TBARS) formation in rat's brain, kidney and liver homogenates. Major constituents of essential oil identified by gas chromatography and mass spectrometry (GCMS) were beta-sesquiphellandrene (38.69%), alpha-curcumene (18.44%) and p-mentha-1,4 (8)-diene (16.29%). Atomic absorption spectroscopy (AAS) was used for the quantitative estimation of Calcium (Ca), Magnesium (Mg), Iron (Fe), Copper (Cu), Zinc (Zn), Chromium (Cr), Nickel (Ni) and Manganese (Mn). The extract showed highest Mg (49.4 mg/l) concentration followed by Ca (35.42 mg/l) and Fe (1.27 mg/l). Our data revealed that the ethanolic extract of Curcuma Longa at 1-10 mg/kg significantly inhibited TBARS production in all tested homogenates. Crude extracts and essential oil were tested against three gram positive bacteria i.e. Bacillus subtilis, Bacillus atrophoeus, Staphylococcus aureus, six gram negative bacteria i.e. Escherichia coli, Klebsiella pneumonias, Salmonella typhi, Pseudomonas aeruginosa, Erwinia carotovora, Agrobacterium tumefaciens and one fungal strain namely Candida albicans by disc diffusion assay. Essential oil showed highest anti-microbial activity as compared to the crude extracts. The present study confirms the significant antimicrobial and antioxidant potential of the studied plant, which can be considered as a diet supplement for a variety of oxidative stress induced or infectious diseases.

  18. Onset dominance in lateralization.

    Science.gov (United States)

    Freyman, R L; Zurek, P M; Balakrishnan, U; Chiang, Y C

    1997-03-01

    Saberi and Perrott [Acustica 81, 272-275 (1995)] found that the in-head lateralization of a relatively long-duration pulse train could be controlled by the interaural delay of the single pulse pair that occurs at onset. The present study examined this further, using an acoustic pointer measure of lateralization, with stimulus manipulations designed to determine conditions under which lateralization was consistent with the interaural onset delay. The present stimuli were wideband pulse trains, noise-burst trains, and inharmonic complexes, 250 ms in duration, chosen for the ease with which interaural delays and correlations of select temporal segments of the stimulus could be manipulated. The stimulus factors studied were the periodicity of the ongoing part of the signal as well as the multiplicity and ambiguity of interaural delays. The results, in general, showed that the interaural onset delay controlled lateralization when the steady state binaural cues were relatively weak, either because the spectral components were only sparsely distributed across frequency or because the interaural time delays were ambiguous. Onset dominance can be disrupted by sudden stimulus changes within the train, and several examples of such changes are described. Individual subjects showed strong left-right asymmetries in onset effectiveness. The results have implications for understanding how onset and ongoing interaural delay cues contribute to the location estimates formed by the binaural auditory system.

  19. Lipid Structure in Triolein Lipid Droplets

    DEFF Research Database (Denmark)

    Chaban, Vitaly V; Khandelia, Himanshu

    2014-01-01

    Lipid droplets (LDs) are primary repositories of esterified fatty acids and sterols in animal cells. These organelles originate on the lumenal or cytoplasmic side of endoplasmic reticulum (ER) membrane and are released to the cytosol. In contrast to other intracellular organelles, LDs are composed...... of a mass of hydrophobic lipid esters coved by phospholipid monolayer. The small size and unique architecture of LDs makes it complicated to study LD structure by modern experimental methods. We discuss coarse-grained molecular dynamics (MD) simulations of LD formation in systems containing 1-palmitoyl-2...... to coarse-grained simulations, the presence of PE lipids at the interface has a little impact on distribution of components and on the overall LD structure. (4) The thickness of the lipid monolayer at the surface of the droplet is similar to the thickness of one leaflet of a bilayer. Computer simulations...

  20. The lipid raft proteome of Borrelia burgdorferi.

    Science.gov (United States)

    Toledo, Alvaro; Pérez, Alberto; Coleman, James L; Benach, Jorge L

    2015-11-01

    Eukaryotic lipid rafts are membrane microdomains that have significant amounts of cholesterol and a selective set of proteins that have been associated with multiple biological functions. The Lyme disease agent, Borrelia burgdorferi, is one of an increasing number of bacterial pathogens that incorporates cholesterol onto its membrane, and form cholesterol glycolipid domains that possess all the hallmarks of eukaryotic lipid rafts. In this study, we isolated lipid rafts from cultured B. burgdorferi as a detergent resistant membrane (DRM) fraction on density gradients, and characterized those molecules that partitioned exclusively or are highly enriched in these domains. Cholesterol glycolipids, the previously known raft-associated lipoproteins OspA and OpsB, and cholera toxin partitioned into the lipid rafts fraction indicating compatibility with components of the DRM. The proteome of lipid rafts was analyzed by a combination of LC-MS/MS or MudPIT. Identified proteins were analyzed in silico for parameters that included localization, isoelectric point, molecular mass and biological function. The proteome provided a consistent pattern of lipoproteins, proteases and their substrates, sensing molecules and prokaryotic homologs of eukaryotic lipid rafts. This study provides the first analysis of a prokaryotic lipid raft and has relevance for the biology of Borrelia, other pathogenic bacteria, as well as for the evolution of these structures. All MS data have been deposited in the ProteomeXchange with identifier PXD002365 (http://proteomecentral.proteomexchange.org/dataset/PXD002365).

  1. [Lateral lumbar disk herniation].

    Science.gov (United States)

    Deburge, A; Barre, E; Guigui, P

    A retrospective study of 41 lateral discal hernias observed between 1984 and 1991 were studied among the 1080 discal hernias treated during this period. CT scan, performed in all cases, distinguished several different types of hernia: foramen hernias (26), extraforamen hernias (12), mixed forms (5) associated with canal component (11). Thirteen disco scans were required. Nucleolysis was performed in 24 patients (58%) and surgical treatment was the first intention choice in 17 (41%). Outcome, evaluated with a function score developed in the unit were good in the 17 surgery cases (100%). In the nucleolysis patients results were good or excellent in 13, average in 4, and poor in 7. Five of the nucleolysis failures were later operated leading to good results in 3, average in 1 and no change in 1. Indications for surgery are more frequent in this type of discal hernia and results in our surgical series were better than those for chemonucleolysis.

  2. Treatment of lateral epicondylitis.

    Science.gov (United States)

    Johnson, Greg W; Cadwallader, Kara; Scheffel, Scot B; Epperly, Ted D

    2007-09-15

    Lateral epicondylitis is a common overuse syndrome of the extensor tendons of the forearm. It is sometimes called tennis elbow, although it can occur with many activities. The condition affects men and women equally and is more common in persons 40 years or older. Despite the prevalence of lateral epicondylitis and the numerous treatment strategies available, relatively few high-quality clinical trials support many of these treatment options; watchful waiting is a reasonable option. Topical nonsteroidal anti-inflammatory drugs, corticosteroid injections, ultrasonography, and iontophoresis with nonsteroidal anti-inflammatory drugs appear to provide short-term benefits. Use of an inelastic, nonarticular, proximal forearm strap (tennis elbow brace) may improve function during daily activities. Progressive resistance exercises may confer modest intermediate-term results. Evidence is mixed on oral nonsteroidal antiinflammatory drugs, mobilization, and acupuncture. Patients with refractory symptoms may benefit from surgical intervention. Extracorporeal shock wave therapy, laser treatment, and electromagnetic field therapy do not appear to be effective.

  3. Lateral Attitude Change.

    Science.gov (United States)

    Glaser, Tina; Dickel, Nina; Liersch, Benjamin; Rees, Jonas; Süssenbach, Philipp; Bohner, Gerd

    2015-08-01

    The authors propose a framework distinguishing two types of lateral attitude change (LAC): (a) generalization effects, where attitude change toward a focal object transfers to related objects, and (b) displacement effects, where only related attitudes change but the focal attitude does not change. They bring together examples of LAC from various domains of research, outline the conditions and underlying processes of each type of LAC, and develop a theoretical framework that enables researchers to study LAC more systematically in the future. Compared with established theories of attitude change, the LAC framework focuses on lateral instead of focal attitude change and encompasses both generalization and displacement. Novel predictions and designs for studying LAC are presented.

  4. Clinical psychology and amyotrophic lateral sclerosis

    Directory of Open Access Journals (Sweden)

    Francesco Pagnini

    2010-07-01

    Full Text Available Amyotrophic Lateral Sclerosis is a fatal and progressive disease, characterized by progressive muscles weakness, with consequent loss of physical capacities. Psychologists can play an important role in ALS care, by providing clinical activities in every step of the disease, including support and counseling activities directed to patients, their caregivers and to physicians.

  5. The lateral angle revisited

    DEFF Research Database (Denmark)

    Morgan, Jeannie; Lynnerup, Niels; Hoppa, R.D.

    2013-01-01

    measurements taken from computed tomography (CT) scans. Previous reports have observed that the lateral angle size in females is significantly larger than in males. The method was applied to an independent series of 77 postmortem CT scans (42 males, 35 females) to validate its accuracy and reliability...... method appears to be of minimal practical use in forensic anthropology and archeology. © 2013 American Academy of Forensic Sciences....

  6. Lateral Control”

    DEFF Research Database (Denmark)

    Rasmussen, Hanne Nina; Veierskov, Bjarke; Hansen-Møller, Jens;

    2010-01-01

    pattern changes followed from destipitation, but few from decapitation. Growth reactions suggest that resource allocation to main branch buds inhibits leader growth in normal trees, a kind of “lateral control.” Auxin and ABA content in buds and stems was largely unaffected by treatments. Data suggest...... that subapical leader tissues beneath the apical bud group are a primary source of cytokinin regulation. Keywords ABA - Apical control - Auxin - Bud development - Cytokinin - Plant architecture...

  7. Atomic force microscopy of model lipid membranes.

    Science.gov (United States)

    Morandat, Sandrine; Azouzi, Slim; Beauvais, Estelle; Mastouri, Amira; El Kirat, Karim

    2013-02-01

    Supported lipid bilayers (SLBs) are biomimetic model systems that are now widely used to address the biophysical and biochemical properties of biological membranes. Two main methods are usually employed to form SLBs: the transfer of two successive monolayers by Langmuir-Blodgett or Langmuir-Schaefer techniques, and the fusion of preformed lipid vesicles. The transfer of lipid films on flat solid substrates offers the possibility to apply a wide range of surface analytical techniques that are very sensitive. Among them, atomic force microscopy (AFM) has opened new opportunities for determining the nanoscale organization of SLBs under physiological conditions. In this review, we first focus on the different protocols generally employed to prepare SLBs. Then, we describe AFM studies on the nanoscale lateral organization and mechanical properties of SLBs. Lastly, we survey recent developments in the AFM monitoring of bilayer alteration, remodeling, or digestion, by incubation with exogenous agents such as drugs, proteins, peptides, and nanoparticles.

  8. Characterization of freeze-fractured epithelial plasma membranes on nanometer scale with ToF-SIMS.

    Science.gov (United States)

    Draude, Felix; Körsgen, Martin; Pelster, Andreas; Schwerdtle, Tanja; Müthing, Johannes; Arlinghaus, Heinrich F

    2015-03-01

    Time-of-flight secondary ion mass spectrometry (ToF-SIMS) was used to characterize the freeze-fracturing process of human epithelial PANC-1 and UROtsa cells. For this purpose, phosphatidylcholine, sphingomyelin, phosphatidylethanolamine, and phosphatidylserine standard samples were investigated to find specific signals with both high specificity and signal intensity. The results were used to investigate single cells of subconfluent cell layers prepared with a special silicon wafer sandwich preparation technique. This freeze-fracturing technique strips cell membranes off the cells, isolating them on opposing silicon wafer substrates. Criteria were found for defining regions with stripped off cell membranes and, on the opposing wafer, complementary regions with the remaining cells. Measured ethanolamine/choline and serine/choline ratios in these regions clearly showed that in the freeze-fracturing process, the lipid bilayer of the plasma membrane is split along its central zone. Accordingly, only the outer lipid monolayer is stripped off the cell, while the inner lipid monolayer remains attached to the cell on the opposing wafer, thus allowing detailed analysis of a single lipid monolayer. Furthermore, it could be shown that using different washing procedures did not influence the transmembrane lipid distribution. Under optimized preparation conditions, it became feasible to detect lipids with a lateral resolution of approximately 100 nm. The data indicate that ToF-SIMS would be a very useful technique to study with very high lateral resolution changes in lipid composition caused, for example, by lipid storage diseases or pharmaceuticals that interfere with the lipid metabolism.

  9. Lateral Elbow Tendinopathy

    Science.gov (United States)

    Bhabra, Gev; Wang, Allan; Ebert, Jay R.; Edwards, Peter; Zheng, Monica; Zheng, Ming H.

    2016-01-01

    Lateral elbow tendinopathy, commonly known as tennis elbow, is a condition that can cause significant functional impairment in working-age patients. The term tendinopathy is used to describe chronic overuse tendon disorders encompassing a group of pathologies, a spectrum of disease. This review details the pathophysiology of tendinopathy and tendon healing as an introduction for a system grading the severity of tendinopathy, with each of the 4 grades displaying distinct histopathological features. Currently, there are a large number of nonoperative treatments available for lateral elbow tendinopathy, with little guidance as to when and how to use them. In fact, an appraisal of the clinical trials, systematic reviews, and meta-analyses studying these treatment modalities reveals that no single treatment reliably achieves outstanding results. This may be due in part to the majority of clinical studies to date including all patients with chronic tendinopathy rather than attempting to categorize patients according to the severity of disease. We relate the pathophysiology of the different grades of tendinopathy to the basic science principles that underpin the mechanisms of action of the nonoperative treatments available to propose a treatment algorithm guiding the management of lateral elbow tendinopathy depending on severity. We believe that this system will be useful both in clinical practice and for the future investigation of the efficacy of treatments. PMID:27833925

  10. Lipids of mitochondria.

    Science.gov (United States)

    Horvath, Susanne E; Daum, Günther

    2013-10-01

    A unique organelle for studying membrane biochemistry is the mitochondrion whose functionality depends on a coordinated supply of proteins and lipids. Mitochondria are capable of synthesizing several lipids autonomously such as phosphatidylglycerol, cardiolipin and in part phosphatidylethanolamine, phosphatidic acid and CDP-diacylglycerol. Other mitochondrial membrane lipids such as phosphatidylcholine, phosphatidylserine, phosphatidylinositol, sterols and sphingolipids have to be imported. The mitochondrial lipid composition, the biosynthesis and the import of mitochondrial lipids as well as the regulation of these processes will be main issues of this review article. Furthermore, interactions of lipids and mitochondrial proteins which are highly important for various mitochondrial processes will be discussed. Malfunction or loss of enzymes involved in mitochondrial phospholipid biosynthesis lead to dysfunction of cell respiration, affect the assembly and stability of the mitochondrial protein import machinery and cause abnormal mitochondrial morphology or even lethality. Molecular aspects of these processes as well as diseases related to defects in the formation of mitochondrial membranes will be described.

  11. Polyene-lipids: a new tool to image lipids

    DEFF Research Database (Denmark)

    Kuerschner, Lars; Ejsing, Christer S.; Ekroos, Kim

    2005-01-01

    conjugated double bonds as a new type of lipid tag. Polyene-lipids exhibit a unique structural similarity to natural lipids, which results in minimal effects on the lipid properties. Analyzing membrane phase partitioning, an important biophysical and biological property of lipids, we demonstrated...... the superiority of polyene-lipids to both NBD- and BODIPY-tagged lipids. Cells readily take up various polyene-lipid precursors and generate the expected end products with no apparent disturbance by the tag. Applying two-photon excitation microscopy, we imaged the distribution of polyene-lipids in living...

  12. Very large database of lipids: rationale and design.

    Science.gov (United States)

    Martin, Seth S; Blaha, Michael J; Toth, Peter P; Joshi, Parag H; McEvoy, John W; Ahmed, Haitham M; Elshazly, Mohamed B; Swiger, Kristopher J; Michos, Erin D; Kwiterovich, Peter O; Kulkarni, Krishnaji R; Chimera, Joseph; Cannon, Christopher P; Blumenthal, Roger S; Jones, Steven R

    2013-11-01

    Blood lipids have major cardiovascular and public health implications. Lipid-lowering drugs are prescribed based in part on categorization of patients into normal or abnormal lipid metabolism, yet relatively little emphasis has been placed on: (1) the accuracy of current lipid measures used in clinical practice, (2) the reliability of current categorizations of dyslipidemia states, and (3) the relationship of advanced lipid characterization to other cardiovascular disease biomarkers. To these ends, we developed the Very Large Database of Lipids (NCT01698489), an ongoing database protocol that harnesses deidentified data from the daily operations of a commercial lipid laboratory. The database includes individuals who were referred for clinical purposes for a Vertical Auto Profile (Atherotech Inc., Birmingham, AL), which directly measures cholesterol concentrations of low-density lipoprotein, very low-density lipoprotein, intermediate-density lipoprotein, high-density lipoprotein, their subclasses, and lipoprotein(a). Individual Very Large Database of Lipids studies, ranging from studies of measurement accuracy, to dyslipidemia categorization, to biomarker associations, to characterization of rare lipid disorders, are investigator-initiated and utilize peer-reviewed statistical analysis plans to address a priori hypotheses/aims. In the first database harvest (Very Large Database of Lipids 1.0) from 2009 to 2011, there were 1 340 614 adult and 10 294 pediatric patients; the adult sample had a median age of 59 years (interquartile range, 49-70 years) with even representation by sex. Lipid distributions closely matched those from the population-representative National Health and Nutrition Examination Survey. The second harvest of the database (Very Large Database of Lipids 2.0) is underway. Overall, the Very Large Database of Lipids database provides an opportunity for collaboration and new knowledge generation through careful examination of granular lipid data on

  13. Nonadditive Compositional Curvature Energetics of Lipid Bilayers

    Science.gov (United States)

    Sodt, A. J.; Venable, R. M.; Lyman, E.; Pastor, R. W.

    2016-09-01

    The unique properties of the individual lipids that compose biological membranes together determine the energetics of the surface. The energetics of the surface, in turn, govern the formation of membrane structures and membrane reshaping processes, and thus they will underlie cellular-scale models of viral fusion, vesicle-dependent transport, and lateral organization relevant to signaling. The spontaneous curvature, to the best of our knowledge, is always assumed to be additive. We describe observations from simulations of unexpected nonadditive compositional curvature energetics of two lipids essential to the plasma membrane: sphingomyelin and cholesterol. A model is developed that connects molecular interactions to curvature stress, and which explains the role of local composition. Cholesterol is shown to lower the number of effective Kuhn segments of saturated acyl chains, reducing lateral pressure below the neutral surface of bending and favoring positive curvature. The effect is not observed for unsaturated (flexible) acyl chains. Likewise, hydrogen bonding between sphingomyelin lipids leads to positive curvature, but only at sufficient concentration, below which the lipid prefers negative curvature.

  14. Language lateralization in schizophrenia

    NARCIS (Netherlands)

    Sommer, I.E.C.

    2004-01-01

    Schizophrenia is a severe chronic psychiatric illness that affects approximately 1-2% of the populations worldwide. Schizophrenia is characterized by episodes of psychosis, in which patients experience hallucinations (false perceptions) and delusions (false beliefs). Apart from the psychotic episode

  15. Effect of different lipids and surfactants on formulation of solid lipid nanoparticles incorporating tamoxifen citrate

    Directory of Open Access Journals (Sweden)

    S U Upadhyay

    2012-01-01

    Full Text Available Tamoxifen Citrate (TC is an estrogen receptor antagonist and drug of choice for hormone sensitive breast cancer. Solid Lipid Nanoparticles loaded with TC were prepared by High Shear Homogenization followed by Ultrasonication. The aim of the present work is to study the effect of four different Solid Lipids and three Surfactants on Formulation and Stability of SLN. They were characterized for Particle size, Polydispersity Index and Zeta Potential by Zetasizer Nano. SLN prepared by Solid Lipid Compritol 888 (Glyceryldibehenate and Tween 80 (1% showed desired Particle Size of 206.9 nm, PDI of 0.046 and Zeta Potential of 9.32 mV.

  16. The lateral line microcosmos.

    Science.gov (United States)

    Ghysen, Alain; Dambly-Chaudière, Christine

    2007-09-01

    The lateral-line system is a simple sensory system comprising a number of discrete sense organs, the neuromasts, distributed over the body of fish and amphibians in species-specific patterns. Its development involves fundamental biological processes such as long-range cell migration, planar cell polarity, regeneration, and post-embryonic remodeling. These aspects have been extensively studied in amphibians by experimental embryologists, but it is only recently that the genetic bases of this development have been explored in zebrafish. This review discusses progress made over the past few years in this field.

  17. Edelfosine and miltefosine effects on lipid raft properties: membrane biophysics in cell death by antitumor lipids.

    Science.gov (United States)

    Castro, Bruno M; Fedorov, Aleksander; Hornillos, Valentin; Delgado, Javier; Acuña, A Ulises; Mollinedo, Faustino; Prieto, Manuel

    2013-07-03

    Edelfosine (1-O-octadecyl-2-O-methyl-sn-glycero-phosphocholine) and miltefosine (hexadecylphosphocholine) are synthetic alkylphospholipids (ALPs) that are reported to selectively accumulate in tumor cell membranes, inducing Fas clustering and activation on lipid rafts, triggering apoptosis. However, the exact mechanism by which these lipids elicit these events is still not fully understood. Recent studies propose that their mode of action might be related with alterations of lipid rafts biophysical properties caused by these lipid drugs. To achieve a clear understanding of this mechanism, we studied the effects of pharmacologically relevant amounts of edelfosine and miltefosine in the properties of model and cellular membranes. The influence of these molecules on membrane order, lateral organization, and lipid rafts molar fraction and size were studied by steady-state and time-resolved fluorescence methods, Förster resonance energy transfer (FRET), confocal and fluorescence lifetime imaging microscopy (FLIM). We found that the global membrane and lipid rafts biophysical properties of both model and cellular membranes were not significantly affected by both the ALPs. Nonetheless, in model membranes, a mild increase in membrane fluidity induced by both alkyl lipids was detected, although this effect was more noticeable for edelfosine than miltefosine. This absence of drastic alterations shows for the first time that ALPs mode of action is unlikely to be directly linked to alterations of lipid rafts biophysical properties caused by these drugs. The biological implications of this result are discussed in the context of ALPs effects on lipid metabolism, mitochondria homeostasis modulation, and their relationship with tumor cell death.

  18. Studying lipid-protein interactions with electron paramagnetic resonance spectroscopy of spin-labeled lipids.

    Science.gov (United States)

    Páli, Tibor; Kóta, Zoltán

    2013-01-01

    Spin label electron paramagnetic resonance (EPR) of lipid-protein interactions reveals crucial features of the structure and assembly of integral membrane proteins. Spin label EPR spectroscopy is the technique of choice to characterize the protein-solvating lipid shell in its highly dynamic nature, because the EPR spectra of lipids that are spin labeled close to the terminal methyl end of their acyl chains display two spectral components, those corresponding to lipids directly contacting the protein and those corresponding to lipids in the bulk fluid bilayer regions of the membrane. In this chapter, typical spin label EPR procedures are presented that allow determination of the stoichiometry of interaction of spin-labeled lipids with the intra-membranous region of membrane proteins or polypeptides, as well as the association constant of the spin-labeled lipid with respect to the host lipid. The lipids giving rise to the so-called immobile spectral component in the EPR spectrum of such samples are identified as the motionally restricted first-shell lipids solvating membrane proteins in biomembranes. Stoichiometry and selectivity are directly related to the structure of the intra-membranous sections of membrane-associated proteins or polypeptides and can be used to study the state of assembly of such proteins in the membrane. Since these characteristics of lipid-protein interactions are discussed in detail in the literature [see Marsh (Eur Biophys J 39:513-525, 2010) for a most recent review], here we focus more on how to spin label model and biomembranes and how to measure and analyze the two-component EPR spectra of spin-labeled lipids in phospholipid bilayers that contain proteins or polypeptides. After a description of how to prepare spin-labeled model and native biological membranes, we present the reader with computational procedures for determining the molar fraction of motionally restricted lipids when both, one, or none of the pure isolated-mobile or

  19. Status of Lipid Profile in Pregnancy

    Directory of Open Access Journals (Sweden)

    Deepak Parchwani

    2011-02-01

    Full Text Available Pregnancy greatly increases demand for metabolic fuels that are needed for growth and development of the fetus and its support structures. The total gestation related energy cost has been estimated at approximately 83000 kcal. The major change in energy expenditure and in the accumulation of fat occurs at different times during pregnancy. In the current study a serial study of serum lipids was performed in a group of women throughout gestation and six weeks post partum while they were having their usual diet and unrestricted daily activity. The control group consisted of non pregnant healthy women of child bearing age. Data was analyzed by SPSS software. All lipid fractions underwent a gradual and persistent rise throughout pregnancy with the exception of HDL-C i.e. a progressive rise was observed in serum total cholesterol, serum triglyceride, serum VLDL and LDL-C as pregnancy advances, while serum HDL-C showed a biphasic pattern, as initial rise and then decline in later third of pregnancy. However, during early pregnancy the values of all lipid fractions do not differ significantly from those for normal non pregnant controls. No significant difference was observed in vegetarian and non-vegetarian group in any of the lipid fractions in different trimester of pregnancy—so diet had no significant influence on lipid synthesis during pregnancy. [National J of Med Res 2011; 1(1.000: 10-12

  20. Creativity in later life.

    Science.gov (United States)

    Price, K A; Tinker, A M

    2014-08-01

    The ageing population presents significant challenges for the provision of social and health services. Strategies are needed to enable older people to cope within a society ill prepared for the impacts of these demographic changes. The ability to be creative may be one such strategy. This review outlines the relevant literature and examines current public health policy related to creativity in old age with the aim of highlighting some important issues. As well as looking at the benefits and negative aspects of creative activity in later life they are considered in the context of the theory of "successful ageing". Creative activity plays an important role in the lives of older people promoting social interaction, providing cognitive stimulation and giving a sense of self-worth. Furthermore, it is shown to be useful as a tool in the multi-disciplinary treatment of health problems common in later life such as depression and dementia. There are a number of initiatives to encourage older people to participate in creative activities such as arts-based projects which may range from visual arts to dance to music to intergenerational initiatives. However, participation shows geographical variation and often the responsibility of provision falls to voluntary organisations. Overall, the literature presented suggests that creative activity could be a useful tool for individuals and society. However, further research is needed to establish the key factors which contribute to patterns of improved health and well-being, as well as to explore ways to improve access to services.

