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Sample records for hyaluronan derivative hylan

  1. Intra-Articular Viscosupplementation With Hylan G-F 20 To Treat Osteoarthritis of the Knee

    Science.gov (United States)

    2005-01-01

    Executive Summary Objective To assess the effectiveness and cost-effectiveness of hylan G-F 20 as a substitute for existing treatments for pain due to osteoarthritis (OA) of the knee, other viscosupplementation devices, and/or as an adjunct to conventional therapy. Hylan G-F 20 (brand name Synvisc, which is manufactured by Genzyme) is a high molecular weight derivative of hyaluronan, a component of joint synovial fluid. It acts as a lubricant and shock absorber. It is administered by injection into the joint space to treat pain associated with OA of the knee. Although the injection procedure is an insured service in Ontario, the device, hylan G-F 20, is not. Clinical Need Osteoarthritis is prevalent in 10% to 12% of Ontario adults, and exceeds 40% in Ontario residents aged 65 years and older. About one-half of these people have mild, moderate, or severe OA of the knee. Conventional treatment involves a combination of nonpharmacological management (e.g., weight loss, exercise, social support, and patient education), drugs, (e.g., acetaminophen, COX-2 inhibitors, nonsteroidal anti-inflammatory drugs with/without misoprostol, intra-articular glucocorticoids, opioids, and topical analgesics) and surgical interventions, such as debridement and total knee replacement, when pharmacological management fails. The growing burden of OA of the knee in the aging Ontario population combined with recent safety concerns about COX-2 inhibitors and long wait times for total joint replacement is placing pressure on the demand for new, effective technologies to manage the pain of OA. The Technology Hylan G-F 20 is derived from rooster comb hyaluronan (HA). At the time of writing, eight viscosupplement hyaluronic products are licensed in Canada. Hylan G-F 20 is distinguished from the other products by its chemical structure (i.e., cross-linked hyaluronan, hence hylan) and relatively higher molecular weight, which may bestow greater therapeutic viscoelastic properties. A complete

  2. Intra-articular viscosupplementation with hylan g-f 20 to treat osteoarthritis of the knee: an evidence-based analysis.

    Science.gov (United States)

    2005-01-01

    To assess the effectiveness and cost-effectiveness of hylan G-F 20 as a substitute for existing treatments for pain due to osteoarthritis (OA) of the knee, other viscosupplementation devices, and/or as an adjunct to conventional therapy. Hylan G-F 20 (brand name Synvisc, which is manufactured by Genzyme) is a high molecular weight derivative of hyaluronan, a component of joint synovial fluid. It acts as a lubricant and shock absorber. It is administered by injection into the joint space to treat pain associated with OA of the knee. Although the injection procedure is an insured service in Ontario, the device, hylan G-F 20, is not. Osteoarthritis is prevalent in 10% to 12% of Ontario adults, and exceeds 40% in Ontario residents aged 65 years and older. About one-half of these people have mild, moderate, or severe OA of the knee. Conventional treatment involves a combination of nonpharmacological management (e.g., weight loss, exercise, social support, and patient education), drugs, (e.g., acetaminophen, COX-2 inhibitors, nonsteroidal anti-inflammatory drugs with/without misoprostol, intra-articular glucocorticoids, opioids, and topical analgesics) and surgical interventions, such as debridement and total knee replacement, when pharmacological management fails. The growing burden of OA of the knee in the aging Ontario population combined with recent safety concerns about COX-2 inhibitors and long wait times for total joint replacement is placing pressure on the demand for new, effective technologies to manage the pain of OA. Hylan G-F 20 is derived from rooster comb hyaluronan (HA). At the time of writing, eight viscosupplement hyaluronic products are licensed in Canada. Hylan G-F 20 is distinguished from the other products by its chemical structure (i.e., cross-linked hyaluronan, hence hylan) and relatively higher molecular weight, which may bestow greater therapeutic viscoelastic properties. A complete treatment cycle of hylan G-F 20 involves an intra

  3. Pain relief and improved physical function in knee osteoarthritis patients receiving ongoing hylan G-F 20, a high-molecular-weight hyaluronan, versus other treatment options: data from a large real-world longitudinal cohort in Canada

    Directory of Open Access Journals (Sweden)

    Petrella RJ

    2015-10-01

    Full Text Available Robert J Petrella,1,2 Craig Wakeford31Departments of Family Medicine, Medicine (Cardiology and Kinesiology, University of Western Ontario; 2Aging, Rehabilitation & Geriatric Care Research Centre, Lawson Health Research Institute, London, ON; 3Health Economics and Health Outcomes, Sanofi-Aventis Inc., Laval, QC, CanadaAbstract: From the Southwestern Ontario database, one of the largest primary-care datasets in Canada, 1,263 patients with osteoarthritis (OA of one or both knees were identified who received two consecutive series of intra-articular (IA injections of hylan G-F 20 preparation and no other prescribed OA medications, and were evaluated fully between 2006 and 2012. A cohort of 3,318 demographically matched OA patients who had not been treated with IA injection therapy was identified from the same database for comparison. Responses to therapy were assessed by means of a 10-point visual analog scale (VAS for pain at rest and after completion of a 6-minute walk test (6MWT, while physical capacity was measured by performance in the 6MWT itself. After two cycles of hylan G-F 20 therapy, the average VAS score for pain at rest declined from 7.82±1.27 at baseline to 4.16±1.51 (average change 3.66±1.78, significantly more than the reduction of 3.12±2.03 seen in the reference group [P<0.012] and the average VAS score for pain after the 6MWT decreased by 5.56±1.74 points (from 9.58±0.4 at baseline to 4.02±1.67 at the final assessment, a significantly larger change than that seen in the reference group (Δ2.99±1.85; P<0.001 for intergroup comparison. Distance walked in the 6MWT increased on average by 115 m, significantly more than that seen in the reference group (Δ91 m; P<0.001 for intergroup comparison. These findings from a primary-care database suggest sustained benefits in terms of pain and physical function from repeat cycles of IA injections of hylan G-F 20 and no other prescribed OA medications in adults with OA of the knee

  4. Nanostructure of hyaluronan acyl-derivatives in the solid state

    Czech Academy of Sciences Publication Activity Database

    Chmelař, J.; Bělský, P.; Mrázek, J.; Švadlák, D.; Hermannová, M.; Šlouf, Miroslav; Krakovský, I.; Šmejkalová, D.; Velebný, V.

    2018-01-01

    Roč. 195, 1 September (2018), s. 468-475 ISSN 0144-8617 R&D Projects: GA TA ČR(CZ) TE01020118 Institutional support: RVO:61389013 Keywords : hyaluronan * hydrophobization * nanostructure Subject RIV: CD - Macromolecular Chemistry OBOR OECD: Polymer science Impact factor: 4.811, year: 2016

  5. Priming Adipose-Derived Mesenchymal Stem Cells with Hyaluronan Alters Growth Kinetics and Increases Attachment to Articular Cartilage

    Directory of Open Access Journals (Sweden)

    Peter Succar

    2016-01-01

    Full Text Available Background. Biological therapeutics such as adipose-derived mesenchymal stem cell (MSC therapy are gaining acceptance for knee-osteoarthritis (OA treatment. Reports of OA-patients show reductions in cartilage defects and regeneration of hyaline-like-cartilage with MSC-therapy. Suspending MSCs in hyaluronan commonly occurs in animals and humans, usually without supporting data. Objective. To elucidate the effects of different concentrations of hyaluronan on MSC growth kinetics. Methods. Using a range of hyaluronan concentrations, we measured MSC adherence and proliferation on culture plastic surfaces and a novel cartilage-adhesion assay. We employed time-course and dispersion imaging to assess MSC binding to cartilage. Cytokine profiling was also conducted on the MSC-secretome. Results. Hyaluronan had dose-dependent effects on growth kinetics of MSCs at concentrations of entanglement point (1 mg/mL. At higher concentrations, viscosity effects outweighed benefits of additional hyaluronan. The cartilage-adhesion assay highlighted for the first time that hyaluronan-primed MSCs increased cell attachment to cartilage whilst the presence of hyaluronan did not. Our time-course suggested patients undergoing MSC-therapy for OA could benefit from joint-immobilisation for up to 8 hours. Hyaluronan also greatly affected dispersion of MSCs on cartilage. Conclusion. Our results should be considered in future trials with MSC-therapy using hyaluronan as a vehicle, for the treatment of OA.

  6. Hylan G-F 20 Versus Low Molecular Weight Hyaluronic Acids for Knee Osteoarthritis: A Meta-Analysis.

    Science.gov (United States)

    Zhao, Hongmou; Liu, Hongliang; Liang, Xiaojun; Li, Yi; Wang, Junhu; Liu, Cheng

    2016-10-01

    Hyaluronic acid injection has been reported to decrease pain compared with baseline levels in knee joint osteoarthritis. Hylan G-F 20 is distinguished from the other products by its chemical structure and relatively higher molecular weight. Many trials have compared hylan G-F 20 and low molecular weight hyaluronic acids (LMWHAs); however, their relative efficacy and safety are still debated. The aim was to compare the effectiveness and safety of intra-articular injection of hylan G-F 20 and LMWHA in the treatment of knee joint osteoarthritis. A comprehensive search of the literature up to February 2016 was performed; multiple databases were searched with 'Synvisc' or 'hylan' or 'hyaluronan' as free word terms. The pain-related outcomes and treatment-related adverse events from intent-to-treat analyzed studies were pooled for meta-analysis; other functional outcomes were included in the qualitative analysis. Twenty trials with a total of 3034 patients and 3153 knees were included, with a pooled dropout rate of 7.2 %. The pooled pain-related outcomes at 2 to 3 months reached a statistically significant difference in favor of hylan G-F 20 (I 2  = 88 %; random effects; P = 0.02), and the significance still existed with exclusion (in order to eliminate heterogeneity) of the three studies that most favored hylan G-F 20 (I 2  = 51 %; fixed effect; P = 0.03). No significant difference was reached for other group and subgroup analyses. No significant difference was reached in comparing the patients with treatment-related adverse events (seven trials; 2025 patients; P = 0.13) or the treatment-related adverse events (six trials; 1633 patients; P = 0.14). According to the current results, limited evidence showed a superior effect favoring hylan G-F 20 over LMWHA in the period from 2 to 3 months post-injection for pain-related outcomes. There was no evidence of increased risk of treatment-related adverse events for hylan G-F 20 injections.

  7. Arrival time distributions of product ions reveal isomeric ratio of deprotonated molecules in ion mobility-mass spectrometry of hyaluronan-derived oligosaccharides

    Czech Academy of Sciences Publication Activity Database

    Hermanová, M.; Iordache, A.-M.; Slováková, K.; Havlíček, Vladimír; Pelantová, Helena; Lemr, Karel

    2015-01-01

    Roč. 50, č. 6 (2015), s. 854-863 ISSN 1076-5174 R&D Projects: GA ČR(CZ) GAP206/12/1150 Institutional support: RVO:61388971 Keywords : tyramine-based hyaluronan derivatives * isomer discrimination * ion mobility Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 2.541, year: 2015

  8. Hyaluronan in human malignancies

    International Nuclear Information System (INIS)

    Sironen, R.K.; Tammi, M.; Tammi, R.; Auvinen, P.K.; Anttila, M.; Kosma, V-M.

    2011-01-01

    Hyaluronan, a major macropolysaccharide in the extracellular matrix of connective tissues, is intimately involved in the biology of cancer. Hyaluronan accumulates into the stroma of various human tumors and modulates intracellular signaling pathways, cell proliferation, motility and invasive properties of malignant cells. Experimental and clinicopathological evidence highlights the importance of hyaluronan in tumor growth and metastasis. A high stromal hyaluronan content is associated with poorly differentiated tumors and aggressive clinical behavior in human adenocarcinomas. Instead, the squamous cell carcinomas and malignant melanomas tend to have a reduced hyaluronan content. In addition to the stroma-cancer cell interaction, hyaluronan can influence stromal cell recruitment, tumor angiogenesis and epithelial-mesenchymal transition. Hyaluronan receptors, hyaluronan synthases and hyaluronan degrading enzymes, hyaluronidases, are involved in the modulation of cancer progression, depending on the tumor type. Furthermore, intracellular signaling and angiogenesis are affected by the degradation products of hyaluronan. Hyaluronan has also therapeutic implications since it is involved in multidrug resistance.

  9. Hyaluronan in human malignancies

    Energy Technology Data Exchange (ETDEWEB)

    Sironen, R.K. [Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio (Finland); Department of Pathology, Kuopio University Hospital, P.O. Box 1777, FI-70211 Kuopio (Finland); Tammi, M.; Tammi, R. [Institute of Biomedicine, Anatomy, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio (Finland); Auvinen, P.K. [Department of Oncology, Kuopio University Hospital, P.O. Box 1777, FI-70211 Kuopio (Finland); Anttila, M. [Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio (Finland); Department of Gynecology and Obstetrics, Kuopio University Hospital, P.O. Box 1777, FI-70211 Kuopio (Finland); Kosma, V-M., E-mail: Veli-Matti.Kosma@uef.fi [Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio (Finland); Department of Pathology, Kuopio University Hospital, P.O. Box 1777, FI-70211 Kuopio (Finland)

    2011-02-15

    Hyaluronan, a major macropolysaccharide in the extracellular matrix of connective tissues, is intimately involved in the biology of cancer. Hyaluronan accumulates into the stroma of various human tumors and modulates intracellular signaling pathways, cell proliferation, motility and invasive properties of malignant cells. Experimental and clinicopathological evidence highlights the importance of hyaluronan in tumor growth and metastasis. A high stromal hyaluronan content is associated with poorly differentiated tumors and aggressive clinical behavior in human adenocarcinomas. Instead, the squamous cell carcinomas and malignant melanomas tend to have a reduced hyaluronan content. In addition to the stroma-cancer cell interaction, hyaluronan can influence stromal cell recruitment, tumor angiogenesis and epithelial-mesenchymal transition. Hyaluronan receptors, hyaluronan synthases and hyaluronan degrading enzymes, hyaluronidases, are involved in the modulation of cancer progression, depending on the tumor type. Furthermore, intracellular signaling and angiogenesis are affected by the degradation products of hyaluronan. Hyaluronan has also therapeutic implications since it is involved in multidrug resistance.

  10. Hyaluronan preserves the proliferation and differentiation potentials of long-term cultured murine adipose-derived stromal cells

    International Nuclear Information System (INIS)

    Chen, P.-Y.; Huang, Lynn L.H.; Hsieh, H.-J.

    2007-01-01

    For long-term culture, murine adipose-derived stromal cells (mADSCs) at latter passages demonstrated a marked decline in proliferative activity, exhibited senescent morphology and reduced differentiation potentials, particularly osteogenesis. To extend the lifespan of mADSCs, two culture conditions containing hyaluronan (HA) was compared in our study, one as a culture medium supplement (SHA), and the other where HA was pre-coated on culture surface (CHA). mADSCs cultivated with SHA exhibited a prolonged lifespan, reduced cellular senescence, and enhanced osteogenic potential compared to regular culture condition (control). Upon CHA treatment, mADSCs tended to form cell aggregates with gradual growth profiles, while their differentiation activities remained similar to SHA groups. After transferring mADSCs from CHA to control surface, they were shown to have an extended lifespan and an increase of osteogenic potential. Our results suggested that HA can be useful for preserving the proliferation and differentiation potentials of long-term cultured mADSCs

  11. Production methods for hyaluronan

    NARCIS (Netherlands)

    Boeriu, C.G.; Springer, J.; Kooy, F.K.; Broek, van den L.A.M.; Eggink, G.

    2013-01-01

    Hyaluronan is a polysaccharide with multiple functions in the human body being involved in creating flexible and protective layers in tissues and in many signalling pathways during embryonic development, wound healing, inflammation, and cancer. Hyaluronan is an important component of active

  12. Hyaluronan and Stone Disease

    Science.gov (United States)

    Asselman, Marino

    2008-09-01

    Kidney stones cannot be formed as long as crystals are passed in the urine. However, when crystals are retained it becomes possible for them to aggregate and form a stone. Crystals are expected to be formed not earlier than the distal tubules and collecting ducts. Studies both in vitro and in vivo demonstrate that calcium oxalate monohydrate crystals do not adhere to intact distal epithelium, but only when the epithelium is proliferating or regenerating, so that it possesses dedifferentiated cells expressing hyaluronan, osteopontin (OPN) and their mutual receptor CD44 at the apical cell membrane. The polysaccharide hyaluronan is an excellent crystal binding molecule because of its negative ionic charge. We hypothesized that the risk for crystal retention in the human kidney would be increased when tubular cells express hyaluronan at their apical cell membrane. Two different patient categories in which nephrocalcinosis frequently occurs were studied to test this hypothesis (preterm neonates and kidney transplant patients). Hyaluronan (and OPN) expression at the luminal membrane of tubular cells indeed was observed, which preceded subsequent retention of crystals in the distal tubules. Tubular nephrocalcinosis has been reported to be associated with decline of renal function and thus further studies to extend our knowledge of the mechanisms of retention and accumulation of crystals in the kidney are warranted. Ultimately, this may allow the design of new strategies for the prevention and treatment of both nephrocalcinosis and nephrolithiasis in patients.

  13. Hyaluronan Biosynthesis in Prostate Cancer

    National Research Council Canada - National Science Library

    McCarthy, James B

    2006-01-01

    Despite advances in the diagnosis and treatment of prostate cancer in the last several years metastasis represents the major cause of frustration and failure in the successful treatment of prostate cancer patients. Hyaluronan (HA...

  14. Acquisition of epithelial-mesenchymal transition and cancer stem-like phenotypes within chitosan-hyaluronan membrane-derived 3D tumor spheroids.

    Science.gov (United States)

    Huang, Yen-Jang; Hsu, Shan-Hui

    2014-12-01

    Cancer drug development has to go through rigorous testing and evaluation processes during pre-clinical in vitro studies. However, the conventional two-dimensional (2D) in vitro culture is often discounted by the insufficiency to present a more typical tumor microenvironment. The multicellular tumor spheroids have been a valuable model to provide more comprehensive assessment of tumor in response to therapeutic strategies. Here, we applied chitosan-hyaluronan (HA) membranes as a platform to promote three-dimensional (3D) tumor spheroid formation. The biological features of tumor spheroids of human non-small cell lung cancer (NSCLC) cells on chitosan-HA membranes were compared to those of 2D cultured cells in vitro. The cells in tumor spheroids cultured on chitosan-HA membranes showed higher levels of stem-like properties and epithelial-mesenchymal transition (EMT) markers, such as NANOG, SOX2, CD44, CD133, N-cadherin, and vimentin, than 2D cultured cells. Moreover, they exhibited enhanced invasive activities and multidrug resistance by the upregulation of MMP2, MMP9, BCRC5, BCL2, MDR1, and ABCG2 as compared with 2D cultured cells. The grafting densities of HA affected the tumor sphere size and mRNA levels of genes on the substrates. These evidences suggest that chitosan-HA membranes may offer a simple and valuable biomaterial platform for rapid generation of tumor spheroids in vitro as well as for further applications in cancer stem cell research and cancer drug screening. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Immunologic roles of hyaluronan.

    Science.gov (United States)

    Mummert, Mark E

    2005-01-01

    Hyaluronan (HA), a large glycosaminoglycan composed of D-N-acetylglucosamine and D-glucuronic acid, is expressed in virtually all tissues and has long been considered to serve as a structural component or filling material in the tissue interstitium (Filler Theory). This idea was revised with the discovery of HA-binding proteins that introduced the concept that HA may also serve as an adhesive substrate for cellular trafficking (Adhesion Theory). Most recently, it has been shown that HA fragments can deliver maturational signals to dendritic cells (DCs) and high molecular weight HA polymers can deliver costimulatory signals to T-cells (Signaling Theory). Thus, HA may represent an important component of the immune system. Recently, we have evaluated the impact of HA on Langerhans cell (LC) maturation and migration using a novel peptide inhibitor of HA function, termed Pep-1 (GAHWQFNALTVR). As skin-specific members of the DC family, LCs are crucial for the initiation of cutaneous immune responses. Local injections of Pep-1 prevented hapten-induced LC migration from the epidermis, providing the first experimental evidence that HA facilitates their emigration. Moreover, Pep-1 also significantly inhibited the hapten-induced maturation of LCs in vivo as assessed by cell morphology, costimulatory molecule expression, and their ability to induce proliferation of allogeneic T-cells. HA therefore has dual functionality to facilitate LC migration and maturation, the two critical events for the initiation of adaptive immune responses. Finally, we have observed that DC-dependent, antigen-specific T-cell proliferation and cytokine secretion is blocked by Pep-1. These results have revealed a previously unrecognized role for HA in antigen presentation. Thus, far from an inert structural biopolymer, HA represents a multifunctional carbohydrate mediator of immune processes.

  16. Enzymatic production of hyaluronan oligo- and polysaccharides

    NARCIS (Netherlands)

    Kooy, F.K.