  1. Brainmining emotive lateral solutions

    Directory of Open Access Journals (Sweden)

    Theodore Scaltsas

    2016-07-01

    Full Text Available BrainMining is a theory of creative thinking that shows how we should exploit the mind’s spontaneous natural disposition to use old solutions to address new problems – our Anchoring Cognitive Bias. BrainMining develops a simple and straightforward method to transform recalcitrant problems into types of problems which we have solved before, and then apply an old type of solution to them. The transformation makes the thinking lateral by matching up disparate types of problem and solution. It emphasises the role of emotive judgements that the agent makes, when she discerns whether a change of the values or the emotions and feelings in a situation, which would expand the space of solutions available for the problem at hand, would be acceptable or appropriate in the situation. A lateral solution for an intractable problem is thus spontaneously brainmined from the agent’s old solutions, to solve a transformed version of the intractable problem, possibly involving changes in the value system or the emotional profile of the situation, which the agent judges, emotively, will be acceptable, and even appropriate in the circumstances.

  2. Lateral Lumbar Interbody Fusion

    Science.gov (United States)

    Hughes, Alexander; Girardi, Federico; Sama, Andrew; Lebl, Darren; Cammisa, Frank

    2015-01-01

    The lateral lumbar interbody fusion (LLIF) is a relatively new technique that allows the surgeon to access the intervertebral space from a direct lateral approach either anterior to or through the psoas muscle. This approach provides an alternative to anterior lumbar interbody fusion with instrumentation, posterior lumbar interbody fusion, and transforaminal lumbar interbody fusion for anterior column support. LLIF is minimally invasive, safe, better structural support from the apophyseal ring, potential for coronal plane deformity correction, and indirect decompression, which have has made this technique popular. LLIF is currently being utilized for a variety of pathologies including but not limited to adult de novo lumbar scoliosis, central and foraminal stenosis, spondylolisthesis, and adjacent segment degeneration. Although early clinical outcomes have been good, the potential for significant neurological and vascular vertebral endplate complications exists. Nevertheless, LLIF is a promising technique with the potential to more effectively treat complex adult de novo scoliosis and achieve predictable fusion while avoiding the complications of traditional anterior surgery and posterior interbody techniques. PMID:26713134

  3. Lipidomic and proteomic analysis of Caenorhabditis elegans lipid droplets and identification of ACS-4 as a lipid droplet-associated protein

    Energy Technology Data Exchange (ETDEWEB)

    Vrablik, Tracy L. [Washington State Univ., Pullman, WA (United States); Petyuk, Vladislav A. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Larson, Emily M. [Washington State Univ., Pullman, WA (United States); Smith, Richard D. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Watts, Jennifer [Washington State Univ., Pullman, WA (United States)

    2015-06-27

    Lipid droplets are cytoplasmic organelles that store neutral lipids for membrane synthesis and energy reserves. In this study, we characterized the lipid and protein composition of purified C. elegans lipid droplets. These lipid droplets are composed mainly of triacylglycerols, surrounded by a phospholipid monolayer composed primarily of phosphatidylcholine and phosphatidylethanolamine. The fatty acid composition of the triacylglycerols was rich in fatty acid species obtained from the dietary E. coli, including cyclopropane fatty acids and cis-vaccenic acid. Unlike other organisms, C. elegans lipid droplets contain very little cholesterol or cholesterol esters. Comparison of the lipid droplet proteomes of wild type and high-fat daf-2 mutant strains shows a relative decrease of MDT-28 abundance in lipid droplets isolated from daf-2 mutants. Functional analysis of lipid droplet proteins identified in our proteomic studies indicated an enrichment of proteins required for growth and fat homeostasis in C. elegans.

  4. Lipids and lipid binding proteins: a perfect match.

    Science.gov (United States)

    Glatz, Jan F C

    2015-02-01

    Lipids serve a great variety of functions, ranging from structural components of biological membranes to signaling molecules affecting various cellular functions. Several of these functions are related to the unique physico-chemical properties shared by all lipid species, i.e., their hydrophobicity. The latter, however, is accompanied by a poor solubility in an aqueous environment and thus a severe limitation in the transport of lipids in aqueous compartments such as blood plasma and the cellular soluble cytoplasm. Specific proteins which can reversibly and non-covalently associate with lipids, designated as lipid binding proteins or lipid chaperones, greatly enhance the aqueous solubility of lipids and facilitate their transport between tissues and within tissue cells. Importantly, transport of lipids across biological membranes also is facilitated by specific (membrane-associated) lipid binding proteins. Together, these lipid binding proteins determine the bio-availability of their ligands, and thereby markedly influence the subsequent processing, utilization, or signaling effect of lipids. The bio-availability of specific lipid species thus is governed by the presence of specific lipid binding proteins, the affinity of these proteins for distinct lipid species, and the presence of competing ligands (including pharmaceutical compounds). Recent studies suggest that post-translational modifications of lipid binding proteins may have great impact on lipid-protein interactions. As a result, several levels of regulation exist that together determine the bio-availability of lipid species. This short review discusses the significance of lipid binding proteins and their potential application as targets for therapeutic intervention.

  5. Lipid Rafts Identified on Synaptic Vesicles from Rat Brain

    Institute of Scientific and Technical Information of China (English)

    HE Li; L(U) Jihua; ZHOU Qinghua; SUI Senfang

    2006-01-01

    For a long time, lipid rafts have been thought to participate in regulating neurotransmitter release. However,the existence of lipid rafts on synaptic vesicles (SVs) and the mechanism by which exocytosis-relative proteins distribute on this structure have not been fully investigated. There is also much controversial data concerning rafts on SVs and synaptic vesicle proteins which makes the results difficult to interpret. This study systematically analyzed the existence and properties of lipid rafts on purified SVs by sucrose density gradient centrifugation, cholesterol depletion, and temperature variation. The data reveals that typical lipid rafts on SVs are both cholesterol dependent and temperature sensitive. Previous confusing results may have been caused by improper treatment or side effects of particular reagent. We also screened the lateral distribution of major exocytosis-related SV proteins and found that only the synaptobrevin (syb) and synaptotagmin (syt) produce detectable association with lipid rafts in 1% Triton X-100.

  6. Electroporation of heterogeneous lipid membranes.

    Science.gov (United States)

    Reigada, Ramon

    2014-03-01

    Electroporation is the basis for the transfection of genetic material and for drug delivery to cells, including electrochemotherapy for cancer. By means of molecular dynamics many aspects of membrane electroporation have been unveiled at the molecular detail in simple, homogeneous, lipid bilayers. However, the correspondence of these findings \\with the process happening in cell membranes requires, at least, the consideration of laterally structured membranes. Here, I present a systematic molecular dynamics study of bilayers composed of different liquid-ordered and liquid-disordered lipid phases subjected to a transversal electric field. The simulations reveal two significant results. First, the electric field mainly affects the properties of the disordered phases, so that electroporation takes place in these membrane regions. Second, the smaller the disordered domains are, the faster they become electroporated. These findings may have a relevant significance in the experimental application of cell electroporation in vivo since it implies that electro-induced and pore-mediated transport processes occur in particularly small disordered domains of the plasma membrane, thus locally affecting only specific regions of the cell.

  7. Big, Fat World of Lipids

    Science.gov (United States)

    ... Science Home Page The Big, Fat World of Lipids By Emily Carlson Posted August 9, 2012 Cholesterol ... ways to diagnose and treat lipid-related conditions. Lipid Encyclopedia Just as genomics and proteomics spurred advances ...

  8. Preparation and Characterization of Vincristine Sulfate-loaded Solid Lipid Nanoparticles%硫酸长春新碱固体脂质纳米粒的制备及其性质考察

    Institute of Scientific and Technical Information of China (English)

    夏爱晓; 宋倩倩; 孙渊; 周鹏; 杜有功; 李范珠

    2013-01-01

    OBJECTIVE To prepare vincristine sulfate-solid lipid nanoparticles(VCR-SLN) with single stearic acid glyceride as its lipid matrix and investigate its characterization. METHODS Multiple emulsion-solvent diffusion technique was adopted to prepare VCR-SLN and the orthogonal design was applied to optimize its formula and technology. Its morphology, particle size, ζ potential, drug entrapment efficiency, drug loading capacity and in vitro release of the VCR-SLN were investigated. RESULTS VCR-SLN were spherelike and smooth, the mean particles size was (144.83±2.71)nm, ζ potential was (-24.77±0.513)mV, entrapment efficiency was (40.54±0.45)%, drug loading capacity was (1.14±0.074)%. The release profile of vincristine sulfate in vitro fitted Weibull equation. CONCLUSION VCR-SLN can be prepared very well by multiple emulsion-solvent diffusion technique.%目的 以单硬脂酸甘油酯为载体材料,采用复乳溶剂挥发法制备硫酸长春新碱固体脂质纳米粒(VCR-SLN),并考察其理化性质.方法 采用复乳溶剂挥发法制备VCR-SLN,以正交设计优化处方及制备工艺,并考察其形态、粒径、Zeta电位、包封率、载药量和体外释放.结果 VCR-SLN为类球形实体粒子,平均粒径为(144.83±2.71)nm,Zeta电位为(-24.77±0.513)mV,包封率为(40.54±0.45)%,载药量为(1.14±0.074)%.药物体外释放曲线符合Weibull方程.结论 复乳溶剂挥发法适用于制备硫酸长春新碱固体脂质纳米粒.

  9. LIPID BIOMARKER ANALYSIS OF MARINE DINOFLAGELLATES

    Science.gov (United States)

    Many marine eukaryotic algae have been shown to possess characteristic chemotaxonomic lipid biomarkers. Dinoflagellates in particular are often characterized by the presence of sterols and pigments that are rarely found in other classes of algae. To evaluate the utility of chemic...

  10. Inducing morphological changes in lipid bilayer membranes with microfabricated substrates

    Science.gov (United States)

    Liu, Fangjie; Collins, Liam F.; Ashkar, Rana; Heberle, Frederick A.; Srijanto, Bernadeta R.; Collier, C. Patrick

    2016-11-01

    Lateral organization of lipids and proteins into distinct domains and anchoring to a cytoskeleton are two important strategies employed by biological membranes to carry out many cellular functions. However, these interactions are difficult to emulate with model systems. Here we use the physical architecture of substrates consisting of arrays of micropillars to systematically control the behavior of supported lipid bilayers - an important step in engineering model lipid membrane systems with well-defined functionalities. Competition between attractive interactions of supported lipid bilayers with the underlying substrate versus the energy cost associated with membrane bending at pillar edges can be systematically investigated as functions of pillar height and pitch, chemical functionalization of the microstructured substrate, and the type of unilamellar vesicles used for assembling the supported bilayer. Confocal fluorescent imaging and AFM measurements highlight correlations that exist between topological and mechanical properties of lipid bilayers and lateral lipid mobility in these confined environments. This study provides a baseline for future investigations into lipid domain reorganization on structured solid surfaces and scaffolds for cell growth.

  11. Epicondilite lateral do cotovelo

    OpenAIRE

    Cohen,Marcio; Motta Filho,Geraldo da Rocha

    2012-01-01

    A epicondilite lateral, também conhecida como cotovelo do tenista, é uma condição comum que acomete de 1 a 3% da população. O termo epicondilite sugere inflamação, embora a análise histológica tecidual não demonstre um processo inflamatório. A estrutura acometida com mais frequência é a origem do tendão extensor radial curto do carpo e o mecanismo de lesão está associado à sua sobrecarga. O tratamento incruento é o de escolha e inclui: repouso, fisioterapia, infiltração com cortisona ou plasm...

  12. Vitiligo Lateral Lower Lip

    Directory of Open Access Journals (Sweden)

    Sahoo Antaryami

    2002-01-01

    Full Text Available Vitiligo characteristically affecting the lateral lower lip (LLL is a common presentation in South Orissa. This type of lesion has rarely been described in literature. One hundred eighteen such cases were studied during the period from October 1999 to September, 2000. LLL vitiligo constituted 16.39% of all vitiligo patients. Both sexes were affected equally. The peak age of onset was in the 2nd decade, mean duration of illness 21.46 months. Fifty six patients had unilateral lesion (38 on the left and 18 on the right. Among the 62 patients having bilateral lesions, the onset was more frequent on the left (38 than either the right (8 or both sides together (16. All the patients were right handed. Association with local factors like infection, trauma, cheilitis, FDE etc were associated in 38.98% of cases, but systemic or autoimmune diseases were not associated. Positive family history was found in 22% of cases.

  13. Lateral conduction infrared photodetector

    Science.gov (United States)

    Kim, Jin K.; Carroll, Malcolm S.

    2011-09-20

    A photodetector for detecting infrared light in a wavelength range of 3-25 .mu.m is disclosed. The photodetector has a mesa structure formed from semiconductor layers which include a type-II superlattice formed of alternating layers of InAs and In.sub.xGa.sub.1-xSb with 0.ltoreq.x.ltoreq.0.5. Impurity doped regions are formed on sidewalls of the mesa structure to provide for a lateral conduction of photo-generated carriers which can provide an increased carrier mobility and a reduced surface recombination. An optional bias electrode can be used in the photodetector to control and vary a cut-off wavelength or a depletion width therein. The photodetector can be formed as a single-color or multi-color device, and can also be used to form a focal plane array which is compatible with conventional read-out integrated circuits.

  14. Avanti lipid tools: connecting lipids, technology, and cell biology.

    Science.gov (United States)

    Sims, Kacee H; Tytler, Ewan M; Tipton, John; Hill, Kasey L; Burgess, Stephen W; Shaw, Walter A

    2014-08-01

    Lipid research is challenging owing to the complexity and diversity of the lipidome. Here we review a set of experimental tools developed for the seasoned lipid researcher, as well as, those who are new to the field of lipid research. Novel tools for probing protein-lipid interactions, applications for lipid binding antibodies, enhanced systems for the cellular delivery of lipids, improved visualization of lipid membranes using gold-labeled lipids, and advances in mass spectrometric analysis techniques will be discussed. Because lipid mediators are known to participate in a host of signal transduction and trafficking pathways within the cell, a comprehensive lipid toolbox that aids the science of lipidomics research is essential to better understand the molecular mechanisms of interactions between cellular components. This article is part of a Special Issue entitled Tools to study lipid functions.

  15. Biotechnology Applications of Tethered Lipid Bilayer Membranes

    Directory of Open Access Journals (Sweden)

    Joshua A. Jackman

    2012-12-01

    Full Text Available The importance of cell membranes in biological systems has prompted the development of model membrane platforms that recapitulate fundamental aspects of membrane biology, especially the lipid bilayer environment. Tethered lipid bilayers represent one of the most promising classes of model membranes and are based on the immobilization of a planar lipid bilayer on a solid support that enables characterization by a wide range of surface-sensitive analytical techniques. Moreover, as the result of molecular engineering inspired by biology, tethered bilayers are increasingly able to mimic fundamental properties of natural cell membranes, including fluidity, electrical sealing and hosting transmembrane proteins. At the same time, new methods have been employed to improve the durability of tethered bilayers, with shelf-lives now reaching the order of weeks and months. Taken together, the capabilities of tethered lipid bilayers have opened the door to biotechnology applications in healthcare, environmental monitoring and energy storage. In this review, several examples of such applications are presented. Beyond the particulars of each example, the focus of this review is on the emerging design and characterization strategies that made these applications possible. By drawing connections between these strategies and promising research results, future opportunities for tethered lipid bilayers within the biotechnology field are discussed.

  16. Characterization of high-dose and high-energy implanted gate and source diode and analysis of lateral spreading of p gate profile in high voltage SiC static induction transistors

    Science.gov (United States)

    Onose, Hidekatsu; Kobayashi, Yutaka; Onuki, Jin

    2017-03-01

    The effect of the p gate dose on the characteristics of the gate-source diode in SiC static induction transistors (SIT) was investigated. It was found that a dose of 1.5 × 1014 cm-2 yields a pn junction breakdown voltage higher than 60 V and good forward characteristics. A normally on SiC SIT was fabricated and demonstrated. A blocking voltage higher than 2.0 kV at a gate-source voltage of -50 V and on-resistance of 70 mΩ cm2 were obtained. Device simulations were performed to investigate the effect of the lateral spreading. By comparing the measured I-V curves with simulation results, the lateral spreading factor was estimated to be about 0.5. The lateral spreading detrimentally affected the electrical properties of the SIT made using implantations at energies higher than 1 MeV.

  17. THE LIPID CONSTITUENTS OF WHOLE AND PAROTID SALIVA

    Science.gov (United States)

    Chloroform: methanol extracts of whole and parotid saliva were subjected to paper chromatography to further characterize their lipid components. The...the sample materials. Whole and parotid saliva had similar nonphosphatides, but differed in their phospholipid composition. (Author)

  18. Development and evaluation of lipid nanoparticles for camptothecin de-livery: a comparison of solid lipid nanoparticles, nanostructured lipid car-riers, and lipid emulsion

    Institute of Scientific and Technical Information of China (English)

    Zih-rou HUANG; Shu-chiou HUA; Yueh-lung YANG; Jia-you FANG

    2008-01-01

    Aim:Camptothecin is an anticancer drug that acta against a broad spectrum of tumors. The clinical application of camptothecin is limited by its insolubility, instability, and toxicity problems. The aim of this study was to develop and characterize lipid nanoparticles with different lipid cores which can circumvent these problems. Methods: Lipid nanoparticles made of Precirol (solid lipid nanoparticles; SLN-P), Compritol (SLN-C), Precirol+squalene (nanostructured lipid carriers; NLC), and squalene (a lipid emulsion; LE) as the lipid core ma-terial were prepared. These systems were assessed and compared by evaluat-ing the mean diameter, surface charge, molecular environment, camptothecin release, and cell viability against a melanoma. The safety and storage stability of these systems were also preliminarily examined. Results: The particle size ranged from 190 to 310 nm, with the NLC and LE showing the smallest and largest sizes, respectively. The in vitro drug release occurred in a sustained manner in decreasing order as follows: LE>NLC>SLN-P>SLN-C. It was found that varying the type of inner phase had profound effects on cell viability. The SLN-P generally showed higher cytotoxicity than the free control. The treat-ment of melanomas with the camptothecin-loaded SLN-C and NLC yielded cytotoxicity comparable to that of the free form. The percentage of erythrocyte hemolysis by all nanoparticles was ≤5%, suggesting a good tolerance to lipid nanoparticles. Conclusion: The results collectively suggest that the SLN-P may have the potential to serve as a delivery system for parenteral camptothecin ad-ministration because of the sustained drug release, strong cytotoxicity, limited hemolysis, and good storage stability.

  19. Nature as a source of inspiration for cationic lipid synthesis.

    Science.gov (United States)

    Labas, Romain; Beilvert, Fanny; Barteau, Benoit; David, Stéphanie; Chèvre, Raphaël; Pitard, Bruno

    2010-02-01

    Synthetic gene delivery systems represent an attractive alternative to viral vectors for DNA transfection. Cationic lipids are one of the most widely used non-viral vectors for the delivery of DNA into cultured cells and are easily synthesized, leading to a large variety of well-characterized molecules. This review discusses strategies for the design of efficient cationic lipids that overcome the critical barriers of in vitro transfection. A particular focus is placed on natural hydrophilic headgroups and lipophilic tails that have been used to synthesize biocompatible and non-toxic cationic lipids. We also present chemical features that have been investigated to enhance the transfection efficiency of cationic lipids by promoting the escape of lipoplexes from the endosomal compartment and DNA release from DNA-liposome complexes. Transfection efficiency studies using these strategies are likely to improve the understanding of the mechanism of cationic lipid-mediated gene delivery and to help the rational design of novel cationic lipids.

  20. Regulation of lipid metabolism

    Institute of Scientific and Technical Information of China (English)

    Peng LI

    2011-01-01

    @@ Lipids including cholesterol, phospholipids, fatty acids and triacylglycerols are important cellular constituents involved in membrane structure, energy homeostasis and many biological processes such as signal transduction, organelle development and cell differentiation.Recently, the area of lipid metabolism has drawn a great deal of attention due to its emerging role in the development of metabolic disorders such as obesity, diabetes, atherosclerosis and liver steatosis.We decided to organize a special issue of Frontiers in Biology focusing on our current understanding of lipid metabolism.

  1. Lateral Thinking and Technology Education.

    Science.gov (United States)

    Waks, Shlomo

    1997-01-01

    Presents an analysis of technology education and its relevance to lateral thinking. Discusses prospects for utilizing technology education as a platform and a contextual domain for nurturing lateral thinking. Argues that technology education is an appropriate environment for developing complementary incorporation of vertical and lateral thinking.…

  2. SOLID LIPID NANOPARTICLES: AN ADVANCED DRUG DELIVERY SYSTEM

    Directory of Open Access Journals (Sweden)

    Raghu Nandan Reddy* and Arshia Shariff

    2013-01-01

    Full Text Available Solid lipid nanoparticles are at the forefront of the rapidly developing field of nanotechnology with several potential applications in drug delivery, research and clinical medicine, as well as in other varied sciences. Solid lipid nanoparticle (SLN dispersions have been proposed as a new type of colloidal drug carrier system suitable for intravenous administration. Solid lipid nanoparticles (SLNs technology represents a promising new approach to lipophilic drug delivery. Solid lipid nanoparticles are spherical lipid particles ranging in size from 1 to 1000 nm and are dispersed in water or in aqueous surfactant solution. It is identical to an oil-in-water emulsion, but the liquid lipid (oil of the emulsion has been replaced by a solid lipid, i.e., yielding Solid Lipid Nanoparticles. SLN are particles made from solid lipid or lipid blends produced by high pressure homogenization. The biodegradable and bioacceptable nature of SLNs makes them less toxic as compared to polymeric nanoparticles. SLNs can also be used to improve the bioavailability of drugs. In this present review this new approach is discussed in terms of their advantages, disadvantages, methods, characterization, pharmacokinetic studies, in-vivo studies, in-vitro studies, and special features

  3. Lipid anti-lipid antibody responses correlate with disease activity in systemic lupus erythematosus.

    Directory of Open Access Journals (Sweden)

    Vojislav Jovanović

    Full Text Available Systemic lupus erythematosus (SLE is a chronic autoimmune disorder characterized by broad clinical manifestations including cardiovascular and renal complications with periodic disease flares and significant morbidity and mortality. One of the main contributing factors to the pathology of SLE is the accumulation and impaired clearance of immune complexes of which the principle components are host auto-antigens and antibodies. The contribution of host lipids to the formation of these autoimmune complexes remains poorly defined. The aim of the present study was to identify and analyze candidate lipid autoantigens and their corresponding anti-lipid antibody responses in a well-defined SLE patient cohort using a combination of immunological and biophysical techniques. Disease monitoring in the SLE cohort was undertaken with serial British Isles Lupus Assessment Group (BILAG scoring. Correlations between specific lipid/anti-lipid responses were investigated as disease activity developed from active flares to quiescent during a follow up period. We report a significant negative correlation between anti-lipid antibodies for 24S-hydroxycholesterol, cardiolipin and phosphatidylserine with SLE disease activity. Taken together, these data suggest that lipid autoantigens represent a new family of biomarkers that can be employed to monitor disease activity plus the efficacy of therapeutic intervention in SLE.

  4. [Lateral lumbar disk hernia].

    Science.gov (United States)

    Monod, A; Desmoineaux, P; Deburge, A

    1990-01-01

    Lateral lumbar disc herniations (L.D.H.) develop in the foramen, and compress the nerve root against the overlying vertebral pedicle. In our study of L.D.H. from the clinical, radiographical, and therapeutical aspects, we reviewed 23 cases selected from the 590 patients treated for discal herniation from 1984 to 1987. The frequency of L.D.H. in this series was 3.8 per cent. The clinical pattern brings out some suggestive signs of L.D.H. (frequency of cruralgia, a seldom very positive Lasegue's test, the paucity of spinal signs, non impulsive pain). Saccoradiculography and discography rarely evidenced the L.D.H.. The T.D.M. was the investigation of choice on condition that it was correctly used. When the image was doubtful, disco-CT confirmation should be proceeded too. This latter method of investigation enabled the possibility of sequestration to be explored. 14 patients were treated by chemonucleolysis, with 9 successful outcomes. The 5 failures were cases where chemonucleolysis should not have been indicated, mainly due to associated osseous stenosis. 9 patients underwent immediate surgery with good results in each case.