    2010-01-01

    Hyaluronan oligo- and polysaccharides are abundant in the human body. Depending on the chain length, hyaluronan is an important structural component or is involved in influencing cell responses during embryonic development, healing processes, inflammation and cancer. Due to these diverse roles of

  17. EVALUATION OF SAFETY AND EFFECTIVENESS OF HYLAN GF-20 IN PATIENTS WITH KNEE OSTEOARTHRITIS IN REAL LIFE PRACTICE: PRELIMINARY RESULTS

    Directory of Open Access Journals (Sweden)

    G. V. Kuropatkin

    2016-01-01

    Full Text Available Combined conservative treatment of osteoarthritis includes intra-articular injections of hyaluronic acid. The paper presents the interim results of a prospective observational multicenter non-comparative study conducted in accordance with routine clinical practice to assess the safety and effectiveness of Hylan GF-20 in patients with knee osteoarthritis. The primary objective of the study is to assess walking and rest pain severity by WOMAC VA3.1 scale after 26 weeks and 52 weeks compared to the baseline. To date, 42 patients completed the study (71.43% women, 28.57% men, patients mean age is 59.79 years. After intraarticular injection of Hylan GF-20 patients were examined after 3, 6 and 12 months. After 3 months a positive clinical response was observed: pain severity decreased by 51.31% (p<0,001 on WOMAC A, joint stiffness decreased by 51.02% (p<0,001 on WOMAC B, daily life difficulties decreased by 42.03% (p<0,001 on WOMAC C. The same tendency was observed in the following periods. By week 52 pain severity reduced by 53.25% (p<0,001 on WOMAC A, joint stiffness by 41.63% (p<0,001 on WOMAC B, daily life difficulties -by 47.55% (p<0.001 on WOMAC C. Level of clinical response didn't correlate with the osteoarthritis stage. Therapy resulted in improvement of life quality of patients with knee osteoarthritis by 36% (p<0,001 according to the questionnaire EQ-5D. The general patients status according to physicians improved by 33.96% (p<0,001 on VAS, and by 45.91% (p<0,001 according to patients response on VAS. By week 52 of follow-up 11,90% of patients demonstrated a decrease in required concomitant therapy of osteoarthritis. Given the chronic nature of the osteoarthritis it's the most important that the therapeutic effect of Hylan GF-20 maintains until week 52. The above results confirm the efficiency of intraar-ticular injection of hyaluronic acid in patients with knee osteoarthritis especially in early disease stage.

  18. Hyaluronan: from biomimetic to industrial business strategy.

    Science.gov (United States)

    Murano, Erminio; Perin, Danilo; Khan, Riaz; Bergamin, Massimo

    2011-04-01

    Hyaluronan (hyaluronic acid) is a naturally occurring polysaccharide of a linear repeating disaccharide unit consisting of beta-(1-->4)-linked D-glucopyranuronic acid and beta-(1-->3)-linked 2-acetamido-2-deoxy-D-glucopyranose, which is present in extracellular matrices, the synovial fluid of joints, and scaffolding that comprises cartilage. In its mechanism of synthesis, its size, and its physico-chemical properties, hyaluronan is unique amongst other glycosaminoglycans. The network-forming, viscoelastic and its charge characteristics are important to many biochemical properties of living tissues. It is an important pericellular and cell surface constituent; its interaction with other macromolecules such as proteins, participates in regulating cell behavior during numerous morphogenic, restorative, and pathological processes in the body. The knowledge of HA in diseases such as various forms of cancers, arthritis and osteoporosis has led to new impetus in research and development in the preparation of biomaterials for surgical implants and drug conjugates for targeted delivery. A concise and focused review on hyaluronan is timely. This review will cover the following important aspects of hyaluronan: (i) biological functions and synthesis in nature; (ii) current industrial production and potential biosynthetic processes of hyaluronan; (iii) chemical modifications of hyaluronan leading to products of commercial significance; and (iv) and the global market position and manufacturers of hyaluronan.

  19. Antisense inhibition of hyaluronan synthase-2 in human osteosarcoma cells inhibits hyaluronan retention and tumorigenicity

    International Nuclear Information System (INIS)

    Nishida, Yoshihiro; Knudson, Warren; Knudson, Cheryl B.; Ishiguro, Naoki

    2005-01-01

    Osteosarcoma is a common malignant bone tumor associated with childhood and adolescence. The results of numerous studies have suggested that hyaluronan plays an important role in regulating the aggressive behavior of various types of cancer cells. However, no studies have addressed hyaluronan with respect to osteosarcomas. In this investigation, the mRNA expression copy number of three mammalian hyaluronan synthases (HAS) was determined using competitive RT-PCR in the osteoblastic osteosarcoma cell line, MG-63. MG-63 are highly malignant osteosarcoma cells with an abundant hyaluronan-rich matrix. The results demonstrated that HAS-2 is the predominant HAS in MG-63. Accumulation of intracellular hyaluronan increased in association with the proliferative phase of these cells. The selective inhibition of HAS-2 mRNA in MG-63 cells by antisense phosphorothioate oligonucleotides resulted in reduced hyaluronan accumulation by these cells. As expected, the reduction in hyaluronan disrupted the assembly of cell-associated matrices. However, of most interest, coincident with the reduction in hyaluronan, there was a substantial decrease in cell proliferation, a decrease in cell motility and a decrease in cell invasiveness. These data suggest that hyaluronan synthesized by HAS-2 in MG-63 plays a crucial role in osteosarcoma cell proliferation, motility, and invasion

  20. Hydration dynamics of hyaluronan and dextran.

    Science.gov (United States)

    Hunger, Johannes; Bernecker, Anja; Bakker, Huib J; Bonn, Mischa; Richter, Ralf P

    2012-07-03

    Hyaluronan is a polysaccharide, which is ubiquitous in vertebrates and has been reported to be strongly hydrated in a biological environment. We study the hydration of hyaluronan in solution using the rotational dynamics of water as a probe. We measure these dynamics with polarization-resolved femtosecond-infrared and terahertz time-domain spectroscopies. Both experiments reveal that a subensemble of water molecules is slowed down in aqueous solutions of hyaluronan amounting to ∼15 water molecules per disaccharide unit. This quantity is consistent with what would be expected for the first hydration shell. Comparison of these results to the water dynamics in aqueous dextran solution, a structurally similar polysaccharide, yields remarkably similar results. This suggests that the observed interaction with water is a common feature for hydrophilic polysaccharides and is not specific to hyaluronan. Copyright © 2012 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  1. Hybrid Complexes of High and Low Molecular Weight Hyaluronans Highly Enhance HASCs Differentiation: Implication for Facial Bioremodelling

    Directory of Open Access Journals (Sweden)

    Antonietta Stellavato

    2017-11-01

    Full Text Available Background/Aims: Adipose-derived Stem Cells (ASCs are used in Regenerative Medicine, including fat grafting, recovery from local tissue ischemia and scar remodeling. The aim of this study was to evaluate hyaluronan based gel effects on ASCs differentiation and proliferation. Methods: Comparative analyses using high (H and low (L molecular weight hyaluronans (HA, hyaluronan hybrid cooperative complexes (HCCs, and high and medium cross-linked hyaluronan based dermal fillers were performed. Human ASCs were characterized by flow cytometry using CD90, CD34, CD105, CD29, CD31, CD45 and CD14 markers. Then, cells were treated for 7, 14 and 21 days with hyaluronans. Adipogenic differentiation was evaluated using Oil red-O staining and expression of leptin, PPAR-γ, LPL and adiponectin using qRT-PCR. Adiponectin was analyzed by immunofluorescence, PPAR-γ and adiponectin were analyzed using western blotting. ELISA assays for adiponectin and leptin were performed. Results: HCCs highly affected ASCs differentiation by up-regulating adipogenic genes and related proteins, that were also secreted in the culture medium. H-HA and L-HA induced a lower level of ASCs differentiation. Conclusion: HCCs-based formulations clearly enhance adipogenic differentiation and proliferation, when compared with linear HA and cross-linked hyaluronans. Injection of HCCs in subdermal fat compartment may recruit and differentiate stem cells in adipocytes, and considerably improving fat tissue renewal.

  2. Hyaluronan polymeric micelles for topical drug delivery

    Czech Academy of Sciences Publication Activity Database

    Šmejkalová, D.; Muthný, T.; Nešporová, K.; Hermannová, M.; Achbergerová, E.; Huerta-Angelesa, G.; Marek Svoboda, M.; Čepa, M.; Machalová, V.; Luptáková, Dominika; Velebný, V.

    2017-01-01

    Roč. 156, JAN 20 (2017), s. 86-96 ISSN 0144-8617 Institutional support: RVO:61388971 Keywords : Skin penetration * Polymeric micelle * Hyaluronan Subject RIV: CE - Biochemistry OBOR OECD: Biochemistry and molecular biology Impact factor: 4.811, year: 2016

  3. 18 month observational study on efficacy of intraarticular hyaluronic acid (Hylan G-F 20 injections under ultrasound guidance in hip osteoarthritis

    Directory of Open Access Journals (Sweden)

    Cristiano Padalino

    2011-09-01

    Full Text Available Objective: To evaluate the efficacy and the tolerability of viscosupplementation (VS with hyaluronic acid (Hylan GF 20 in a cohort of 36 patients affected by hip osteoarthritis through a 18 months follow-up. Methods: Viscosupplementation was performed with an anteriorsagittal approach, under ultrasound guidance. 36 patients were administered hyaluronic acid intraarticularly in the hip, with a unique injection of Hylan G-F20, which could be repeated after at least 3 months. Treatment efficacy was assessed by functional index WOMAC, pain evaluation on a visual analogue scale and NSAID consumption. All such parameters were recorded at the time of the first injection and then 3, 6, 9, 12 and 18 months later. Results: Statistically significant reduction of all parameters was observed three months after the injection, and was still maintained at the timepoints 6, 9, 12 and 18 months. No local side effects have been observed, nor systemic complications. Conclusions: Our data show that viscosupplementation is a promising approach for hip osteoarthritis, providing beneficial effects in a long-tern follow up. Yet, the topic deserves further and wider studies, so to define the number of injections to administer and suggest a fit interval between subsequent injections.

  4. Pleural tissue hyaluronan produced by postmortem ventilation in rabbits.

    Science.gov (United States)

    Wang, P M; Lai-Fook, S J

    2000-01-01

    We developed a method that used Alcian blue bound to hyaluronan to measure pleural hyaluronan in rabbits postmortem. Rabbits were killed, then ventilated with 21% O2--5% CO2--74% N2 for 3 h. The pleural liquid was removed by suction and 5 ml Alcian blue stock solution (0.33 mg/ml, 3.3 pH) was injected into each chest cavity. After 10 min, the Alcian blue solution was removed and the unbound Alcian blue solution (supernatant) separated by centrifugation and filtration. The supernatant transmissibility (T) was measured spectrophotometrically at 613 nm. Supernatant Alcian blue concentration (Cab) was obtained from a calibration curve of T versus dilutions of stock solution Cab. Alcian blue bound to pleural tissue hyaluronan was obtained by subtracting supernatant Cab from stock solution Cab. Pleural tissue hyaluronan was obtained from a calibration curve of hyaluronan versus Alcian blue bound to hyaluronan. Compared with control rabbits, pleural tissue hyaluronan (0.21 +/- 0.04 mg/kg) increased twofold, whereas pleural liquid volume decreased by 30% after 3 h of ventilation. Pleural effusions present 3 h postmortem without ventilation did not change pleural tissue hyaluronan from control values. Thus ventilation-induced pleural liquid shear stress, not increased filtration, was the stimulus for the increased hyaluronan produced from pleural mesothelial cells.

  5. Formation and properties of hyaluronan/nano Ag and hyaluronan-lecithin/nano Ag films.

    Science.gov (United States)

    Khachatryan, Gohar; Khachatryan, Karen; Grzyb, Jacek; Fiedorowicz, Maciej

    2016-10-20

    A facile and environmentally friendly method of the preparation of silver nanoparticles embedded in hyaluronan (Hyal/Ag) and hyaluronan-lecithin (Hyal-L/Ag) matrix was developed. Thin, elastic foils were prepared from gels by an in situ synthesis of Ag in an aqueous solution of sodium hyaluronate (Hyal), using aq. d-(+)-xylose solution as a reducing agent. The gels were applied to a clean, smooth, defatted Teflon surface and left for drying in the air. The dry foils were stored in a closed container. UV-vis spectroscopy, transmission electron microscopy (TEM) and Fourier transform infrared (FTIR) spectra confirmed formation of about 10nm ball-shaped Ag nanoparticles situated within the polysaccharide template. Thermal properties of the composites were characterized involving differential scanning calorimetry (DSC) and thermogravimetric (TGA) analyses, whereas molecular weights of polysaccharide chains of the matrix were estimated with the size exclusion chromatography coupled with multiangle laser light scattering and refractometric detectors (HPSEC-MALLS-RI). An increase in the molecular weight of the hyaluronate after generation of Ag nanoparticles was observed. The foils showed specific properties. The study confirmed that silver nanoparticles can be successfully prepared with environmentally friendly method, using hyaluronan as a stabilizing template. Hyaluronan and hyaluronan-lecithin matrices provide nanocrystals uniform in size and shape. The composites demonstrated a bacteriostatic activity. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Hyaluronan and calcium carbonate hybrid nanoparticles for colorectal cancer chemotherapy

    Science.gov (United States)

    Bai, Jinghui; Xu, Jian; Zhao, Jian; Zhang, Rui

    2017-09-01

    A hybrid drug delivery system (DDS) composed of hyaluronan and calcium carbonate (CC) was developed. By taking advantage of the tumor-targeting ability of hyaluronan and the drug-loading property of CC, the well-formed hyaluronan-CC nanoparticles were able to serve as a DDS targeting colorectal cancer with a decent drug loading content, which is beneficial in the chemotherapy of colorectal cancer. In this study, hyaluronan-CC nanoparticles smaller than 100 nm were successfully developed to load the wide-range anti-cancer drug adriamycin (Adr) to construct hyaluronan-CC/Adr nanoparticles. On the other hand, we also found that hyaluronan-CC/Adr nanoparticles can possibly increase the uptake ratio of Adr into HT29 colorectal cancer cells when compared with hyaluronan-free nanoparticles (CC/Adr) via the CD44 receptor-mediated endocytosis via competitive uptake and in vivo imaging assays. Note that both in vitro (CCK-8 assay on HT29 cells) and in vivo (anti-cancer assay on HT-29 tumor-bearing nude mice model) experiments revealed that hyaluronan-CC/Adr nanoparticles exhibited stronger anti-cancer activity than free Adr or CC/Adr nanoparticles with minimized toxic side effects and preferable cancer-suppression potential.

  7. Factors that influence serum hyaluronan levels in hemodialysis patients.

    Science.gov (United States)

    de Medina, M; Ashby, M; Diego, J; Pennell, J P; Hill, M; Schiff, E R; Perez, G O

    1999-01-01

    Serum hyaluronan levels are increased in dialysis patients. We evaluated several factors that influence serum hyaluronan levels in 184 patients on chronic hemodialysis (duration 2.3 +/- 2.3 [SD] years). The levels were higher than normal in the whole group and in a subgroup of 133 patients without chronic infection, liver disease, or rheumatoid arthritis (215 +/- 19 and 205 +/- 22 microg/L, respectively). There was a tendency for the levels to be higher in a subgroup of patients with hepatitis c virus (HCV) infection. There was no correlation between hyaluronan levels, alanine aminotransferase (ALT), and duration or dose of dialysis. A weak but highly significant negative correlation between serum albumin levels and serum hyaluronan and ferritin levels was seen. The data suggest that chronic inflammation may explain, at least in part, the increased hyaluronan levels found in chronic dialysis patients.

  8. Intra-Articular, Single-Shot Hylan G-F 20 Hyaluronic Acid Injection Compared with Corticosteroid in Knee Osteoarthritis: A Double-Blind, Randomized Controlled Trial.

    Science.gov (United States)

    Tammachote, Nattapol; Kanitnate, Supakit; Yakumpor, Thanasak; Panichkul, Phonthakorn

    2016-06-01

    The treatment of knee osteoarthritis with hyaluronic acid or corticosteroid injection has been widely used. The purpose of this study was to compare the efficacy of hyaluronic acid (hylan G-F 20) with triamcinolone acetonide as a single intra-articular injection for knee osteoarthritis. This study was a prospective, randomized, double-blind clinical trial. Participants with symptomatic knee osteoarthritis were recruited. They were randomized to receive a single-shot, intra-articular injection of either 6 mL of hylan G-F 20 or 6 mL of a solution comprising 1 mL of 40-mg triamcinolone acetonide and 5 mL of 1% lidocaine with epinephrine. The primary outcomes were knee pain severity, knee function, and range of motion at 6 months. Ninety-nine patients were assessed before injection and underwent a 6-month follow-up. Patients and evaluators were blinded. Multilevel regression models were used to estimate differences between the groups. At the 6-month follow-up, compared with patients who took hylan G-F 20, patients who took triamcinolone acetonide had similar improvement in knee pain, knee function, and range of motion. The difference in mean outcome scores between groups was, with regard to knee pain, a visual analog scale (VAS) score of 3 points (95% confidence interval [95% CI], -6 to 11 points); with regard to knee function, a modified Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score of 0 points (95% CI, -8 to 6 points); and, with regard to range of motion, flexion of -1° (95% CI, -5° to 2°) and extension of 0° (95% CI, -0.5° to 0.5°). However, patients who took triamcinolone acetonide had better pain improvement from 24 hours until 1 week after injection; the mean difference between groups with regard to the VAS score was 12 points (95% CI, 5 to 20 points; p = 0.002) at 24 hours and 9 points (95% CI, 1 to 15 points; p = 0.018) at 1 week. At 2 weeks after injection, patients who took triamcinolone acetonide also had better knee

  9. Human Milk Hyaluronan Enhances Innate Defense of the Intestinal Epithelium*

    Science.gov (United States)

    Hill, David R.; Rho, Hyunjin K.; Kessler, Sean P.; Amin, Ripal; Homer, Craig R.; McDonald, Christine; Cowman, Mary K.; de la Motte, Carol A.

    2013-01-01

    Breast-feeding is associated with enhanced protection from gastrointestinal disease in infants, mediated in part by an array of bioactive glycan components in milk that act through molecular mechanisms to inhibit enteric pathogen infection. Human milk contains hyaluronan (HA), a glycosaminoglycan polymer found in virtually all mammalian tissues. We have shown that synthetic HA of a specific size range promotes expression of antimicrobial peptides in intestinal epithelium. We hypothesize that hyaluronan from human milk also enhances innate antimicrobial defense. Here we define the concentration of HA in human milk during the first 6 months postpartum. Importantly, HA isolated from milk has a biological function. Treatment of HT-29 colonic epithelial cells with human milk HA at physiologic concentrations results in time- and dose-dependent induction of the antimicrobial peptide human β-defensin 2 and is abrogated by digestion of milk HA with a specific hyaluronidase. Milk HA induction of human β-defensin 2 expression is also reduced in the presence of a CD44-blocking antibody and is associated with a specific increase in ERK1/2 phosphorylation, suggesting a role for the HA receptor CD44. Furthermore, oral administration of human milk-derived HA to adult, wild-type mice results in induction of the murine Hβ D2 ortholog in intestinal mucosa and is dependent upon both TLR4 and CD44 in vivo. Finally, treatment of cultured colonic epithelial cells with human milk HA enhances resistance to infection by the enteric pathogen Salmonella typhimurium. Together, our observations suggest that maternally provided HA stimulates protective antimicrobial defense in the newborn. PMID:23950179

  10. Hyaluronan in vaginal secretions: association with recurrent vulvovaginal candidiasis.

    Science.gov (United States)

    Lev-Sagie, Ahinoam; Nyirjesy, Paul; Tarangelo, Nicholas; Bongiovanni, Ann Marie; Bayer, Cynthia; Linhares, Iara M; Giraldo, Paulo C; Ledger, William J; Witkin, Steven S

    2009-08-01

    We evaluated whether vaginal concentrations of hyaluronan were altered in women with recurrent vulvovaginal candidiasis (RVVC). Lavage samples from 17 women with acute RVVC, 27 women who were receiving a maintenance antifungal regimen, and 24 control women were tested for hyaluronan and interleukin (IL)-6, IL-12, and IL-23 by enzyme-linked immunosorbent assay. Median vaginal hyaluronan concentrations were 33.8 ng/mL (range, 21.6-66.3 ng/mL) in women with acute RVVC, 15.0 ng/mL (range, 11.2-50.6 ng/mL) in women who were receiving maintenance therapy, and 4.2 ng/mL (range, 3.6-12.0 ng/mL) in control subjects (P vaginal hyaluronan concentration was 27.4 ng/mL (range, 15.4-37.7 ng/mL) when Candida was detected by microscopy and 9.5 ng/mL (range, 7.7-14.6 ng/mL) in microscopy-negative cases (P = .0354). Elevated hyaluronan levels were associated with itching plus burning (40.7 ng/mL) or itching plus discharge (42.1 ng/mL), as opposed to itching only (6.2 ng/mL; P = .0152). Hyaluronan and IL-6 levels were correlated (P = .0009). Hyaluronan release is a component of the host response to a candidal infection and may contribute to symptoms.

  11. Importance of hyaluronan biosynthesis and degradation in cell differentiation and tumor formation

    Directory of Open Access Journals (Sweden)

    Heldin P.

    2003-01-01

    Full Text Available Hyaluronan is an important connective tissue glycosaminoglycan. Elevated hyaluronan biosynthesis is a common feature during tissue remodeling under both physiological and pathological conditions. Through its interactions with hyaladherins, hyaluronan affects several cellular functions such as cell migration and differentiation. The activities of hyaluronan-synthesizing and -degrading enzymes have been shown to be regulated in response to growth factors. During tumor progression hyaluronan stimulates tumor cell growth and invasiveness. Thus, elucidation of the molecular mechanisms which regulate the activities of hyaluronan-synthesizing and -degrading enzymes during tumor progression is highly desired.