  5. Lateral laryngopharyngeal diverticulum: anatomical and videofluoroscopic study

    Energy Technology Data Exchange (ETDEWEB)

    Costa, Milton Melciades Barbosa [Universidade Federal do Rio de Janeiro ICB/CCS/UFRJ, Laboratorio de Motilidade Digestiva e Imagem, S. F1-008, Departamento de Anatomia, Rio de Janeiro (Brazil); Koch, Hilton Augusto [Universidade Federal do Rio de Janeiro ICB/CCS/UFRJ, Departamento de Radiologia, Rio de Janeiro (Brazil)

    2005-07-01

    The aims were to characterize the anatomical region where the lateral laryngopharyngeal protrusion occurs and to define if this protrusion is a normal or a pathological entity. This protrusion was observed on frontal contrasted radiographs as an addition image on the upper portion of the laryngopharynx. We carried out a plane-by-plane qualitative anatomical study through macroscopic and mesoscopic surgical dissection on 12 pieces and analyzed through a videofluoroscopic method on frontal incidence the pharyngeal phase of the swallowing process of 33 patients who had a lateral laryngopharyngeal protrusion. The anatomical study allowed us to identify the morphological characteristics that configure the high portion of the piriform recess as a weak anatomical point. The videofluoroscopic study allowed us to observe the laryngopharyngeal protrusion and its relation to pharyngeal repletion of the contrast medium. All kinds of the observed protrusions could be classified as ''lateral laryngopharyngeal diverticula.'' The lateral diverticula were more frequent in older people. These lateral protrusions can be found on one or both sides, usually with a small volume, without sex or side prevalence. This formation is probably a sign of a pharyngeal transference difficulty associated with a deficient tissue resistance in the weak anatomical point of the high portion of the piriform recess. (orig.)

  6. Metabolism. Part III: Lipids.

    Science.gov (United States)

    Bodner, George M.

    1986-01-01

    Describes the metabolic processes of complex lipids, including saponification, activation and transport, and the beta-oxidation spiral. Discusses fatty acid degradation in regard to biochemical energy and ketone bodies. (TW)

  7. Lipid Storage Diseases

    Science.gov (United States)

    ... weeks. What are the types of lipid storage disease? Gaucher disease is caused by a deficiency of the enzyme ... infection. The disease affects males and females equally. Gaucher disease has three common clinical subtypes. Type 1 (or ...

  8. A comparative study of the fatty acid composition of prochloron lipids

    Science.gov (United States)

    Kenrick, J. R.; Deane, E. M.; Bishop, D. G.

    1983-01-01

    The chemical analysis of lipids of Prochloron isolated from several hosts is discussed. The object was to determine whether differences in lipid composition could be used to characterize organisms from different sources. Major lipid components are given. An analysis of fatty acid composition of individual lipids slowed a distinctive disstribution of fatty acids. While present results do not justify the use of fatty acid content in the taxonomy of Prochlon, the variations found in the lipids of cells from the same host harvested from different areas, or at different times in the same area, suggest that a study of the effects of temperature and light intensity on lipid composition would be rewarding.

  9. The management of amyotrophic lateral sclerosis.

    LENUS (Irish Health Repository)

    Phukan, Julie

    2009-02-01

    The terms amyotrophic lateral sclerosis (ALS) or motor neuron disease (MND) refer to a condition characterized by motor system degeneration with relative preservation of other pathways. Although there have been advances in symptomatic treatment, ALS remains an incurable condition. Advances in ALS management prolong survival but simultaneously raise challenging ethical dilemmas for physicians, patients and their families. Here, we review current practice in the management of ALS including pharmacological treatment, nutritional management, respiratory care, and evolving strategies in the management of cognitive impairment.

  10. Role of Lipids in Brain Injury and Diseases.

    Science.gov (United States)

    Adibhatla, Rao Muralikrishna; Hatcher, J F

    2007-08-01

    Lipid metabolism is of particular interest due to its high concentration in CNS. The importance of lipids in cell signaling and tissue physiology is demonstrated by many CNS disorders and injuries that involve deregulated metabolism. The long suffering lipid field is gaining reputation and respect as evidenced through the Center of Biomedical Research Excellence in Lipidomics and Pathobiology (COBRE), Lipid MAPS (Metabolites And Pathways Strategy) Consortium sponsored by NIH, European initiatives for decoding the lipids through genomic approaches, and Genomics of Lipid-associated Disorder (GOLD) project initiated by Austrian government. This review attempts to provide an overview of the lipid imbalances associated with neurological disorders (Alzheimer's, Parkinson's; Niemann-Pick; Multiple sclerosis, Huntington, amyotrophic lateral sclerosis, schizophrenia, bipolar disorders and epilepsy) and CNS injury (Stroke, traumatic brain injury; and spinal cord injury) and a few provocative thoughts. Lipidomic analyses along with RNA silencing will provide new insights into the role of lipid intermediates in cell signaling and hopefully open new avenues for prevention or treatment options.

  11. Perspectives on marine zooplankton lipids

    DEFF Research Database (Denmark)

    Kattner, G.; Hagen, W.; Lee, R.F.

    2007-01-01

    We developed new perspectives to identify important questions and to propose approaches for future research on marine food web lipids. They were related to (i) structure and function of lipids, (ii) lipid changes during critical life phases, (iii) trophic marker lipids, and (iv) potential impact ...

  12. Diamond heteroepitaxial lateral overgrowth

    Science.gov (United States)

    Tang, Yung-Hsiu

    This dissertation describes improvements in the growth of single crystal diamond by microwave plasma-assisted chemical vapor deposition (CVD). Heteroepitaxial (001) diamond was grown on 1 cm. 2 a-plane sapphiresubstrates using an epitaxial (001) Ir thin-film as a buffer layer. Low-energy ion bombardment of the Ir layer, a process known as bias-enhanced nucleation, is a key step in achieving a high density of diamond nuclei. Bias conditions were optimized to form uniformly-high nucleation densities across the substrates, which led to well-coalesced diamond thin films after short growth times. Epitaxial lateral overgrowth (ELO) was used as a means of decreasing diamond internal stress by impeding the propagation of threading dislocations into the growing material. Its use in diamond growth requires adaptation to the aggressive chemical and thermal environment of the hydrogen plasma in a CVD reactor. Three ELO variants were developed. The most successful utilized a gold (Au) mask prepared by vacuum evaporation onto the surface of a thin heteroepitaxial diamond layer. The Au mask pattern, a series of parallel stripes on the micrometer scale, was produced by standard lift-off photolithography. When diamond overgrows the mask, dislocations are largely confined to the substrate. Differing degrees of confinement were studied by varying the stripe geometry and orientation. Significant improvement in diamond quality was found in the overgrown regions, as evidenced by reduction of the Raman scattering linewidth. The Au layer was found to remain intact during diamond overgrowth and did not chemically bond with the diamond surface. Besides impeding the propagation of threading dislocations, it was discovered that the thermally-induced stress in the CVD diamond was significantly reduced as a result of the ductile Au layer. Cracking and delamination of the diamond from the substrate was mostly eliminated. When diamond was grown to thicknesses above 0.1 mm it was found that

  13. Lipid mixtures prepared with well-defined synthetic ceramides closely mimic the unique stratum corneum lipid phase behavior.

    Science.gov (United States)

    de Jager, Miranda W; Gooris, Gert S; Ponec, Maria; Bouwstra, Joke A

    2005-12-01

    Lipid lamellae present in the outermost layer of the skin, the stratum corneum, form the main barrier for the diffusion of molecules through the skin. The presence of a unique 13 nm lamellar phase and its high crystallinity are characteristic for the stratum corneum lipid phase behavior. In the present study, small-angle and wide-angle X-ray diffraction were used to examine the organization in lipid mixtures prepared with a unique set of well-defined synthetic ceramides, varying from each other in head group architecture and acyl chain length. The results show that equimolar mixtures of cholesterol, free fatty acids, and synthetic ceramides (resembling the composition of pig ceramides) closely resemble the lamellar and lateral stratum corneum lipid organization, both at room and higher temperatures. Exclusion of several ceramide classes from the mixture does not affect the lipid organization. However, complete substitution of ceramide 1 (acylceramide with a sphingosine base) with ceramide 9 (acylceramide with a phytosphingosine base) reduces the formation of the long periodicity lamellar phase. This indicates that the head group architecture of acylceramides affects the lipid organization. In conclusion, lipid mixtures prepared with well-defined synthetic ceramides offer an attractive tool with which to unravel the importance of the molecular structure of individual ceramides for proper lipid organization.

  14. Apolipoprotein gene involved in lipid metabolism

    Science.gov (United States)

    Rubin, Edward; Pennacchio, Len A.

    2007-07-03

    Methods and materials for studying the effects of a newly identified human gene, APOAV, and the corresponding mouse gene apoAV. The sequences of the genes are given, and transgenic animals which either contain the gene or have the endogenous gene knocked out are described. In addition, single nucleotide polymorphisms (SNPs) in the gene are described and characterized. It is demonstrated that certain SNPs are associated with diseases involving lipids and triglycerides and other metabolic diseases. These SNPs may be used alone or with SNPs from other genes to study individual risk factors. Methods for intervention in lipid diseases, including the screening of drugs to treat lipid-related or diabetic diseases are also disclosed.

  15. LATERAL SURVIVAL: AN OT ACCOUNT

    Directory of Open Access Journals (Sweden)

    Moira Yip

    2004-12-01

    Full Text Available When laterals are the targets of phonological processes, laterality may or may not survive. In a fixed feature geometry, [lateral] should be lost if its superordinate node is eliminated by either the spreading of a neighbouring node, or by coda neutralization. So if [lateral] is under Coronal (Blevins 1994, it should be lost under Place assimilation, and if [lateral] is under Sonorant Voicing (Rice & Avery 1991 it should be lost by rules that spread voicing. Yet in some languages lateral survives such spreading intact. Facts like these argue against a universal attachment of [lateral] under either Coronal or Sonorant Voicing, and in favour of an account in terms of markedness constraints on feature-co-occurrence (Padgett 2000. The core of an OT account is that IFIDENTLAT is ranked above whatever causes neutralization, such as SHARE-F or *CODAF. laterality will survive. If these rankings are reversed, we derive languages in which laterality is lost. The other significant factor is markedness. High-ranked feature co-occurrence constraints like *LATDORSAL can block spreading from affecting laterals at all.

  16. Amyotrophic lateral sclerosis

    Directory of Open Access Journals (Sweden)

    Leigh P Nigel

    2009-02-01

    Full Text Available Abstract Amyotrophic lateral sclerosis (ALS is a neurodegenerative disease characterised by progressive muscular paralysis reflecting degeneration of motor neurones in the primary motor cortex, corticospinal tracts, brainstem and spinal cord. Incidence (average 1.89 per 100,000/year and prevalence (average 5.2 per100,000 are relatively uniform in Western countries, although foci of higher frequency occur in the Western Pacific. The mean age of onset for sporadic ALS is about 60 years. Overall, there is a slight male prevalence (M:F ratio~1.5:1. Approximately two thirds of patients with typical ALS have a spinal form of the disease (limb onset and present with symptoms related to focal muscle weakness and wasting, where the symptoms may start either distally or proximally in the upper and lower limbs. Gradually, spasticity may develop in the weakened atrophic limbs, affecting manual dexterity and gait. Patients with bulbar onset ALS usually present with dysarthria and dysphagia for solid or liquids, and limbs symptoms can develop almost simultaneously with bulbar symptoms, and in the vast majority of cases will occur within 1–2 years. Paralysis is progressive and leads to death due to respiratory failure within 2–3 years for bulbar onset cases and 3–5 years for limb onset ALS cases. Most ALS cases are sporadic but 5–10% of cases are familial, and of these 20% have a mutation of the SOD1 gene and about 2–5% have mutations of the TARDBP (TDP-43 gene. Two percent of apparently sporadic patients have SOD1 mutations, and TARDBP mutations also occur in sporadic cases. The diagnosis is based on clinical history, examination, electromyography, and exclusion of 'ALS-mimics' (e.g. cervical spondylotic myelopathies, multifocal motor neuropathy, Kennedy's disease by appropriate investigations. The pathological hallmarks comprise loss of motor neurones with intraneuronal ubiquitin-immunoreactive inclusions in upper motor neurones and TDP-43

  17. Partitioning of Lipids at Domain Boundaries in Model Membranes

    NARCIS (Netherlands)

    Schafer, Lars V.; Marrink, Siewert J.

    2010-01-01

    Line-active molecules ("linactants") that bind to the boundary interface between different fluid lipid domains in membranes have a strong potential as regulators of the lateral heterogeneity that is important for many biological processes. Here, we use molecular dynamics simulations in combination w

  18. Concerted diffusion of lipids in raft-like membranes

    NARCIS (Netherlands)

    Apajalahti, Touko; Niemela, Perttu; Govindan, Praveen Nedumpully; Miettinen, Markus S.; Salonen, Emppu; Marrink, Siewert-Jan; Vattulainen, Ilpo

    2010-01-01

    Currently, there is no comprehensive model for the dynamics of cellular membranes. The understanding of even the basic dynamic processes, such as lateral diffusion of lipids, is still quite limited. Recent studies of one-component membrane systems have shown that instead of single-particle motions,

  19. Lipidomic and proteomic analysis of Caenorhabditis elegans lipid droplets and identification of ACS-4 as a lipid droplet-associated protein.

    Science.gov (United States)

    Vrablik, Tracy L; Petyuk, Vladislav A; Larson, Emily M; Smith, Richard D; Watts, Jennifer L

    2015-10-01

    Lipid droplets are cytoplasmic organelles that store neutral lipids for membrane synthesis and energy reserves. In this study, we characterized the lipid and protein composition of purified Caenorhabditis elegans lipid droplets. These lipid droplets are composed mainly of triacylglycerols, surrounded by a phospholipid monolayer composed primarily of phosphatidylcholine and phosphatidylethanolamine. The fatty acid composition of the triacylglycerols is rich in fatty acid species obtained from the dietary Escherichia coli, including cyclopropane fatty acids and cis-vaccenic acid. Unlike other organisms, C. elegans lipid droplets contain very little cholesterol or cholesterol esters. Comparison of the lipid droplet proteomes of wild type and high-fat daf-2 mutant strains shows a very similar proteome in both strains, except that the most abundant protein in the C. elegans lipid droplet proteome, MDT-28, is relatively less abundant in lipid droplets isolated from daf-2 mutants. Functional analysis of lipid droplet proteins identified in our proteomic studies indicated an enrichment of proteins required for growth and fat homeostasis in C. elegans. Finally, we confirmed the localization of one of the newly identified lipid droplet proteins, ACS-4. We found that ACS-4 localizes to the surface of lipid droplets in the C. elegans intestine and skin. This study bolsters C. elegans as a model to study the dynamics and functions of lipid droplets in a multicellular organism.

  20. Non-polar lipids characterization of Quinoa (Chenopodium quinoa) seed by comprehensive two-dimensional gas chromatography with flame ionization/mass spectrometry detection and non-aqueous reversed-phase liquid chromatography with atmospheric pressure chemical ionization mass spectrometry detection.

    Science.gov (United States)

    Fanali, Chiara; Beccaria, Marco; Salivo, Simona; Tranchida, Peter; Tripodo, Giusy; Farnetti, Sara; Dugo, Laura; Dugo, Paola; Mondello, Luigi

    2015-07-08

    A chemical characterization of major lipid components, namely, triacylglycerols, fatty acids and the unsaponifiable fraction, in a Quinoa seed lipids sample is reported. To tackle such a task, non-aqueous reversed-phase high-performance liquid chromatography with mass spectrometry detection was employed. The latter was interfaced with atmospheric pressure chemical ionization for the analysis of triacylglycerols. The main triacylglycerols (>10%) were represented by OLP, OOL and OLL (P = palmitoyl, O = oleoyl, L = linoleoyl); the latter was present in the oil sample at the highest percentage (18.1%). Furthermore, fatty acid methyl esters were evaluated by gas chromatography with flame ionization detection. 89% of the total fatty acids was represented by unsaturated fatty acid methyl esters with the greatest percentage represented by linoleic and oleic acids accounting for approximately 48 and 28%, respectively. An extensive characterization of the unsaponifiable fraction of Quinoa seed lipids was performed for the first time, by using comprehensive two-dimensional gas chromatography with dual mass spectrometry/flame ionization detection. Overall, 66 compounds of the unsaponifiable fraction were tentatively identified, many constituents of which (particularly sterols) were confirmed by using gas chromatography with high-resolution time-of-flight mass spectrometry.

  1. The mechanism of lipids extraction from wet microalgae Scenedesmus sp. by ionic liquid assisted subcritical water

    Science.gov (United States)

    Yu, Zhuanni; Chen, Xiaolin; Xia, Shuwei

    2016-06-01

    In this paper, the total sugar concentration, protein concentration, lipid yield and morphology characteristics of the algae residue were determined to explain the mechanism of lipids extraction from wet microalgae Scenedesmus sp. by ionic liquid assisted subcritical water. The results showed similar variation for the sugar, protein and lipid. However, the total sugar was more similar to lipids yield, so the results showed that the reaction between ionic liquid and cellulose and hemicellulose in cell wall was the most important step which determined the lipids extration directly. And the total sugar variation may be representing the lipids yield. For later lipids extraction, we can determine the total sugar concentration to predict the extraction end product.

  2. Solid Lipid Nanoparticles of Guggul Lipid as Drug Carrier for Transdermal Drug Delivery

    Directory of Open Access Journals (Sweden)

    Praveen Kumar Gaur

    2013-01-01

    Full Text Available Diclofenac sodium loaded solid lipid nanoparticles (SLNs were formulated using guggul lipid as major lipid component and analyzed for physical parameters, permeation profile, and anti-inflammatory activity. The SLNs were prepared using melt-emulsion sonication/low temperature-solidification method and characterized for physical parameters, in vitro drug release, and accelerated stability studies, and formulated into gel. Respective gels were compared with a commercial emulgel (CEG and plain carbopol gel containing drug (CG for ex vivo and in vivo drug permeation and anti-inflammatory activity. The SLNs were stable with optimum physical parameters. GMS nanoparticle 1 (GMN-1 and stearic acid nanoparticle 1 (SAN-1 gave the highest in vitro drug release. Guggul lipid nanoparticle gel 3 (GLNG-3 showed 104.68 times higher drug content than CEG in receptor fluid. The enhancement ratio of GLNG-3 was 39.43 with respect to CG. GLNG-3 showed almost 8.12 times higher Cmax than CEG at 4 hours. The AUC value of GLNG-3 was 15.28 times higher than the AUC of CEG. GLNG-3 showed edema inhibition up to 69.47% in the first hour. Physicochemical properties of major lipid component govern the properties of SLN. SLN made up of guggul lipid showed good physical properties with acceptable stability. Furthermore, it showed a controlled drug release profile along with a promising permeation profile.

  3. LIPID PEROXIDATION IN PREECLAMPSIA

    Directory of Open Access Journals (Sweden)

    T.Sharmila Krishna

    2015-03-01

    Full Text Available Hypertension in pregnancy is a leading cause of both maternal and fetal mortality and morbidity. Preeclampsia is characterised by hypertension and proteinuria. Lipid peroxidation is an important factor in the pathophysiology of Preeclampsia. The present study was undertaken to determine Serum Malondialdehyde (MDA levels , a product of lipid peroxidation , in clinically diagnosed Preeclamptic women(n=30 and the values were compared with that of Normotensive pregnant women (n=30 aged between 18-30yrs. All of them were in their third trimester and were primigravida. Serum MDA was estimated by TBARS (thiobarbituric acid reactive substances method. We observed that Serum MDA levels were significantly increased in Preeclamptic women (p <0.000 as compared to that of Normotensive pregnant women . Increased levels of lipid peroxiation product - MDA may contribute to the pathophysiology of Preeclampsia.

  4. Lipid Ion Channels

    CERN Document Server

    Heimburg, Thomas

    2010-01-01

    The interpretation electrical phenomena in biomembranes is usually based on the assumption that the experimentally found discrete ion conduction events are due to a particular class of proteins called ion channels while the lipid membrane is considered being an inert electrical insulator. The particular protein structure is thought to be related to ion specificity, specific recognition of drugs by receptors and to macroscopic phenomena as nerve pulse propagation. However, lipid membranes in their chain melting regime are known to be highly permeable to ions, water and small molecules, and are therefore not always inert. In voltage-clamp experiments one finds quantized conduction events through protein-free membranes in their melting regime similar to or even undistinguishable from those attributed to proteins. This constitutes a conceptual problem for the interpretation of electrophysiological data obtained from biological membrane preparations. Here, we review the experimental evidence for lipid ion channels...

  5. Intramyocellular lipid kinetics and insulin resistance

    OpenAIRE

    Guo ZengKui

    2007-01-01

    Abstract More than fifteen years ago it was discovered that intramyocellular triglyceride (imcTG) content in skeletal muscle is abnormally high in conditions of lipid oversupply (e.g. high fat feeding) and, later, obesity, type 2 diabetes (T2D) and other metabolic conditions. This imcTG excess is robustly associated with muscle insulin resistance (MIR). However, to date the pathways responsible for the imcTG excess and the mechanisms underlying the imcTG-MIR correlation remain unclear. A curr...

  6. Dynamics and stability of lipid bilayers modulated by thermosensitive polypeptides, cholesterols, and PEGylated lipids.

    Science.gov (United States)

    Lee, Hwankyu; Kim, Hyun Ryoung; Park, Jae Chan

    2014-02-28

    Lipid bilayers, which consist of dipalmitoylglycerophosphocholines (DPPCs), PEGylated lipids, cholesterols, and elastin-like polypeptides (ELPs; [VPGVG]3) at different molar ratios, were simulated. Simulations were carried out for 2 μs using the coarse-grained (CG) model that had captured the experimentally observed phase behavior of PEGylated lipids and lateral diffusivity of DPPC bilayers. Starting with the initial position of ELPs on the bilayer surface, ELPs insert into the hydrophobic region of the bilayer because of their interaction with lipid tails, consistent with previous all-atom simulations. Lateral diffusion coefficients of DPPCs significantly increase in the bilayer composed of more ELPs and less cholesterols, showing their opposite effects on the bilayer dynamics. In particular, ELPs modulate the dynamics and phase for the disordered liquid bilayer, but not for the ordered gel bilayer, indicating that ELPs can destabilize only the disordered bilayer. In the ordered bilayer, ELP chains tend to have a spherical shape and slowly diffuse, while they are extended and diffuse faster in the disordered bilayer, indicating the effect of the bilayer phase on the conformation and diffusivity of ELPs. These findings explain the experimental observation that the ELP-conjugated liposomes are stable at 310 K (ordered phase) but become unstable and release the encapsulated drugs at 315 K (disordered phase), which suggests the effects of ELPs and cholesterols. Since the cholesterol-stabilized bilayer can be destabilized by the extended shaped ELPs only in the disordered phase (not in the ordered phase), the inclusion of cholesterols is required to safely shield drugs at 310 K as well as allow ELPs to disrupt lipids and destabilize the liposomes at 315 K.