  12. Effect of molecular weight and concentration of hyaluronan on cell proliferation and osteogenic differentiation in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Ningbo, E-mail: curl-zhao@163.com; Wang, Xin, E-mail: 394041230@qq.com; Qin, Lei, E-mail: qinlei30@126.com; Guo, Zhengze, E-mail: zhzeguo@163.com; Li, Dehua, E-mail: lidehuafmmu@163.com

    2015-09-25

    Hyaluronan (HA), the simplest glycosaminoglycan and a major component of the extracellular matrix, exists in various tissues. It is involved in some critical biological procedures, including cellular signaling, cell adhesion and proliferation, and cell differentiation. The effect of molecular weight (MW) and concentration of HA on cell proliferation and differentiation was controversial. In this study, we investigated the effect of MW and concentration of HA on the proliferation and osteogenic differentiation of rabbit bone marrow-derived stem cells in vitro. Results showed that high MW HA decreased the cell adhesion rate in a concentration-dependant manner. The cell adhesion rate was decreased by increasing MW of HA. Cell proliferation was significantly enhanced by low MW HA (P < 0.05). The factorial analysis indicated that MW and concentration had an interactive effect on the cell adhesion rate and cell proliferation (P < 0.05). High MW HA increased the mRNA expressions of ALP, RUNX-2 and OCN. The higher the MW was, the higher the mRNA expressions were. The factorial analysis indicated that MW and concentration had an interactive effect on ALP mRNA expression (P < 0.05). HA of higher MW and higher concentration promoted bone formation. These findings provide some useful information in understanding the mechanism underlying the effect of MW and concentration of HA on cell proliferation and differentiation. - Highlights: • Effect of hyaluronan on cell proliferation and differentiation is evaluated in vitro. • Hyaluronan of low molecular weight increases cell proliferation. • Hyaluronan of high molecular weight promotes cell osteogenic differentiation. • Molecular weight and concentration of hyaluronan show interactive effect.

  13. Lubrication synergy: Mixture of hyaluronan and dipalmitoylphosphatidylcholine (DPPC) vesicles

    DEFF Research Database (Denmark)

    Raj, Akanksha; Wang, Min; Zander, Thomas

    2017-01-01

    consisting of non-homogeneous phospholipid bilayer with hyaluronan/DPPC aggregates on top. The presence of these aggregates generates a long-range repulsive surface force as two such surfaces are brought together. However, the aggregates are easily deformed, partly rearranged into multilayer structures......Phospholipids and hyaluronan have been implied to fulfil important roles in synovial joint lubrication. Since both components are present in synovial fluid, self-assembly structures formed by them should also be present. We demonstrate by small angle X-ray scattering that hyaluronan associates...... with the outer shell of dipalmitoylphophatidylcholine (DPPC) vesicles in bulk solution. Further, we follow adsorption to silica from mixed hyaluronan/DPPC vesicle solution by Quartz Crystal Microbalance with Dissipation measurements. Atomic Force Microscope imaging visualises the adsorbed layer structure...

  14. Hyaluronan-lecithin foils and their properties

    International Nuclear Information System (INIS)

    BiaIopiotrowicz, Tomasz; Janczuk, BronisIaw; Fiedorowicz, Maciej; Khachatryan, Gohar; Tomasik, Piotr; Bakos, Dusan

    2006-01-01

    Thin, elastic foils of good resistance to the air exposure, patented as wound healing aids, were prepared by evaporation of a blend of lecithin (L) and sodium hyaluronan (H) taken under varying proportions. The contact angle for water, glycerol, formamide, ethylene glycol and diiodomethane, was determined for these foils. The contact angle was correlated against the H:L foil composition. For all liquids but formamide the highest contact angle was noted for the H:L = 2:1 (g g -1 ) ratio. The contact angles provided estimation of the work of adhesion. At the same L:H ratio the work of adhesion was the lowest. It was suggested that lecithin cross-linked hyaluronan. Since the work of adhesion of the studied liquids was similar to that of diiodomethane, it could be concluded that almost all functional groups on the foil surface were completely blocked. Perhaps, at H:L = 2:1 (g g -1 ) a stoichiometric complex of hyaluronic acid with lecithin was formed, and polar functional groups from both reagents were involved. Foils seem to be electrostatic complexes of H with L. Foils with the H:L equal to 2:1 exhibited specific properties confirmed by the IR reflectance spectra of the foils. The thermogravimetry (TG/DTG) also revealed unique thermal behaviour confirming other specific properties of the foil of this composition. For the same ratio a thorough inspection of the scanning electron micrographs (SEM) revealed few irregularly distributed perforations of 1-2 μm in diameter seen as black points, which can be recognized as pores. Properties of the foils determined in the contact angle measurements are nicely backed by the results from thermogravimetric and scanning electron microscopic studies

  15. Cytocompatible in situ forming chitosan/hyaluronan hydrogels via a metal-free click chemistry for soft tissue engineering.

    Science.gov (United States)

    Fan, Ming; Ma, Ye; Mao, Jiahui; Zhang, Ziwei; Tan, Huaping

    2015-07-01

    Injectable hydrogels are important cell scaffolding materials for tissue engineering and regenerative medicine. Here, we report a new class of biocompatible and biodegradable polysaccharide hydrogels derived from chitosan and hyaluronan via a metal-free click chemistry, without the addition of copper catalyst. For the metal-free click reaction, chitosan and hyaluronan were modified with oxanorbornadiene (OB) and 11-azido-3,6,9-trioxaundecan-1-amine (AA), respectively. The gelation is attributed to the triazole ring formation between OB and azido groups of polysaccharide derivatives. The molecular structures were verified by FT-IR spectroscopy and elemental analysis, giving substitution degrees of 58% and 47% for chitosan-OB and hyaluronan-AA, respectively. The in vitro gelation, morphologies, equilibrium swelling, compressive modulus and degradation of the composite hydrogels were examined. The potential of the metal-free hydrogel as a cell scaffold was demonstrated by encapsulation of human adipose-derived stem cells (ASCs) within the gel matrix in vitro. Cell culture showed that this metal-free hydrogel could support survival and proliferation of ASCs. A preliminary in vivo study demonstrated the usefulness of the hydrogel as an injectable scaffold for adipose tissue engineering. These characteristics provide a potential opportunity to use the metal-free click chemistry in preparation of biocompatible hydrogels for soft tissue engineering applications. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  16. Modulation of hyaluronan synthase activity in cellular membrane fractions.

    Science.gov (United States)

    Vigetti, Davide; Genasetti, Anna; Karousou, Evgenia; Viola, Manuela; Clerici, Moira; Bartolini, Barbara; Moretto, Paola; De Luca, Giancarlo; Hascall, Vincent C; Passi, Alberto

    2009-10-30

    Hyaluronan (HA), the only non-sulfated glycosaminoglycan, is involved in morphogenesis, wound healing, inflammation, angiogenesis, and cancer. In mammals, HA is synthesized by three homologous HA synthases, HAS1, HAS2, and HAS3, that polymerize the HA chain using UDP-glucuronic acid and UDP-N-acetylglucosamine as precursors. Since the amount of HA is critical in several pathophysiological conditions, we developed a non-radioactive assay for measuring the activity of HA synthases (HASs) in eukaryotic cells and addressed the question of HAS activity during intracellular protein trafficking. We prepared three cellular fractions: plasma membrane, cytosol (containing membrane proteins mainly from the endoplasmic reticulum and Golgi), and nuclei. After incubation with UDP-sugar precursors, newly synthesized HA was quantified by polyacrylamide gel electrophoresis of fluorophore-labeled saccharides and high performance liquid chromatography. This new method measured HAS activity not only in the plasma membrane fraction but also in the cytosolic membranes. This new technique was used to evaluate the effects of 4-methylumbeliferone, phorbol 12-myristate 13-acetate, interleukin 1beta, platelet-derived growth factor BB, and tunicamycin on HAS activities. We found that HAS activity can be modulated by post-translational modification, such as phosphorylation and N-glycosylation. Interestingly, we detected a significant increase in HAS activity in the cytosolic membrane fraction after tunicamycin treatment. Since this compound is known to induce HA cable structures, this result links HAS activity alteration with the capability of the cell to promote HA cable formation.

  17. Altered expression of versican and hyaluronan in melanocytic tumors of dogs.

    Science.gov (United States)

    Docampo, María-José; Rabanal, Rosa M; Miquel-Serra, Laia; Hernández, Daniel; Domenzain, Clelia; Bassols, Anna

    2007-12-01

    To analyze the expression of versican and hyaluronan in melanocytomas and malignant melanomas of dogs, to correlate their expression with expression of the hyaluronan receptor CD44, and to identify enzymes responsible for the synthesis and degradation of hyaluronan in canine dermal fibroblasts and canine melanoma cell lines. 35 biopsy specimens from melanocytic tumors of dogs, canine primary dermal fibroblasts, and 3 canine melanoma cell lines. Versican, hyaluronan, and CD44 were detected in tumor samples by use of histochemical or immunohistochemical methods. Expression of hyaluronan-metabolizing enzymes was analyzed with a reverse transcriptase-PCR assay. Versican was found only in some hair follicles and around some blood vessels in normal canine skin, whereas hyaluronan was primarily found within the dermis. Hyaluronan was found in connective tissue of the oral mucosa. Versican and, to a lesser extent, hyaluronan were significantly overexpressed in malignant melanomas, compared with expression in melanocytomas. No significant difference was found between malignant tumors from oral or cutaneous origin. The expression of both molecules was correlated, but hyaluronan had a more extensive distribution than versican. Versican and hyaluronan were mainly associated with tumor stroma. Canine fibroblasts and melanoma cell lines expressed hyaluronan synthase 2 and 3 (but not 1) and hyaluronidase 1 and 2. Versican may be useful as a diagnostic marker for melanocytic tumors in dogs. Knowledge of the enzymes involved in hyaluronan metabolism could reveal new potential therapeutic targets.

  18. Provisional matrix: A role for versican and hyaluronan.

    Science.gov (United States)

    Wight, Thomas N

    2017-07-01

    Hyaluronan and versican are extracellular matrix (ECM) components that are enriched in the provisional matrices that form during the early stages of development and disease. These two molecules interact to create pericellular "coats" and "open space" that facilitate cell sorting, proliferation, migration, and survival. Such complexes also impact the recruitment of leukocytes during development and in the early stages of disease. Once thought to be inert components of the ECM that help hold cells together, it is now quite clear that they play important roles in controlling cell phenotype, shaping tissue response to injury and maintaining tissue homeostasis. Conversion of hyaluronan-/versican-enriched provisional matrix to collagen-rich matrix is a "hallmark" of tissue fibrosis. Targeting the hyaluronan and versican content of provisional matrices in a variety of diseases including, cardiovascular disease and cancer, is becoming an attractive strategy for intervention. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Hyaluronidase and hyaluronan in insect venom allergy.

    Science.gov (United States)

    King, Te Piao; Wittkowski, Knut M

    2011-01-01

    Insect venoms contain an allergen hyaluronidase that catalyzes the hydrolysis of hyaluronan (HA), a polymer of disaccharide GlcUA-GlcNAc in skin. HAs depending on their size have variable function in inflammation and immunity. This paper reports on whether hyaluronidase, HA polymers and oligomers can promote antibody response in mice. HA oligomers (8- to 50-mer; 3-20 kDa) were obtained by bee venom hyaluronidase digestion of HA polymers (750- to 5,000-mer; 300-2,000 kDa). Antibody responses in mice were compared following 3 biweekly subcutaneous injection of ovalbumin (OVA) with or without test adjuvant. OVA-specific IgG1 levels were approximately 2 times higher in BALB/c and C3H/HeJ mice receiving OVA and HA oligomer or polymer than those treated with OVA alone, and no increase in total IgE level was observed. In C57Bl/6 mice, observed increases in IgG1 and IgE were 3.5- and 1.7-fold, respectively, for the oligomer and 16- and 5-fold (p Insect venoms also have cytolytic peptides and phospholipases with inflammatory roles. These activities found in mice may contribute to venom allergenicity in susceptible people. Copyright © 2011 S. Karger AG, Basel.

  20. 4-Methylumbelliferone inhibits hyaluronan synthesis by depletion of cellular UDP-glucuronic acid and downregulation of hyaluronan synthase 2 and 3

    International Nuclear Information System (INIS)

    Kultti, Anne; Pasonen-Seppaenen, Sanna; Jauhiainen, Marjo; Rilla, Kirsi J.; Kaernae, Riikka; Pyoeriae, Emma; Tammi, Raija H.; Tammi, Markku I.

    2009-01-01

    Hyaluronan accumulation on cancer cells and their surrounding stroma predicts an unfavourable disease outcome, suggesting that hyaluronan enhances tumor growth and spreading. 4-Methylumbelliferone (4-MU) inhibits hyaluronan synthesis and retards cancer spreading in experimental animals through mechanisms not fully understood. These mechanisms were studied in A2058 melanoma cells, MCF-7 and MDA-MB-361 breast, SKOV-3 ovarian and UT-SCC118 squamous carcinoma cells by analysing hyaluronan synthesis, UDP-glucuronic acid (UDP-GlcUA) content, and hyaluronan synthase (HAS) mRNA levels. The maximal inhibition in hyaluronan synthesis ranged 22-80% in the cell lines tested. Active glucuronidation of 4-MU produced large quantities of 4-MU-glucuronide, depleting the cellular UDP-GlcUA pool. The maximal reduction varied between 38 and 95%. 4-MU also downregulated HAS mRNA levels: HAS3 was 84-60% lower in MDA-MB-361, A2058 and SKOV-3 cells. HAS2 was the major isoenzyme in MCF-7 cells and lowered by 81%, similar to 88% in A2058 cells. These data indicate that both HAS substrate and HAS2 and/or HAS3 mRNA are targeted by 4-MU. Despite different target point sensitivities, the reduction of hyaluronan caused by 4-MU was associated with a significant inhibition of cell migration, proliferation and invasion, supporting the importance of hyaluronan synthesis in cancer, and the therapeutic potential of hyaluronan synthesis inhibition.

  1. 4-Methylumbelliferone inhibits hyaluronan synthesis by depletion of cellular UDP-glucuronic acid and downregulation of hyaluronan synthase 2 and 3

    Energy Technology Data Exchange (ETDEWEB)

    Kultti, Anne, E-mail: anne.kultti@uku.fi [Institute of Biomedicine, Anatomy, University of Kuopio, P.O.B. 1627, FIN-70211 Kuopio (Finland); Pasonen-Seppaenen, Sanna [Institute of Biomedicine, Anatomy, University of Kuopio, P.O.B. 1627, FIN-70211 Kuopio (Finland); Jauhiainen, Marjo [Department of Pharmaceutical Chemistry, University of Kuopio, FIN-70211 Kuopio (Finland); Rilla, Kirsi J.; Kaernae, Riikka; Pyoeriae, Emma; Tammi, Raija H.; Tammi, Markku I. [Institute of Biomedicine, Anatomy, University of Kuopio, P.O.B. 1627, FIN-70211 Kuopio (Finland)

    2009-07-01

    Hyaluronan accumulation on cancer cells and their surrounding stroma predicts an unfavourable disease outcome, suggesting that hyaluronan enhances tumor growth and spreading. 4-Methylumbelliferone (4-MU) inhibits hyaluronan synthesis and retards cancer spreading in experimental animals through mechanisms not fully understood. These mechanisms were studied in A2058 melanoma cells, MCF-7 and MDA-MB-361 breast, SKOV-3 ovarian and UT-SCC118 squamous carcinoma cells by analysing hyaluronan synthesis, UDP-glucuronic acid (UDP-GlcUA) content, and hyaluronan synthase (HAS) mRNA levels. The maximal inhibition in hyaluronan synthesis ranged 22-80% in the cell lines tested. Active glucuronidation of 4-MU produced large quantities of 4-MU-glucuronide, depleting the cellular UDP-GlcUA pool. The maximal reduction varied between 38 and 95%. 4-MU also downregulated HAS mRNA levels: HAS3 was 84-60% lower in MDA-MB-361, A2058 and SKOV-3 cells. HAS2 was the major isoenzyme in MCF-7 cells and lowered by 81%, similar to 88% in A2058 cells. These data indicate that both HAS substrate and HAS2 and/or HAS3 mRNA are targeted by 4-MU. Despite different target point sensitivities, the reduction of hyaluronan caused by 4-MU was associated with a significant inhibition of cell migration, proliferation and invasion, supporting the importance of hyaluronan synthesis in cancer, and the therapeutic potential of hyaluronan synthesis inhibition.

  2. Carboxymethyl Hyaluronan-Stabilized Nanoparticles for Anticancer Drug Delivery.

    Science.gov (United States)

    Woodman, Jessica L; Suh, Min Sung; Zhang, Jianxing; Kondaveeti, Yuvabharath; Burgess, Diane J; White, Bruce A; Prestwich, Glenn D; Kuhn, Liisa T

    2015-01-01

    Carboxymethyl hyaluronic acid (CMHA) is a semisynthetic derivative of HA that is recognized by HA binding proteins but contains an additional carboxylic acid on some of the 6-hydroxyl groups of the N-acetyl glucosamine sugar units. These studies tested the ability of CMHA to stabilize the formation of calcium phosphate nanoparticles and evaluated their potential to target therapy resistant, CD44(+)/CD24(-/low) human breast cancer cells (BT-474EMT). CMHA stabilized particles (nCaP(CMHA)) were loaded with the chemotherapy drug cis-diamminedichloroplatinum(II) (CDDP) to form nCaP(CMHA)CDDP. nCaP(CMHA)CDDP was determined to be poorly crystalline hydroxyapatite, 200 nm in diameter with a -43 mV zeta potential. nCaP(CMHA)CDDP exhibited a two-day burst release of CDDP that tapered resulting in 86% release by 7 days. Surface plasmon resonance showed that nCaP(CMHA)CDDP binds to CD44, but less effectively than CMHA or hyaluronan. nCaP(CMHA-AF488) was taken up by CD44(+)/CD24(-) BT-474EMT breast cancer cells within 18 hours. nCaP(CMHA)CDDP was as cytotoxic as free CDDP against the BT-474EMT cells. Subcutaneous BT-474EMT tumors were more reproducibly inhibited by a near tumor dose of 2.8 mg/kg CDDP than a 7 mg/kg dose nCaP(CMHA)CDDP. This was likely due to a lack of distribution of nCaP(CMHA)CDDP throughout the dense tumor tissue that limited drug diffusion.

  3. Quantification and characterization of enzymatically produced hyaluronan with fluorophore-assisted carbohydrate electrophoresis.

    Science.gov (United States)

    Kooy, Floor K; Ma, Muyuan; Beeftink, Hendrik H; Eggink, Gerrit; Tramper, Johannes; Boeriu, Carmen G

    2009-01-15

    Hyaluronan (HA) is a polysaccharide with high-potential medical applications, depending on the chain length and the chain length distribution. Special interest goes to homogeneous HA oligosaccharides, which can be enzymatically produced using Pasteurella multocida hyaluronan synthase (PmHAS). We have developed a sensitive, simple, and fast method, based on fluorophore-assisted carbohydrate electrophoresis (FACE), for characterization and quantification of polymerization products. A chromatographic pure fluorescent template was synthesized from HA tetrasaccharide (HA4) and 2-aminobenzoic acid. HA4-fluor and HA4 were used as template for PmHAS-mediated polymerization of nucleotide sugars. All products, fluorescent and nonfluorescent, were analyzed with gel electrophoresis and quantified using lane densitometry. Comparison of HA4- and HA4-fluor-derived polymers showed that the fluorophore did not negatively influence the PmHAS-mediated polymerization. Only even-numbered oligosaccharide products were observed using HA4-fluor or HA4 as template. The fluorophore intensity was linearly related to its concentration, and the limit of detection was determined to be 7.4pmol per product band. With this assay, we can now differentiate oligosaccharides of size range DP2 (degree of polymerization 2) to approximately DP400, monitor the progress of polymerization reactions, and measure subtle differences in polymerization rate. Quantifying polymerization products enables us to study the influence of experimental conditions on HA synthesis.

  4. Removal rate of ( sup 3 H)hyaluronan injected subcutaneously in rabbits

    Energy Technology Data Exchange (ETDEWEB)

    Reed, R.K.; Laurent, U.B.; Fraser, J.R.; Laurent, T.C. (Univ. of Bergen (Norway))

    1990-08-01

    Hyaluronan is an important constituent of the extracellular matrix in skin, and recent studies suggest that there is a pool of easily removable (free) hyaluronan drained by lymph. The removal rate of free hyaluronan in skin was measured from the elimination of ({sup 3}H)hyaluronan, injected subcutaneously in 13 rabbits. The removal of radioactivity was determined from appearance of {sup 3}H in plasma. During the first 24 h after injection, 10-87% of the tracer entered blood, less in injectates with high concentrations of hyaluronan. The removal was monoexponential with a half-life of 0.5-1 day when concentration of hyaluronan was 5 mg/ml or less. When hyaluronan concentration was 10 mg/ml or higher, the removal was slow for about 24 h and then became similar to that in experiments with low hyaluronan concentration. Free hyaluronan at physiological concentrations is thus turned over with the same rate as serum albumin, supporting the concept that hyaluronan is removed essentially by lymph flow to be degraded in lymph nodes and liver.

  5. Removal rate of [3H]hyaluronan injected subcutaneously in rabbits

    International Nuclear Information System (INIS)

    Reed, R.K.; Laurent, U.B.; Fraser, J.R.; Laurent, T.C.

    1990-01-01

    Hyaluronan is an important constituent of the extracellular matrix in skin, and recent studies suggest that there is a pool of easily removable (free) hyaluronan drained by lymph. The removal rate of free hyaluronan in skin was measured from the elimination of [ 3 H]hyaluronan, injected subcutaneously in 13 rabbits. The removal of radioactivity was determined from appearance of 3 H in plasma. During the first 24 h after injection, 10-87% of the tracer entered blood, less in injectates with high concentrations of hyaluronan. The removal was monoexponential with a half-life of 0.5-1 day when concentration of hyaluronan was 5 mg/ml or less. When hyaluronan concentration was 10 mg/ml or higher, the removal was slow for about 24 h and then became similar to that in experiments with low hyaluronan concentration. Free hyaluronan at physiological concentrations is thus turned over with the same rate as serum albumin, supporting the concept that hyaluronan is removed essentially by lymph flow to be degraded in lymph nodes and liver

  6. Atomistic fingerprint of hyaluronan-CD44 binding

    DEFF Research Database (Denmark)

    Vuorio, Joni; Vattulainen, Ilpo; Martinez-Seara, Hector

    2017-01-01

    that hyaluronan can bind CD44 with three topographically different binding modes that in unison define an interaction fingerprint, thus providing a plausible explanation for the disagreement between the earlier studies. Our results confirm that the known crystallographic mode is the strongest of the three binding...

  7. Hyaluronan minimizes effects of UV irradiation on human keratinocytes

    Czech Academy of Sciences Publication Activity Database

    Hašová, M.; Crhák, Tomáš; Šafaříková, Barbora; Dvořáková, J.; Muthný, T.; Velebný, V.; Kubala, Lukáš

    2011-01-01

    Roč. 303, č. 4 (2011), s. 277-284 ISSN 0340-3696 R&D Projects: GA ČR(CZ) GA305/08/1704 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : hyaluronan * keratinocyte * ultraviolet light Subject RIV: BO - Biophysics Impact factor: 2.279, year: 2011

  8. The effect of different molecular weight hyaluronan on macrophage physiology

    Czech Academy of Sciences Publication Activity Database

    Krejčová, Daniela; Pekarová, Michaela; Šafránková, B.; Kubala, Lukáš

    2009-01-01

    Roč. 30, č. 1 (2009), s. 106-111 ISSN 0172-780X R&D Projects: GA ČR(CZ) GA305/08/1704 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : inflammation * phagocytes * hyaluronan Subject RIV: BO - Biophysics Impact factor: 1.047, year: 2009

  9. Hypochlorite-mediated fragmentation of hyaluronan, chondroitin sulfates, and related N-acetyl glycosamines

    DEFF Research Database (Denmark)

    Rees, Martin D; Hawkins, Clare Louise; Davies, Michael Jonathan

    2003-01-01

    Myeloperoxidase released from activated phagocytes reacts with H(2)O(2) in the presence of chloride ions to give hypochlorous acid. This oxidant has been implicated in the fragmentation of glycosaminoglycans, such as hyaluronan and chondroitin sulfates. In this study it is shown that reaction...... processes. In the case of glycosaminoglycan-derived amidyl radicals, evidence has been obtained in studies with model glycosides that these radicals undergo rapid intramolecular abstraction reactions to give carbon-centered radicals at C-2 on the N-acetyl glycosamine rings (via a 1,2-hydrogen atom shift......) and at C-4 on the neighboring uronic acid residues (via 1,5-hydrogen atom shifts). The C-4 carbon-centered radicals, and analogous species derived from model glycosides, undergo pH-independent beta-scission reactions that result in glycosidic bond cleavage. With N-acetyl glucosamine C-1 alkyl glycosides...

  10. Study of interactions between hyaluronan and cationic surfactants by means of calorimetry, turbidimetry, potentiometry and conductometry.

    Science.gov (United States)

    Krouská, J; Pekař, M; Klučáková, M; Šarac, B; Bešter-Rogač, M

    2017-02-10

    The thermodynamics of the micelle formation of the cationic surfactants tetradecyltrimethylammonium bromide (TTAB) and cetyltrimethylammonium bromide (CTAB) with and without the addition of hyaluronan of two molecular weights was studied in aqueous solution by titration calorimetry. Macroscopic phase separation, which was detected by calorimetry and also by conductometry, occurs when charges on the surfactant and hyaluronan are balanced. In contrast, turbidimetry and potentiometry showed hyaluronan-surfactant interactions at very low surfactant concentrations. The observed differences between systems prepared with CTAB and TTAB indicate that besides the electrostatic interactions, which probably predominate, hydrophobic effects also play a significant role in hyaluronan interactions with cationic surfactants. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Modulation of hyaluronan synthase activity in cellular membrane fractions

    OpenAIRE

    Vigetti, Davide; Genasetti, A; Karousou, Evgenia; Viola, Manuela; Clerici, M; Bartolini, B; Moretto, Paola; DE LUCA, Giancarlo; Hascall, Vc; Passi, Alberto

    2009-01-01

    Hyaluronan (HA), the only non-sulfated glycosaminoglycan, is involved in morphogenesis, wound healing, inflammation, angiogenesis, and cancer. In mammals, HA is synthesized by three homologous HA synthases, HAS1, HAS2, and HAS3, that polymerize the HA chain using UDP-glucuronic acid and UDP-N-acetylglucosamine as precursors. Since the amount of HA is critical in several pathophysiological conditions, we developed a non-radioactive assay for measuring the activity of HA synthases (HASs) in euk...

  12. Quantification and characterization of enzymatically produced hyaluronan with fluorophore-assisted carbohydrate electrophoresis

    NARCIS (Netherlands)

    Kooy, F.K.; Muyuan Ma,; Beeftink, H.H.; Eggink, G.; Tramper, J.; Boeriu, C.G.

    2009-01-01

    Hyaluronan (HA) is a polysaccharide with high-potential medical applications, depending on the chain length and the chain length distribution. Special interest goes to homogeneous HA oligosaccharides, which can be enzymatically produced using Pasteurella multocida hyaluronan synthase (PmHAS). We

  13. Expression of Hyaluronan Synthases (HAS1–3) and Hyaluronidases (HYAL1–2) in Serous Ovarian Carcinomas: Inverse Correlation between HYAL1 and Hyaluronan Content

    International Nuclear Information System (INIS)

    Nykopp, Timo K; Anttila, Maarit; Rilla, Kirsi; Sironen, Reijo; Tammi, Markku I; Tammi, Raija H; Hämäläinen, Kirsi; Heikkinen, Anna-Mari; Komulainen, Marja; Kosma, Veli-Matti

    2009-01-01

    Hyaluronan, a tumor promoting extracellular matrix polysaccharide, is elevated in malignant epithelial ovarian tumors, and associates with an unfavorable prognosis. To explore possible contributors to the accumulation of hyaluronan, we examined the expression of hyaluronan synthases (HAS1, HAS2 and HAS3) and hyaluronidases (HYAL1 and HYAL2), correlated with hyaluronidase enzyme activity hyaluronan content and HAS1–3 immunoreactivity. Normal ovaries (n = 5) and 34 serous epithelial ovarian tumors, divided into 4 groups: malignant grades 1+2 (n = 10); malignant grade 3 (n = 10); borderline (n = 4) and benign epithelial tumors (n = 10), were analyzed for mRNA by real-time RT-PCR and compared to hyaluronidase activity, hyaluronan staining, and HAS1–3 immunoreactivity in tissue sections of the same specimens. The levels of HAS2 and HAS3 mRNA (HAS1 was low or absent), were not consistently increased in the carcinomas, and were not significantly correlated with HAS protein or hyaluronan accumulation in individual samples. Instead, the median of HYAL1 mRNA level was 69% lower in grade 3 serous ovarian cancers compared to normal ovaries (P = 0.01). The expression of HYAL1, but not HYAL2, significantly correlated with the enzymatic activity of tissue hyaluronidases (r = 0.5; P = 0.006). An inverse correlation was noted between HYAL1 mRNA and the intensity of hyaluronan staining of the corresponding tissue sections (r = -0.4; P = 0.025). The results indicate that in serous epithelial ovarian malignancies HAS expression is not consistently elevated but HYAL1 expression is significantly reduced and correlates with the accumulation of hyaluronan. (233 words)

  14. Hyaluronan synthase 3 (HAS3) overexpression downregulates MV3 melanoma cell proliferation, migration and adhesion

    International Nuclear Information System (INIS)

    Takabe, Piia; Bart, Geneviève; Ropponen, Antti; Rilla, Kirsi; Tammi, Markku; Tammi, Raija; Pasonen-Seppänen, Sanna

    2015-01-01

    Malignant skin melanoma is one of the most deadly human cancers. Extracellular matrix (ECM) influences the growth of malignant tumors by modulating tumor cells adhesion and migration. Hyaluronan is an essential component of the ECM, and its amount is altered in many tumors, suggesting an important role for hyaluronan in tumorigenesis. Nonetheless its role in melanomagenesis is not understood. In this study we produced a MV3 melanoma cell line with inducible expression of the hyaluronan synthase 3 (HAS3) and studied its effect on the behavior of the melanoma cells. HAS3 overexpression expanded the cell surface hyaluronan coat and decreased melanoma cell adhesion, migration and proliferation by cell cycle arrest at G1/G0. Melanoma cell migration was restored by removal of cell surface hyaluronan by Streptomyces hyaluronidase and by receptor blocking with hyaluronan oligosaccharides, while the effect on cell proliferation was receptor independent. Overexpression of HAS3 decreased ERK1/2 phosphorylation suggesting that inhibition of MAP-kinase signaling was responsible for these suppressive effects on the malignant phenotype of MV3 melanoma cells. - Highlights: • Inducible HAS3-MV3 melanoma cell line was generated using Lentiviral transduction. • HAS3 overexpression inhibits MV3 cell migration via hyaluronan–receptor interaction. • HAS3 overexpression decreases MV3 melanoma cell proliferation and adhesion. • ERK1/2 phosphorylation is downregulated by 50% in HAS3 overexpressing cells. • The results suggest that hyaluronan has anti-cancer like effects in melanoma

  15. Hyaluronan synthase 3 (HAS3) overexpression downregulates MV3 melanoma cell proliferation, migration and adhesion

    Energy Technology Data Exchange (ETDEWEB)

    Takabe, Piia, E-mail: piia.takabe@uef.fi [University of Eastern Finland, Institute of Biomedicine, 70211 Kuopio (Finland); Bart, Geneviève [University of Eastern Finland, Institute of Biomedicine, 70211 Kuopio (Finland); Ropponen, Antti [University of Eastern Finland, Institute of Clinical Medicine, 70211 Kuopio (Finland); Rilla, Kirsi; Tammi, Markku; Tammi, Raija; Pasonen-Seppänen, Sanna [University of Eastern Finland, Institute of Biomedicine, 70211 Kuopio (Finland)

    2015-09-10

    Malignant skin melanoma is one of the most deadly human cancers. Extracellular matrix (ECM) influences the growth of malignant tumors by modulating tumor cells adhesion and migration. Hyaluronan is an essential component of the ECM, and its amount is altered in many tumors, suggesting an important role for hyaluronan in tumorigenesis. Nonetheless its role in melanomagenesis is not understood. In this study we produced a MV3 melanoma cell line with inducible expression of the hyaluronan synthase 3 (HAS3) and studied its effect on the behavior of the melanoma cells. HAS3 overexpression expanded the cell surface hyaluronan coat and decreased melanoma cell adhesion, migration and proliferation by cell cycle arrest at G1/G0. Melanoma cell migration was restored by removal of cell surface hyaluronan by Streptomyces hyaluronidase and by receptor blocking with hyaluronan oligosaccharides, while the effect on cell proliferation was receptor independent. Overexpression of HAS3 decreased ERK1/2 phosphorylation suggesting that inhibition of MAP-kinase signaling was responsible for these suppressive effects on the malignant phenotype of MV3 melanoma cells. - Highlights: • Inducible HAS3-MV3 melanoma cell line was generated using Lentiviral transduction. • HAS3 overexpression inhibits MV3 cell migration via hyaluronan–receptor interaction. • HAS3 overexpression decreases MV3 melanoma cell proliferation and adhesion. • ERK1/2 phosphorylation is downregulated by 50% in HAS3 overexpressing cells. • The results suggest that hyaluronan has anti-cancer like effects in melanoma.

  16. Effect of Carboxymethylation on the Rheological Properties of Hyaluronan.

    Science.gov (United States)

    Wendling, Rian J; Christensen, Amanda M; Quast, Arthur D; Atzet, Sarah K; Mann, Brenda K

    2016-01-01

    Chemical modifications made to hyaluronan to enable covalent crosslinking to form a hydrogel or to attach other molecules may alter the physical properties as well, which have physiological importance. Here we created carboxymethyl hyaluronan (CMHA) with varied degree of modification and investigated the effect on the viscosity of CMHA solutions. Viscosity decreased initially as modification increased, with a minimum viscosity for about 30-40% modification. This was followed by an increase in viscosity around 45-50% modification. The pH of the solution had a variable effect on viscosity, depending on the degree of carboxymethyl modification and buffer. The presence of phosphates in the buffer led to decreased viscosity. We also compared large-scale production lots of CMHA to lab-scale and found that large-scale required extended reaction times to achieve the same degree of modification. Finally, thiolated CMHA was disulfide crosslinked to create hydrogels with increased viscosity and shear-thinning aspects compared to CMHA solutions.

  17. The Anomalies of Hyaluronan Structures in Presence of Surface Active Phospholipids—Molecular Mass Dependence

    Directory of Open Access Journals (Sweden)

    Piotr Bełdowski

    2018-03-01

    Full Text Available Interactions between hyaluronan (A- and phospholipids play a key role in many systems in the human body. One example is the articular cartilage system, where the synergistic effect of such interactions supports nanoscale lubrication. A molecular dynamics simulation has been performed to understand the process of formation of hydrogen bonds inside the hyaluronan network, both in the presence and absence of phospholipids. Additionally, the effect of the molecular mass of (A- was analyzed. The main finding of this work is a robust demonstration of the optimal parameters (H-bond energy, molecular mass influencing the facilitated lubrication mechanism of the articular cartilage system. Simulation results show that the presence of phospholipids has the greatest influence on hyaluronan at low molecular mass. We also show the specific sites of H-bonding between chains. Simulation results can help to understand how hyaluronan and phospholipids interact at several levels of articular cartilage system functioning.

  18. Influence of serum albumin on intracellular delivery of drug-loaded hyaluronan polymeric micelles

    Czech Academy of Sciences Publication Activity Database

    Nešporová, K.; Sogorková, J.; Smejkalova, D.; Kulhánek, J.; Huerta-Angeles, G.; Kubala, Lukáš; Velebný, V.

    2016-01-01

    Roč. 511, č. 1 (2016), s. 638-647 ISSN 0378-5173 Institutional support: RVO:68081707 Keywords : Polymeric micelle * Hyaluronan * Fatty acid Subject RIV: BO - Biophysics Impact factor: 3.649, year: 2016

  19. Hyaluronan and hyaluronectin in the extracellular matrix of human brain tumour stroma.

    Science.gov (United States)

    Delpech, B; Maingonnat, C; Girard, N; Chauzy, C; Maunoury, R; Olivier, A; Tayot, J; Creissard, P

    1993-01-01

    Hyaluronan (HA) and the hyaluronan-binding glycoprotein hyaluronectin (HN) were measured in 23 gliomas and 8 meningiomas and their location was revisited in 35 tumours. A clear-cut difference was found in the HN/HA ratio values of glioblastomas (below 0.5) and that of astrocytomas (above 0.5 P edification of the extracellular matrix. In meningiomas only the stroma would be responsible for HA and HN production.

  20. A Hyaluronan-Based Scaffold for the in Vitro Construction of Dental Pulp-Like Tissue

    Directory of Open Access Journals (Sweden)

    Letizia Ferroni

    2015-03-01

    Full Text Available Dental pulp tissue supports the vitality of the tooth, but it is particularly vulnerable to external insults, such as mechanical trauma, chemical irritation or microbial invasion, which can lead to tissue necrosis. In the present work, we present an endodontic regeneration method based on the use of a tridimensional (3D hyaluronan scaffold and human dental pulp stem cells (DPSCs to produce a functional dental pulp-like tissue in vitro. An enriched population of DPSCs was seeded onto hyaluronan-based non-woven meshes in the presence of differentiation factors to induce the commitment of stem cells to neuronal, glial, endothelial and osteogenic phenotypes. In vitro experiments, among which were gene expression profiling and immunofluorescence (IF staining, proved the commitment of DPSCs to the main components of dental pulp tissue. In particular, the hyaluronan-DPSCs construct showed a dental pulp-like morphology consisting of several specialized cells growing inside the hyaluronan fibers. Furthermore, these constructs were implanted into rat calvarial critical-size defects. Histological analyses and gene expression profiling performed on hyaluronan-DPSCs grafts showed the regeneration of osteodentin-like tissue. Altogether, these data suggest the regenerative potential of the hyaluronan-DPSC engineered tissue.

  1. The effects of hyaluronan and its fragments on lipid models exposed to UV irradiation.

    Science.gov (United States)

    Trommer, Hagen; Wartewig, Siegfried; Böttcher, Rolf; Pöppl, Andreas; Hoentsch, Joachim; Ozegowski, Jörg H; Neubert, Reinhard H H

    2003-03-26

    The effects of hyaluronan and its degradation products on irradiation-induced lipid peroxidation were investigated. Liposomal skin lipid models with increasing complexity were used. Hyaluronan and its fragments were able to reduce the amount of lipid peroxidation secondary products quantified by the thiobarbituric acid (TBA) assay. The qualitative changes were studied by mass spectrometry. To elucidate the nature of free radical involvement electron paramagnetic resonance (EPR) studies were carried out. The influence of hyaluronan and its fragments on the concentration of hydroxyl radicals generated by the Fenton system was examined using the spin trapping technique. Moreover, the mucopolysaccharide's ability to react with stable radicals was checked. The quantification assay of 2,2-diphenyl-1-picrylhydrazyl hydrate (DPPH) showed no concentration changes of the stable radical caused by hyaluronan. Hyaluronan was found to exhibit prooxidative effects in the Fenton assay in a concentration dependent manner. A transition metal chelation was proposed as a mechanism of this behavior. Considering human skin and its constant exposure to UV light and oxygen and an increased pool of iron in irradiated skin the administration of hyaluronan or its fragments in cosmetic formulations or sunscreens could be helpful for the protection of the human skin. Copyright 2003 Elsevier Science B.V.

  2. A hyaluronan-based scaffold for the in vitro construction of dental pulp-like tissue.

    Science.gov (United States)

    Ferroni, Letizia; Gardin, Chiara; Sivolella, Stefano; Brunello, Giulia; Berengo, Mario; Piattelli, Adriano; Bressan, Eriberto; Zavan, Barbara

    2015-03-02

    Dental pulp tissue supports the vitality of the tooth, but it is particularly vulnerable to external insults, such as mechanical trauma, chemical irritation or microbial invasion, which can lead to tissue necrosis. In the present work, we present an endodontic regeneration method based on the use of a tridimensional (3D) hyaluronan scaffold and human dental pulp stem cells (DPSCs) to produce a functional dental pulp-like tissue in vitro. An enriched population of DPSCs was seeded onto hyaluronan-based non-woven meshes in the presence of differentiation factors to induce the commitment of stem cells to neuronal, glial, endothelial and osteogenic phenotypes. In vitro experiments, among which were gene expression profiling and immunofluorescence (IF) staining, proved the commitment of DPSCs to the main components of dental pulp tissue. In particular, the hyaluronan-DPSCs construct showed a dental pulp-like morphology consisting of several specialized cells growing inside the hyaluronan fibers. Furthermore, these constructs were implanted into rat calvarial critical-size defects. Histological analyses and gene expression profiling performed on hyaluronan-DPSCs grafts showed the regeneration of osteodentin-like tissue. Altogether, these data suggest the regenerative potential of the hyaluronan-DPSC engineered tissue.