  7. Lentivirus-ABCG1 instillation reduces lipid accumulation and improves lung compliance in GM-CSF knock-out mice

    Energy Technology Data Exchange (ETDEWEB)

    Malur, Anagha; Huizar, Isham [Program in Lung Cell Biology and Translational Research, Division of Pulmonary, Critical Care and Sleep Medicine, East Carolina University, Greenville, NC (United States); Wells, Greg [Department of Microbiology and Immunology, East Carolina University, Greenville, NC (United States); Barna, Barbara P. [Program in Lung Cell Biology and Translational Research, Division of Pulmonary, Critical Care and Sleep Medicine, East Carolina University, Greenville, NC (United States); Malur, Achut G. [Department of Microbiology and Immunology, East Carolina University, Greenville, NC (United States); Thomassen, Mary Jane, E-mail: thomassenm@ecu.edu [Program in Lung Cell Biology and Translational Research, Division of Pulmonary, Critical Care and Sleep Medicine, East Carolina University, Greenville, NC (United States); Department of Microbiology and Immunology, East Carolina University, Greenville, NC (United States)

    2011-11-18

    Highlights: Black-Right-Pointing-Pointer Lentivirus-ABCG1 reduces lipid accumulation in lungs of GM-CSF knock-out mice. Black-Right-Pointing-Pointer Up-regulation of ABCG1 improves lung function. Black-Right-Pointing-Pointer Upregulation of ABCG1 improves surfactant metabolism. -- Abstract: We have shown decreased expression of the nuclear transcription factor, peroxisome proliferator-activated receptor-gamma (PPAR{gamma}) and the PPAR{gamma}-regulated ATP-binding cassette transporter G1 (ABCG1) in alveolar macrophages from patients with pulmonary alveolar proteinosis (PAP). PAP patients also exhibit neutralizing antibodies to granulocyte-macrophage colony stimulating factor (GM-CSF), an upregulator of PPAR{gamma}. In association with functional GM-CSF deficiency, PAP lung is characterized by surfactant-filled alveolar spaces and lipid-filled alveolar macrophages. Similar pathology characterizes GM-CSF knock-out (KO) mice. We reported previously that intratracheal instillation of a lentivirus (lenti)-PPAR{gamma} plasmid into GM-CSF KO animals elevated ABCG1 and reduced alveolar macrophage lipid accumulation. Here, we hypothesized that instillation of lenti-ABCG1 might be sufficient to decrease lipid accumulation and improve pulmonary function in GM-CSF KO mice. Animals received intratracheal instillation of lenti-ABCG1 or control lenti-enhanced Green Fluorescent Protein (eGFP) plasmids and alveolar macrophages were harvested 10 days later. Alveolar macrophage transduction efficiency was 79% as shown by lenti-eGFP fluorescence. Quantitative PCR analyses indicated a threefold (p = 0.0005) increase in ABCG1 expression with no change of PPAR{gamma} or ABCA1 in alveolar macrophages of lenti-ABCG1 treated mice. ABCG1 was unchanged in control lenti-eGFP and PBS-instilled groups. Oil Red O staining detected reduced intracellular neutral lipid in alveolar macrophages from lenti-ABCG1 treated mice. Extracellular cholesterol and phospholipids were also decreased as shown by

  8. A Pascalian lateral drift sensor

    Energy Technology Data Exchange (ETDEWEB)

    Jansen, H., E-mail: hendrik.jansen@desy.de

    2016-09-21

    A novel concept of a layer-wise produced semiconductor sensor for precise particle tracking is proposed herein. In contrast to common semiconductor sensors, local regions with increased doping concentration deep in the bulk termed charge guides increase the lateral drift of free charges on their way to the read-out electrode. This lateral drift enables charge sharing independent of the incident position of the traversing particle. With a regular grid of charge guides the lateral charge distribution resembles a normalised Pascal's triangle for particles that are stopped in depths lower than the depth of the first layer of the charge guides. For minimum ionising particles a sum of binomial distributions describes the lateral charge distribution. This concept decouples the achievable sensor resolution from the pitch size as the characteristic length is replaced by the lateral distance of the charge guides.

  9. A Pascalian lateral drift sensor

    Science.gov (United States)

    Jansen, H.

    2016-09-01

    A novel concept of a layer-wise produced semiconductor sensor for precise particle tracking is proposed herein. In contrast to common semiconductor sensors, local regions with increased doping concentration deep in the bulk termed charge guides increase the lateral drift of free charges on their way to the read-out electrode. This lateral drift enables charge sharing independent of the incident position of the traversing particle. With a regular grid of charge guides the lateral charge distribution resembles a normalised Pascal's triangle for particles that are stopped in depths lower than the depth of the first layer of the charge guides. For minimum ionising particles a sum of binomial distributions describes the lateral charge distribution. This concept decouples the achievable sensor resolution from the pitch size as the characteristic length is replaced by the lateral distance of the charge guides.

  10. Customized MFM probes with high lateral resolution

    Directory of Open Access Journals (Sweden)

    Óscar Iglesias-Freire

    2016-07-01

    Full Text Available Magnetic force microscopy (MFM is a widely used technique for magnetic imaging. Besides its advantages such as the high spatial resolution and the easy use in the characterization of relevant applied materials, the main handicaps of the technique are the lack of control over the tip stray field and poor lateral resolution when working under standard conditions. In this work, we present a convenient route to prepare high-performance MFM probes with sub-10 nm (sub-25 nm topographic (magnetic lateral resolution by following an easy and quick low-cost approach. This allows one to not only customize the tip stray field, avoiding tip-induced changes in the sample magnetization, but also to optimize MFM imaging in vacuum (or liquid media by choosing tips mounted on hard (or soft cantilevers, a technology that is currently not available on the market.

  11. Computationally efficient prediction of area per lipid

    DEFF Research Database (Denmark)

    Chaban, Vitaly V.

    2014-01-01

    Area per lipid (APL) is an important property of biological and artificial membranes. Newly constructed bilayers are characterized by their APL and newly elaborated force fields must reproduce APL. Computer simulations of APL are very expensive due to slow conformational dynamics. The simulated d....... Thus, sampling times to predict accurate APL are reduced by a factor of 10. (C) 2014 Elsevier B.V. All rights reserved....

  12. Lipid Therapy for Intoxications

    NARCIS (Netherlands)

    Robben, Joris Henricus; Dijkman, Marieke Annet

    2017-01-01

    This review discusses the use of intravenous lipid emulsion (ILE) in the treatment of intoxications with lipophilic agents in veterinary medicine. Despite growing scientific evidence that ILE has merit in the treatment of certain poisonings, there is still uncertainty on the optimal composition of t

  13. Lipids in cheese

    Science.gov (United States)

    Lipids are present in cheese at levels above 20 percent and are analyzed by several techniques. Scanning electron microscopy and confocal laser scanning microscopy are used to examine the microstructure, gas chromatography is employed to look at fatty acid composition, and differential scanning cal...

  14. Amphotericin B Lipid Complex Injection

    Science.gov (United States)

    Amphotericin B lipid complex injection is used to treat serious, possibly life-threatening fungal infections in people who did not respond ... to tolerate conventional amphotericin B therapy. Amphotericin B lipid complex injection is in a class of medications ...

  15. Lipid nanotube or nanowire sensor

    Science.gov (United States)

    Noy, Aleksandr; Bakajin, Olgica; Letant, Sonia; Stadermann, Michael; Artyukhin, Alexander B.

    2009-06-09

    A sensor apparatus comprising a nanotube or nanowire, a lipid bilayer around the nanotube or nanowire, and a sensing element connected to the lipid bilayer. Also a biosensor apparatus comprising a gate electrode; a source electrode; a drain electrode; a nanotube or nanowire operatively connected to the gate electrode, the source electrode, and the drain electrode; a lipid bilayer around the nanotube or nanowire, and a sensing element connected to the lipid bilayer.

  16. Delivery of siRNA Complexed with Palmitoylated α-Peptide/β-Peptoid Cell-Penetrating Peptidomimetics: Membrane Interaction and Structural Characterization of a Lipid-Based Nanocarrier System

    DEFF Research Database (Denmark)

    Jing, Xiaona; Foged, Camilla; Martin-Bertelsen, Birte;

    2016-01-01

    on the interaction with model membranes and the cellular uptake. Palmitoylation enhanced the peptidomimetic adsorption to supported lipid bilayers as studied by ellipsometry. However, both palmitoylation and increased peptidomimetic chain length were found to be beneficial in the cellular uptake studies using...

  17. Complex links between dietary lipids, endogenous endotoxins and metabolic inflammation.

    Science.gov (United States)

    Laugerette, Fabienne; Vors, Cécile; Peretti, Noël; Michalski, Marie-Caroline

    2011-01-01

    Metabolic diseases such as obesity are characterized by a subclinical inflammatory state that contributes to the development of insulin resistance and atherosclerosis. Recent reports also indicate that (i) there are alterations of the intestinal microbiota in metabolic diseases and (ii) absorption of endogenous endotoxins (namely lipopolysaccharides, LPS) can occur, particularly during the digestion of lipids. The aim of the present review is to highlight recently gained knowledge regarding the links between high fat diets, lipid digestion, intestinal microbiota and metabolic endotoxemia & inflammation.

  18. Stratum Corneum Lipids: Their Role for the Skin Barrier Function in Healthy Subjects and Atopic Dermatitis Patients.

    Science.gov (United States)

    van Smeden, Jeroen; Bouwstra, Joke A

    2016-01-01

    Human skin acts as a primary barrier between the body and its environment. Crucial for this skin barrier function is the lipid matrix in the outermost layer of the skin, the stratum corneum (SC). Two of its functions are (1) to prevent excessive water loss through the epidermis and (2) to avoid that compounds from the environment permeate into the viable epidermal and dermal layers and thereby provoke an immune response. The composition of the SC lipid matrix is dominated by three lipid classes: cholesterol, free fatty acids and ceramides. These lipids adopt a highly ordered, 3-dimensional structure of stacked densely packed lipid layers (lipid lamellae): the lateral and lamellar lipid organization. The way in which these lipids are ordered depends on the composition of the lipids. One very common skin disease in which the SC lipid barrier is affected is atopic dermatitis (AD). This review addresses the SC lipid composition and organization in healthy skin, and elaborates on how these parameters are changed in lesional and nonlesional skin of AD patients. Concerning the lipid composition, the changes in the three main lipid classes and the importance of the carbon chain lengths of the lipids are discussed. In addition, this review addresses how these changes in lipid composition induce changes in lipid organization and subsequently correlate with an impaired skin barrier function in both lesional and nonlesional skin of these patients. Furthermore, the effect of filaggrin and mutations in the filaggrin gene on the SC lipid composition is critically discussed. Also, the breakdown products of filaggrin, the natural moisturizing factor molecules and its relation to SC-pH is described. Finally, the paper discusses some major changes in epidermal lipid biosynthesis in patients with AD and other related skin diseases, and how inflammation has a deteriorating effect on the SC lipids and SC biosynthesis. The review ends with perspectives on future studies in relation to

  19. Phase Diagrams and Ordering in Charged Membranes: Binary Mixtures of Charged and Neutral Lipids.

    Science.gov (United States)

    Shimokawa, Naofumi; Himeno, Hiroki; Hamada, Tsutomu; Takagi, Masahiro; Komura, Shigeyuki; Andelman, David

    2016-07-07

    We propose a model describing the phase behavior of two-component membranes consisting of binary mixtures of electrically charged and neutral lipids. We take into account the structural phase transition (main-transition) of the hydrocarbon chains, and investigate the interplay between this phase transition and the lateral phase separation. The presence of charged lipids significantly affects the phase behavior of the multicomponent membrane. Due to the conservation of lipid molecular volume, the main-transition temperature of charged lipids is lower than that of neutral ones. Furthermore, as compared with binary mixtures of neutral lipids, the membrane phase separation in binary mixtures of charged lipids is suppressed, in accord with recent experiments. We distinguish between two types of charged membranes: mixtures of charged saturated lipid/neutral unsaturated lipid and a second case of mixtures of neutral saturated lipid/charged unsaturated lipid. The corresponding phase behavior is calculated and shown to be very different. Finally, we discuss the effect of added salt on the phase separation and the temperature dependence of the lipid molecular area.

  20. Lateral inhibition during nociceptive processing

    DEFF Research Database (Denmark)

    Quevedo, Alexandre S.; Mørch, Carsten Dahl; Andersen, Ole Kæseler

    2017-01-01

    of skin. Thus, the stimulation of the skin region between the endpoints of the lines appears to produce inhibition. These findings indicate that lateral inhibition limits spatial summation of pain and is an intrinsic component of nociceptive information processing. Disruption of such lateral inhibition......Spatial summation of pain is the increase of perceived intensity that occurs as the stimulated area increases. Spatial summation of pain is sub-additive in that increasing the stimulus area produces a disproportionately small increase in the perceived intensity of pain. A possible explanation...... for sub-additive summation may be that convergent excitatory information is modulated by lateral inhibition. To test the hypothesis that lateral inhibition may limit spatial summation of pain, we delivered different patterns of noxious thermal stimuli to the abdomens of 15 subjects using a computer...

  1. Lateral gene transfer, rearrangement, reconciliation

    NARCIS (Netherlands)

    Patterson, M.D.; Szollosi, G.; Daubin, V.; Tannier, E.

    2013-01-01

    Background. Models of ancestral gene order reconstruction have progressively integrated different evolutionary patterns and processes such as unequal gene content, gene duplications, and implicitly sequence evolution via reconciled gene trees. These models have so far ignored lateral gene transfer,

  2. Diagnosing and treating lateral epicondylitis.

    OpenAIRE

    1994-01-01

    Lateral epicondylitis is often encountered in primary care. Although its diagnosis can be fairly straightforward, its treatment is often difficult. This review examines the epidemiology, pathophysiology, and clinical presentation of tennis elbow. Management options are discussed.

  3. Cerebral Laterality and Verbal Processes

    Science.gov (United States)

    Sherman, Jay L.; And Others

    1976-01-01

    Research suggests that we process information by way of two distinct and functionally separate coding systems. Their location, somewhat dependent on cerebral laterality, varies in right- and left-handed persons. Tests this dual coding model. (Editor/RK)

  4. Lipid domains in bicelles containing unsaturated lipids and cholesterol.

    Science.gov (United States)

    Cho, Hyo Soon; Dominick, Johnna L; Spence, Megan M

    2010-07-22

    We have created a stable bicelle system capable of forming micrometer-scale lipid domains that orient in a magnetic field, suitable for structural biology determination in solid-state NMR. The bicelles consisted of a mixture of cholesterol, saturated lipid (DMPC), and unsaturated lipid (POPC), a mixture commonly used to create domains in model membranes, along with a short chain lipid (DHPC) that allows formation of the bicelle phase. While maintaining a constant molar ratio of long to short chain lipids, q = ([POPC]+[DMPC])/[DHPC] = 3, we varied the concentrations of the unsaturated lipid, POPC, and cholesterol to observe the effects of the components on bicelle stability. Using (31)P solid-state NMR, we observed that unsaturated lipids (POPC) greatly destabilized the alignment of the membranes in the magnetic field, while cholesterol stabilized their alignment. By combining cholesterol and unsaturated lipids in the bicelles, we created membranes aligning uniformly in the magnetic field, despite very high concentrations of unsaturated lipids. These bicelles, with high concentrations of both cholesterol and unsaturated lipid, showed similar phase behavior to bicelles commonly used in structural biology, but aligned over a wider temperature range (291-314 K). Domains were observed by measuring time-dependent diffusion constants reflecting restricted diffusion of the lipids within micrometer-scale regions of the bicelles. Micron-scale domains have never been observed in POPC/DMPC/cholesterol vesicles, implying that bilayers in bicelles show different phase behavior than their counterparts in vesicles, and that bilayers in bicelles favor domain formation.

  5. Lateral Asymmetries in Human Evolution

    OpenAIRE

    John L. Bradshaw; Nettleton, Norman C.

    1989-01-01

    Lateral asymmetries are not confined to humans. Palaeozoic trilobites and calcichordates are now known to have been asymmetrical; song control in passerines is vested in the left cerebral hemisphere; learning which is lateralized to the left forebrain of chicks includes imprinting, visual discrimination learning and auditory habituation, while responses to novelty, attack and copulation are activated by the right; in rats the right hemisphere is involved in emotional behavior and spatial disc...

  6. Visualization of lipid domains in giant unilamellar vesicles using an environment-sensitive membrane probe based on 3-hydroxyflavone.

    Science.gov (United States)

    Klymchenko, Andrey S; Oncul, Sule; Didier, Pascal; Schaub, Emmanuel; Bagatolli, Luis; Duportail, Guy; Mély, Yves

    2009-02-01

    We characterized the recently introduced environment-sensitive fluorescent membrane probe based on 3-hydroxyflavone, F2N12S, in model lipid membranes displaying liquid disordered (Ld) phase, liquid ordered (Lo) phase, or their coexistence. Steady-state fluorescence studies in large unilamellar vesicles show that the probe dual emission drastically changes with the lipid bilayer phase, which can be correlated with the difference in their hydration. Using two-photon excitation microscopy on giant unilamellar vesicles, the F2N12S probe was found to bind both Ld and Lo phases, allowing visualization of the individual phases from the fluorescence intensity ratio of its two emission bands. By using a linearly polarized excitation light, a strong photoselection was observed for F2N12S in the Lo phase, indicating that its fluorophore is nearly parallel to the lipid chains of the bilayer. In contrast, the absence of the photoselection with the Ld phase indicated no predominant orientation of the probe in the Ld phase. Comparison of the present results with those reported previously for F2N12S in living cells suggests a high content of the Lo phase in the outer leaflet of the cell plasma membranes. Taking into account the high selectivity of F2N12S for the cell plasma membranes and its suitability for both single- and two-photon excitation, applications of this probe to study membrane lateral heterogeneity in biological membranes are foreseen.

  7. The Effect of Lidocaine · HCl on the Fluidity of Native and Model Membrane Lipid Bilayers.

    Science.gov (United States)

    Park, Jun-Seop; Jung, Tae-Sang; Noh, Yang-Ho; Kim, Woo-Sung; Park, Won-Ick; Kim, Young-Soo; Chung, In-Kyo; Sohn, Uy Dong; Bae, Soo-Kyung; Bae, Moon-Kyoung; Jang, Hye-Ock; Yun, Il

    2012-12-01

    The purpose of this study is to investigated the mechanism of pharmacological action of local anesthetic and provide the basic information about the development of new effective local anesthetics. Fluorescent probe techniques were used to evaluate the effect of lidocaine·HCl on the physical properties (transbilayer asymmetric lateral and rotational mobility, annular lipid fluidity and protein distribution) of synaptosomal plasma membrane vesicles (SPMV) isolated from bovine cerebral cortex, and liposomes of total lipids (SPMVTL) and phospholipids (SPMVPL) extracted from the SPMV. An experimental procedure was used based on selective quenching of 1,3-di(1-pyrenyl)propane (Py-3-Py) and 1,6-diphenyl-1,3,5-hexatriene (DPH) by trinitrophenyl groups, and radiationless energy transfer from the tryptophans of membrane proteins to Py-3-Py. Lidocaine·HCl increased the bulk lateral and rotational mobility of neuronal and model membrane lipid bilayes, and had a greater fluidizing effect on the inner monolayer than the outer monolayer. Lidocaine·HCl increased annular lipid fluidity in SPMV lipid bilayers. It also caused membrane proteins to cluster. The most important finding of this study is that there is far greater increase in annular lipid fluidity than that in lateral and rotational mobilities by lidocaine·HCl. Lidocaine·HCl alters the stereo or dynamics of the proteins in the lipid bilayers by combining with lipids, especially with the annular lipids. In conclusion, the present data suggest that lidocaine, in addition to its direct interaction with proteins, concurrently interacts with membrane lipids, fluidizing the membrane, and thus inducing conformational changes of proteins known to be intimately associated with membrane lipid.

  8. Model studies of lipid flip-flop in membranes

    DEFF Research Database (Denmark)

    Parisio, Giulia; Ferrarini, Alberta; Sperotto, Maria Maddalena

    2016-01-01

    Biomembranes, which are made of a lipid bilayer matrix where proteins are embedded or attached, constitute a physical barrier for cell and its internal organelles. With regard to the distribution of their molecular components, biomembranes are both laterally heterogeneous and transversally...... asymmetric, and because of this they are sites of vital biochemical activities. Lipids may translocate from one leaflet of the bilayer to the opposite either spontaneously or facilitated by proteins, hence they contribute to the regulation of membrane asymmetry on which cell functioning, differentiation...

  9. Phototropism and gravitropism in lateral roots of Arabidopsis.

    Science.gov (United States)

    Kiss, John Z; Miller, Kelley M; Ogden, Lisa A; Roth, Kelly K

    2002-01-01

    Gravitropism and, to a lesser extent, phototropism have been characterized in primary roots, but little is known about structural/functional aspects of these tropisms in lateral roots. Therefore, in this study, we report on tropistic responses in lateral roots of Arabidopsis thaliana. Lateral roots initially are plagiogravitropic, but when they reach a length of approximately 10 mm, these roots grow downward and exhibit positive orthogravitropism. Light and electron microscopic studies demonstrate a correlation between positive gravitropism and development of columella cells with large, sedimented amyloplasts in wild-type plants. Lateral roots display negative phototropism in response to white and blue light and positive phototropism in response to red light. As is the case with primary roots, the photoresponse is weak relative to the graviresponse, but phototropism is readily apparent in starchless mutant plants, which are impaired in gravitropism. To our knowledge, this is the first report of phototropism of lateral roots in any plant species.

  10. Dysregulated lipid metabolism in cancer

    Institute of Scientific and Technical Information of China (English)

    2012-01-01

    Alteration of lipid metabolism has been increasingly recognized as a hallmark of cancer cells. The changes of expression and activity of lipid metabolizing enzymes are directly regulated by the activity of oncogenic signals. The dependence of tumor cells on the dysregulated lipid metabolism suggests that proteins involved in this process are excellent chemotherapeutic targets for cancer treatment. There are currently several drugs under development or in clinical trials that are based on specifically targeting the altered lipid metabolic pathways in cancer cells. Further understanding of dysregulated lipid metabolism and its associated signaling pathways will help us to better design efficient cancer therapeutic strategy.

  11. [Operative treatment of lateral hyperpressure syndrome of the patella].

    Science.gov (United States)

    Franke, J; Riede, D; Rudolph, F

    1980-04-01

    The lateral hyperpressure syndrome of the patella according to Ficat is characterized as a main cause of chondropathia patellae. Symptoms and course as well as roentgenology of this syndrome are illustrated. The logical method of treatment of this syndrome is the lateral release-operation according to Viernstein and Weigert. With this operation we gained good and very good results in 77 per cent of the 30 operated knee-joints.

  12. Clinical neurorestorative progress in amyotrophic lateral sclerosis

    Directory of Open Access Journals (Sweden)

    Chen L

    2015-08-01

    Full Text Available Lin Chen,1,2,5 Hongyun Huang,3 Haitao Xi,4,5 Gengsheng Mao3 1Medical Center, Tsinghua University, 2Tsinghua University Yuquan Hospital, 3General Hospital of Chinese People's Armed Police Forces, 4Beijing Rehabilitation Hospital of Capital Medical University, 5Beijing Hongtianji Neuroscience Academy, Beijing, People’s Republic of China Abstract: Amyotrophic lateral sclerosis is a progressive and fatal neurodegenerative disease characterized by progressive paralysis and motor neuron death. In addition to symptomatic managements such as ventilation and nutritional support, neurorestorative therapies have demonstrated anti-neurodegenerative potential and may improve quality of life for patients. Currently, clinical neurorestorative strategies include pharmacological management (granulocyte colony stimulating factor, neuromodulatory intervention (repetitive transcranial magnetic and cortical stimulation, cell transplantation (bone marrow stromal cells, olfactory ensheathing cells, granulocyte colony stimulating factor-mobilized peripheral blood stromal cells, hematopoietic stem and progenitor cells, neural stem/progenitor cells, CD133+ cells and CD34+ cells, bioengineering and tissue engineering therapy, and combined neurorehabilitative treatment. In this review, we describe the latest progress in clinical neurorestorative management of amyotrophic lateral sclerosis and discuss the underlying evidence base. Keywords: amyotrophic lateral sclerosis, neurorestorative treatment, cell transplantation, clinical trial

  13. CIDE proteins and lipid metabolism.

    Science.gov (United States)

    Xu, Li; Zhou, Linkang; Li, Peng

    2012-05-01

    Lipid homeostasis is maintained through the coordination of lipid metabolism in various tissues, including adipose tissue and the liver. The disruption of lipid homeostasis often results in the development of metabolic disorders such as obesity, diabetes mellitus, liver steatosis, and cardiovascular diseases. Cell death-inducing DNA fragmentation factor 45-like effector family proteins, including Cidea, Cideb, and Fsp27 (Cidec), are emerging as important regulators of various lipid metabolic pathways and play pivotal roles in the development of metabolic disorders. This review summarizes the latest cell death-inducing DNA fragmentation factor 45-like effector protein discoveries related to the control of lipid metabolism, with emphasis on the role of these proteins in lipid droplet growth in adipocytes and in the regulation of very low-density lipoprotein lipidation and maturation in hepatocytes.

  14. [Nitric oxide and lipid peroxidation].

    Science.gov (United States)

    Cristol, J P; Maggi, M F; Guérin, M C; Torreilles, J; Descomps, B

    1995-01-01

    Nitric oxide (NO) is a free radical produced enzymatically in biological systems from the guanidino group of L-arginine. Its large spectrum of biological effects is achieved through chemical interactions with different targets including oxygen (O2), superoxide (O2o-) and other oxygen reactive species (ROS), transition metals and thiols. Superoxide anions and other ROS have been reported to react with NO to produce peroxynitrite anions that can decompose to form nitrogen dioxide (NO2) and hydroxyl radial (OHo). Thus, NO has been reported to have a dual effect on lipid peroxidation (prooxidant via the peroxynitrite or antioxydant via the chelation of ROS). In the present study we have investigated in different models the in vitro and in vivo action of NO on lipid peroxidation. Copper-induced LDL oxidation were used as an in vitro model. Human LDL (100 micrograms ApoB/ml) were incubated in oxygene-saturated PBS buffer in presence or absence of Cu2+ (2.5 microM) with increasing concentrations of NO donnors (sodium nitroprussiate or nitroso-glutathione). LDL oxidation was monitored continuously for conjugated diene formation (234 nm) and 4-hydroxynonenal (HNE) accumulation. Exogenous NO prevents in a dose dependent manner the progress of copper-induced oxidation. Ischaemia-reperfusion injury (I/R), characterized by an overproduction of ROS, is used as an in vivo model. Anaesthetized rats were submitted to 1 hour renal ischaemia following by 2 hours of reperfusion. Sham-operated rats (SOP) were used as control. Lipid peroxidation was evaluated by measuring the HNE accumulated in rats kidneys in presence or absence of L-arginine or D-arginine infusion. L-arginine, but not D-arginine, enhances HNE accumulation in I/R but not in SOP (< 0.050 pmol/g tissue in SOP versus 0.6 nmol/g tissue in I/R), showing that, in this experimental conditions, NO produced from L-arginine, enhances the toxicity of ROS. This study shows that the pro- or antioxydant effects of NO are different

  15. Lipids and immune function.

    Science.gov (United States)

    Vitale, J J; Broitman, S A

    1981-09-01

    There is in vitro and in vivo evidence to suggest that dietary lipids play a role in modulating immune function. A review of the current literature on the interrelationships among dietary lipids, blood cholesterol levels, immunosuppression, and tumorigenesis makes for a very strong argument that (a) immunosuppression may be causally related to lymphoproliferative disorders, as well as to tumorigenesis and (b) diets high in polyunsaturated fat, relative to diets high in saturated fat, are more immunosuppressive and are better promotors of tumorigenesis. The effects of dietary fat on immune function seem to be mediated though its component parts, the unsaturated fatty acids, specially linoleic, linolenic, and arachidonic. It is not clear how these components affect immune function. Several studies suggest that one effect is mediated by altering the lipid component of the cell membrane and thus its fluidity; the more fluid the membrane, the less responsive it is. Thus, fluidity of both immune cells and those to be destroyed or protected may be affected. The effects of saturated as well as unsaturated fatty acids may be mediated by modulating serum lipoprotein levels, prostaglandin metabolism, and cholesterol concentrations and metabolism.