  3. Controlling adsorption of albumin with hyaluronan on silica surfaces and sulfonated latex particles.

    Science.gov (United States)

    Berts, Ida; Fragneto, Giovanna; Porcar, Lionel; Hellsing, Maja S; Rennie, Adrian R

    2017-10-15

    Polysaccharides are known to modify binding of proteins at interfaces and this paper describes studies of these interactions and how they are modified by pH. Specifically, the adsorption of human serum albumin on to polystyrene latex and to silica is described, focusing on how this is affected by hyaluronan. Experiments were designed to test how such binding might be modified under relevant physiological conditions. Changes in adsorption of albumin alone and the co-adsorption of albumin and hyaluronan are driven by electrostatic interactions. Multilayer binding is found to be regulated by the pH of the solution and the molecular mass and concentration of hyaluronan. Highest adsorption was observed at pH below 4.8 and for low molecular mass hyaluronan (≤150kDa) at concentrations above 2mgml -1 . On silica with grafted hyaluronan, albumin absorption is reversed by changes in solvent pH due to their strong electrostatic attraction. Albumin physisorbed on silica surfaces is also rinsed away with dilute hyaluronan solution at pH 4.8. The results demonstrate that the protein adsorption can be controlled both by changes of pH and by interaction with other biological macromolecules. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Hyaluronan synthases (HAS1-3) and hyaluronidases (HYAL1-2) in the accumulation of hyaluronan in endometrioid endometrial carcinoma

    International Nuclear Information System (INIS)

    Nykopp, Timo K; Rilla, Kirsi; Tammi, Markku I; Tammi, Raija H; Sironen, Reijo; Hämäläinen, Kirsi; Kosma, Veli-Matti; Heinonen, Seppo; Anttila, Maarit

    2010-01-01

    Hyaluronan accumulation correlates with the degree of malignancy in many solid tumor types, including malignant endometrial carcinomas. To elucidate the mechanism of hyaluronan accumulation, we examined the expression levels of the hyaluronan synthases (HAS1, HAS2 and HAS3) and hyaluronidases (HYAL1 and HYAL2), and correlated them with hyaluronan content and HAS1-3 immunoreactivity. A total of 35 endometrial tissue biopsies from 35 patients, including proliferative and secretory endometrium (n = 10), post-menopausal proliferative endometrium (n = 5), complex atypical hyperplasia (n = 4), grade 1 (n = 8) and grade 2 + 3 (n = 8) endometrioid adenocarcinomas were divided for gene expression by real-time RT-PCR, and paraffin embedded blocks for hyaluronan and HAS1-3 cytochemistry. The mRNA levels of HAS1-3 were not consistently changed, while the immunoreactivity of all HAS proteins was increased in the cancer epithelium. Interestingly, HAS3 mRNA, but not HAS3 immunoreactivity, was increased in post-menopausal endometrium compared to normal endometrium (p = 0.003). The median of HYAL1 mRNA was 10-fold and 15-fold lower in both grade 1 and grade 2+3 endometrioid endometrial cancers, as compared to normal endometrium (p = 0.004-0.006), and post-menopausal endometrium (p = 0.002), respectively. HYAL2 mRNA was also reduced in cancer (p = 0.02) and correlated with HYAL1 (r = 0.8, p = 0.0001). There was an inverse correlation between HYAL1 mRNA and the epithelial hyaluronan staining intensity (r = -0.6; P = 0.001). The results indicated that HYAL1 and HYAL2 were coexpressed and significantly downregulated in endometrioid endometrial cancer and correlated with the accumulation of hyaluronan. While immunoreactivity for HASs increased in the cancer cells, tumor mRNA levels for HASs were not changed, suggesting that reduced turnover of HAS protein may also have contributed to the accumulation of hyaluronan

  5. Hyaluronan- and heparin-reduced silver nanoparticles with antimicrobial properties

    Science.gov (United States)

    Kemp, Melissa M; Kumar, Ashavani; Clement, Dylan; Ajayan, Pulickel; Mousa, Shaker

    2009-01-01

    Aims Silver nanoparticles exhibit unique antibacterial properties that make these ideal candidates for biological and medical applications. We utilized a clean method involving a single synthetic step to prepare silver nanoparticles that exhibit antimicrobial activity. Materials & methods These nanoparticles were prepared by reducing silver nitrate with diaminopyridinylated heparin (DAPHP) and hyaluronan (HA) polysaccharides and tested for their efficacy in inhibiting microbial growth. Results & discussion The resulting silver nanoparticles exhibit potent antimicrobial activity against Staphylococcus aureus and modest activity against Escherichia coli. Silver–HA showed greater antimicrobial activity than silver–DAPHP, while silver–glucose nanoparticles exhibited very weak antimicrobial activity. Neither HA nor DAPHP showed activity against S. aureus or E. coli. Conclusion These results suggest that DAPHP and HA silver nanoparticles have potential in antimicrobial therapeutic applications. PMID:19505245

  6. Hyaluronan synthase mediates dye translocation across liposomal membranes

    Directory of Open Access Journals (Sweden)

    Medina Andria P

    2012-01-01

    Full Text Available Abstract Background Hyaluronan (HA is made at the plasma membrane and secreted into the extracellular medium or matrix by phospolipid-dependent hyaluronan synthase (HAS, which is active as a monomer. Since the mechanism by which HA is translocated across membranes is still unresolved, we assessed the presence of an intraprotein pore within HAS by adding purified Streptococcus equisimilis HAS (SeHAS to liposomes preloaded with the fluorophore Cascade Blue (CB. Results CB translocation (efflux was not observed with mock-purified material from empty vector control E. coli membranes, but was induced by SeHAS, purified from membranes, in a time- and dose-dependent manner. CB efflux was eliminated or greatly reduced when purified SeHAS was first treated under conditions that inhibit enzyme activity: heating, oxidization or cysteine modification with N-ethylmaleimide. Reduced CB efflux also occurred with SeHAS K48E or K48F mutants, in which alteration of K48 within membrane domain 2 causes decreased activity and HA product size. The above results used liposomes containing bovine cardiolipin (BCL. An earlier study testing many synthetic lipids found that the best activating lipid for SeHAS is tetraoleoyl cardiolipin (TO-CL and that, in contrast, tetramyristoyl cardiolipin (TM-CL is an inactivating lipid (Weigel et al, J. Biol. Chem. 281, 36542, 2006. Consistent with the effects of these CL species on SeHAS activity, CB efflux was more than 2-fold greater in liposomes made with TO-CL compared to TM-CL. Conclusions The results indicate the presence of an intraprotein pore in HAS and support a model in which HA is translocated to the exterior by HAS itself.

  7. Effect of depletion of interstitial hyaluronan on hydraulic conductance in rabbit knee synovium

    Science.gov (United States)

    Coleman, P J; Scott, D; Abiona, A; Ashhurst, D E; Mason, R M; Levick, J R

    1998-01-01

    The hydraulic resistance of the synovial lining to fluid outflow from a joint cavity () is important for the retention of intra-articular lubricant. The resistance has been attributed in part to extracellular glycosaminoglycans, including hyaluronan and chondroitin sulphates. Increased permeability in joints infused with testicular hyaluronidase, which digests both chondroitin sulphates and hyaluronan, supports this view. In this study the importance of interstitial hyaluronan per se was assessed using leech and Streptomyces hyaluronidases, which degrade only hyaluronan. Ringer solution was infused into the knee joint cavity of anaesthetized rabbits for 30 min, with or without hyaluronidase, after which intra-articular pressure (Pj) was raised and the relation between pressure and outflow determined. Treatment with Streptomyces, leech or testicular hyaluronidases increased the fluid escape rates by similar factors, namely 4- to 6-fold. After Streptomyces hyaluronidase treatment the slope d/dPj, which at low pressures represents synovial hydraulic conductance, increased from a control of 0.90 ± 0.20 μl min−1 cmH2O−1 (mean ± s.e.m., n = 6) to 4.52 ± 0.70 μl min−1 cmH2O−1. The slope d/dPj increased to a similar level after testicular hyaluronidase, namely to 4.14 ± 1.06 μl min−1 cmH2O−1 (control, 0.54 ± 0.24 μl min−1 cmH2O−1). Streptomyces and leech hyaluronidases were as effective as testicular hyaluronidase (no statistically significant differences) despite differences in substrate specificity. It was shown using histochemical and immunohistochemical techniques that hyaluronan was removed from the synovium by leech, Streptomyces and testicular hyaluronidases. The binding of antibodies 2-B-6 and 3-B-3 showed that the core proteins of the chondroitin sulphate proteoglycans remained intact after treatment with hyaluronidases, and the binding of 5-D-4 showed that keratan sulphate was unaffected. An azocasein digestion assay confirmed that the

  8. A Hyaluronan-Based Injectable Hydrogel Improves the Survival and Integration of Stem Cell Progeny following Transplantation

    Directory of Open Access Journals (Sweden)

    Brian G. Ballios

    2015-06-01

    Full Text Available The utility of stem cells and their progeny in adult transplantation models has been limited by poor survival and integration. We designed an injectable and bioresorbable hydrogel blend of hyaluronan and methylcellulose (HAMC and tested it with two cell types in two animal models, thereby gaining an understanding of its general applicability for enhanced cell distribution, survival, integration, and functional repair relative to conventional cell delivery in saline. HAMC improves cell survival and integration of retinal stem cell (RSC-derived rods in the retina. The pro-survival mechanism of HAMC is ascribed to the interaction of the CD44 receptor with HA. Transient disruption of the retinal outer limiting membrane, combined with HAMC delivery, results in significantly improved rod survival and visual function. HAMC also improves the distribution, viability, and functional repair of neural stem and progenitor cells (NSCs. The HAMC delivery system improves cell transplantation efficacy in two CNS models, suggesting broad applicability.

  9. Modulation of Hyaluronan Synthesis by the Interaction between Mesenchymal Stem Cells and Osteoarthritic Chondrocytes

    Directory of Open Access Journals (Sweden)

    Eliane Antonioli

    2015-01-01

    Full Text Available Bone marrow mesenchymal stem cells (BM-MSCs are considered a good source for cellular therapy in cartilage repair. But, their potential to repair the extracellular matrix, in an osteoarthritic environment, is still controversial. In osteoarthritis (OA, anti-inflammatory action and extracellular matrix production are important steps for cartilage healing. This study examined the interaction of BM-MSC and OA-chondrocyte on the production of hyaluronan and inflammatory cytokines in a Transwell system. We compared cocultured BM-MSCs and OA-chondrocytes with the individually cultured controls (monocultures. There was a decrease in BM-MSCs cell count in coculture with OA-chondrocytes when compared to BM-MSCs alone. In monoculture, BM-MSCs produced higher amounts of hyaluronan than OA-chondrocytes and coculture of BM-MSCs with OA-chondrocytes increased hyaluronan production per cell. Hyaluronan synthase-1 mRNA expression was upregulated in BM-MSCs after coculture with OA-chondrocytes, whereas hyaluronidase-1 was downregulated. After coculture, lower IL-6 levels were detected in BM-MSCs compared with OA-chondrocytes. These results indicate that, in response to coculture with OA-chondrocytes, BM-MSCs change their behavior by increasing production of hyaluronan and decreasing inflammatory cytokines. Our results indicate that BM-MSCs per se could be a potential tool for OA regenerative therapy, exerting short-term effects on the local microenvironment even when cell:cell contact is not occurring.

  10. Hyaluronan synthesis in cultured tobacco cells (BY-2) expressing a chlorovirus enzyme: cytological studies.

    Science.gov (United States)

    Rakkhumkaew, Numfon; Shibatani, Shigeo; Kawasaki, Takeru; Fujie, Makoto; Yamada, Takashi

    2013-04-01

    Extraction of hyaluronan from animals or microbial fermentation has risks including contamination with pathogens and microbial toxins. In this work, tobacco cultured-cells (BY-2) were successfully transformed with a chloroviral hyaluronan synthase (cvHAS) gene to produce hyaluronan. Cytological studies revealed accumulation of HA on the cells, and also in subcellular fractions (protoplasts, miniplasts, vacuoplasts, and vacuoles). Transgenic BY-2 cells harboring a vSPO-cvHAS construct containing the vacuolar targeting signal of sporamin connected to the N-terminus of cvHAS accumulated significant amounts of HA in vacuoles. These results suggested that cvHAS successfully functions on the vacuolar membrane and synthesizes/transports HA into vacuoles. Efficient synthesis of HA using this system provides a new method for practical production of HA. Copyright © 2012 Wiley Periodicals, Inc.

  11. Hyaluronan Immobilized Polyurethane as a Blood Contacting Material

    Directory of Open Access Journals (Sweden)

    Feirong Gong

    2010-01-01

    Full Text Available Hyaluronan (hyaluronic acid, HA was immobilized onto the surface of amino-functionalized polyurethane films with the goal of obtaining a novel kind of biomaterial which had the potential in blood-contacting applications. The amino-functionalized polyurethane was prepared by synthesized acidic polyurethane whose pendant carboxyl groups were treated with an excess amount of 1,3-diaminopropane in the presence of N,N-carbonyldiimidazole (CDI. Attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR, Raman spectroscopy (RS, scanning electron microscopy (SEM, and water contact angle measurement were used to confirm the surface changes at each step of treatment, both in morphologies and chemical compositions. APTT and PT results showed that HA immobilization could prolong the blood coagulation time, thus HA-immobilized polyurethane (PU-HA exhibited improved blood compatibility. Cytotoxicity analysis showed that the PU-HA films synthesized in this study were cytocompatible and could support human vein endothelial cells (HUVECs adhesion and proliferation.

  12. Cervical hyaluronan biology in pregnancy, parturition and preterm birth.

    Science.gov (United States)

    Mahendroo, Mala

    2018-03-03

    Cervical hyaluronan (HA) synthesis is robustly induced in late pregnancy in numerous species including women and mice. Recent evidence highlights the diverse and dynamic functions of HA in cervical biology that stem from its expression in the cervical stroma, epithelia and immune cells, changes in HA molecular weight and cell specific expression of HA binding partners. Mice deficient in HA in the lower reproductive tract confirm a structural role of HA to increase spacing and disorganization of fibrillar collagen, though this function is not critical for pregnancy and parturition. In addition, cervical HA depletion via targeted deletion of HA synthase genes, disrupts cell signaling required for the differentiation of epithelia and their mucosal and junctional barrier, resulting in increased susceptibility to ascending infection-mediated preterm birth. Finally the generation of HA disaccharides by bacterial hyaluronidases as made by Group B streptococcus can ligate toll like receptors TLR2/4 thus preventing appropriate inflammatory responses as needed to fight ascending infection and preterm birth. This review summarizes our current understanding of HA's novel and unique roles in cervical remodeling in the process of birth. Copyright © 2017 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.

  13. Chromosomal localization of the human and mouse hyaluronan synthase genes

    Energy Technology Data Exchange (ETDEWEB)

    Spicer, A.P.; McDonald, J.A. [Mayo Clinic Scottsdale, AZ (United States); Seldin, M.F. [Univ. of California Davis, CA (United States)] [and others

    1997-05-01

    We have recently identified a new vertebrate gene family encoding putative hyaluronan (HA) synthases. Three highly conserved related genes have been identified, designated HAS1, HAS2, and HAS3 in humans and Has1, Has2, and Has3 in the mouse. All three genes encode predicted plasma membrane proteins with multiple transmembrane domains and approximately 25% amino acid sequence identity to the Streptococcus pyogenes HA synthase, HasA. Furthermore, expression of any one HAS gene in transfected mammalian cells leads to high levels of HA biosynthesis. We now report the chromosomal localization of the three HAS genes in human and in mouse. The genes localized to three different positions within both the human and the mouse genomes. HAS1 was localized to the human chromosome 19q13.3-q13.4 boundary and Has1 to mouse Chr 17. HAS2 was localized to human chromosome 8q24.12 and Has2 to mouse Chr 15. HAS3 was localized to human chromosome 16q22.1 and Has3 to mouse Chr 8. The map position for HAS1 reinforces the recently reported relationship between a small region of human chromosome 19q and proximal mouse chromosome 17. HAS2 mapped outside the predicted critical region delineated for the Langer-Giedion syndrome and can thus be excluded as a candidate gene for this genetic syndrome. 33 refs., 2 figs.

  14. IL-10 Induction from Implants Delivering Pancreatic Islets and Hyaluronan

    Directory of Open Access Journals (Sweden)

    Paul L. Bollyky

    2013-01-01

    Full Text Available Local induction of pro-tolerogenic cytokines, such as IL-10, is an appealing strategy to help facilitate transplantation of islets and other tissues. Here, we describe a pair of implantable devices that capitalize on our recent finding that hyaluronan (HA promotes IL-10 production by activated T cells. The first device is an injectable hydrogel made of crosslinked HA and heparan sulfate loaded with anti-CD3/anti-CD28 antibodies and IL-2. T cells embedded within this hydrogel prior to polymerization go on to produce IL-10 in vivo. The second device is a bioengineered implant consisting of a polyvinyl alcohol sponge scaffold, supportive collagen hydrogel, and alginate spheres mediating sustained release of HA in fluid form. Pancreatic islets that expressed ovalbumin (OVA antigen were implanted within this device for 14 days into immunodeficient mice that received OVA-specific DO.11.10 T cells and a subsequent immunization with OVA peptide. Splenocytes harvested from these mice produced IL-10 upon re-challenge with OVA or anti-CD3 antibodies. Both of these devices represent model systems that will be used, in future studies, to further evaluate IL-10 induction by HA, with the objective of improving the survival and function of transplanted islets in the setting of autoimmune (type 1 diabetes.

  15. Regulation of Hyaluronan Synthesis in Vascular Diseases and Diabetes

    Directory of Open Access Journals (Sweden)

    Paola Moretto

    2015-01-01

    Full Text Available Cell microenvironment has a critical role determining cell fate and modulating cell responses to injuries. Hyaluronan (HA is a ubiquitous extracellular matrix glycosaminoglycan that can be considered a signaling molecule. In fact, interacting with several cell surface receptors can deeply shape cell behavior. In vascular biology, HA triggers smooth muscle cells (SMCs dedifferentiation which contributes to vessel wall thickening. Furthermore, HA is able to modulate inflammation by altering the adhesive properties of endothelial cells. In hyperglycemic conditions, HA accumulates in vessels and can contribute to the diabetic complications at micro- and macrovasculature. Due to the pivotal role in favoring atherogenesis and neointima formation after injuries, HA could be a new target for cardiovascular pathologies. This review will focus on the recent findings regarding the regulation of HA synthesis in human vascular SMCs. In particular, the effects of the intracellular HA substrates availability, adenosine monophosphate-activated protein kinase (AMPK, and protein O-GlcNAcylation on the main HA synthetic enzyme (i.e., HAS2 will be discussed.

  16. Hyaluronan Protects Bovine Articular Chondrocytes against Cell Death Induced by Bupivacaine under Supraphysiologic Temperatures

    Science.gov (United States)

    Liu, Sen; Zhang, Qing-Song; Hester, William; O’Brien, Michael J.; Savoie, Felix H.; You, Zongbing

    2013-01-01

    Background Bupivacaine and supraphysiologic temperature can independently reduce cell viability of articular chondrocytes. In combination these two deleterious factors could further impair cell viability. Hypothesis Hyaluronan may protect chondrocytes from death induced by bupivacaine at supraphysiologic temperatures. Study Design Controlled laboratory study. Methods Bovine articular chondrocytes were treated with hyaluronan at physiologic (37°C) and supraphysiologic temperatures (45°C and 50°C) for one hour, and then exposed to bupivacaine for one hour at room temperature. Cell viability was assessed at three time points: immediately after treatment, six hours later, and twenty-four hours later using flow cytometry and fluorescence microscopy. The effects of hyaluronan on the levels of sulfated glycosaminoglycan in the chondrocytes were determined using Alcian blue staining. Results (1) Bupivacaine alone did not induce noticeable chondrocyte death at 37°C; (2) bupivacaine and temperature synergistically increased chondrocyte death, that is, when the chondrocytes were conditioned to 45°C and 50°C, 0.25% and 0.5% bupivacaine increased the cell death rate by 131% to 383% in comparison to the phosphate-buffered saline control group; and, (3) addition of hyaluronan reduced chondrocyte death rates to approximately 14% and 25% at 45°C and 50°C, respectively. Hyaluronan’s protective effects were still observed at six and twenty-four hours after bupivacaine treatment at 45°C. However, at 50°C, hyaluronan delayed but did not prevent the cell death caused by bupivacaine. One-hour treatment with hyaluronan significantly increased sulfated glycosaminoglycan levels in the chondrocytes. Conclusions Bupivacaine and supraphysiologic temperature synergistically increase chondrocyte death and hyaluronan may protect articular chondrocytes from death caused by bupivacaine. Clinical Relevance This study provides a rationale to perform pre-clinical and clinical studies to

  17. Localization of hyaluronan with a hyaluronan-specific hyaluronic acid binding protein in the placenta in pre-eclampsia.