  16. Size and phospholipid coating of lipid droplets in the diet of young mice modify body fat accumulation in adulthood

    NARCIS (Netherlands)

    Oosting, Annemarie; Kegler, Diane; Wopereis, Harm J.; Teller, Inga C.; van de Heijning, Bert J. M.; Verkade, Henkjan J.; van der Beek, Eline M.

    2012-01-01

    BACKGROUND: In addition to contemporary lifestyle factors that contribute to the increased obesity prevalence worldwide, early nutrition is associated with sustained effects on later life obesity. We hypothesized that physical properties of dietary lipids contribute to this nutritional programming.

  17. Impact of Lipid Nutrition on Neural Stem/Progenitor Cells

    Directory of Open Access Journals (Sweden)

    Nobuyuki Sakayori

    2013-01-01

    Full Text Available The neural system originates from neural stem/progenitor cells (NSPCs. Embryonic NSPCs first proliferate to increase their numbers and then produce neurons and glial cells that compose the complex neural circuits in the brain. New neurons are continually produced even after birth from adult NSPCs in the inner wall of the lateral ventricle and in the hippocampal dentate gyrus. These adult-born neurons are involved in various brain functions, including olfaction-related functions, learning and memory, pattern separation, and mood control. NSPCs are regulated by various intrinsic and extrinsic factors. Diet is one of such important extrinsic factors. Of dietary nutrients, lipids are important because they constitute the cell membrane, are a source of energy, and function as signaling molecules. Metabolites of some lipids can be strong lipid mediators that also regulate various biological activities. Recent findings have revealed that lipids are important regulators of both embryonic and adult NSPCs. We and other groups have shown that lipid signals including fat, fatty acids, their metabolites and intracellular carriers, cholesterol, and vitamins affect proliferation and differentiation of embryonic and adult NSPCs. A better understanding of the NSPCs regulation by lipids may provide important insight into the neural development and brain function.

  18. Lipid nanoparticles as vehicles for topical psoralen delivery: solid lipid nanoparticles (SLN) versus nanostructured lipid carriers (NLC).

    Science.gov (United States)

    Fang, Jia-You; Fang, Chia-Lang; Liu, Chi-Hsien; Su, Yu-Han

    2008-10-01

    Solid lipid nanoparticles (SLN) were developed by using Precirol ATO 5 as the solid core of the particles for topical psoralen delivery. Nanostructured lipid carriers (NLC) consisting of Precirol and squalene, a liquid lipid, were also prepared for comparison. SLN and NLC showed respective mean particle sizes of approximately 300 and 200nm, respectively. Viscosity, polarity, and differential scanning calorimetry (DSC) studies were performed to characterize the physicochemical properties of the SLN and NLC. The viscosity of all nanoparticulate systems exhibited Newtonian behavior except the NLC with Tween 80 and soybean phospholipids as the emulsifiers (NLC-Tw). According to the DSC thermograms, the melting peak of Precirol shifted from 58 to 55 degrees C after incorporating squalene into the solid lipid cores (of NLC), which suggests defects in the crystalline lattice of the lipid cores and smaller particle sizes. Three psoralen derivatives for psoriasis treatments were loaded in SLN and NLC to examine their ability to permeate skin. The permeability of psoralens increased in the order of 8-methoxypsoralen (8-MOP)>5-methoxypsoralen (5-MOP)>4,5,8-trimethylpsoralen (TMP). Enhanced permeation and controlled release of psoralen delivery were both achieved using the NLC. The in vitro permeation results showed that NLC-Tw increased the 8-MOP flux 2.8 times over that of a conventional emulsion. Hyperproliferative or psoriasis-like skin produced by repeated strippings in the dorsal skin of nude mouse was also used as a permeation barrier. The results showed that the entrapment of 8-MOP in nanoparticulate systems could minimize the permeation differentiation between normal and hyperproliferative skin compared to the free drug in an aqueous control.

  19. Redox Regulation in Amyotrophic Lateral Sclerosis

    Directory of Open Access Journals (Sweden)

    Sonam Parakh

    2013-01-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is a neurodegenerative disease that results from the death of upper and lower motor neurons. Due to a lack of effective treatment, it is imperative to understand the underlying mechanisms and processes involved in disease progression. Regulations in cellular reduction/oxidation (redox processes are being increasingly implicated in disease. Here we discuss the possible involvement of redox dysregulation in the pathophysiology of ALS, either as a cause of cellular abnormalities or a consequence. We focus on its possible role in oxidative stress, protein misfolding, glutamate excitotoxicity, lipid peroxidation and cholesterol esterification, mitochondrial dysfunction, impaired axonal transport and neurofilament aggregation, autophagic stress, and endoplasmic reticulum (ER stress. We also speculate that an ER chaperone protein disulphide isomerase (PDI could play a key role in this dysregulation. PDI is essential for normal protein folding by oxidation and reduction of disulphide bonds, and hence any disruption to this process may have consequences for motor neurons. Addressing the mechanism underlying redox regulation and dysregulation may therefore help to unravel the molecular mechanism involved in ALS.

  20. Redox regulation in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Parakh, Sonam; Spencer, Damian M; Halloran, Mark A; Soo, Kai Y; Atkin, Julie D

    2013-01-01

    Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that results from the death of upper and lower motor neurons. Due to a lack of effective treatment, it is imperative to understand the underlying mechanisms and processes involved in disease progression. Regulations in cellular reduction/oxidation (redox) processes are being increasingly implicated in disease. Here we discuss the possible involvement of redox dysregulation in the pathophysiology of ALS, either as a cause of cellular abnormalities or a consequence. We focus on its possible role in oxidative stress, protein misfolding, glutamate excitotoxicity, lipid peroxidation and cholesterol esterification, mitochondrial dysfunction, impaired axonal transport and neurofilament aggregation, autophagic stress, and endoplasmic reticulum (ER) stress. We also speculate that an ER chaperone protein disulphide isomerase (PDI) could play a key role in this dysregulation. PDI is essential for normal protein folding by oxidation and reduction of disulphide bonds, and hence any disruption to this process may have consequences for motor neurons. Addressing the mechanism underlying redox regulation and dysregulation may therefore help to unravel the molecular mechanism involved in ALS.

  1. Characterization of the pharmacokinetics of human recombinant erythropoietin in blood and brain when administered immediately after lateral fluid percussion brain injury and its pharmacodynamic effects on IL-1beta and MIP-2 in rats.

    Science.gov (United States)

    Lieutaud, Thomas; Andrews, Peter J D; Rhodes, Jonathan K J; Williamson, Robert

    2008-10-01

    This study sought to determine the bio-availability of recombinant human erythropoietin (EPO) in the brain and blood and its effects on the cerebral concentrations of the inflammatory mediators interleukin-1beta (IL-1beta) and macrophage-inflammation protein-2 (MIP-2) following lateral fluid percussion brain injury (FPI) in the rat. After induction of moderate FPI (1.6-1.8 atm), EPO was injected intraperitoneally (IP) or intravenously (IV) at doses of 1000-5000 U/kg in a randomized and blinded manner. Animals were then sacrificed at time points (4, 8, 12, 24 h) post-trauma, and the brain concentrations of EPO, IL-1beta, and MIP-2 were determined. EPO administration leads to a dose-dependent increase in the brain concentration of the drug; however, this could only be detected at doses of 3000 and 5000 U/kg. The cerebral concentration peaked in the first 4 h following trauma. EPO concentrations were significantly higher and decreased more slowly in the traumatized cortex compared to the contralateral side (p<0.0125). IV EPO (5000 U/kg) produced slightly higher concentrations of EPO than same doses injected IP; however, this was not significant. At a dose of 5000 U/kg, EPO significantly reduced the increase in IL-1beta at 8 and 12 h in both cortical sides. It also reduced the increase in MIP-2 but only after 8 h, on the contralateral side and after 12 h on the ipsilateral side. Our results suggest that EPO crosses the blood-brain barrier (BBB) by 4 h after trauma and is localized primarily in the traumatized cortex. Further, it has biological efficacy at 8 h on several inflammatory proteins, yet must be employed at high doses to cross the BBB.

  2. Optineurin and amyotrophic lateral sclerosis.

    Science.gov (United States)

    Maruyama, Hirofumi; Kawakami, Hideshi

    2013-07-01

    Amyotrophic lateral sclerosis is a devastating disease, and thus it is important to identify the causative gene and resolve the mechanism of the disease. We identified optineurin as a causative gene for amyotrophic lateral sclerosis. We found three types of mutations: a homozygous deletion of exon 5, a homozygous Q398X nonsense mutation and a heterozygous E478G missense mutation within its ubiquitin-binding domain. Optineurin negatively regulates the tumor necrosis factor-α-induced activation of nuclear factor kappa B. Nonsense and missense mutations abolished this function. Mutations related to amyotrophic lateral sclerosis also negated the inhibition of interferon regulatory factor-3. The missense mutation showed a cyotoplasmic distribution different from that of the wild type. There are no specific clinical symptoms related to optineurin. However, severe brain atrophy was detected in patients with homozygous deletion. Neuropathologically, an E478G patient showed transactive response DNA-binding protein of 43 kDa-positive neuronal intracytoplasmic inclusions in the spinal and medullary motor neurons. Furthermore, Golgi fragmentation was identified in 73% of this patient's anterior horn cells. In addition, optineurin is colocalized with fused in sarcoma in the basophilic inclusions of amyotrophic lateral sclerosis with fused in sarcoma mutations, and in basophilic inclusion body disease. These findings strongly suggest that optineurin is involved in the pathogenesis of amyotrophic lateral sclerosis.

  3. Lipid droplets as ubiquitous fat storage organelles in C. elegans

    Directory of Open Access Journals (Sweden)

    Guo Fengli

    2010-12-01

    Full Text Available Abstract Background Lipid droplets are a class of eukaryotic cell organelles for storage of neutral fat such as triacylglycerol (TAG and cholesterol ester (CE. We and others have recently reported that lysosome-related organelles (LROs are not fat storage structures in the nematode C. elegans. We also reported the formation of enlarged lipid droplets in a class of peroxisomal fatty acid β-oxidation mutants. In the present study, we seek to provide further evidence on the organelle nature and biophysical properties of fat storage structures in wild-type and mutant C. elegans. Results In this study, we provide biochemical, histological and ultrastructural evidence of lipid droplets in wild-type and mutant C. elegans that lack lysosome related organelles (LROs. The formation of lipid droplets and the targeting of BODIPY fatty acid analogs to lipid droplets in live animals are not dependent on lysosomal trafficking or peroxisome dysfunction. However, the targeting of Nile Red to lipid droplets in live animals occurs only in mutants with defective peroxisomes. Nile Red labelled-lipid droplets are characterized by a fluorescence emission spectrum distinct from that of Nile Red labelled-LROs. Moreover, we show that the recently developed post-fix Nile Red staining method labels lipid droplets exclusively. Conclusions Our results demonstrate lipid droplets as ubiquitous fat storage organelles and provide a unified explanation for previous studies on fat labelling methods in C. elegans. These results have important applications to the studies of fat storage and lipid droplet regulation in the powerful genetic system, C. elegans.

  4. Exploring lipids with nonlinear optical microscopy in multiple biological systems

    Science.gov (United States)

    Alfonso-Garcia, Alba

    Lipids are crucial biomolecules for the well being of humans. Altered lipid metabolism may give rise to a variety of diseases that affect organs from the cardiovascular to the central nervous system. A deeper understanding of lipid metabolic processes would spur medical research towards developing precise diagnostic tools, treatment methods, and preventive strategies for reducing the impact of lipid diseases. Lipid visualization remains a complex task because of the perturbative effect exerted by traditional biochemical assays and most fluorescence markers. Coherent Raman scattering (CRS) microscopy enables interrogation of biological samples with minimum disturbance, and is particularly well suited for label-free visualization of lipids, providing chemical specificity without compromising on spatial resolution. Hyperspectral imaging yields large datasets that benefit from tailored multivariate analysis. In this thesis, CRS microscopy was combined with Raman spectroscopy and other label-free nonlinear optical techniques to analyze lipid metabolism in multiple biological systems. We used nonlinear Raman techniques to characterize Meibum secretions in the progression of dry eye disease, where the lipid and protein contributions change in ratio and phase segregation. We employed similar tools to examine lipid droplets in mice livers aboard a spaceflight mission, which lose their retinol content contributing to the onset of nonalcoholic fatty-liver disease. We also focused on atherosclerosis, a disease that revolves around lipid-rich plaques in arterial walls. We examined the lipid content of macrophages, whose variable phenotype gives rise to contrasting healing and inflammatory activities. We also proposed new label-free markers, based on lifetime imaging, for macrophage phenotype, and to detect products of lipid oxidation. Cholesterol was also detected in hepatitis C virus infected cells, and in specific strains of age-related macular degeneration diseased cells by

  5. Lateral epicondylitis of the elbow.

    Science.gov (United States)

    Tosti, Rick; Jennings, John; Sewards, J Milo

    2013-04-01

    Lateral epicondylitis, or "tennis elbow," is a common musculotendinous degenerative disorder of the extensor origin at the lateral humeral epicondyle. Repetitive occupational or athletic activities involving wrist extension and supination are thought to be causative. The typical symptoms include lateral elbow pain, pain with wrist extension, and weakened grip strength. The diagnosis is made clinically through history and physical examination; however, a thorough understanding of the differential diagnosis is imperative to prevent unnecessary testing and therapies. Most patients improve with nonoperative measures, such as activity modification, physical therapy, and injections. A small percentage of patients will require surgical release of the extensor carpi radialis brevis tendon. Common methods of release may be performed via percutaneous, arthroscopic, or open approaches.

  6. Solid lipid nanoparticles: A modern formulation approach in drug delivery system

    Directory of Open Access Journals (Sweden)

    Mukherjee S

    2009-01-01

    Full Text Available Solid lipid nanoparticles are at the forefront of the rapidly developing field of nanotechnology with several potential applications in drug delivery, clinical medicine and research, as well as in other varied sciences. Due to their unique size-dependent properties, lipid nanoparticles offer the possibility to develop new therapeutics. The ability to incorporate drugs into nanocarriers offers a new prototype in drug delivery that could be used for secondary and tertiary levels of drug targeting. Hence, solid lipid nanoparticles hold great promise for reaching the goal of controlled and site specific drug delivery and hence have attracted wide attention of researchers. This review presents a broad treatment of solid lipid nanoparticles discussing their advantages, limitations and their possible remedies. The different types of nanocarriers which were based on solid lipid like solid lipid nanoparticles, nanostructured lipid carriers, lipid drug conjugates are discussed with their structural differences. Different production methods which are suitable for large scale production and applications of solid lipid nanoparticles are described. Appropriate analytical techniques for characterization of solid lipid nanoparticles like photon correlation spectroscopy, scanning electron microscopy, differential scanning calorimetry are highlighted. Aspects of solid lipid nanoparticles route of administration and their biodistribution are also incorporated. If appropriately investigated, solid lipid nanoparticles may open new vistas in therapy of complex diseases.

  7. Assessing the nature of lipid raft membranes

    DEFF Research Database (Denmark)

    Niemelä, Perttu S; Ollila, Samuli; Hyvönen, Marja T

    2007-01-01

    The paradigm of biological membranes has recently gone through a major update. Instead of being fluid and homogeneous, recent studies suggest that membranes are characterized by transient domains with varying fluidity. In particular, a number of experimental studies have revealed the existence....... However, despite the proposed importance of these domains, their properties, and even the precise nature of the lipid phases, have remained open issues mainly because the associated short time and length scales have posed a major challenge to experiments. In this work, we employ extensive atom......-scale simulations to elucidate the properties of ternary raft mixtures with CHOL, palmitoylsphingomyelin (PSM), and palmitoyloleoylphosphatidylcholine. We simulate two bilayers of 1,024 lipids for 100 ns in the liquid-ordered phase and one system of the same size in the liquid-disordered phase. The studies provide...

  8. [Lipid parameters of the skin, cerebellum, and medulla oblongata during immersion stress in rats].

    Science.gov (United States)

    Gribanov, G A; Kostiuk, N V; Abramov, Iu V; Bykov, V A; Rebrov, L B; Volodina, T V; Pertsov, S S

    1999-01-01

    The influence of short-form water immersion stress of rats on lipids in the skin, the cerebellum and the medulla oblongata was studied. The level of total lipids and absolute and relative contents of the main lipid fractions (phospholipids, nonesterified cholesterol, free fatty acids, triglycerides, and cholesterol esters) were measured. Stress induced delayed changes of the lipid component of the skin. The first significant changes of lipid fractions were only observed 20 h later after the stress procedure. These changes were retained (being at nearly constant levels) till the end of the second day. The decrease in contents of total lipids and esterified cholesterol was revealed in the cerebellum of stressed rats (in comparison to these levels in control rats). These results suggest the involvement of cholesterol metabolic system in the stress reaction. The content of total lipids decreased also in the medulla oblongata. However, levels of the main lipid fractions changed differently. The content of diglycerides increased and the content of cholesterol decreased. The data obtained suggest that degradation of triglycerides is the principle pathway of metabolic conversions of lipids. Free fatty acids formed during these processes are probably involved in the synthesis of phospholipids and cholesterol esters. The data indicate absolutely different mechanisms of interrelations between individual lipid fractions in the brain regions studied. Various roles of the brain structures in the stress response of the body may account for the differences revealed.

  9. Lipid nanocarriers: influence of lipids on product development and pharmacokinetics.

    Science.gov (United States)

    Pathak, Kamla; Keshri, Lav; Shah, Mayank

    2011-01-01

    Lipid nanocarriers are on the forefront of the rapidly developing field of nanotechnology with several potential applications in drug delivery. Owing to their size-dependent properties, lipid nanoparticles offer the possibility for development of new therapeutics and an alternative system to other colloidal counterparts for drug administration. An important point to be considered in the selection of a lipid for the carrier system is its effect on the properties of the nanocarrier and also its intended use, as different types of lipids differ in their nature. Researchers around the globe have tapped the potential of solid lipid nanoparticles (SLNs) in developing formulation(s) that can be administered by various routes such as oral, ocular, parenteral, topical, and pulmonary. Since the start of this millennium, a new generation of lipid nanoparticles, namely nanostructured lipid carriers (NLCs), lipid drug conjugates (LDCs), and pharmacosomes, has evolved that have the potential to overcome the limitations of SLNs. The current review article presents broad considerations on the influence of various types of lipids on the diverse characteristics of nanocarriers, encompassing their physicochemical, formulation, pharmacokinetic, and cytotoxic aspects.

  10. How can lipid nanocarriers improve transdermal delivery of olanzapine?

    Science.gov (United States)

    Iqbal, Nimra; Vitorino, Carla; Taylor, Kevin M G

    2016-11-23

    The development of a transdermal nanocarrier drug delivery system with potential for the treatment of psychiatric disorders, such as schizophrenia and bipolar disorder, is described. Lipid nanocarriers (LN), encompassing various solid:liquid lipid compositions were formulated and assessed as potential nanosystems for transdermal delivery of olanzapine. A previously optimized method of hot high pressure homogenization (HPH) was adopted for the production of the LN, which comprised solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC) and nanoemulsions (NE). Precirol( ®) was selected as the solid lipid for progression of studies. SLN exhibited the best performance for transdermal delivery of olanzapine, based on in vitro release and permeation studies, coupled with results from physicochemical characterization of several solid:liquid lipid formulations. Stability tests, performed to give an indication of long-term storage behavior of the formulations, were in good agreement with previous studies for the best choice of solid:liquid lipid ratio. Overall, these findings highlight the SLN-based formulation as promising for the further inclusion in and production of transdermal patches, representing an innovative therapeutic approach.

  11. Microporous device for local electric recordings on model lipid bilayers

    Science.gov (United States)

    Kaufeld, Theresa; Steinem, Claudia; Schmidt, Christoph F.

    2015-01-01

    A powerful approach for characterizing lipid membranes and embedded proteins is the reconstitution of model lipid bilayers. The extreme fragility of 5 nm thick bilayers is a challenge for device design and requires a trade off of stability against accessibility. We here present a microporous lab-on-chip device that allows us to form stable, solvent-free lipid bilayers from giant unilamellar vesicles (GUVs) in a geometry that provides a unique set of access possibilities. The device is constructed around a micro-fabricated silicon chip with clusters of 1 µm-diameter pores and provides optical access to the lipid bilayers for high-NA epifluorescence imaging. At the same time, solvent exchange is possible on both sides of the lipid bilayer. Complete coverage can be achieved with GUVs, so that voltages can be applied across the lipid bilayer and single-channel currents can be measured using external or integrated silver/silver chloride electrodes. We describe the micro-fabrication by standard cleanroom techniques and the characterization of the device by atomic force microscopy, scanning electron microscopy and impedance spectroscopy. In proof-of-concept experiments we demonstrate that the device is capable of low-noise, single-ion-channel recordings. Electronic Supplementary Information (ESI) available: See DOI: 10.1039/b000000x/

  12. Mapping Condition-Dependent Regulation of Lipid Metabolism in Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Jewett, Michael Christopher; Workman, Christopher; Nookaew, Intawat

    2013-01-01

    levels, and lipid levels are currently lacking. Here, we map condition-dependent regulation controlling lipid metabolism in Saccharomyces cerevisiae by measuring 5636 mRNAs, 50 metabolites, 97 lipids, and 57 13C-reaction fluxes in yeast using a three-factor full-factorial design. Correlation analysis......Lipids play a central role in cellular function as constituents of membranes, as signaling molecules, and as storage materials. Although much is known about the role of lipids in regulating specific steps of metabolism, comprehensive studies integrating genome-wide expression data, metabolite...... across eight environmental conditions revealed 2279 gene expression level-metabolite/lipid relationships that characterize the extent of transcriptional regulation in lipid metabolism relative to major metabolic hubs within the cell. To query this network, we developed integrative methods for correlation...

  13. Independent mobility of proteins and lipids in the plasma membrane of Escherichia coli.

    Science.gov (United States)

    Nenninger, Anja; Mastroianni, Giulia; Robson, Alexander; Lenn, Tchern; Xue, Quan; Leake, Mark C; Mullineaux, Conrad W

    2014-06-01

    Fluidity is essential for many biological membrane functions. The basis for understanding membrane structure remains the classic Singer-Nicolson model, in which proteins are embedded within a fluid lipid bilayer and able to diffuse laterally within a sea of lipid. Here we report lipid and protein diffusion in the plasma membrane of live cells of the bacterium Escherichia coli, using Fluorescence Recovery after Photobleaching (FRAP) and Total Internal Reflection Fluorescence (TIRF) microscopy to measure lateral diffusion coefficients. Lipid and protein mobility within the membrane were probed by visualizing an artificial fluorescent lipid and a simple model membrane protein consisting of a single membrane-spanning alpha-helix with a Green Fluorescent Protein (GFP) tag on the cytoplasmic side. The effective viscosity of the lipid bilayer is strongly temperature-dependent, as indicated by changes in the lipid diffusion coefficient. Surprisingly, the mobility of the model protein was unaffected by changes in the effective viscosity of the bulk lipid, and TIRF microscopy indicates that it clusters in segregated, mobile domains. We suggest that this segregation profoundly influences the physical behaviour of the protein in the membrane, with strong implications for bacterial membrane function and bacterial physiology.

  14. Signal integration by lipid-mediated spatial cross talk between Ras nanoclusters.

    Science.gov (United States)

    Zhou, Yong; Liang, Hong; Rodkey, Travis; Ariotti, Nicholas; Parton, Robert G; Hancock, John F

    2014-03-01

    Lipid-anchored Ras GTPases form transient, spatially segregated nanoclusters on the plasma membrane that are essential for high-fidelity signal transmission. The lipid composition of Ras nanoclusters, however, has not previously been investigated. High-resolution spatial mapping shows that different Ras nanoclusters have distinct lipid compositions, indicating that Ras proteins engage in isoform-selective lipid sorting and accounting for different signal outputs from different Ras isoforms. Phosphatidylserine is a common constituent of all Ras nanoclusters but is only an obligate structural component of K-Ras nanoclusters. Segregation of K-Ras and H-Ras into spatially and compositionally distinct lipid assemblies is exquisitely sensitive to plasma membrane phosphatidylserine levels. Phosphatidylserine spatial organization is also modified by Ras nanocluster formation. In consequence, Ras nanoclusters engage in remote lipid-mediated communication, whereby activated H-Ras disrupts the assembly and operation of spatially segregated K-Ras nanoclusters. Computational modeling and experimentation reveal that complex effects of caveolin and cortical actin on Ras nanoclustering are similarly mediated through regulation of phosphatidylserine spatiotemporal dynamics. We conclude that phosphatidylserine maintains the lateral segregation of diverse lipid-based assemblies on the plasma membrane and that lateral connectivity between spatially remote lipid assemblies offers important previously unexplored opportunities for signal integration and signal processing.

  15. Dynamic clustering and dispersion of lipid rafts contribute to fusion competence of myogenic cells

    Energy Technology Data Exchange (ETDEWEB)

    Mukai, Atsushi [Department of Regenerative Medicine, National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, 36-3 Gengo, Morioka, Oobu, Aichi 474-8522 (Japan); Kurisaki, Tomohiro [Department of Growth Regulation, Institute for Frontier Medical Sciences, Kyoto University, 53 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507 (Japan); Sato, Satoshi B. [Research Center for Low Temperature and Material Sciences, Kyoto University, Yoshida-honmachi, Kyoto 606-8501 (Japan); Kobayashi, Toshihide [Lipid Biology Laboratory, Discovery Research Institute, RIKEN, Wako, Saitama 351-0198 (Japan); Kondoh, Gen [Laboratory of Animal Experiments for Regeneration, Institute for Frontier Medical Sciences, Kyoto University, 53 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507 (Japan); Hashimoto, Naohiro, E-mail: nao@nils.go.jp [Department of Regenerative Medicine, National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, 36-3 Gengo, Morioka, Oobu, Aichi 474-8522 (Japan)

    2009-10-15

    Recent research indicates that the leading edge of lamellipodia of myogenic cells (myoblasts and myotubes) contains presumptive fusion sites, yet the mechanisms that render the plasma membrane fusion-competent remain largely unknown. Here we show that dynamic clustering and dispersion of lipid rafts contribute to both cell adhesion and plasma membrane union during myogenic cell fusion. Adhesion-complex proteins including M-cadherin, {beta}-catenin, and p120-catenin accumulated at the leading edge of lamellipodia, which contains the presumptive fusion sites of the plasma membrane, in a lipid raft-dependent fashion prior to cell contact. In addition, disruption of lipid rafts by cholesterol depletion directly prevented the membrane union of myogenic cell fusion. Time-lapse recording showed that lipid rafts were laterally dispersed from the center of the lamellipodia prior to membrane fusion. Adhesion proteins that had accumulated at lipid rafts were also removed from the presumptive fusion sites when lipid rafts were laterally dispersed. The resultant lipid raft- and adhesion complex-free area at the leading edge fused with the opposing plasma membrane. These results demonstrate a key role for dynamic clustering/dispersion of lipid rafts in establishing fusion-competent sites of the myogenic cell membrane, providing a novel mechanistic insight into the regulation of myogenic cell fusion.

  16. Budding Transition of Asymmetric Two-component Lipid Domains

    CERN Document Server

    Wolff, Jean; Andelman, David

    2016-01-01

    We propose a model that accounts for the budding transition of asymmetric two-component lipid domains, where the two monolayers (leaflets) have different average compositions controlled by independent chemical potentials. Assuming a coupling between the local curvature and local lipid composition in each of the leaflets, we discuss the morphology and thermodynamic behavior of asymmetric lipid domains. The membrane free-energy contains three contributions: the bending energy, the line tension, and a Landau free-energy for a lateral phase separation. Within a mean-field treatment, we obtain various phase diagrams containing fully budded, dimpled, and flat states as a function of the two leaflet compositions. The global phase behavior is analyzed, and depending on system parameters, the phase diagrams include one-phase, two-phase and three-phase regions. In particular, we predict various phase coexistence regions between different morphologies of domains, which may be observed in multi-component membranes or ves...

  17. Monolayer curvature stabilizes nanoscale raft domains in mixed lipid bilayers

    CERN Document Server

    Meinhardt, Sebastian; Schmid, Friederike

    2013-01-01

    According to the lipid raft hypothesis, biological lipid membranes are laterally heterogeneous and filled with nanoscale ordered "raft" domains, which are believed to play an important role for the organization of proteins in membranes. However, the mechanisms stabilizing such small rafts are not clear, and even their existence is sometimes questioned. Here we report the observation of raft-like structures in a coarse-grained molecular model for multicomponent lipid bilayers. On small scales, our membranes demix into a liquid ordered (lo) and a liquid disordered (ld) phase. On large scales, phase separation is suppressed and gives way to a microemulsion-type state that contains nanometer size lo domains in a ld environment. Furthermore, we introduce a mechanism that generates rafts of finite size by a coupling between monolayer curvature and local composition. We show that mismatch between the spontaneous curvatures of monolayers in the lo and ld phase induces elastic interactions, which reduce the line tensi...

  18. Lipides polaires marins

    OpenAIRE

    Fanni Jacques; Linder Michel; Parmentier Michel

    2004-01-01

    Les lipides polaires marins, notamment les phospholipides (PL), retiennent depuis quelques années l’attention des chercheurs et des industriels en raison de leur composition, particulièrement riche en acides gras polyinsaturés à longue chaîne (AGPI-LC). Ils combinent ainsi les propriétés reconnues des AGPI-LC à l’intérêt métabolique et structural des phospholipides. Les sources sont nombreuses et d’accès très diversifié. Le défi industriel provient de leurs caractéristiques amphiphiles et aro...

  19. Later Zhou Sejong's Cultural Policy

    Institute of Scientific and Technical Information of China (English)

    PAN Qing

    2015-01-01

    Sejong wanted to stabilize the control. He paid attention to strengthen cultural enlightenment and implement cultural policy from educating people, choosing capable person, repairing history, limiting Buddhism, respecting Confucianism and other aspects. The wind of literature rise gradually. It is conducive to research the developmental trajectory of Later Zhou Dynasty.

  20. Lipid Raft Alterations in Aged-Associated Neuropathologies.

    Science.gov (United States)

    Marin, Raquel; Fabelo, Noemí; Fernández-Echevarría, Cecilia; Canerina-Amaro, Ana; Rodríguez-Barreto, Deiene; Quinto-Alemany, David; Mesa-Herrera, Fátima; Díaz, Mario

    2016-01-01

    Lipid rafts are membrane microdomains particularly enriched in cholesterol, sphingolipids and saturated fatty acids. These microstructures play a key role in a plethora of mechanisms involved in cell signaling, synapsis, cell-cell communication and cell survival. In the last years, increasing evidence indicate that lipid rafts may be altered in age-related neuropathologies, such as Alzheimer's disease and Parkinson disease even at asymptomatic stages. In particular, important changes in raft lipid composition are observed with the progression of these diseases, then inducing alterations in their physicochemical properties. Furthermore, these phenomena contribute to neuropathological events related to amyloidogenesis, aberrant protein aggregation and toxic cell signalling. In this review, we discuss some relevant data on the age-related molecular changes occurring in lipid rafts since the first stages of these neurodegenerative diseases. Further characterization of specific parameters associated with alterations of these microdomains may provide potential tools of diagnosis and prediction of these neuropathologies.

  1. Asymmetric heat transfer from nanoparticles in lipid bilayers

    Science.gov (United States)

    Potdar, Dipti; Sammalkorpi, Maria

    2015-12-01

    Here, we use molecular dynamics simulations to characterize the heat transfer properties of lipid bilayer - gold nanoparticle systems in which the nanoparticle acts as a heat source. The focus is on dipalmitoylphosphatidylcholine (DPPC) lipid bilayers and thiolated alcohol and alkyl functionalized nanoparticles as prototype hydrophilic and hydrophobic nanoparticles. We find hydrophilic nanoparticles which are partly in contact with the surrounding water environment are more efficient in transferring heat to the system than hydrophobic ones which reside surrounded by the membrane. This is because of the hydrogen bonding capability of the hydroxy pentanethiol and the more efficient heat conductivity through water than the lipid bilayer. Additionally, we find the heat conductance is strongly asymmetric and has a discontinuity between the bilayer leaflets. In total, the findings provide understanding on heat transport from localized heat sources in lipid bilayers and could bear significance, e.g., in engineering and controlling photoactivated triggering of liposomal systems.

  2. Absorption Of Dietary Lipid Components

    OpenAIRE

    Abdulkadir Hurşit

    2015-01-01

    Although the digestion and absorption of lipids that are necessary for the survival of living organisms are well known in general terms, nevertheless how different lipids to be digested, how it is distributed into the bloodstream, and how to be used by the cells, are unknown issues by most non specialist people. In recent years, knowledge of lipid digestion and absorption has expanded considerably. More insight has been gained in the mechanism of action of H + pump as a transport system in fa...

  3. Alteration of cellular lipids and lipid metabolism markers in RTL-W1 cells exposed to model endocrine disrupters.

    Science.gov (United States)

    Dimastrogiovanni, Giorgio; Córdoba, Marlon; Navarro, Isabel; Jáuregui, Olga; Porte, Cinta

    2015-08-01

    This work investigates the suitability of the rainbow trout liver cell line (RTL-W1) as an in-vitro model to study the ability of model endocrine disrupters, namely TBT, TPT, 4-NP, BPA and DEHP, to act as metabolic disrupters by altering cellular lipids and markers of lipid metabolism. Among the tested compounds, BPA and DEHP significantly increased the intracellular accumulation of triacylglycerols (TAGs), while all the compounds -apart from TPT-, altered membrane lipids - phosphatidylcholines (PCs) and plasmalogen PCs - indicating a strong interaction of the toxicants with cell membranes and cell signaling. RTL-W1 expressed a number of genes involved in lipid metabolism that were modulated by exposure to BPA, TBT and TPT (up-regulation of FATP1 and FAS) and 4-NP and DEHP (down-regulation of FAS and LPL). Multiple and complex modes of action of these chemicals were observed in RTL-W1 cells, both in terms of expression of genes related to lipid metabolism and alteration of cellular lipids. Although further characterization is needed, this might be a useful model for the detection of chemicals leading to steatosis or other diseases associated with lipid metabolism in fish.

  4. Intramyocellular lipids: maker vs. marker of insulin resistance

    OpenAIRE

    Guo, ZengKui

    2007-01-01

    Fifteen years ago it was discovered that intramyocellular triglyceride (imcTG) content in skeletal muscle is abnormally high in lipid oversupply models and, later, in obesity, type 2 diabetes (T2D) and other metabolically diseased conditions. The imcTG abnormality was also found to be significantly correlated with muscle insulin resistance (MIR). As skeletal muscle is the main site for insulin-mediated glucose utilization, the research on this topic has been active since. However, to date the...

  5. Non-additive compositional curvature energetics of lipid bilayers

    Science.gov (United States)

    Sodt, A.J.; Venable, R.M.; Lyman, E.; Pastor, R.W.

    2016-01-01

    The unique properties of the individual lipids that compose biological membranes together determine the energetics of the surface. The energetics of the surface in turn govern the formation of membrane structures and membrane reshaping processes, and will thus underlie cellular-scale models of viral fusion, vesicle-dependent transport, and lateral organization relevant to signaling. The spontaneous curvature, to the best of our knowledge, is always assumed to be additive. The letter describes observations from simulations of unexpected non-additive compositional curvature energetics of two lipids essential to the plasma membrane: sphingomyelin and cholesterol. A model is developed that connects molecular interactions to curvature stress, and which explains the role of local composition. Cholesterol is shown to lower the number of effective Kuhn segments of saturated acyl chains, reducing lateral pressure below the neutral surface of bending and favoring positive curvature. The effect is not observed for unsaturated (flexible) acyl chains. Likewise, hydrogen bonding between sphingomyelin lipids leads to positive curvature, but only at sufficient concentration, below which the lipid prefers negative curvature. PMID:27715135

  6. Lipid hydroperoxides in plants.

    Science.gov (United States)

    Griffiths, G; Leverentz, M; Silkowski, H; Gill, N; Sánchez-Serrano, J J

    2000-12-01

    Hydroperoxides are the primary oxygenated products of polyunsaturated fatty acids and were determined spectrophotometrically based on their reaction with an excess of Fe2+ at low pH in the presence of the dye Xylenol Orange. Triphenylphosphine-mediated hydroxide formation was used to authenticate the signal generated by the hydroperoxides. The method readily detected lipid peroxidation in a range of plant tissues including Phaseolus hypocotyls (26 +/- 5 nmol.g of fresh weight(-1); mean +/- S.D.), Alstroemeria floral tissues (sepals, 66+/-13 nmol.g of fresh weight(-1); petals, 49+/-6 nmol.g of fresh weight(-1)), potato leaves (334+/-75 nmol.g of fresh weight(-1)), broccoli florets (568+/-68 nmol.g of fresh weight(-1)) and Chlamydomonas cells (602+/-40 nmol.g of wet weight(-1)). Relative to the total fatty acid content of the tissues, the percentage hydroperoxide content was within the range of 0.6-1.7% for all tissue types (photosynthetic and non-photosynthetic) and represents the basal oxidation level of membrane fatty acids in plant cells. Leaves of transgenic potato with the fatty acid hydroperoxide lyase enzyme expressed in the antisense orientation were elevated by 38%, indicating a role for this enzyme in the maintenance of cellular levels of lipid hydroperoxides.

  7. Preparation and preliminary characterization of lyophilized astragaloside Ⅳ- loaded nanostructured lipid carriers%黄芪甲苷纳米结构脂质载体冻干粉的制备及其初步质量评价

    Institute of Scientific and Technical Information of China (English)

    陈佳; 龚涛

    2011-01-01

    目的 制备黄芪甲苷纳米结构脂质载体(AST-NLC),初步研究其冻干工艺,并考察其理化性质.方法 采用薄膜-超声分散法制备AST-NLC;选用不同冻干保护剂制备AST-NLC冻干粉末,以外观、色泽、再分散性、粒径和PDI为综合指标,优选保护剂的种类和浓度,拟定冻干工艺;考察AST-NLC的形态和冻干前后的粒径分布、Zeta电位、包封率及载药量.结果 以10%的蔗糖作为冻干保护剂、-40℃超低温冰箱中预冻4h后,迅速放入冷冻干燥机中冷冻干燥24h,所得冻干粉末的外观、色泽、再分散性均较好;AST-NLC在透射电镜下呈球形;冻干前(后)的平均粒径为104.3±1.25 nm(144.1±17.08nn),PDI为0.118±0.033(0.132±0.055),Zeta电位为-7.00±0.35 mV(-11.2±0.9 mV),包封率为94.37%±0.39%(96.60%±0.45%),载药量为2.80%±0.02%(2.60%±0.05%).结论 所用AST-NLC的制备工艺简便,制得的AST-NLC包封率较高;采用优化后的冻干工艺可得到令人满意的AST-NLC冻干粉末.%OBJECTIVE To prepare and characterize the lyophilized Astragaloside IV -loaded nanostructured lipid carriers (AST -NLC). METHODS AST - NLC was prepared by film - ultrasound dispersion technique. The lyophilized AST - NLC were prepared using different supporting agent. The type and concentration of the supporting agents were optimized by the shape,color,redispersion, size and PDI of the lyophilized AST - NLC. The characteristics of AST - NLC, including shape, size, PDI, Zeta potential, entrapment efficiency( EE% ) and drug loading ( DL% ) , before and after freeze - drying were investigated. RESULTS Satisfied lyophilized AST - NLC could be prepared using 10% sucrose as the supporting agent. The freeze - drying process was as follow; pre - cooled at 40℃ for 4 h,freeze -drying for 24 h. AST - NLC presented a spherical shape under transmission elecctron microscopy(TEM). The characteristics before freeze - drying were as follows: average diameter

  8. Coarse-grained molecular dynamics simulation of binary charged lipid membranes: Phase separation and morphological dynamics

    CERN Document Server

    Ito, Hiroaki; Shimokawa, Naofumi

    2016-01-01

    Biomembranes, which are mainly composed of neutral and charged lipids, exhibit a large variety of functional structures and dynamics. Here, we report a coarse-grained molecular dynamics (MD) simulation of the phase separation and morphological dynamics in charged lipid bilayer vesicles. The screened long-range electrostatic repulsion among charged head groups delays or inhibits the lateral phase separation in charged vesicles compared with neutral vesicles, suggesting the transition of the phase-separation mechanism from spinodal decomposition to nucleation or homogeneous dispersion. Moreover, the electrostatic repulsion causes morphological changes, such as pore formation, and further transformations into disk, string, and bicelle structures, which are spatiotemporally coupled to the lateral segregation of charged lipids. Based on our coarse-grained MD simulation, we propose a plausible mechanism of pore formation at the molecular level. The pore formation in a charged-lipid-rich domain is initiated by the p...

  9. Microemulsion extrusion technique: a new method to produce lipid nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Jesus, Marcelo Bispo de, E-mail: dejesusmb@gmail.com; Radaic, Allan [University of Campinas-UNICAMP, Department of Biochemistry, Institute of Biology (Brazil); Zuhorn, Inge S. [University of Groningen, Department of Membrane Cell Biology, University Medical Center (Netherlands); Paula, Eneida de [University of Campinas-UNICAMP, Department of Biochemistry, Institute of Biology (Brazil)

    2013-10-15

    Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) have been intensively investigated for different applications, including their use as drug and gene delivery systems. Different techniques have been employed to produce lipid nanoparticles, of which high pressure homogenization is the standard technique that is adopted nowadays. Although this method has a high efficiency, does not require the use of organic solvents, and allows large-scale production, some limitations impede its application at laboratory scale: the equipment is expensive, there is a need of huge amounts of surfactants and co-surfactants during the preparation, and the operating conditions are energy intensive. Here, we present the microemulsion extrusion technique as an alternative method to prepare lipid nanoparticles. The parameters to produce lipid nanoparticles using microemulsion extrusion were established, and the lipid particles produced (SLN, NLC, and liposomes) were characterized with regard to size (from 130 to 190 nm), zeta potential, and drug (mitoxantrone) and gene (pDNA) delivery properties. In addition, the particles' in vitro co-delivery capacity (to carry mitoxantrone plus pDNA encoding the phosphatase and tensin homologue, PTEN) was tested in normal (BALB 3T3 fibroblast) and cancer (PC3 prostate and MCF-7 breast) cell lines. The results show that the microemulsion extrusion technique is fast, inexpensive, reproducible, free of organic solvents, and suitable for small volume preparations of lipid nanoparticles. Its application is particularly interesting when using rare and/or costly drugs or ingredients (e.g., cationic lipids for gene delivery or labeled lipids for nanoparticle tracking/diagnosis)

  10. Microemulsion extrusion technique: a new method to produce lipid nanoparticles

    Science.gov (United States)

    de Jesus, Marcelo Bispo; Radaic, Allan; Zuhorn, Inge S.; de Paula, Eneida

    2013-10-01

    Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) have been intensively investigated for different applications, including their use as drug and gene delivery systems. Different techniques have been employed to produce lipid nanoparticles, of which high pressure homogenization is the standard technique that is adopted nowadays. Although this method has a high efficiency, does not require the use of organic solvents, and allows large-scale production, some limitations impede its application at laboratory scale: the equipment is expensive, there is a need of huge amounts of surfactants and co-surfactants during the preparation, and the operating conditions are energy intensive. Here, we present the microemulsion extrusion technique as an alternative method to prepare lipid nanoparticles. The parameters to produce lipid nanoparticles using microemulsion extrusion were established, and the lipid particles produced (SLN, NLC, and liposomes) were characterized with regard to size (from 130 to 190 nm), zeta potential, and drug (mitoxantrone) and gene (pDNA) delivery properties. In addition, the particles' in vitro co-delivery capacity (to carry mitoxantrone plus pDNA encoding the phosphatase and tensin homologue, PTEN) was tested in normal (BALB 3T3 fibroblast) and cancer (PC3 prostate and MCF-7 breast) cell lines. The results show that the microemulsion extrusion technique is fast, inexpensive, reproducible, free of organic solvents, and suitable for small volume preparations of lipid nanoparticles. Its application is particularly interesting when using rare and/or costly drugs or ingredients (e.g., cationic lipids for gene delivery or labeled lipids for nanoparticle tracking/diagnosis).

  11. Update of the LIPID MAPS comprehensive classification system for lipids

    NARCIS (Netherlands)

    Fahy, E.; Subramaniam, S.; Murphy, R.C.; Nishijima, M.; Raetz, C.R.H.; Shimizu, T.; Spener, F.; van Meer, G.; Wakelam, M.J.O.; Dennis, E.A.

    2009-01-01

    In 2005, the International Lipid Classification and Nomenclature Committee under the sponsorship of the LIPID MAPS Consortium developed and established a “Comprehensive Classification System for Lipids” based on well-defined chemical and biochemical principles and using an ontology that is extensibl

  12. The three-portal technique in arthroscopic lateral epicondylitis release

    Directory of Open Access Journals (Sweden)

    Ashok Gowda

    2017-01-01

    Full Text Available Lateral epicondylitis, commonly referred to as tennis elbow, is a syndrome characterized by pain over the origin of the common extensor muscles of the fingers, hand and wrist at the lateral epicondyle. Reports of 70-90% response to conservative treatment at one year have been documented in the literature though refractory cases often require surgical management. Arthroscopic treatment of lateral epicondylitis allows for intra-articular visualization for concomitant pathology and localization of the Extensor Carpi Radialis Brevis tendon. Additionally, compared to the open technique, the arthroscopic technique has a lower morbidity and an earlier return to work and activity. Here we describe a three portal technique for improved visualization in arthroscopic lateral epicondylitis release.

  13. Solid lipid nanoparticles for parenteral drug delivery

    NARCIS (Netherlands)

    Wissing, S.A.; Kayser, Oliver; Muller, R.H.

    2004-01-01

    This review describes the use of nanoparticles based on solid lipids for the parenteral application of drugs. Firstly, different types of nanoparticles based on solid lipids such as "solid lipid nanoparticles" (SLN), "nanostructured lipid carriers" (NLC) and "lipid drug conjugate" (LDC) nanoparticle

  14. Membrane curvature enables N-Ras lipid anchor sorting to liquid-ordered membrane phases

    DEFF Research Database (Denmark)

    Larsen, Jannik Bruun; Jensen, Martin Borch; Bhatia, Vikram Kjøller;

    2015-01-01

    Trafficking and sorting of membrane-anchored Ras GTPases are regulated by partitioning between distinct membrane domains. Here, in vitro experiments and microscopic molecular theory reveal membrane curvature as a new modulator of N-Ras lipid anchor and palmitoyl chain partitioning. Membrane...... curvature was essential for enrichment in raft-like liquid-ordered phases; enrichment was driven by relief of lateral pressure upon anchor insertion and most likely affects the localization of lipidated proteins in general....

  15. Craving creativity in later life

    DEFF Research Database (Denmark)

    Fristrup, Tine

    2013-01-01

    but it also raises questions as to what constitutes a ‘good’ and ‘active’ life in all societies. The conflicting aspect of the discursive battlefield on active ageing constitutes a fight for authority: Who has the ‘right’ to define the meaning of being ‘active’ and how can ‘activity’ be identified? ‘Active......’ is to be understood according to the interpretations available in different knowledge perspectives in order to discipline the future knowledge production of ageing and control the processes of subjectification in later life as the disciplining of ‘Population Ageing’: Becoming a subject to active ageing. Dominant...... discourses on ‘active ageing’ are challenged by the focus of museums and archives on using heritage and participatory arts as an arena to performAGE in later life by craving creativity as a notion of age and opportunity....

  16. Amyotrophic lateral sclerosis: genetic susceptibility factors and pleiotropy

    NARCIS (Netherlands)

    Diekstra, F.P.

    2015-01-01

    Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive muscle weakness, spasticity, dysarthria and, ultimately, respiratory muscle insufficiency. These symptoms are caused by the loss of motor neurons in both the brain and in the anterior horn of the sp

  17. Laterally Loaded Piles in Clay

    DEFF Research Database (Denmark)

    Christensen, Helle; Niewald, Gitte

    1992-01-01

    The ultimate lateral resistance of a pile element moved horizontally can be analyzed by the theory of plasticity. At a certain depth the movements around the pile are purely horizontal and upper bound solutions can be estimated theoretically under undrained circumstances. Model tests...... in the laboratory show ultimate resistances close to the estimated limits and p - y curves close to curves based on test results from full-scale piles. Rough and smooth piles with circular and square cross sections are investigated....