    Science.gov (United States)

    Matejevic, D; Neudeck, H; Graf, R; Müller, T; Dietl, J

    2001-01-01

    Hyaluronan (HA), a high molecular weight polysaccharide, is a major component of connective tissue and is thus present in the extracellular matrix of most tissues. Increased serum concentrations have been reported in association with pre-eclampsia and liver malfunction, amongst other disorders. We have performed histochemical investigations with a HA-specific hyaluronic acid binding protein in placentas from uncomplicated pregnancies and from patients with pre-eclampsia. Staining for HA was found in the stroma and blood vessel walls of stem villi in all the placentas investigated. The syncytiotrophoblast and cytotrophoblast cells usually remained unstained. In addition, reactivity for HA was found within and on the surface of intervillous and perivillous fibrinoid deposits. Since fibrinoid deposits are increased in pre-eclampsia, our findings suggest that the increased HA serum concentrations in cases of pre-eclampsia could result from the stroma of the infarcted villi and from the fibrinoid deposits. HA may reach the maternal blood through fibrinoid gaps. Copyright 2001 S. Karger AG, Basel

  18. Viscoelastic Properties of Hyaluronan in Physiological Conditions [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Mary K. Cowman

    2015-08-01

    Full Text Available Hyaluronan (HA is a high molecular weight glycosaminoglycan of the extracellular matrix (ECM, which is particularly abundant in soft connective tissues. Solutions of HA can be highly viscous with non-Newtonian flow properties. These properties affect the movement of HA-containing fluid layers within and underlying the deep fascia. Changes in the concentration, molecular weight, or even covalent modification of HA in inflammatory conditions, as well as changes in binding interactions with other macromolecules, can have dramatic effects on the sliding movement of fascia. The high molecular weight and the semi-flexible chain of HA are key factors leading to the high viscosity of dilute solutions, and real HA solutions show additional nonideality and greatly increased viscosity due to mutual macromolecular crowding. The shear rate dependence of the viscosity, and the viscoelasticity of HA solutions, depend on the relaxation time of the molecule, which in turn depends on the HA concentration and molecular weight. Temperature can also have an effect on these properties. High viscosity can additionally affect the lubricating function of HA solutions. Immobility can increase the concentration of HA, increase the viscosity, and reduce lubrication and gliding of the layers of connective tissue and muscle. Over time, these changes can alter both muscle structure and function. Inflammation can further increase the viscosity of HA-containing fluids if the HA is modified via covalent attachment of heavy chains derived from Inter-α-Inhibitor. Hyaluronidase hydrolyzes HA, thus reducing its molecular weight, lowering the viscosity of the extracellular matrix fluid and making outflow easier. It can also disrupt any aggregates or gel-like structures that result from HA being modified. Hyaluronidase is used medically primarily as a dispersion agent, but may also be useful in conditions where altered viscosity of the fascia is desired, such as in the treatment of

  19. Mucoadhesive Polymer Hyaluronan as Biodegradable Cationic/Zwitterionic-Drug Delivery Vehicle

    Directory of Open Access Journals (Sweden)

    Francisco Torrens

    2015-01-01

    Full Text Available Mucoadhesive polymers in pharmaceutical formulations release drugs in mucosal areas. They interact and fix to mucus via molecular interpenetration, etc., which increase drug bioavailability. Polymers physicochemical properties affect formulation mucoadhesion, rheological behaviour and drug absorption. Hyaluronan (HA is selected as a mucoadhesive and biodegradable polymer. Geometric, topological and fractal analyses are carried out with program TOPO. Reference calculations are performed with algorithm GEPOL. Procedure TOPO underestimates molecular volume by 0.7%. Error results 5% in surface area and derived topological indices. Solvent-accessible surface is undercalculated by 3%: from hexamer HA to HA·3Ca and hydrate, the hydrophobic term rises by 42% and decays by 26%, and hydrophilic part drops by 14% and rises by 58% in agreement with the number of H-bonds. Accessibility rises by 9% and decays by 8%. Fractal dimension is underevaluated by 1% and for HA it results 1.566; on going to HA·3Ca and hydrate it rises by 2% and 1%. External-atoms dimension increases by 11%: for HA it results 1.725. When going to HA·3Ca and hydrate, it augments by 4% and 0.3%. On going from HA to HA·3Ca and hydrate, nonburied minus molecular dimension enlarges by 20% and decays by 9%. The hydrate globularity is lower than for water, Ca2+ and averages of O-atoms in HA. Ca2+ rugosity is smaller than for hydrate, averages of O-atoms in HA and water. Ca2+ and water accessibilities are greater than for hydrate. As cations exchange in HA·3Ca requires Ca2+ alteration, rises of drug zwitterionic character and acidic pH increase absorption.

  20. Breaching the Castle Walls: Hyaluronan-Depletion as a Therapeutic Approach to Cancer Therapy

    Directory of Open Access Journals (Sweden)

    H Michael eShepard

    2015-08-01

    Full Text Available Hyaluronan (HA has many functions in the extracellular milieu of normal and diseased tissues. Disease-associated HA accumulation has been shown to predict a worsened prognosis in cancer patients, with tumors having a high extracellular HA content (HA-high being more aggressive than their HA-low counterparts. HA-high tumor aggressiveness is derived from the specialized biomechanical and molecular properties of the HA-based assembly of HA binding proteins and the growth-promoting factors that accumulate in it. Biophysical characteristics of an HA-high tumor microenvironment include high tumor interstitial pressure, compression of tumor vasculature, and resulting tumor hypoxia. Within the tumor cell membrane, HA receptors, primarily CD44 and RHAMM, anchor the HA-high extracellular network. HA-CD44 association on the tumor cell surface enhances receptor tyrosine kinase activity to drive tumor progression and treatment resistance. Together, malignant cells in this HA-high matrix may evolve dependency on it for growth. This yields the hypothesis that depleting HA in HA-high tumors may be associated with a therapeutic benefit. A pegylated form of recombinant human hyaluronidase PH20 (PEGPH20 has been deployed as a potential cancer therapeutic in HA-high tumors. PEGPH20 can collapse this matrix by degrading the HA-assembled tumor extracellular framework, leading to tumor growth inhibition, preferentially in HA-high tumors. Enzymatic depletion of HA by PEGPH20 results in re-expansion of the tumor vasculature, reduction in tumor hypoxia, and increased penetration of therapeutic molecules into the tumor. Finally, HA depletion results in reduced signaling via CD44/RHAMM. Taken together, HA-depletion strategies accomplish their antitumor effects by multiple mechanisms that include targeting both biophysical and molecular signaling pathways. Ongoing clinical trials are examining the potential of PEGPH20 in combination with partner therapeutics in several

  1. Hyaluronan degrading silica nanoparticles for skin cancer therapy

    Science.gov (United States)

    Scodeller, P.; Catalano, P. N.; Salguero, N.; Duran, H.; Wolosiuk, A.; Soler-Illia, G. J. A. A.

    2013-09-01

    We report the first nanoformulation of Hyaluronidase (Hyal) and its enhanced adjuvant effect over the free enzyme. Hyaluronic acid (HA) degrading enzyme Hyal was immobilized on 250 nm silica nanoparticles (SiNP) maintaining specific activity of the enzyme via the layer-by-layer self-assembly technique. This process was characterized by dynamic light scattering (DLS), zeta potential, infrared and UV-Vis spectroscopy, transmission electron microscopy (TEM) and enzymatic activity measurements. The nanoparticles were tested in vivo as adjuvants of carboplatin (CP), peritumorally injected in A375 human melanoma bearing mice and compared with the non-immobilized enzyme, on the basis of equal enzymatic activity. Alcian Blue staining of A375 tumors indicated large overexpression of hyaluronan. At the end of the experiment, tumor volume reduction with SiNP-immobilized Hyal was significantly enhanced compared to non-immobilized Hyal. Field emission scanning electron microscopy (FE-SEM) images together with energy dispersive X-ray spectroscopy (EDS) spectra confirmed the presence of SiNP on the tumor. We mean a proof of concept: this extracellular matrix (ECM) degrading enzyme, immobilized on SiNP, is a more effective local adjuvant of cancer drugs than the non-immobilized enzyme. This could prove useful in future therapies using other or a combination of ECM degrading enzymes.We report the first nanoformulation of Hyaluronidase (Hyal) and its enhanced adjuvant effect over the free enzyme. Hyaluronic acid (HA) degrading enzyme Hyal was immobilized on 250 nm silica nanoparticles (SiNP) maintaining specific activity of the enzyme via the layer-by-layer self-assembly technique. This process was characterized by dynamic light scattering (DLS), zeta potential, infrared and UV-Vis spectroscopy, transmission electron microscopy (TEM) and enzymatic activity measurements. The nanoparticles were tested in vivo as adjuvants of carboplatin (CP), peritumorally injected in A375 human

  2. Hyaluronan in aged collagen matrix increases prostate epithelial cell proliferation

    Science.gov (United States)

    Damodarasamy, Mamatha; Vernon, Robert B.; Chan, Christina K.; Plymate, Stephen R.; Wight, Thomas N.

    2015-01-01

    The extracellular matrix (ECM) of the prostate, which is comprised primarily of collagen, becomes increasingly disorganized with age, a property that may influence the development of hyperplasia and cancer. Collageous ECM extracted from the tails of aged mice exhibits many characteristics of collagen in aged tissues, including the prostate. When polymerized into a 3-dimensional (3D) gel, these collagen extracts can serve as models for the study of specific cell-ECM interactions. In the present study, we examined the behaviors of human prostatic epithelial cell lines representing normal prostate epithelial cells (PEC), benign prostatic hyperplasia (BPH-1), and adenocarcinoma (LNCaP) cultured in contact with 3D gels made from collagen extracts of young and aged mice. We found that proliferation of PEC, BPH-1, and LNCaP cells were all increased by culture on aged collagen gels relative to young collagen gels. In examining age-associated differences in the composition of the collagen extracts, we found that aged and young collagen had a similar amount of several collagen-associated ECM components, but aged collagen had a much greater content of the glycosaminoglycan hyaluronan (HA) than young collagen. The addition of HA (of similar size and concentration to that found in aged collagen extracts) to cells placed in young collagen elicited significantly increased proliferation in BPH-1 cells, but not in PEC or LNCaP cells, relative to controls not exposed to HA. Of note, histochemical analyses of human prostatic tissues showed significantly higher expression of HA in BPH and prostate cancer stroma relative to stroma of normal prostate. Collectively, these results suggest that changes in ECM involving increased levels of HA contribute to the growth of prostatic epithelium with aging. PMID:25124870

  3. Biodistribution imaging of a paclitaxel-hyaluronan bioconjugate

    Energy Technology Data Exchange (ETDEWEB)

    Banzato, Alessandra; Rondina, Maria [Department of Oncology and Surgical Sciences, University of Padua, I-35128 Padova (Italy); Melendez-Alafort, Laura; Zangoni, Elena; Nadali, Anna [Department of Pharmaceutical Sciences, University of Padua, Padova (Italy); Renier, Davide [Fidia Farmaceutici, Abano Terme (Italy); Moschini, Giuliano [Department of Physics, University of Padua, Padova (Italy); Mazzi, Ulderico [Department of Pharmaceutical Sciences, University of Padua, Padova (Italy); Zanovello, Paola [Department of Oncology and Surgical Sciences, University of Padua, I-35128 Padova (Italy); Istituto Oncologico Veneto, IOV-IRCCS, Padova (Italy); Rosato, Antonio [Department of Oncology and Surgical Sciences, University of Padua, I-35128 Padova (Italy); Istituto Oncologico Veneto, IOV-IRCCS, Padova (Italy)], E-mail: antonio.rosato@unipd.it

    2009-07-15

    Introduction: Gamma-ray detectors represent sensitive and noninvasive instruments to evaluate in vivo the metabolic trapping of radiopharmaceuticals. This study aimed to assess the imaging biodistribution of a [{sup 99m}Tc]-radiolabelled new prototype bioconjugate composed of paclitaxel linked to hyaluronan (ONCOFID-P). Methods: A small gamma camera providing high-resolution images was employed. Imaging of biodistribution following intravenous, intraperitoneal, intravesical and oral administration was carried out for a 2-h period in anesthetized mice receiving [{sup 99m}Tc]ONCOFID-P. At the end of the observation time, radioactivity in organs was directly measured. As a control, groups of mice were treated with free [{sup 3}H]paclitaxel given according to the same administration routes, and organ biodistribution of the drug was assessed after 2 h. Results: Intravenous inoculation of [{sup 99m}Tc]ONCOFID-P was followed by a rapid and strong liver uptake. In fact, almost 80% of the imaging signal was detected in this organ 10 min after injection and such value remained constant thereafter, thus indicating that the bioconjugate given through the intravenous route could be well suited to targeting primary or metastatic liver neoplasias. Imaging of the bladder, abdomen and gastrointestinal tract after local administration disclosed that the radiolabelled compound remained confined to the cavities, suggesting a potential regional application for transitional bladder cell carcinomas, ovarian cancers and gastric tumors, respectively. Free [{sup 3}H]paclitaxel biodistribution profoundly differed from that of [{sup 99m}Tc]ONCOFID-P. Conclusions: Conjugation of drugs with polymers results in new chemical entities characterized by a modified biodistribution pattern. Therefore, preclinical studies based on imaging analysis of such new compounds can suggest novel therapeutic applications.

  4. Force Spectroscopy of Hyaluronan by AFM; From H-bonded Networks Towards Single Chain Behavior

    NARCIS (Netherlands)

    Giannotti, M.I.; Rinaudo, Marguerite; Vancso, Gyula J.

    2007-01-01

    The conformational behavior of hyaluronan (HA) polysaccharide chains in aqueous NaCl solution was characterized directly at the single-molecule level. This comunication reports on one of the first single-chain atomic force microscopy (AFM) experiments performed at variable temperatures,

  5. Effects of ventilation on hyaluronan and protein concentration in pleural liquid of anesthetized and conscious rabbits.

    Science.gov (United States)

    Wang, P M; Lai-Fook, S J

    1998-01-01

    The hypothesis of this study is that pleural lubrication is enhanced by hyaluronan acting as a boundary lubricant in pleural liquid and by pleural filtration as reflected in changes in protein concentration with ventilation. Anesthetized rabbits were injected intravenously with Evans blue dye and ventilated with 100% O2 at either of two levels of ventilation for 6 h. Postmortem values of hyaluronan, total protein, and Evans blue-dyed albumin (EBA) concentrations in pleural liquid were greater at the higher ventilation, consistent with increases in boundary lubrication, pleural membrane permeability, and pleural filtration. To determine whether these effects were caused by hyperoxia or anesthesia, conscious rabbits were ventilated with either 3% CO2 or room air in a box for 6, 12, or 24 h. Similar to the anesthetized rabbits, pleural liquid hyaluronan concentration after 24 h was higher in the conscious rabbits with the hypercapnic-induced greater ventilation. By contrast, the time course of total protein and EBA in pleural liquid was similar in both groups of conscious rabbits, indicating no effect of ventilation on pleural permeability. The increase in pleural liquid hyaluronan concentration might be the result of mesothelial cell stimulation by a ventilation-induced increase in pleural liquid shear stress.

  6. Synthesis of a hexasaccharide partial sequence of hyaluronan for click chemistry and more

    Directory of Open Access Journals (Sweden)

    Marina Bantzi

    2015-04-01

    Full Text Available In the present work, the synthesis of a hexasaccharide partial sequence of hyaluronan equipped with a terminal azido moiety is reported. This hexasaccharide can be used for the attachment on surfaces by means of click chemistry and after suitable deprotection for biophysical studies.

  7. Hyaluronan hydrogels with a low degree of modification as scaffolds for cartilage engineering.

    Science.gov (United States)

    La Gatta, Annalisa; Ricci, Giulia; Stellavato, Antonietta; Cammarota, Marcella; Filosa, Rosanna; Papa, Agata; D'Agostino, Antonella; Portaccio, Marianna; Delfino, Ines; De Rosa, Mario; Schiraldi, Chiara

    2017-10-01

    In the field of cartilage engineering, continuing efforts have focused on fabricating scaffolds that favor maintenance of the chondrocytic phenotype and matrix formation, in addition to providing a permeable, hydrated, microporous structure and mechanical support. The potential of hyaluronan-based hydrogels has been well established, but the ideal matrix remains to be developed. This study describes the development of hyaluronan sponges-based scaffolds obtained by lysine methyl-ester crosslinking. The reaction conditions are optimized with minimal chemical modifications to obtain materials that closely resemble elements in physiological cellular environments. Three hydrogels with different amounts of crosslinkers were produced that show morphological, water-uptake, mechanical, and stability properties comparable or superior to those of currently available hyaluronan-scaffolds, but with significantly fewer hyaluronan modifications. Primary human chondrocytes cultured with the most promising hydrogel were viable and maintained lineage identity for 3 weeks. They also secreted cartilage-specific matrix proteins. These scaffolds represent promising candidates for cartilage engineering. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Effect of hyaluronan on osteogenic differentiation of porcine bone marrow stromal cells in vitro

    DEFF Research Database (Denmark)

    Zou, Lijin; Zou, Xuenong; Chen, Li

    2007-01-01

    Hyaluronan (HA) plays a predominant role in tissue morphogenesis, cell migration, proliferation, and cell differentiation. The aims of the present study were to investigate whether (i) prolonged presence of high concentration (4.0 mg/mL) 800 KDa HA and (ii) pretreatment with HA can modify osteoge...

  9. Increased Levels of Type I and III Collagen and Hyaluronan in Scleroderma Skin

    DEFF Research Database (Denmark)

    Søndergaard, Klaus; Heickendorff, Lene; L, Risteli

    1997-01-01

    The aminoterminal propeptide of type III procollagen (PIIINP) and the carboxyterminal propeptide of type I procollagen (PICP) and hyaluronan (HA) were measured in plasma and suction blister fluid from 13 systemic sclerosis patients and 11 healthy volunteers. Suction blisters and skin biopsies were...

  10. Chondroitin sulfate addition to CD44H negatively regulates hyaluronan binding

    International Nuclear Information System (INIS)

    Ruffell, Brian; Johnson, Pauline

    2005-01-01

    CD44 is a widely expressed cell adhesion molecule that binds hyaluronan, an extracellular matrix glycosaminoglycan, in a tightly regulated manner. This regulated interaction has been implicated in inflammation and tumor metastasis. CD44 exists in the standard form, CD44H, or as higher molecular mass isoforms due to alternative splicing. Here, we identify serine 180 in human CD44H as the site of chondroitin sulfate addition and show that lack of chondroitin sulfate addition at this site enhances hyaluronan binding by CD44. A CD44H-immunoglobulin fusion protein expressed in HEK293 cells, and CD44H expressed in murine L fibroblast cells were modified by chondroitin sulfate, as determined by reduced sulfate incorporation after chondroitinase ABC treatment. Mutation of serine 180 or glycine 181 in CD44H reduced chondroitin sulfate addition and increased hyaluronan binding, indicating that serine 180 is the site for chondroitin sulfate addition in CD44H and that this negatively regulates hyaluronan binding

  11. Nebulized hyaluronan ameliorates lung inflammation in cystic fibrosis mice.

    Science.gov (United States)

    Gavina, Manuela; Luciani, Alessandro; Villella, Valeria R; Esposito, Speranza; Ferrari, Eleonora; Bressani, Ilaria; Casale, Alida; Bruscia, Emanuela M; Maiuri, Luigi; Raia, Valeria

    2013-08-01

    Chronic lung inflammation with increased susceptibility to bacterial infections cause much of the morbidity and mortality in patients with cystic fibrosis (CF), the most common severe, autosomal recessively inherited disease in the Caucasian population. Exogenous inhaled hyaluronan (HA) can exert a protective effect against injury and beneficial effects of HA have been shown in experimental models of chronic respiratory diseases. Our objective was to examine whether exogenous administration of nebulized HA might interfere with lung inflammation in CF. F508del homozygous mice (Cftr(F508del) ) and transgenic mice overexpressing the ENaC channel β-subunit (Scnn1b-Tg) were treated with nebulized HA (0.5 mg/mouse/day for 7 days). Tumor necrosis factor-alpha (TNFα), macrophage inflammatory protein-2 (MIP-2), myeloperoxidase (MPO) levels, and macrophage infiltration were assessed on lung tissues. IB3-1 and CFBE41o-epithelial cell lines were cultured with HA (24 hr, 100 µg/ml) and Reactive Oxygen Species (ROS), Tissue Transglutaminase (TG2) SUMOylation and Peroxisome Proliferator Activated Receptor gamma (PPARγ) and phospho-p42/p44 levels were measured by dichlorodihydrofluorescein assay, or fluorescence resonance energy transfer (FRET) microscopy or immunoblots. Nebulized HA reduced TNFα expression (P < 0.005); TNFα, MIP-2, and MPO protein levels (P < 0.05); MPO activity (P < 0.05); and CD68+ cells counts (P < 0.005) in lung tissues of Cftr(F508del) and Scnn1b-Tg mice, compared with saline-treated mice. HA reduced ROS, TG2 SUMOylation, TG2 activity, phospho-p42-44, and increased PPARγ protein in both IB3-1 and CFBE41o cells (P < 0.05). Nebulized HA is effective in controlling inflammation in vivo in mice CF airways and in vitro in human airway epithelial cells. We provide the proof of concept for the use of inhaled HA as a potential anti-inflammatory drug in CF therapy. Copyright © 2012 Wiley Periodicals, Inc.

  12. Advances and advantages of nanomedicine in the pharmacological targeting of hyaluronan-CD44 interactions and signaling in cancer.

    Science.gov (United States)

    Skandalis, Spyros S; Gialeli, Chrisostomi; Theocharis, Achilleas D; Karamanos, Nikos K

    2014-01-01

    Extensive experimental evidence in cell and animal tumor models show that hyaluronan-CD44 interactions are crucial in both malignancy and resistance to cancer therapy. Because of the intimate relationship between the hyaluronan-CD44 system and tumor cell survival and growth, it is an increasingly investigated area for applications to anticancer chemotherapeutics. Interference with the hyaluronan-CD44 interaction by targeting drugs to CD44, targeting drugs to the hyaluronan matrix, or interfering with hyaluronan matrix/tumor cell-associated CD44 interactions is a viable strategy for cancer treatment. Many of these methods can decrease tumor burden in animal models but have yet to show significant clinical utility. Recent advances in nanomedicine have offered new valuable tools for cancer detection, prevention, and treatment. The enhanced permeability and retention effect has served as key rationale for using nanoparticles to treat solid tumors. However, the targeted and uniform delivery of these particles to all regions of tumors in sufficient quantities requires optimization. An ideal nanocarrier should be equipped with selective ligands that are highly or exclusively expressed on target cells and thus endow the carriers with specific targeting capabilities. In this review, we describe how the hyaluronan-CD44 system may provide such an alternative in tumors expressing specific CD44 variants. © 2014 Elsevier Inc. All rights reserved.

  13. Hyaluronan, CD44, and Emmprin Regulate Lactate Efflux and Membrane Localization of Monocarboxylate Transporters in Human Breast Carcinoma Cells

    Science.gov (United States)

    Slomiany, Mark G.; Grass, G. Daniel; Robertson, Angela D.; Yang, Xiao Y.; Maria, Bernard L.; Beeson, Craig; Toole, Bryan P.

    2013-01-01

    Interactions of hyaluronan with CD44 in tumor cells play important cooperative roles in various aspects of malignancy and drug resistance. Emmprin (CD147; basigin)is a cell surface glycoprotein of the immunoglobulin superfamily that is highly up-regulated in malignant cancer cells and stimulates hyaluronan production, as well as several downstream signaling pathways. Emmprin also interacts with various monocarboxylate transporters (MCT). Malignant cancer cells use the glycolytic pathway and require MCTs to efflux lactate that results from glycolysis. Glycolysis and lactate secretion contribute to malignant cell behaviors and drug resistance in tumor cells. In the present study, we find that perturbation of endogenous hyaluronan, using small hyaluronan oligosaccharides, rapidly inhibits lactate efflux from breast carcinoma cells; down-regulation of emmprin, using emmprin small interfering RNA, also results in decreased efflux. In addition, we find that CD44 coimmunoprecipitates with MCT1, MCT4, and emmprin and colocalizes with these proteins at the plasma membrane. Moreover, after treatment of the cells with hyaluronan oligosaccharides, CD44, MCT1, and MCT4 become localized intracellularly whereas emmprin remains at the cell membrane. Together, these data indicate that constitutive interactions among hyaluronan, CD44, and emmprin contribute to regulation of MCT localization and function in the plasma membrane of breast carcinoma cells. PMID:19176383

  14. Adiponectin promotes hyaluronan synthesis along with increases in hyaluronan synthase 2 transcripts through an AMP-activated protein kinase/peroxisome proliferator-activated receptor-α-dependent pathway in human dermal fibroblasts

    International Nuclear Information System (INIS)

    Yamane, Takumi; Kobayashi-Hattori, Kazuo; Oishi, Yuichi

    2011-01-01

    Highlights: ► Adiponectin promotes hyaluronan synthesis along with an increase in HAS2 transcripts. ► Adiponectin also increases the phosphorylation of AMPK. ► A pharmacological activator of AMPK increases mRNA levels of PPARα and HAS2. ► Adiponectin-induced HAS2 mRNA expression is blocked by a PPARα antagonist. ► Adiponectin promotes hyaluronan synthesis via an AMPK/PPARα-dependent pathway. -- Abstract: Although adipocytokines affect the functions of skin, little information is available on the effect of adiponectin on the skin. In this study, we investigated the effect of adiponectin on hyaluronan synthesis and its regulatory mechanisms in human dermal fibroblasts. Adiponectin promoted hyaluronan synthesis along with an increase in the mRNA levels of hyaluronan synthase 2 (HAS2), which plays a primary role in hyaluronan synthesis. Adiponectin also increased the phosphorylation of AMP-activated protein kinase (AMPK). A pharmacological activator of AMPK, 5-aminoimidazole-4-carboxamide-1β-ribofuranoside (AICAR), increased mRNA levels of peroxisome proliferator-activated receptor-α (PPARα), which enhances the expression of HAS2 mRNA. In addition, AICAR increased the mRNA levels of HAS2. Adiponectin-induced HAS2 mRNA expression was blocked by GW6471, a PPARα antagonist, in a concentration-dependent manner. These results show that adiponectin promotes hyaluronan synthesis along with increases in HAS2 transcripts through an AMPK/PPARα-dependent pathway in human dermal fibroblasts. Thus, our study suggests that adiponectin may be beneficial for retaining moisture in the skin, anti-inflammatory activity, and the treatment of a variety of cutaneous diseases.

  15. The Biological Role of Hyaluronan-Rich Oocyte-Cumulus Extracellular Matrix in Female Reproduction

    Czech Academy of Sciences Publication Activity Database

    Nagyová, Eva

    2018-01-01

    Roč. 19, č. 1 (2018), č. článku 283. E-ISSN 1422-0067 R&D Projects: GA MŠk EF15_003/0000460 Institutional support: RVO:67985904 Keywords : extracellular matrix * hyaluronan * inter-alpha-trypsin inhibitor Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Biochemistry and molecular biology Impact factor: 3.226, year: 2016

  16. Charged Triazole Cross-Linkers for Hyaluronan-Based Hybrid Hydrogels

    Directory of Open Access Journals (Sweden)

    Maike Martini

    2016-09-01

    Full Text Available Polyelectrolyte hydrogels play an important role in tissue engineering and can be produced from natural polymers, such as the glycosaminoglycan hyaluronan. In order to control charge density and mechanical properties of hyaluronan-based hydrogels, we developed cross-linkers with a neutral or positively charged triazole core with different lengths of spacer arms and two terminal maleimide groups. These cross-linkers react with thiolated hyaluronan in a fast, stoichiometric thio-Michael addition. Introducing a positive charge on the core of the cross-linker enabled us to compare hydrogels with the same interconnectivity, but a different charge density. Positively charged cross-linkers form stiffer hydrogels relatively independent of the size of the cross-linker, whereas neutral cross-linkers only form stable hydrogels at small spacer lengths. These novel cross-linkers provide a platform to tune the hydrogel network charge and thus the mechanical properties of the network. In addition, they might offer a wide range of applications especially in bioprinting for precise design of hydrogels.

  17. Butyrate-Loaded Chitosan/Hyaluronan Nanoparticles: A Suitable Tool for Sustained Inhibition of ROS Release by Activated Neutrophils

    DEFF Research Database (Denmark)

    Sacco, Pasquale; Decleva, Eva; Tentor, Fabio

    2017-01-01

    that butyrate inhibits neutrophil ROS release in a dose and time-dependent fashion. Given the short half-life of butyrate, chitosan/hyaluronan nanoparticles are next designed and developed as controlled release carriers able to provide cells with a long-lasting supply of this SCFA. Notably, while the inhibition...... of neutrophil ROS production by free butyrate declines over time, that of butyrate-loaded chitosan/hyaluronan nanoparticles (B-NPs) is sustained. Additional valuable features of these nanoparticles are inherent ROS scavenger activity, resistance to cell internalization, and mucoadhesiveness. B-NPs appear...

  18. Hyaluronan protection of corneal endothelial cells against extracellular histones after phacoemulsification.

    Science.gov (United States)

    Kawano, Hiroki; Sakamoto, Taiji; Ito, Takashi; Miyata, Kazunori; Hashiguchi, Teruto; Maruyama, Ikuro

    2014-11-01

    To determine the effect of histones on corneal endothelial cells generated during cataract surgery. Kagoshima University Hospital, Kagoshima, Japan. Experimental study. Standard phacoemulsification was performed on enucleated pig eyes. Histones in the anterior segment of the eye were determined by immunohistochemistry. Cultured human corneal endothelial cells were exposed to histones for 18 hours, and cell viability was determined by 2-(2-methoxy-4-nitrophenyl)-3-(4-nitro-phenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium, monosodium salt assay. The concentration of interleukin-6 (IL-6) in the culture medium of human corneal endothelial cells was measured using enzyme-linked immunosorbent assay. The effects of signal inhibitors U0126, SB203580, and SP600125 were evaluated. The protective effect of hyaluronan against histones was evaluated in human corneal endothelial cells with and without hyaluronan. Cellular debris containing histones was observed in the anterior chamber of pig eyes after phacoemulsification. Exposure of human corneal endothelial cells to 50 μg/mL of histones or more led to cytotoxic effects. The IL-6 concentration was significantly increased dose dependently after exposure of human corneal endothelial cells to histones (Phistone-induced IL-6 production was significantly decreased by extracellular signal-regulated kinases 1/2 and p-38 mitogen-activated protein kinase inhibitors (Phistones caused formation of histone aggregates, decreased the cytotoxic effects of the histones, and blocked the increase in IL-6 (PHistones were released extracellularly during phacoemulsification and exposure of human corneal endothelial cells to histones increased the IL-6 secretion. The intraoperative use of hyaluronan may decrease the cytotoxic effects of histones released during cataract surgery. No author has a financial or proprietary interest in any material or method mentioned. Copyright © 2014 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

  19. Cleavage of Hyaluronan and CD44 Adhesion Molecule Regulate Astrocyte Morphology via Rac1 Signalling.

    Directory of Open Access Journals (Sweden)

    Anna Konopka

    Full Text Available Communication of cells with their extracellular environment is crucial to fulfill their function in physiological and pathophysiological conditions. The literature data provide evidence that such a communication is also important in case of astrocytes. Mechanisms that contribute to the interaction between astrocytes and extracellular matrix (ECM proteins are still poorly understood. Hyaluronan is the main component of ECM in the brain, where its major receptor protein CD44 is expressed by a subset of astrocytes. Considering the fact that functions of astrocytes are tightly coupled with changes in their morphology (e.g.: glutamate clearance in the synaptic cleft, migration, astrogliosis, we investigated the influence of hyaluronan cleavage by hyaluronidase, knockdown of CD44 by specific shRNA and CD44 overexpression on astrocyte morphology. Our results show that hyaluronidase treatment, as well as knockdown of CD44, in astrocytes result in a "stellate"-like morphology, whereas overexpression of CD44 causes an increase in cell body size and changes the shape of astrocytes into flattened cells. Moreover, as a dynamic reorganization of the actin cytoskeleton is supposed to be responsible for morphological changes of cells, and this reorganization is controlled by small GTPases of the Rho family, we hypothesized that GTPase Rac1 acts as a downstream effector for hyaluronan and CD44 in astrocytes. We used FRET-based biosensor and a dominant negative mutant of Rac1 to investigate the involvement of Rac1 activity in hyaluronidase- and CD44-dependent morphological changes of astrocytes. Both, hyaluronidase treatment and knockdown of CD44, enhances Rac1 activity while overexpression of CD44 reduces the activity state in astrocytes. Furthermore, morphological changes were blocked by specific inhibition of Rac1 activity. These findings indicate for the first time that regulation of Rac1 activity is responsible for hyaluronidase and CD44-driven morphological

  20. Cleavage of Hyaluronan and CD44 Adhesion Molecule Regulate Astrocyte Morphology via Rac1 Signalling.

    Science.gov (United States)

    Konopka, Anna; Zeug, Andre; Skupien, Anna; Kaza, Beata; Mueller, Franziska; Chwedorowicz, Agnieszka; Ponimaskin, Evgeni; Wilczynski, Grzegorz M; Dzwonek, Joanna

    2016-01-01

    Communication of cells with their extracellular environment is crucial to fulfill their function in physiological and pathophysiological conditions. The literature data provide evidence that such a communication is also important in case of astrocytes. Mechanisms that contribute to the interaction between astrocytes and extracellular matrix (ECM) proteins are still poorly understood. Hyaluronan is the main component of ECM in the brain, where its major receptor protein CD44 is expressed by a subset of astrocytes. Considering the fact that functions of astrocytes are tightly coupled with changes in their morphology (e.g.: glutamate clearance in the synaptic cleft, migration, astrogliosis), we investigated the influence of hyaluronan cleavage by hyaluronidase, knockdown of CD44 by specific shRNA and CD44 overexpression on astrocyte morphology. Our results show that hyaluronidase treatment, as well as knockdown of CD44, in astrocytes result in a "stellate"-like morphology, whereas overexpression of CD44 causes an increase in cell body size and changes the shape of astrocytes into flattened cells. Moreover, as a dynamic reorganization of the actin cytoskeleton is supposed to be responsible for morphological changes of cells, and this reorganization is controlled by small GTPases of the Rho family, we hypothesized that GTPase Rac1 acts as a downstream effector for hyaluronan and CD44 in astrocytes. We used FRET-based biosensor and a dominant negative mutant of Rac1 to investigate the involvement of Rac1 activity in hyaluronidase- and CD44-dependent morphological changes of astrocytes. Both, hyaluronidase treatment and knockdown of CD44, enhances Rac1 activity while overexpression of CD44 reduces the activity state in astrocytes. Furthermore, morphological changes were blocked by specific inhibition of Rac1 activity. These findings indicate for the first time that regulation of Rac1 activity is responsible for hyaluronidase and CD44-driven morphological changes of

  1. Synthesis and Characterization of Rhodamine B-ethylenediamine-hyaluronan Acid as Potential Biological Functional Materials

    Science.gov (United States)

    Li, Y. L.; Wang, W. X.; Wang, Y.; Zhang, W. B.; Gong, H. M.; Liu, M. X.

    2018-05-01

    The purpose of this study is to synthesize and characterize fluorescent polymers, rhodamine B-ethylenediamine-hyaluronan acid (RhB-EA-HA). RhB-EA-HA was successfully synthesized by ester ammonolysis reaction and amidation reaction. Moreover, the structural properties of RhB-EA-HA were characterized by 1H-NMR spectra, UV-vis spectrometry and Fourier transform infrared spectroscopy (FT-IR). RhB-EA-HA can be grafted on the surface of silica nanomaterials, which may be potential biological functional materials for drug delivery system.

  2. Hyaluronan in the neonatal period. An experimental and clinical study in asphyxia and infection

    OpenAIRE

    Østerholt, Helene C. Dale

    2014-01-01

    List of papers. Paper II is removed from the thesis due to publisher restrictions. I. Østerholt HCD, Dannevig I, Wyckoff MH, Liao J, Akgul Y, Ramgopal M, Milja, DS, Cheong N, Longoria C, Mahendroo M, Nakstad B, Saugstad OD and Savani RC Antioxidant protects against increases in low molecular weight hyaluronan and inflammation in asphyxiated newborn pigs resuscitated with 100% oxygen. PLoS One 2012;7(6):e38839 doi:10.1371/journal.pone.0038839 © 2012 Østerholt et al. This is an open-access ...

  3. Can Plasma Hyaluronan and Hyaluronidase Be Used As Markers of the Endothelial Glycocalyx State in Patients with Kidney Disease?

    NARCIS (Netherlands)

    Vlahu, Carmen A.; Krediet, Raymond T.

    2015-01-01

    Hyaluronan (HA) is widely spread in the body and is an important component of the extracellular matrix, including the endothelial glycocalyx (EG). Essential for its vasculoprotective function, HA is involved in vascular permeability and many other processes. In patients with kidney disease, plasma

  4. A hyaluronan-based nerve guide : in vitro cytotoxicity, subcutaneous tissue reactions, and degradation in the rat

    NARCIS (Netherlands)

    Jansen, K; van Wachem, PB; Nicolai, JPA; de Leij, LFMH; van Luyn, MJA; van der Werf, J.F.A.

    We investigated possible cytotoxic effects, biocompatibility, and degradation of a hyaluronan-based conduit for peripheral nerve repair. We subjected the conduits to an in vitro fibroblast cytotoxicity test and concluded that the conduits were not cytotoxic. Subsequently, we implanted the conduits

  5. Hyaluronan-induced masking of ErbB2 and CD44-enhanced trastuzumab internalisation in trastuzumab resistant breast cancer.

    Science.gov (United States)

    Pályi-Krekk, Zsuzsanna; Barok, Márk; Isola, Jorma; Tammi, Markku; Szöllosi, János; Nagy, Peter

    2007-11-01

    Although trastuzumab, a recombinant humanised anti-ErbB2 antibody, is widely used in the treatment of breast cancer, neither its mechanism of action, nor the factors leading to resistance are fully understood. We have previously shown that antibody-dependent cellular cytotoxicity is pivotal in the in vivo effect of trastuzumab against JIMT-1, a cell line showing in vitro resistance to the antibody, and suggested that masking of the trastuzumab-binding epitope by MUC-4, a cell surface mucin, took place. Here, we further explored the role of masking of ErbB2 in connection with CD44 expression and synthesis of its ligand, hyaluronan. We show that high expression of CD44 observed in JIMT-1 cells correlates with ErbB2 downregulation in vivo, while siRNA-mediated inhibition of CD44 expression leads to decreased rate of trastuzumab internalisation and low cell proliferation in vitro. An inhibitor of hyaluronan synthesis, 4-methylumbelliferon (4-MU) significantly reduced the hyaluronan level of JIMT-1 cells both in vivo and in vitro leading to enhanced binding of trastuzumab to ErbB2 and increased ErbB2 down-regulation. Furthermore, the inhibitory effect of trastuzumab on the growth of JIMT-1 xenografts was significantly increased by 4-MU treatment. Our results point to the importance of the CD44-hyaluronan pathway in the escape of tumour cells from receptor-oriented therapy.

  6. EFFECTS OF HYALURONAN ON THREE-DIMENSIONAL MICROARCHITECTURE OF SUBCHONDRAL BONE TISSUES IN GUINEA PIG PRIMARY OSTEOARTHROSIS

    DEFF Research Database (Denmark)

    Ding, Ming

    Introduction: It is not known whether hyaluronan (HA) has any effect on the underlying subchondral bone tissues. This study was to investigate the effects of high molecular weight HA (1.5x106 Daltons) intra-articular injection on subchondral bone tissues. Methods: Fifty-six male guinea pigs (6...

  7. Survival of cord blood haematopoietic stem cells in a hyaluronan hydrogel for ex vivo biomimicry.

    Science.gov (United States)

    Demange, Elise; Kassim, Yusra; Petit, Cyrille; Buquet, Catherine; Dulong, Virginie; Cerf, Didier Le; Buchonnet, Gérard; Vannier, Jean-Pierre

    2013-11-01

    Haematopoietic stem cells (HSCs) and haematopoietic progenitor cells (HPCs) grow in a specified niche in close association with the microenvironment, the so-called 'haematopoietic niche'. Scaffolds have been introduced to overcome the liquid culture limitations, mimicking the presence of the extracellular matrix (ECM). In the present study the hyaluronic acid scaffold, already developed in the laboratory, has been used for the first time to maintain long-term cultures of CD34⁺ haematopoietic cells obtained from human cord blood. One parameter investigated was the impact on ex vivo survival of CD34⁺ cord blood cells (CBCs) on the hyaluronic acid surface, immobilized with peptides containing the RGD motif. This peptide was conjugated by coating the hyaluronan hydrogel and cultured in serum-free liquid phase complemented with stem cell factor (SCF), a commonly indispensable cytokine for haematopoiesis. Our work demonstrated that these hyaluronan hydrogels were superior to traditional liquid cultures by maintaining and expanding the HPCs without the need for additional cytokines, and a colonization of 280-fold increment in the hydrogel compared with liquid culture after 28 days of ex vivo expansion. Copyright © 2012 John Wiley & Sons, Ltd.

  8. Hyaluronan functionalizing QDs as turn-on fluorescent probe for targeted recognition CD44 receptor

    Science.gov (United States)

    Zhou, Shang; Huo, Danqun; Hou, Changjun; Yang, Mei; Fa, Huanbao

    2017-09-01

    The recognition of tumor markers in living cancer cells has attracted increasing interest. In the present study, the turn-on fluorescence probe was designed based on the fluorescence of thiolated chitosan-coated CdTe QDs (CdTe/TCS QDs) quenched by hyaluronan, which could provide the low background signal for sensitive cellular imaging. This system is expected to offer specific recognition of CD44 receptor over other substances owing to the specific affinity of hyaluronan and CD44 receptor ( 8-9 kcal/mol). The probe is stable in aqueous and has little toxicity to living cells; thus, it can be utilized for targeted cancer cell imaging. The living lung cancer cell imaging experiments further demonstrate its value in recognizing cell-surface CD44 receptor with turn-on mode. In addition, the probe can be used to recognize and differentiate the subtypes of lung cancer cells based on the difference of CD44 expression on the surface of lung cancer cells. And, the western blot test further confirmed that the expression level of the CD44 receptor in lung cancer cells is different. Therefore, this probe may be potentially applied in recognizing lung cancer cells with higher contrast and sensitivity and provide new tools for cancer prognosis and therapy. [Figure not available: see fulltext.