  18. Anisotropic metal growth on phospholipid nanodiscs via lipid bilayer expansion

    Science.gov (United States)

    Oertel, Jana; Keller, Adrian; Prinz, Julia; Schreiber, Benjamin; Hübner, René; Kerbusch, Jochen; Bald, Ilko; Fahmy, Karim

    2016-05-01

    Self-assembling biomolecules provide attractive templates for the preparation of metallic nanostructures. However, the intuitive transfer of the “outer shape” of the assembled macromolecules to the final metallic particle depends on the intermolecular forces among the biomolecules which compete with interactions between template molecules and the metal during metallization. The shape of the bio-template may thus be more dynamic than generally assumed. Here, we have studied the metallization of phospholipid nanodiscs which are discoidal particles of ~10 nm diameter containing a lipid bilayer ~5 nm thick. Using negatively charged lipids, electrostatic adsorption of amine-coated Au nanoparticles was achieved and followed by electroless gold deposition. Whereas Au nanoparticle adsorption preserves the shape of the bio-template, metallization proceeds via invasion of Au into the hydrophobic core of the nanodisc. Thereby, the lipidic phase induces a lateral growth that increases the diameter but not the original thickness of the template. Infrared spectroscopy reveals lipid expansion and suggests the existence of internal gaps in the metallized nanodiscs, which is confirmed by surface-enhanced Raman scattering from the encapsulated lipids. Interference of metallic growth with non-covalent interactions can thus become itself a shape-determining factor in the metallization of particularly soft and structurally anisotropic biomaterials.

  19. Cord Blood Metabolome Is Highly Associated with Birth Weight, but Less Predictive for Later Weight Development

    Directory of Open Access Journals (Sweden)

    Christian Hellmuth

    2017-04-01

    Full Text Available Background/Aims: Fetal metabolism may be changed by the exposure to maternal factors, and the route to obesity may already set in utero. Cord blood metabolites might predict growth patterns and later obesity. We aimed to characterize associations of cord blood with birth weight, postnatal weight gain, and BMI in adolescence. Methods: Over 700 cord blood samples were collected from infants participating in the German birth cohort study LISAplus. Glycerophospholipid fatty acids (GPL-FA, polar lipids, non-esterified fatty acids (NEFA, and amino acids were analyzed with a targeted, liquid chromatography-tandem mass spectrometry based metabolomics platform. Cord blood metabolites were related to growth factors by linear regression models adjusted for confounding variables. Results: Cord blood metabolites were highly associated with birth weight. Lysophosphatidylcholines C16:1, C18:1, C20:3, C18:2, C20:4, C14:0, C16:0, C18:3, GPL-FA C20:3n-9, and GPL-FA C22:5n-6 were positively related to birth weight, while higher cord blood concentrations of NEFA C22:6, NEFA C20:5, GPL-FA C18:3n-3, and PCe C38:0 were associated with lower birth weight. Postnatal weight gain and BMI z-scores in adolescents were not significantly associated with cord blood metabolites after adjustment for multiple testing. Conclusion: Potential long-term programming effects of the intrauterine environment and metabolism on later health cannot be predicted with profiling of the cord blood metabolome.

  20. Amyotrophic lateral sclerosis: one or multiple causes?

    Directory of Open Access Journals (Sweden)

    Aline Furtado Bastos

    2011-04-01

    Full Text Available The Amyotrophic lateral sclerosis (ALS is the most common form of motor neuron disease in the adulthood, and it is characterized by rapid and progressive compromise of the upper and lower motor neurons. The majority of the cases of ALS are classified as sporadic and, until now, a specific cause for these cases still is unknown. To present the different hypotheses on the etiology of ALS. It was carried out a search in the databases: Bireme, Scielo and Pubmed, in the period of 1987 to 2011, using the following keywords: Amyotrophic lateral sclerosis, motor neuron disease, etiology, causes and epidemiology and its similar in Portuguese and Spanish. It did not have consensus as regards the etiology of ALS. Researches demonstrates evidences as regards intoxication by heavy metals, environmental and occupational causes, genetic mutations (superoxide dismutase 1, certain viral infections and the accomplishment of vigorous physical activity for the development of the disease. There is still no consensus regarding the involved factors in the etiology of ALS. In this way, new research about these etiologies are necessary, for a better approach of the patients, promoting preventive programs for the disease and improving the quality of life of the patients.

  1. Molecular Dynamics of Lipid Bilayers

    Science.gov (United States)

    1989-08-09

    The aim of this work is to study, by molecular dynamics simulations, the properties of lipid bilayers. We have applied the vectorizable, order-N...fast angle-dependent force/potential algorithms to treat angle bending and torsion. Keywords: Molecular dynamics , Lipid bilayers.

  2. Neuroimaging of Lipid Storage Disorders

    Science.gov (United States)

    Rieger, Deborah; Auerbach, Sarah; Robinson, Paul; Gropman, Andrea

    2013-01-01

    Lipid storage diseases, also known as the lipidoses, are a group of inherited metabolic disorders in which there is lipid accumulation in various cell types, including the central nervous system, because of the deficiency of a variety of enzymes. Over time, excessive storage can cause permanent cellular and tissue damage. The brain is particularly…

  3. Blood lipids and prostate cancer

    DEFF Research Database (Denmark)

    Bull, Caroline J; Bonilla, Carolina; Holly, Jeff M P

    2016-01-01

    Genetic risk scores were used as unconfounded instruments for specific lipid traits (Mendelian randomization) to assess whether circulating lipids causally influence prostate cancer risk. Data from 22,249 prostate cancer cases and 22,133 controls from 22 studies within the international PRACTICAL...

  4. Roles of Lipids in Photosynthesis.

    Science.gov (United States)

    Kobayashi, Koichi; Endo, Kaichiro; Wada, Hajime

    2016-01-01

    Thylakoid membranes in cyanobacterial cells and chloroplasts of algae and higher plants are the sites of oxygenic photosynthesis. The lipid composition of the thylakoid membrane is unique and highly conserved among oxygenic photosynthetic organisms. Major lipids in thylakoid membranes are glycolipids, monogalactosyldiacylglycerol, digalactosyldiacylglycerol and sulfoquinovosyldiacylglycerol, and the phospholipid, phosphatidylglycerol. The identification of almost all genes involved in the biosynthesis of each lipid class over the past decade has allowed the generation and isolation of mutants of various photosynthetic organisms incapable of synthesizing specific lipids. Numerous studies using such mutants have revealed that these lipids play important roles not only in the formation of the lipid bilayers of thylakoid membranes but also in the folding and assembly of the protein subunits in photosynthetic complexes. In addition to the studies with the mutants, recent X-ray crystallography studies of photosynthetic complexes in thylakoid membranes have also provided critical information on the association of lipids with photosynthetic complexes and their activities. In this chapter, we summarize our current understanding about the structural and functional involvement of thylakoid lipids in oxygenic photosynthesis.

  5. The Flexibility of Ectopic Lipids

    Directory of Open Access Journals (Sweden)

    Hannah Loher

    2016-09-01

    Full Text Available In addition to the subcutaneous and the visceral fat tissue, lipids can also be stored in non-adipose tissue such as in hepatocytes (intrahepatocellular lipids; IHCL, skeletal (intramyocellular lipids; IMCL or cardiac muscle cells (intracardiomyocellular lipids; ICCL. Ectopic lipids are flexible fuel stores that can be depleted by physical exercise and repleted by diet. They are related to obesity and insulin resistance. Quantification of IMCL was initially performed invasively, using muscle biopsies with biochemical and/or histological analysis. 1H-magnetic resonance spectroscopy (1H-MRS is now a validated method that allows for not only quantifying IMCL non-invasively and repeatedly, but also assessing IHCL and ICCL. This review summarizes the current available knowledge on the flexibility of ectopic lipids. The available evidence suggests a complex interplay between quantitative and qualitative diet, fat availability (fat mass, insulin action, and physical exercise, all important factors that influence the flexibility of ectopic lipids. Furthermore, the time frame of the intervention on these parameters (short-term vs. long-term appears to be critical. Consequently, standardization of physical activity and diet are critical when assessing ectopic lipids in predefined clinical situations.

  6. Lipid droplets, lipophagy, and beyond.

    Science.gov (United States)

    Wang, Chao-Wen

    2016-08-01

    Lipids are essential components for life. Their various structural and physical properties influence diverse cellular processes and, thereby, human health. Lipids are not genetically encoded but are synthesized and modified by complex metabolic pathways, supplying energy, membranes, signaling molecules, and hormones to affect growth, physiology, and response to environmental insults. Lipid homeostasis is crucial, such that excess fatty acids (FAs) can be harmful to cells. To prevent such lipotoxicity, cells convert excess FAs into neutral lipids for storage in organelles called lipid droplets (LDs). These organelles do not simply manage lipid storage and metabolism but also are involved in protein quality management, pathogenesis, immune responses, and, potentially, neurodegeneration. In recent years, a major trend in LD biology has centered around the physiology of lipid mobilization via lipophagy of fat stored within LDs. This review summarizes key findings in LD biology and lipophagy, offering novel insights into this rapidly growing field. This article is part of a Special Issue entitled: The cellular lipid landscape edited by Tim P. Levine and Anant K. Menon.

  7. Fasting and nonfasting lipid levels

    DEFF Research Database (Denmark)

    Langsted, Anne; Freiberg, Jacob J; Nordestgaard, Børge G

    2008-01-01

    Lipid profiles are usually measured after fasting. We tested the hypotheses that these levels change only minimally in response to normal food intake and that nonfasting levels predict cardiovascular events.......Lipid profiles are usually measured after fasting. We tested the hypotheses that these levels change only minimally in response to normal food intake and that nonfasting levels predict cardiovascular events....

  8. Dysarthria in amyotrophic lateral sclerosis: A review.

    Science.gov (United States)

    Tomik, Barbara; Guiloff, Roberto J

    2010-01-01

    Dysarthria is a motor disorder of speech characterized by abnormalities of the articulation and intelligibility of speech. Phonation and the rate of facial movements may also be affected. Understanding the nature and course of dysarthria in amyotrophic lateral sclerosis (ALS) is important because loss of communication prevents patients from participating in many activities, may lead to social isolation, and reduces the quality of life. The goal of management of dysarthria in ALS patients is to optimize communication effectiveness for as long as possible. The information about dysarthria in ALS is dispersed in physiological, pathological, speech therapy, otorhinolaringological and neurological publications. This review summarizes the current state of knowledge on the clinical features, differential diagnosis, pathophysiology, investigations and management of dysarthria in ALS patients. There is a need to compare the different methods used to assess dysarthria and for controlled clinical trials to assess therapeutic strategies.

  9. [Dysphagia with lateral medullary infarction (Wallenberg's syndrome)].

    Science.gov (United States)

    Oshima, Fumiko

    2011-11-01

    Dysphagia after lateral medullary infarction (LMI) is common. The dysphagia of LMI is dynamically characterized by a failure in triggering of the pharyngeal-phase swallowing movements, reduced output, and lack of coordination (swallowing pattern abnormality). Based on accurate evaluation, we can select suitable rehabilitative approaches for individual patients, including respiratory therapy, food modification, postural changes, and oral care. We focused on the absence of upper esophageal sphincter (UES) opening of the unaffected side of the medullae. The movement pattern was defined as failure of bolus passage through the intact side of the UES, occurring at least once during the videofluorographic evaluation of each individual. Three abnormal patterns of UES opening were classified. The passage pattern abnormality shows the failure of the stereotyped motor sequence. For severe cases, it is necessary to consider long-term treatment, including botulinum toxin injection or surgery to prevent aspiration and adequate nutritional management.

  10. Lipides polaires marins

    Directory of Open Access Journals (Sweden)

    Fanni Jacques

    2004-03-01

    Full Text Available Les lipides polaires marins, notamment les phospholipides (PL, retiennent depuis quelques années l’attention des chercheurs et des industriels en raison de leur composition, particulièrement riche en acides gras polyinsaturés à longue chaîne (AGPI-LC. Ils combinent ainsi les propriétés reconnues des AGPI-LC à l’intérêt métabolique et structural des phospholipides. Les sources sont nombreuses et d’accès très diversifié. Le défi industriel provient de leurs caractéristiques amphiphiles et aromatiques particulièrement marquées qui rend leur extraction très difficile.

  11. Lipids changes in liver cancer

    Institute of Scientific and Technical Information of China (English)

    JIANG Jing-ting; XU Ning; ZHANG Xiao-ying; WU Chang-ping

    2007-01-01

    Liver is one of the most important organs in energy metabolism.Most plasma apolipoproteins and endogenous lipids and lipoproteins are synthesized in the liver.It depends on the integrity of liver cellular function,which ensures homeostasis of lipid and lipoprotein metabolism.When liver cancer occurs,these processes are impaired and the plasma lipid and lipoprotein patterns may be changed.Liver cancer is the fifth common malignant tumor worldwide,and is closely related to the infections of hepatitis B virus (HBV) and hepatitis C virus (HCV).HBV and HCV infections are quite common in China and other Southeast Asian countries.In addition,liver cancer is often followed by a procession of chronic hepatitis or cirrhosis,so that hepatic function is damaged obviously on these bases,which may significantly influence lipid and lipoprotein metabolism in vivo.In this review we summarize the clinical significance of lipid and lipoprotein metabolism under liver cancer.

  12. Effect of curcumin on lateral diffusion of phosphatidylcholines in saturated and unsaturated bilayers.

    Science.gov (United States)

    Filippov, Andrei V; Kotenkov, Sergey A; Munavirov, Bulat; Antzutkin, Oleg N

    2014-09-01

    Curcumin, a dietary polyphenol, is a natural spice with preventive and therapeutic potential for neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. Curcumin possesses a spectrum of antioxidant, anti-inflammatory, anticarcinogenic, and antimutagenic properties. Because of this broad spectrum of pharmacological activity, it has been suggested that, like cholesterol, curcumin exerts its effect on a rather basic biological level, such as on lipid bilayers of biomembranes. The effect of curcumin on translational mobility of lipids in biomembranes has not yet been studied. In this work, we used (1)H NMR diffusometry to explore lateral diffusion in planar-oriented bilayers of dimyristoylphosphatidylcholine (DMPC) and dioleoylphosphatidylcholine (DOPC) at curcumin concentrations of up to 40 mol % and in the temperature range of 298-333 K. The presence of curcumin at much lower concentrations (∼7 mol %) leads to a decrease in the lateral diffusion coefficient of DOPC by a factor of 1.3 at lower temperatures and by a factor of 1.14 at higher temperatures. For DMPC, the diffusion coefficient decreases by a factor of 1.5 at lower temperatures and by a factor of 1.2 at higher temperatures. Further increasing the curcumin concentration has no effect. Comparison with cholesterol showed that curcumin and cholesterol influence lateral diffusion of lipids differently. The effect of curcumin is determined by its solubility in lipid bilayers, which is as low as 10 mol % that is much less than that of cholesteroĺs 66 mol %.

  13. Leukocyte-derived microparticles and scanning electron microscopic structures in two fractions of fresh cerebrospinal fluid in amyotrophic lateral sclerosis: a case report

    Directory of Open Access Journals (Sweden)

    Zachau Anne C

    2012-09-01

    Full Text Available Abstract Introduction Amyotrophic lateral sclerosis is a progressive neurodegenerative disorder characterized by degeneration of motoneuron cells in anterior spinal horns. There is a need for early and accurate diagnosis with this condition. In this case report we used two complementary methods: scanning electron microscopy and fluorescence-activated cell sorting. This is the first report to our knowledge of microparticles in the cerebrospinal fluid of a patient with amyotrophic lateral sclerosis. Case presentation An 80-year-old Swedish man of Caucasian ethnicity presented to our facility with symptoms of amyotrophic lateral sclerosis starting a year before his first hospital examination, such as muscle weakness and twitching in his right hand progressing to arms, body and leg muscles. Electromyography showed classical neurophysiological findings of amyotrophic lateral sclerosis. Routine blood sample results were normal. A lumbar puncture was performed as a routine investigation and his cerebrospinal fluid was normal with regard to cell count and protein levels, and there were no signs of inflammation. However, scanning electron microscopy and fluorescence-activated cell sorting showed pronounced abnormalities compared to healthy controls. Flow cytometry analysis of two fractions of cerebrospinal fluid from our patient with amyotrophic lateral sclerosis was used to measure the specific binding of antibodies to CD42a, CD144 and CD45, and of phosphatidylserine to lactadherin. Our patient displayed over 100 times more phosphatidylserine-positive microparticles and over 400 times more cell-derived microparticles of leukocyte origin in his cerebrospinal fluid compared to healthy control subjects. The first cerebrospinal fluid fraction contained about 50% more microparticles than the second fraction. The scanning electron microscopy filters used with cerebrospinal fluid from our patient were filled with compact aggregates of spherical particles of

  14. Interplay of curvature-induced micro- and nanodomain structures in multicomponent lipid bilayers

    CERN Document Server

    Brodbek, Leonie

    2015-01-01

    We discuss different mechanisms for curvature-induced domain formation in multicomponent lipid membranes and present a theoretical model that allows us to study the interplay between the domains. The model represents the membrane by two coupled monolayers, which each carry an additional order parameter field describing the local lipid composition. The spontaneous curvature of each monolayer is coupled to the local composition, moreover, the lipid compositions on opposing monolayers are coupled to each other. Using this model, we calculate the phase behavior of the bilayer in mean-field approximation. The resulting phase diagrams are surprisingly complex and reveal a variety of phases and phase transitions, including a decorated microdomain phase where nanodomains are aligned along the microdomain boundaries. Our results suggest that external membrane tension can be used to control the lateral organization of nanodomains (which might be associated with lipid "rafts") in a multicomponent lipid bilayer.

  15. Lipid traffic: the ABC of transbilayer movement

    NARCIS (Netherlands)

    Raggers, R.J.; Pomorski, T.; Holthuis, J.C.M.; Kälin, N.; van Meer, G.

    2000-01-01

    Membrane lipids do not spontaneously exchange between the two leaflets of lipid bilayers because the polar headgroups cannot cross the hydrophobic membrane interior. Cellular membranes, notably eukaryotic plasma membranes, are equipped with special proteins that actively translocate lipids from one

  16. Drug release mechanisms of compressed lipid implants.

    Science.gov (United States)

    Kreye, F; Siepmann, F; Siepmann, J

    2011-02-14

    The aim of this study was to elucidate the mass transport mechanisms controlling drug release from compressed lipid implants. The latter steadily gain in importance as parenteral controlled release dosage forms, especially for acid-labile drugs. A variety of lipid powders were blended with theophylline and propranolol hydrochloride as sparingly and freely water-soluble model drugs. Cylindrical implants were prepared by direct compression and thoroughly characterized before and after exposure to phosphate buffer pH 7.4. Based on the experimental results, an appropriate mathematical theory was identified in order to quantitatively describe the resulting drug release patterns. Importantly, broad release spectra and release periods ranging from 1 d to several weeks could easily be achieved by varying the type of lipid, irrespective of the type of drug. Interestingly, diffusion with constant diffusivities was found to be the dominant mass transport mechanism, if the amount of water within the implant was sufficient to dissolve all of the drug. In these cases an analytical solution of Fick's second law could successfully describe the experimentally measured theophylline and propranolol hydrochloride release profiles, even if varying formulation and processing parameters, e.g. the type of lipid, initial drug loading, drug particles size as well as compression force and time. However, based on the available data it was not possible to distinguish between drug diffusion control and water diffusion control. The obtained new knowledge can nevertheless significantly help facilitating the optimization of this type of advanced drug delivery systems, in particular if long release periods are targeted, which require time consuming experimental trials.

  17. How Lipid Membranes Affect Pore Forming Toxin Activity.

    Science.gov (United States)

    Rojko, Nejc; Anderluh, Gregor

    2015-12-15

    Pore forming toxins (PFTs) evolved to permeate the plasma membrane of target cells. This is achieved in a multistep mechanism that usually involves binding of soluble protein monomer to the lipid membrane, oligomerization at the plane of the membrane, and insertion of part of the polypeptide chain across the lipid membrane to form a conductive channel. Introduced pores allow uncontrolled transport of solutes across the membrane, inflicting damage to the target cell. PFTs are usually studied from the perspective of structure-function relationships, often neglecting the important role of the bulk membrane properties on the PFT mechanism of action. In this Account, we discuss how membrane lateral heterogeneity, thickness, and fluidity influence the pore forming process of PFTs. In general, lipid molecules are more accessible for binding in fluid membranes due to steric reasons. When PFT specifically binds ordered domains, it usually recognizes a specific lipid distribution pattern, like sphingomyelin (SM) clusters or SM/cholesterol complexes, and not individual lipid species. Lipid domains were also suggested to act as an additional concentration platform facilitating PFT oligomerization, but this is yet to be shown. The last stage in PFT action is the insertion of the transmembrane segment across the membranes to build the transmembrane pore walls. Conformational changes are a spontaneous process, and sufficient free energy has to be available for efficient membrane penetration. Therefore, fluid bilayers are permeabilized more readily in comparison to highly ordered and thicker liquid ordered lipid phase (Lo). Energetically more costly insertion into the Lo phase can be driven by the hydrophobic mismatch between the thinner liquid disordered phase (Ld) and large protein complexes, which are unable to tilt like single transmembrane segments. In the case of proteolipid pores, membrane properties can directly modulate pore size, stability, and even selectivity. Finally

  18. Lateral diffusion on tubular membranes: quantification of measurements bias.

    Directory of Open Access Journals (Sweden)

    Marianne Renner

    Full Text Available Single Particle Tracking (SPT is a powerful technique for the analysis of the lateral diffusion of the lipid and protein components of biological membranes. In neurons, SPT allows the study of the real-time dynamics of receptors for neurotransmitters that diffuse continuously in and out synapses. In the simplest case where the membrane is flat and is parallel to the focal plane of the microscope the analysis of diffusion from SPT data is relatively straightforward. However, in most biological samples the membranes are curved, which complicates analysis and may lead to erroneous conclusions as for the mode of lateral diffusion. Here we considered the case of lateral diffusion in tubular membranes, such as axons, dendrites or the neck of dendritic spines. Monte Carlo simulations allowed us to evaluate the error in diffusion coefficient (D calculation if the curvature is not taken into account. The underestimation is determined by the diameter of the tubular surface, the frequency of image acquisition and the degree of mobility itself. We found that projected trajectories give estimates that are 25 to 50% lower than the real D in case of 2D-SPT over the tubular surface. The use of 3D-SPT improved the measurements if the frequency of image acquisition was fast enough in relation to the mobility of the molecules and the diameter of the tube. Nevertheless, the calculation of D from the components of displacements in the axis of the tubular structure gave accurate estimate of D, free of geometrical artefacts. We show the application of this approach to analyze the diffusion of a lipid on model tubular membranes and of a membrane-bound GFP on neurites from cultured rat hippocampal neurons.

  19. Lateral diffusion on tubular membranes: quantification of measurements bias.

    Science.gov (United States)

    Renner, Marianne; Domanov, Yegor; Sandrin, Fanny; Izeddin, Ignacio; Bassereau, Patricia; Triller, Antoine

    2011-01-01

    Single Particle Tracking (SPT) is a powerful technique for the analysis of the lateral diffusion of the lipid and protein components of biological membranes. In neurons, SPT allows the study of the real-time dynamics of receptors for neurotransmitters that diffuse continuously in and out synapses. In the simplest case where the membrane is flat and is parallel to the focal plane of the microscope the analysis of diffusion from SPT data is relatively straightforward. However, in most biological samples the membranes are curved, which complicates analysis and may lead to erroneous conclusions as for the mode of lateral diffusion. Here we considered the case of lateral diffusion in tubular membranes, such as axons, dendrites or the neck of dendritic spines. Monte Carlo simulations allowed us to evaluate the error in diffusion coefficient (D) calculation if the curvature is not taken into account. The underestimation is determined by the diameter of the tubular surface, the frequency of image acquisition and the degree of mobility itself. We found that projected trajectories give estimates that are 25 to 50% lower than the real D in case of 2D-SPT over the tubular surface. The use of 3D-SPT improved the measurements if the frequency of image acquisition was fast enough in relation to the mobility of the molecules and the diameter of the tube. Nevertheless, the calculation of D from the components of displacements in the axis of the tubular structure gave accurate estimate of D, free of geometrical artefacts. We show the application of this approach to analyze the diffusion of a lipid on model tubular membranes and of a membrane-bound GFP on neurites from cultured rat hippocampal neurons.

  20. Lipid Models for United-Atom Molecular Dynamics Simulations of Proteins.

    Science.gov (United States)

    Kukol, Andreas

    2009-03-10

    United-atom force fields for molecular dynamics (MD) simulations provide a higher computational efficiency, especially in lipid membrane simulations, with little sacrifice in accuracy, when compared to all-atom force fields. Excellent united-atom lipid models are available, but in combination with depreciated protein force fields. In this work, a united-atom model of the lipid 1,2-dipalmitoyl-sn-glycero-3-phosphocholine has been built with standard parameters of the force field GROMOS96 53a6 that reproduces the experimental area per lipid of a lipid bilayer within 3% accuracy to a value of 0.623 ± 0.011 nm(2) without the assumption of a constant surface area or the inclusion of surface pressure. In addition, the lateral self-diffusion constant and deuterium order parameters of the acyl chains are in agreement with experimental data. Furthermore, models for 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol (POPG) result in areas per lipid of 0.625 nm(2) (DMPC), 0.693 nm(2) (POPC), and 0.700 nm(2) (POPG) from 40 ns MD simulations. Experimental lateral self-diffusion coefficients are reproduced satisfactorily by the simulation. The lipid models can form the basis for molecular dynamics simulations of membrane proteins with current and future versions of united-atom protein force fields.

  1. Alterations in the hypothalamic melanocortin pathway in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Vercruysse, Pauline; Sinniger, Jérôme; El Oussini, Hajer; Scekic-Zahirovic, Jelena; Dieterlé, Stéphane; Dengler, Reinhard; Meyer, Thomas; Zierz, Stephan; Kassubek, Jan; Fischer, Wilhelm; Dreyhaupt, Jens; Grehl, Torsten; Hermann, Andreas; Grosskreutz, Julian; Witting, Anke; Van Den Bosch, Ludo; Spreux-Varoquaux, Odile; Ludolph, Albert C; Dupuis, Luc

    2016-04-01

    Amyotrophic lateral sclerosis, the most common adult-onset motor neuron disease, leads to death within 3 to 5 years after onset. Beyond progressive motor impairment, patients with amyotrophic lateral sclerosis suffer from major defects in energy metabolism, such as weight loss, which are well correlated with survival. Indeed, nutritional intervention targeting weight loss might improve survival of patients. However, the neural mechanisms underlying metabolic impairment in patients with amyotrophic lateral sclerosis remain elusive, in particular due to the lack of longitudinal studies. Here we took advantage of samples collected during the clinical trial of pioglitazone (GERP-ALS), and characterized longitudinally energy metabolism of patients with amyotrophic lateral sclerosis in response to pioglitazone, a drug with well-characterized metabolic effects. As expected, pioglitazone decreased glycaemia, decreased liver enzymes and increased circulating adiponectin in patients with amyotrophic lateral sclerosis, showing its efficacy in the periphery. However, pioglitazone did not increase body weight of patients with amyotrophic lateral sclerosis independently of bulbar involvement. As pioglitazone increases body weight through a direct inhibition of the hypothalamic melanocortin system, we studied hypothalamic neurons producing proopiomelanocortin (POMC) and the endogenous melanocortin inhibitor agouti-related peptide (AGRP), in mice expressing amyotrophic lateral sclerosis-linked mutant SOD1(G86R). We observed lower Pomc but higher Agrp mRNA levels in the hypothalamus of presymptomatic SOD1(G86R) mice. Consistently, numbers of POMC-positive neurons were decreased, whereas AGRP fibre density was elevated in the hypothalamic arcuate nucleus of SOD1(G86R) mice. Consistent with a defect in the hypothalamic melanocortin system, food intake after short term fasting was increased in SOD1(G86R) mice. Importantly, these findings were replicated in two other amyotrophic

  2. Lipid-coated gold nanocomposites for enhanced cancer therapy.

    Science.gov (United States)

    Kang, Ji Hee; Ko, Young Tag

    2015-01-01

    The aim of the work reported here was to develop lipid-coated multifunctional nanocomposites composed of drugs and nanoparticles for use in cancer therapy. We incorporated thermosensitive phospholipids onto the surface of anisotropic gold nanoparticles (AuNPs) to further enhance drug delivery, with possible additional applications for in vivo imaging and photothermal cancer therapy. Lipid-coated nanohybrids loaded with the drug docetaxel (DTX) were prepared by a thin-film formation, hydration, and sonication method. Nanoparticles and their composites were characterized using particle-size analysis, zeta potential measurements, transmission electron microscopy, UV-visible spectroscopy, and reverse-phase high-performance liquid chromatography, demonstrating successful loading of DTX into the lipid bilayer on the surface of the gold nanoparticles. Initial in vitro studies using breast-cancer (MCF-7) and melanoma (B16F10) cell lines demonstrated that the drug-containing nanocomposites at equivalent drug concentrations caused significant cytotoxicity compared to free DTX. Differential flow cytometry analysis confirmed the improved cellular uptake of lipid-coated nanocomposites. Our preliminary results show that DTX-loaded anionic lipid-coated gold nanorod (AL_AuNR_DTX) and cationic lipid-coated gold nanoparticle (CL_AuNP_DTX) possess effective tumor cell-suppression abilities and can therefore be considered promising chemotherapeutic agents. Further evaluation of the therapeutic efficacy of these hybrid nanoparticles combined with external near-infrared photothermal treatment is warranted to assess their synergistic anticancer actions and potential bioimaging applications.

  3. Phloem proteomics reveals new lipid-binding proteins with a putative role in lipid-mediated signaling

    Directory of Open Access Journals (Sweden)

    Allison Marie Barbaglia

    2016-04-01

    Full Text Available Global climate changes inversely affect our ability to grow the food required for an increasing world population. To combat future crop loss due to abiotic stress, we need to understand the signals responsible for changes in plant development and the resulting adaptations, especially the signaling molecules traveling long-distance through the plant phloem. Using a proteomics approach, we had identified several putative lipid-binding proteins in the phloem exudates. Simultaneously, we identified several complex lipids as well as jasmonates. These findings prompted us to propose that phloem (phospho- lipids could act as long-distance developmental signals in response to abiotic stress, and that they are released, sensed, and moved by phloem lipid-binding proteins (Benning et al., 2012. Indeed, the proteins we identified include lipases that could release a signaling lipid into the phloem, putative receptor components, and proteins that could mediate lipid-movement. To test this possible protein-based lipid-signaling pathway, three of the proteins, which could potentially act in a relay, are characterized here: (I a putative GDSL-motif lipase (II a PIG-P-like protein, with a possible receptor-like function; (III and PLAFP (phloem lipid-associated family protein, a predicted lipid-binding protein of unknown function. Here we show that all three proteins bind lipids, in particular phosphatidic acid (PtdOH, which is known to participate in intracellular stress signaling. Genes encoding these proteins are expressed in the vasculature, a prerequisite for phloem transport. Cellular localization studies show that the proteins are not retained in the endoplasmic reticulum but surround the cell in a spotted pattern that has been previously observed with receptors and plasmodesmatal proteins. Abiotic signals that induce the production of PtdOH also regulate the expression of GDSL-lipase and PLAFP, albeit in opposite patterns. Our findings suggest that while

  4. Direct lateral maneuvers in hawkmoths

    Directory of Open Access Journals (Sweden)

    Jeremy S. M. Greeter

    2016-01-01

    Full Text Available We used videography to investigate direct lateral maneuvers, i.e. ‘sideslips’, of the hawkmoth Manduca sexta. M. sexta sideslip by rolling their entire body and wings to reorient their net force vector. During sideslip they increase net aerodynamic force by flapping with greater amplitude, (in both wing elevation and sweep, allowing them to continue to support body weight while rolled. To execute the roll maneuver we observed in sideslips, they use an asymmetric wing stroke; increasing the pitch of the roll-contralateral wing pair, while decreasing that of the roll-ipsilateral pair. They also increase the wing sweep amplitude of, and decrease the elevation amplitude of, the contralateral wing pair relative to the ipsilateral pair. The roll maneuver unfolds in a stairstep manner, with orientation changing more during downstroke than upstroke. This is due to smaller upstroke wing pitch angle asymmetries as well as increased upstroke flapping counter-torque from left-right differences in global reference frame wing velocity about the moth's roll axis. Rolls are also opposed by stabilizing aerodynamic moments from lateral motion, such that rightward roll velocity will be opposed by rightward motion. Computational modeling using blade-element approaches confirm the plausibility of a causal linkage between the previously mentioned wing kinematics and roll/sideslip. Model results also predict high degrees of axial and lateral damping. On the time scale of whole and half wing strokes, left-right wing pair asymmetries directly relate to the first, but not second, derivative of roll. Collectively, these results strongly support a roll-based sideslip with a high degree of roll damping in M. sexta.

  5. SOLID LIPID NANOPARTICLES AND NANO LIPID CARRIERS: AS NOVEL SOLID LIPID BASED DRUG CARRIER

    Directory of Open Access Journals (Sweden)

    Girish B. Singhal

    2011-02-01

    Full Text Available Interest in lipid based drug delivery has developed over the past decade fuelled by a better understanding of the multiple roles lipids may play in enhancing oral bioavailability. Moreover, the emergence of novel excipients with acceptable regulatory and safety profiles coupled with advances in formulation technologies have greatly improved the potential for successful lipid based formulations. Solid lipid nanoparticles (SLN introduced in 1991 represent an alternative carrier system to traditional colloidal carriers, such as emulsions, liposomes and polymeric micro- and nanoparticles. SLN combine advantages of the traditional systems but avoid some of their major disadvantages. This paper reviews the present state of the art regarding production techniques for SLN/ nanostructured lipid carrier (NLC, drug incorporation method and types, stability. The potential of SLN/NLC to be exploited for the different administration routes is also highlighted.

  6. Diagnosis of amyotrophic lateral sclerosis.

    Science.gov (United States)

    Rowland, L P

    1998-10-01

    This review of the differential diagnosis of amyotrophic lateral sclerosis focuses on two themes. The first is practical, how to establish the diagnosis based primarily on clinical findings buttressed by electrodiagnosis. The main considerations are multifocal motor neuropathy and cervical spondylotic myelopathy. The second theme is the relationship of motor neuron disease to other conditions, including benign fasciculation (Denny-Brown, Foley syndrome), paraneoplastic syndromes, lymphoproliferative disease, radiation damage, monomelic amyotrophy (Hirayama syndrome), as well as an association with parkinsonism, dementia and multisystem disorders of the central nervous system.

  7. Detecting lateral genetic material transfer

    CERN Document Server

    Calderón, C; Mireles, V; Miramontes, P

    2012-01-01

    The bioinformatical methods to detect lateral gene transfer events are mainly based on functional coding DNA characteristics. In this paper, we propose the use of DNA traits not depending on protein coding requirements. We introduce several semilocal variables that depend on DNA primary sequence and that reflect thermodynamic as well as physico-chemical magnitudes that are able to tell apart the genome of different organisms. After combining these variables in a neural classificator, we obtain results whose power of resolution go as far as to detect the exchange of genomic material between bacteria that are phylogenetically close.

  8. Lateral Thoracic Maningocele : Anaesthetic Implications

    Directory of Open Access Journals (Sweden)

    Nazeer Ahmed K

    2008-12-01

    Full Text Available Meningomyelocele is a broad term representing herniation of extracranial contents through a congenital defect in the vertebral column. If only cerebrospinal fluid (CSF and meninges herniate, it is termed as a meningocele. A meningoencephalocele is herniation of neural elements along with meninges. Anaesthetic challenges in management of thoracic meningomyelocele include securing the airway with intubation in lateral or supine position, intraoperative prone position with its associated complications and accurate assessment of blood loss and prevention of hypothermia. We report a case of a thoracic meningocele posted for resection and discuss its anaesthetic implications

  9. Exogenous ether lipids predominantly target mitochondria

    DEFF Research Database (Denmark)

    Kuerschner, Lars; Richter, Doris; Hannibal-Bach, Hans Kristian;

    2012-01-01

    Ether lipids are ubiquitous constituents of cellular membranes with no discrete cell biological function assigned yet. Using fluorescent polyene-ether lipids we analyzed their intracellular distribution in living cells by microscopy. Mitochondria and the endoplasmic reticulum accumulated high...... amounts of ether-phosphatidylcholine and ether-phosphatidylethanolamine. Both lipids were specifically labeled using the corresponding lyso-ether lipids, which we established as supreme precursors for lipid tagging. Polyfosine, a fluorescent analogue of the anti-neoplastic ether lipid edelfosine...... in ether lipid metabolism and intracellular ether lipid trafficking....

  10. Barley lipid transfer protein, LTP1, contains a new type of lipid-like post-translational modification

    DEFF Research Database (Denmark)

    Lindorff-Larsen, Kresten; Lerche, Mathilde H.; Poulsen, Flemming Martin;

    2001-01-01

    the formation of cutin and involvement in stress and pathogen responses, but there is yet no direct demonstration of an in vivo function. We have found and characterized a novel post-translational modification of the barley nonspecific lipid transfer protein, LTP1. The protein-modification bond is of a new type...

  11. Physiologic growth hormone replacement improves fasting lipid kinetics in patients with HIV lipodystrophy syndrome

    Science.gov (United States)

    HIV lipodystrophy syndrome (HLS) is characterized by accelerated lipolysis, inadequate fat oxidation, increased hepatic reesterification, and a high frequency of growth hormone deficiency (GHD). The effect of growth hormone (GH) replacement on these lipid kinetic abnormalities is unknown. We aimed ...

  12. Density imbalances and free energy of lipid transfer in supported lipid bilayers

    Science.gov (United States)

    Xing, Chenyue; Faller, Roland

    2009-11-01

    Supported lipid bilayers are an abundant research platform for understanding the behavior of real cell membranes as they allow for additional mechanical stability and at the same time have a fundamental structure approximating cell membranes. However, in computer simulations these systems have been studied only rarely up to now. An important property, which cannot be easily determined by molecular dynamics or experiments, is the unsymmetrical density profiles of bilayer leaflets (density imbalance) inflicted on the membrane by the support. This imbalance in the leaflets composition has consequences for membrane structure and phase behavior, and therefore we need to understand it in detail. The free energy can be used to determine the equilibrium structure of a given system. We employ an umbrella sampling approach to obtain the free energy of a lipid crossing the membrane (i.e., lipid flip-flop) as a function of bilayer composition and hence the equilibrium composition of the supported bilayers. In this paper, we use a variant of the coarse-grained Martini model. The results of the free energy calculation lead to a 5% higher density in the proximal leaflet. Recent data obtained by large scale modeling using a water free model suggested that the proximal leaflet had 3.2% more lipids than the distal leaflet [Hoopes et al., J. Chem. Phys. 129, 175102 (2008)]. Our findings are in line with these results. We compare results of the free energy of transport obtained by pulling the lipid across the membrane in different ways. There are small quantitative differences, but the overall picture is consistent. We additionally characterize the intermediate states, which determine the barrier height and therefore the rate of translocation. Calculations on unsupported bilayers are used to validate the approach and to determine the barrier to flip-flop in a free membrane.

  13. Mapping condition-dependent regulation of lipid metabolism in Saccharomyces cerevisiae.

    Science.gov (United States)

    Jewett, Michael C; Workman, Christopher T; Nookaew, Intawat; Pizarro, Francisco A; Agosin, Eduardo; Hellgren, Lars I; Nielsen, Jens

    2013-11-06

    Lipids play a central role in cellular function as constituents of membranes, as signaling molecules, and as storage materials. Although much is known about the role of lipids in regulating specific steps of metabolism, comprehensive studies integrating genome-wide expression data, metabolite levels, and lipid levels are currently lacking. Here, we map condition-dependent regulation controlling lipid metabolism in Saccharomyces cerevisiae by measuring 5636 mRNAs, 50 metabolites, 97 lipids, and 57 (13)C-reaction fluxes in yeast using a three-factor full-factorial design. Correlation analysis across eight environmental conditions revealed 2279 gene expression level-metabolite/lipid relationships that characterize the extent of transcriptional regulation in lipid metabolism relative to major metabolic hubs within the cell. To query this network, we developed integrative methods for correlation of multi-omics datasets that elucidate global regulatory signatures. Our data highlight many characterized regulators of lipid metabolism and reveal that sterols are regulated more at the transcriptional level than are amino acids. Beyond providing insights into the systems-level organization of lipid metabolism, we anticipate that our dataset and approach can join an emerging number of studies to be widely used for interrogating cellular systems through the combination of mathematical modeling and experimental biology.

  14. Structural properties of lipid reconstructs and lipid composition of normotensive and hypertensive rat vascular smooth muscle cell membranes

    Directory of Open Access Journals (Sweden)

    T.R. Oliveira

    2009-09-01

    Full Text Available Multiple cell membrane alterations have been reported to be the cause of various forms of hypertension. The present study focuses on the lipid portion of the membranes, characterizing the microviscosity of membranes reconstituted with lipids extracted from the aorta and mesenteric arteries of spontaneously hypertensive (SHR and normotensive control rat strains (WKY and NWR. Membrane-incorporated phospholipid spin labels were used to monitor the bilayer structure at different depths. The packing of lipids extracted from both aorta and mesenteric arteries of normotensive and hypertensive rats was similar. Lipid extract analysis showed similar phospholipid composition for all membranes. However, cholesterol content was lower in SHR arteries than in normotensive animal arteries. These findings contrast with the fact that the SHR aorta is hyporeactive while the SHR mesenteric artery is hyperreactive to vasopressor agents when compared to the vessels of normotensive animal strains. Hence, factors other than microviscosity of bulk lipids contribute to the vascular smooth muscle reactivity and hypertension of SHR. The excess cholesterol in the arteries of normotensive animal strains apparently is not dissolved in bulk lipids and is not directly related to vascular reactivity since it is present in both the aorta and mesenteric arteries. The lower cholesterol concentrations in SHR arteries may in fact result from metabolic differences due to the hypertensive state or to genes that co-segregate with those that determine hypertension during the process of strain selection.

  15. Effects of acute exercise on lipid content and dietary lipid uptake in liver and skeletal muscle of lean and diabetic rats.

    Science.gov (United States)

    Janssens, Sharon; Jonkers, Richard A M; Groen, Albert K; Nicolay, Klaas; van Loon, Luc J C; Prompers, Jeanine J

    2015-11-15

    Insulin resistance is associated with ectopic lipid accumulation. Physical activity improves insulin sensitivity, but the impact of exercise on lipid handling in insulin-resistant tissues remains to be elucidated. The present study characterizes the effects of acute exercise on lipid content and dietary lipid partitioning in liver and skeletal muscle of lean and diabetic rats by use of magnetic resonance spectroscopy (MRS). After baseline measurements, rats were randomized to exercise or no-exercise groups. A subset of animals was subjected to MRS directly after 1 h of treadmill running for measurement of total intrahepatocellular lipid (IHCL) and intramyocellular lipid (IMCL) content (n=7 lean and diabetic rats). The other animals were administered 13C-labeled lipids orally after treadmill visit (with or without exercise) followed by MRS measurements after 4 and 24 h to determine the 13C enrichment of IHCL and IMCL (n=8 per group). Total IHCL and IMCL content were fivefold higher in diabetic vs. lean rats (Plean and diabetic rats (Plean rats (Plean and diabetic rats, lipid uptake was 44% reduced after acute exercise (Plean and diabetic rats, and exercise differentially affects dietary lipid uptake in muscle and liver.

  16. Epicondilite lateral do cotovelo Lateral epicondylitis of the elbow

    Directory of Open Access Journals (Sweden)

    Marcio Cohen

    2012-01-01

    Full Text Available A epicondilite lateral, também conhecida como cotovelo do tenista, é uma condição comum que acomete de 1 a 3% da população. O termo epicondilite sugere inflamação, embora a análise histológica tecidual não demonstre um processo inflamatório. A estrutura acometida com mais frequência é a origem do tendão extensor radial curto do carpo e o mecanismo de lesão está associado à sua sobrecarga. O tratamento incruento é o de escolha e inclui: repouso, fisioterapia, infiltração com cortisona ou plasma rico em plaquetas e a utilização de imobilização específica. O tratamento cirúrgico é recomendado quando persistem impotência funcional e dor. Tanto a técnica cirúrgica aberta quanto a artroscópica com ressecção da área tendinosa degenerada apresenta bons resultados na literatura.Lateral epicondylitis, also known as tennis elbow, is a common condition that is estimated to affect 1% to 3% of the population. The word epicondylitis suggests inflammation, although histological analysis on the tissue fails to show any inflammatory process. The structure most commonly affected is the origin of the tendon of the extensor carpi radialis brevis and the mechanism of injury is associated with overloading. Nonsurgical treatment is the preferred method, and this includes rest, physiotherapy, cortisone infiltration, platelet-rich plasma injections and use of specific immobilization. Surgical treatment is recommended when functional disability and pain persist. Both the open and the arthroscopic surgical technique with resection of the degenerated tendon tissue present good results in the literature.

  17. The adrenal specific toxicant mitotane directly interacts with lipid membranes and alters membrane properties depending on lipid composition.

    Science.gov (United States)

    Scheidt, Holger A; Haralampiev, Ivan; Theisgen, Stephan; Schirbel, Andreas; Sbiera, Silviu; Huster, Daniel; Kroiss, Matthias; Müller, Peter

    2016-06-15

    Mitotane (o,p'.-DDD) is an orphan drug approved for the treatment of adrenocortical carcinoma. The mechanisms, which are responsible for this activity of the drug, are not completely understood. It can be hypothesized that an impact of mitotane is mediated by the interaction with cellular membranes. However, an interaction of mitotane with (lipid) membranes has not yet been investigated in detail. Here, we characterized the interaction of mitotane and its main metabolite o,p'-dichlorodiphenyldichloroacetic acid (o,p'-DDA) with lipid membranes by applying a variety of biophysical approaches of nuclear magnetic resonance, electron spin resonance, and fluorescence spectroscopy. We found that mitotane and o,p'-DDA bind to lipid membranes by inserting into the lipid-water interface of the bilayer. Mitotane but not o,p'-DDA directly causes a disturbance of bilayer structure leading to an increased permeability of the membrane for polar molecules. Mitotane induced alterations of the membrane integrity required the presence of phosphatidylethanolamine and/or cholesterol. Collectively, our data for the first time characterize the impact of mitotane on the lipid membrane structure and dynamics, which may contribute to a better understanding of specific mitotane effects and side effects.

  18. Recent advances in cryo-TEM imaging of soft lipid nanoparticles

    DEFF Research Database (Denmark)

    Helvig, Shen Yu; Mat Azmi, Intan Diana Binti; Moghimi, Seyed Moien;

    2015-01-01

    Cryo-transmission electron microscopy (Cryo-TEM), and its technological variations thereof, have become a powerful tool for detailed morphological characterization and 3D tomography of soft lipid and polymeric nanoparticles as well as biological materials such as viruses and DNA without chemical...... fixation. Here, we review and discuss recent advances in Cryo-TEM analysis of lipid-based drug nanocarriers with particular emphasis on morphological and internal nanostructure characterization of lyotropic liquid crystalline nanoparticles such as cubosomes and hexosomes....

  19. Characterization of a key gene in membrane lipid cycle in Synechocystis sp.PCC6803%集胞藻PCC6803膜脂循环关键基因酶学性质和生理功能

    Institute of Scientific and Technical Information of China (English)

    高倩倩; 谈晓明; 吕雪峰

    2012-01-01

    集胞藻PCC6803野生型和其脂酰ACP合酶敲除突变株的自由脂肪酸含量和组成表明膜脂的重构和降解是细胞内自由脂肪酸的来源之一.在这一过程中脂肪酶起到关键性作用.通过基因组数据库检索,发现集胞藻PCC6803基因组中只有一个脂肪酶编码基因sll1969,但是还没有其功能相关的生化证据.为了确定该基因的功能及其在脂肪酸代谢途径中的作用,加深对集胞藻PCC6803脂肪酸代谢途径的了解,文中将sll1969基因在大肠杆菌中过表达和体外纯化,得到重组蛋白Sl11969,并对其酶学性质进行初步分析.在30℃条件下,测得Sl11969以对硝基苯丁酸酯作为底物时的Km和Km和kcat值分别为(1.16--0.01)mmol/L和(332.8±10.0)/min;该脂肪酶的最适反应温度为55℃.通过比较分析sll1969突变株中脂肪酸含量和组成变化,发现sll1969的表达量与细胞自由脂肪酸的产量呈正相关,但S111969不是细胞中唯一的脂肪酶.%Free fatty acid profiles of wild type and fatty acyl-ACP synthase deletion mutant strain of Synechocystis sp. PCC6803 indicated that one origin of these fatty acids is the process of lipid remodeling or lipid degradation. Lipase is the key enzyme involved in this process. The gene sill 969 is the sole gene encodes a putative lipase in Synechocystis sp. PCC6803. To identify the function of this gene and its role in fatty acid metabolism, we cloned the sll1969 from genomic DNA, overexpressed it in Escherichia coli BL21 (DE3) using pET expression system and purified this recombinant enzyme with Nickel-nitrilotriacetic acid affinity chromatography. The enzyme activity was assayed by spectrophotometric with p-nitro-phenylbutyrate as substrate. The Km and Kcat of the enzyme is (1.16±0.01) mmol/L and (332.8±10.0)/min, respectively toward p-nitro-phenylbutyrate at 30℃. The optimal temperature of the enzyme is 55℃. To investigate the biological role of S111969 in fatty acid metabolism in

  20. Lipidology and lipidomics--quo vadis? A new era for the physical chemistry of lipids.

    Science.gov (United States)

    Mouritsen, Ole G

    2011-11-21

    Our picture of lipid membranes has come a long way since Gorter and Grendel in 1925 formulated the lipid bilayer hypothesis. Most modern textbook models of membranes are based on the Singer-Nicolson model from 1972, although we have in recent years seen significant amendments to this model, not least fuelled by the finding of lipid membrane domains and the subsequent 'raft rush'. The science of lipids, lipidology, has now become an established discipline, acknowledging that lipids organize in space and time and display emergent physico-chemical properties that are beyond the chemical nature of the individual molecules and which collectively control membrane function. Recently, lipidomics has been followed as a new discipline in the omics-sequel, characterized by an explosion in detailed data for lipid profiles of tissues, cells, and subcellular components. The focus is now swinging toward enumerating individual lipid species, determining their identity, and quantitating their amount. Time is ripe to marry the two disciplines, both in order to take lipidomics beyond the stage of 'stamp collection' and in order to incorporate into the lipidology approach the new knowledge about the individual lipid species. As an important matchmaker for this marriage, the physical chemistry of lipids in lipid bilayers and membranes is entering a new era of renaissance.