  9. Self-reinforcement and protein sustained delivery of hyaluronan hydrogel by tailoring a dually cross-linked network

    International Nuclear Information System (INIS)

    Luo, Chunhong; Xu, Guoguang; Wang, Xinghui; Tu, Mei; Zeng, Rong; Rong, Jianhua; Zhao, Jianhao

    2015-01-01

    A series of self-reinforcing hyaluronan hydrogels were developed to improve mechanical properties and protein sustained delivery thanks to a dually cross-linked network. Hyaluronan gel particles (HGPs, 1–5 μm in diameter) with different cross-linking densities, i.e. HGPs-1.5, HGPs-3 and HGPs-15, were prepared in an inverse emulsion system and used as the reinforcing phase after glycidyl methacrylation, while glycidyl methacrylated hyaluronan with a substitution degree of 45.2% was synthesized as the matrix phase. These two phases were cross-linked under ultraviolet irradiation to form self-reinforcing hyaluronan hydrogels (srHAs) that showed typical cross-linked structure of HGPs connecting the matrix phase by cross-section observation. In comparison to hyaluronan bulk gels and their blends with HGPs, srHAs distinctly enhanced the mechanical properties and BSA long-term sustained delivery, especially srHA-1.5 showed the highest compressive modulus of 220 ± 15 kPa and the slowest BSA delivery (67% release at 14 d). The 3T3 fibroblast cell culture showed that all the srHAs had no cytotoxicity. - Highlights: • New self-reinforcing HA hydrogels with a dually cross-linked network were developed. • Self-reinforcing HA hydrogels greatly enhanced the mechanical properties. • Self-reinforcing HA hydrogels prolonged the sustained delivery of BSA. • The self-reinforcing mechanism and BSA diffusion mechanism were discussed. • Self-reinforcing HA hydrogels had no cytotoxicity to 3T3 fibroblast cells

  10. The effect of different doses of hyaluronan on sperm morphology, motility, vitality and fertilization capability in mouse

    Directory of Open Access Journals (Sweden)

    S. Sayadi

    2006-07-01

    Full Text Available Background: Hyaluronan has an important role on the permeability and motility of sperm and the interaction of gametes and these can play a considerable role on the fertility rate. Therefore, in this study, we assessed the effect of different doses of hyaluronan on the morphology, motility, vitality and fertility rate of mice. Methods: We used 40 mice (6-8 week in this study which twenty of them were male and the rest were female. The sperm of each male mouse were divided into four groups. The group 1 (control: They were maintained in RPMI media without any hyaluronan supplementation for 2 hour. Hyaluronan with the doses of 750, 1000 and 1250 µg/ml were added into RPMI media in groups 2, 3 and 4, respectively. After 2 hour. incubation, the numbers of sperms were assessed, using haemocytometer. Also, their morphology with papanicolaeu staining and their vitality with Eosin B dye were assessed. As well as sperms motility measured under inverted microscope by observation and fertility rate evaluated after routine IVF by counting two-cell stage embryos. Results: Our results demonstrated that, the dose of 750 µ g/ml has the greatest effect on the motility, vitality and fertility rate of sperms. The effect of dose of 1000 µ g/ml also was positive on them. On the other hand, none of these doses had any effect on sperm morphology. Conclusion: Hyaluronan may have an influence on motility, vitality and fertility rate of sperms and the dose of 750µ g/ml had a significant effect on these factors.

  11. Self-reinforcement and protein sustained delivery of hyaluronan hydrogel by tailoring a dually cross-linked network

    Energy Technology Data Exchange (ETDEWEB)

    Luo, Chunhong; Xu, Guoguang; Wang, Xinghui [Department of Materials Science and Engineering, College of Science and Engineering, Jinan University, Guangzhou 510632 (China); Tu, Mei; Zeng, Rong; Rong, Jianhua [Department of Materials Science and Engineering, College of Science and Engineering, Jinan University, Guangzhou 510632 (China); Engineering Research Center of Artificial Organs and Materials, Ministry of Education, Guangzhou 510632 (China); Zhao, Jianhao, E-mail: jhzhao@jnu.edu.cn [Department of Materials Science and Engineering, College of Science and Engineering, Jinan University, Guangzhou 510632 (China); Engineering Research Center of Artificial Organs and Materials, Ministry of Education, Guangzhou 510632 (China)

    2015-01-01

    A series of self-reinforcing hyaluronan hydrogels were developed to improve mechanical properties and protein sustained delivery thanks to a dually cross-linked network. Hyaluronan gel particles (HGPs, 1–5 μm in diameter) with different cross-linking densities, i.e. HGPs-1.5, HGPs-3 and HGPs-15, were prepared in an inverse emulsion system and used as the reinforcing phase after glycidyl methacrylation, while glycidyl methacrylated hyaluronan with a substitution degree of 45.2% was synthesized as the matrix phase. These two phases were cross-linked under ultraviolet irradiation to form self-reinforcing hyaluronan hydrogels (srHAs) that showed typical cross-linked structure of HGPs connecting the matrix phase by cross-section observation. In comparison to hyaluronan bulk gels and their blends with HGPs, srHAs distinctly enhanced the mechanical properties and BSA long-term sustained delivery, especially srHA-1.5 showed the highest compressive modulus of 220 ± 15 kPa and the slowest BSA delivery (67% release at 14 d). The 3T3 fibroblast cell culture showed that all the srHAs had no cytotoxicity. - Highlights: • New self-reinforcing HA hydrogels with a dually cross-linked network were developed. • Self-reinforcing HA hydrogels greatly enhanced the mechanical properties. • Self-reinforcing HA hydrogels prolonged the sustained delivery of BSA. • The self-reinforcing mechanism and BSA diffusion mechanism were discussed. • Self-reinforcing HA hydrogels had no cytotoxicity to 3T3 fibroblast cells.

  12. Hyaluronan signaling during ozone-induced lung injury requires TLR4, MyD88, and TIRAP.

    Directory of Open Access Journals (Sweden)

    Zhuowei Li

    Full Text Available Ozone exposure is associated with exacerbation of reactive airways disease. We have previously reported that the damage-associated molecular pattern, hyaluronan, is required for the complete biological response to ambient ozone and that hyaluronan fragments signal through toll-like receptor 4 (TLR4. In this study, we further investigated the role of TLR4 adaptors in ozone-induced airway hyperresponsiveness (AHR and the direct response to hyaluronan fragments (HA. Using a murine model of AHR, C57BL/6J, TLR4-/-, MyD88-/-, and TIRAP-/- mice were characterized for AHR after exposure to either ozone (1 ppm × 3 h or HA fragments. Animals were characterized for AHR with methacholine challenge, cellular inflammation, lung injury, and production of pro-inflammatory cytokines. Ozone-exposed C57BL/6J mice developed cellular inflammation, lung injury, pro-inflammatory cytokines, and AHR, while mice deficient in TLR4, MyD88 or TIRAP demonstrated both reduced AHR and reduced levels of pro-inflammatory cytokines including TNFα, IL-1β, MCP-1, IL-6 and KC. The level of hyaluronan was increased after inhalation of ozone in each strain of mice. Direct challenge of mice to hyaluronan resulted in AHR in C57BL/6J mice, but not in TLR4-/-, MyD88-/-, or TIRAP-/- mice. HA-induced cytokine production in wild-type mice was significantly reduced in TLR4-/-, MyD88-/-, or TIRAP-/- mice. In conclusion, our findings support that ozone-induced airway hyperresponsiveness is dependent on the HA-TLR4-MyD88-TIRAP signaling pathway.

  13. Modeling of hyaluronan clearance with application to estimation of lymph flow

    International Nuclear Information System (INIS)

    Rössler, Andreas; Goswami, Nandu; Fink, Martin; Batzel, Jerry J

    2011-01-01

    One of the important factors in blood pressure regulation is the maintenance of the level of blood volume, which depends on several factors including the rate of lymph flow. Lymph flow can be measured directly using cannulation of lymphatic vessels, which is not clinically feasible, or indirectly by the tracer appearance rate, which is the rate at which macromolecules appear into the blood from the peritoneal cavity. However, indirect lymph flow measurements do not always provide consistent results. Through its contribution to osmotic pressure and resistance to flow, the macromolecule hyaluronan takes part in the regulation of tissue hydration and the maintenance of water and protein homeostasis. It arrives in blood plasma through lymph flow. Lymphatic hyaluronic acid (HA, hyaluronan) concentration is several times higher than that in plasma, suggesting that the lymphatic route may account for the majority of HA found in plasma. Furthermore, circulating levels of HA reflect the dynamic state between delivery to—and removal from—the bloodstream. To develop an accurate estimation of the fluid volume distribution and dynamics, the rate of lymph flow needs to be taken into account and hyaluronan could be used as a marker in estimating this flow. To examine the HA distribution and system fluid dynamics, a six-compartment model, which could reflect both the steady-state relationships and qualitative characteristics of the dynamics, was developed. This was then applied to estimate fluid shifts from the interstitial space via the lymphatic system to the plasma during different physiological stresses (orthostatic stress and the stress of ultrafiltration during dialysis). Sensitivity analysis shows that during ultrafiltration, lymph flow is a key parameter influencing the total HA level, thus suggesting that the model may find applications in addressing the problem of estimating lymph flow. Since the fluid balance between interstitium and plasma is maintained by lymph

  14. Thermo-and pH-sensitive hydrogel membranes composed of poly(N-isopropylacrylamide)-hyaluronan for biomedical applications: Influence of hyaluronan incorporation on the membrane properties.

    Science.gov (United States)

    Kamoun, Elbadawy A; Fahmy, Alaa; Taha, Tarek H; El-Fakharany, Esmail M; Makram, Mohamed; Soliman, Hesham M A; Shehata, Hassan

    2018-01-01

    Interpenetrating hydrogel membranes consisting of pH-sensitive hyaluronan (HA) and thermo-sensitive poly(N-isopropylacrylamide) (PNIPAAM) were synthesized using redox polymerization, followed by N,N-methylenebisacrylamide (BIS) and epichlorohydrin (EPI) were added as chemical crosslinkers. The interaction between membrane compositions has been characterized by FTIR spectroscopy and discussed intensively. The result indicates that HA incorporation in membranes increase the gel fraction, swelling uptake, and the flexibility/elasticity of crosslinked membranes, however it reduced oppositely the mechanical elongation of membranes. PNIPAAm-HA hydrogels responded to both temperature and pH changes and the stimuli-responsiveness was reversible. However, in vitro bioevaluation results revealed that the released ampicillin during the burst release time was sharply influenced and increased with increasing HA contents in membranes; afterwards it became sustainable. Whereas, high HA contents in hydrogels unexpectedly impacted negatively on the cells viability, owing to the viscosity of cell culture media changed. A big resistance was observed against microbial growth of Staphylococcus aureus, Salmonella typhi, and Candida albicans in case of pure PNIPAAm hydrogel membranes without HA or ampicillin. However, HA incorporation or the loaded ampicillin in membranes showed unexpected easily microbial growth. The fast release performance with dual pH-thermo-sensitive hydrogels were suggested as promising materials for quick drug carrier in the biomedical field. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Hyaluronan and Hyaluronan-Binding Proteins Accumulate in Both Human Type 1 Diabetic Islets and Lymphoid Tissues and Associate With Inflammatory Cells in Insulitis

    Science.gov (United States)

    Bogdani, Marika; Johnson, Pamela Y.; Potter-Perigo, Susan; Nagy, Nadine; Day, Anthony J.; Bollyky, Paul L.

    2014-01-01

    Hyaluronan (HA) is an extracellular matrix glycosaminoglycan that is present in pancreatic islets, but little is known about its involvement in the development of human type 1 diabetes (T1D). We have evaluated whether pancreatic islets and lymphoid tissues of T1D and nondiabetic organ donors differ in the amount and distribution of HA and HA-binding proteins (hyaladherins), such as inter-α-inhibitor (IαI), versican, and tumor necrosis factor–stimulated gene-6 (TSG-6). HA was dramatically increased both within the islet and outside the islet endocrine cells, juxtaposed to islet microvessels in T1D. In addition, HA was prominent surrounding immune cells in areas of insulitis. IαI and versican were present in HA-rich areas of islets, and both molecules accumulated in diabetic islets and regions exhibiting insulitis. TSG-6 was observed within the islet endocrine cells and in inflammatory infiltrates. These patterns were only observed in tissues from younger donors with disease duration of <10 years. Furthermore, HA and IαI amassed in follicular germinal centers and in T-cell areas in lymph nodes and spleens in T1D patients compared with control subjects. Our observations highlight potential roles for HA and hyaladherins in the pathogenesis of diabetes. PMID:24677718

  16. Nanofilms of hyaluronan/chitosan assembled layer-by-layer: An antibacterial surface for Xylella fastidiosa.

    Science.gov (United States)

    Hernández-Montelongo, Jacobo; Nascimento, Vicente F; Murillo, Duber; Taketa, Thiago B; Sahoo, Prasana; de Souza, Alessandra A; Beppu, Marisa M; Cotta, Monica A

    2016-01-20

    In this work, nanofilms of hyaluronan/chitosan (HA/CHI) assembled layer by layer were synthesized; their application as a potential antimicrobial material was demonstrated for the phytopathogen Xylella fastidiosa, a gram-negative bacterium, here used as a model. For the synthesis, the influence of pH and ionic strength of these natural polymer stem-solutions on final characteristics of the HA/CHI nanofilms was studied in detail. The antibacterial effect was evaluated using widefield fluorescence microscopy. These results were correlated with the chemical properties of the nanofilms, studied by FTIR and Raman spectroscopy, as well as with their morphology and surface properties characterized using SEM and AFM. The present findings can be extended to design and optimize HA/CHI nanofilms with enhanced antimicrobial behavior for other type of phytopathogenic gram-negative bacteria species, such as Xanthomonas citri, Xanthomas campestri and Ralstonia solanacearum. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Local injection of high-molecular hyaluronan promotes wound healing in old rats by increasing angiogenesis.

    Science.gov (United States)

    Huang, Luying; Wang, Yi; Liu, Hua; Huang, Jianhua

    2018-02-02

    Impaired angiogenesis contributes to delayed wound healing in aging. Hyaluronan (HA) has a close relationship with angiogenesis and wound healing. However, HA content decreases with age. In this study, we used high molecular weight HA (HMW-HA) (1650 kDa), and investigated its effects on wound healing in old rats by local injection. We found that HMW-HA significantly increases proliferation, migration and tube formation in endothelial cells, and protects endothelial cells against apoptosis. Local injection of HMW-HA promotes wound healing by increasing angiogenesis in old rats. HMW-HA increases the phosphorylation of Src, ERK and AKT, leading to increased angiogenesis, suggesting that local injection of HMW-HA promotes wound healing in elderly patients.

  18. Effects of inhaled high-molecular weight hyaluronan in inflammatory airway disease.

    Science.gov (United States)

    Lamas, Adelaida; Marshburn, Jamie; Stober, Vandy P; Donaldson, Scott H; Garantziotis, Stavros

    2016-10-03

    Cystic fibrosis (CF) is a chronic inflammatory disease that is affecting thousands of patients worldwide. Adjuvant anti-inflammatory treatment is an important component of cystic fibrosis treatment, and has shown promise in preserving lung function and prolonging life expectancy. Inhaled high molecular weight hyaluronan (HMW-HA) is reported to improve tolerability of hypertonic saline and thus increase compliance, and has been approved in some European countries for use as an adjunct to hypertonic saline treatment in cystic fibrosis. However, there are theoretical concerns that HMW-HA breakdown products may be pro-inflammatory. In this clinical pilot study we show that sputum cytokines in CF patients receiving HMW-HA are not increased, and therefore HMW-HA does not appear to adversely affect inflammatory status in CF airways.

  19. Study on gamma radiation-induced synthesis of gold nanoparticles stabilized by hyaluronan

    International Nuclear Information System (INIS)

    Dang Van Phu; Bui Duy Du

    2013-01-01

    Gold nanoparticles (AuNPs) with diameter from 4 to 10 nm were synthesized by γ-irradiation in hyaluronan (HA) solution without usage of any OH radical scavenger. The size distribution of AuNPs were determined by TEM images. The λ max (517-525 nm) of colloidal AuNPs solutions as prepared was measured by UV-Vis spectroscopy. The influence factor on the size of AuNPs particularly the concentration of Au 3+ , HA and dose rate were investigated. The colloidal solution of AuNPs/HA as synthesized was stable more than 6 months stored under ambient condition. AuNPs with the size less than 10 nm narrow size distribution stabilized by HA which is biocompatible polysaccharide can potentially be applied in biomedicine and cosmetic. (author)

  20. Study on gamma radiation-induced synthesis of gold nanoparticles stabilized by hyaluronan

    International Nuclear Information System (INIS)

    Dang Van Phu; Nguyen Ngoc Duy; Nguyen Tue Anh; Nguyen Quoc Hien

    2011-01-01

    Gold nanoparticles (AuNPs) with diameter from 4 to 10 nm were synthesized in hyaluronan (HA) solution without usage of any reductant and *OH radical scavenger by gamma irradiation reduction. The size and size distribution of AuNPs were determined by TEM images. The λ max (517 - 525 nm) of colloidal AuNPs solutions as prepared were measured by UV-Vis spectroscopy. The influence factors on the size of AuNPs particularly the concentration of Au 3+ , HA and dose rate were investigated. The stability of AuNPs/HA as synthesized was more than 6 months in storage under atmospheric condition. AuNPs with the size less than 10 nm and narrow size distribution stabilized by HA which is biocompatible natural polysaccharide so that AuNPs/HA can potentially be applied in biomedicine and cosmetic. (author)

  1. Cross-Linked Hyaluronan Gel Reduces the Acute Rectal Toxicity of Radiotherapy for Prostate Cancer

    International Nuclear Information System (INIS)

    Wilder, Richard B.; Barme, Greg A.; Gilbert, Ronald F.; Holevas, Richard E.; Kobashi, Luis I.; Reed, Richard R.; Solomon, Ronald S.; Walter, Nancy L.; Chittenden, Lucy; Mesa, Albert V.; Agustin, Jeffrey; Lizarde, Jessica; Macedo, Jorge; Ravera, John; Tokita, Kenneth M.

    2010-01-01

    Purpose: To prospectively analyze whether cross-linked hyaluronan gel reduces the mean rectal dose and acute rectal toxicity of radiotherapy for prostate cancer. Methods and Materials: Between September 2008 and March 2009, we transperitoneally injected 9mL of cross-linked hyaluronan gel (Hylaform; Genzyme Corporation, Cambridge, MA) into the anterior perirectal fat of 10 early-stage prostate cancer patients to increase the separation between the prostate and rectum by 8 to 18mm at the start of radiotherapy. Patients then underwent high-dose rate brachytherapy to 2,200cGy followed by intensity-modulated radiation therapy to 5,040cGy. We assessed acute rectal toxicity using the National Cancer Institute Common Terminology Criteria for Adverse Events v3.0 grading scheme. Results: Median follow-up was 3 months. The anteroposterior dimensions of Hylaform at the start and end of radiotherapy were 13 ± 3mm (mean ± SD) and 10 ± 4mm, respectively. At the start of intensity-modulated radiation therapy, daily mean rectal doses were 73 ± 13cGy with Hylaform vs. 106 ± 20cGy without Hylaform (p = 0.005). There was a 0% incidence of National Cancer Institute Common Terminology Criteria for Adverse Events v3.0 Grade 1, 2, or 3 acute diarrhea in 10 patients who received Hylaform vs. a 29.7% incidence (n = 71) in 239 historical controls who did not receive Hylaform (p = 0.04). Conclusions: By increasing the separation between the prostate and rectum, Hylaform decreased the mean rectal dose. This led to a significant reduction in the acute rectal toxicity of radiotherapy for prostate cancer.

  2. Hyaluronan, Cancer-Associated Fibroblasts and the Tumor Microenvironment in Malignant Progression

    Directory of Open Access Journals (Sweden)

    James B. McCarthy

    2018-05-01

    Full Text Available This review summarizes the roles of CAFs in forming a “cancerized” fibrotic stroma favorable to tumor initiation and dissemination, in particular highlighting the functions of the extracellular matrix component hyaluronan (HA in these processes. The structural complexity of the tumor and its host microenvironment is now well appreciated to be an important contributing factor to malignant progression and resistance-to-therapy. There are multiple components of this complexity, which include an extensive remodeling of the extracellular matrix (ECM and associated biomechanical changes in tumor stroma. Tumor stroma is often fibrotic and rich in fibrillar type I collagen and hyaluronan (HA. Cancer-associated fibroblasts (CAFs are a major source of this fibrotic ECM. CAFs organize collagen fibrils and these biomechanical alterations provide highways for invading carcinoma cells either under the guidance of CAFs or following their epithelial to mesenchymal transition (EMT. The increased HA metabolism of a tumor microenvironment instructs carcinoma initiation and dissemination by performing multiple functions. The key effects of HA reviewed here are its role in activating CAFs in pre-malignant and malignant stroma, and facilitating invasion by promoting motility of both CAFs and tumor cells, thus facilitating their invasion. Circulating CAFs (cCAFs also form heterotypic clusters with circulating tumor cells (CTC, which are considered to be pre-cursors of metastatic colonies. cCAFs are likely required for extravasation of tumors cells and to form a metastatic niche suitable for new tumor colony growth. Therapeutic interventions designed to target both HA and CAFs in order to limit tumor spread and increase response to current therapies are discussed.

  3. Chemotherapy-induced hyaluronan production: a novel chemoresistance mechanism in ovarian cancer

    International Nuclear Information System (INIS)

    Ricciardelli, Carmela; Ween, Miranda P; Lokman, Noor A; Tan, Izza A; Pyragius, Carmen E; Oehler, Martin K

    2013-01-01

    Hyaluronan (HA) an important component of the extracellular matrix, has been linked to tumor progression and drug resistance in several malignancies. However, limited data is available for ovarian cancer. This study investigated the role of hyaluronan (HA) and a potential link between the HA-CD44 pathway and membrane ATP binding cassette (ABC) transporter proteins in ovarian cancer chemoresistance. We investigated the ability of HA to block the cytotoxic effects of the chemotherapy drug carboplatin, and to regulate the expression of ABC transporters in ovarian cancer cells. We also examined HA serum levels in ovarian cancer patients prior to and following chemotherapy and assessed its prognostic relevance. HA increased the survival of carboplatin treated ovarian cancer cells expressing the HA receptor, CD44 (OVCAR-5 and OV-90). Carboplatin significantly increased expression of HAS2, HAS3 and ABCC2 and HA secretion in ovarian cancer cell conditioned media. Serum HA levels were significantly increased in patients following platinum based chemotherapy and at both 1st and 2nd recurrence when compared with HA levels prior to treatment. High serum HA levels (>50 μg/ml) prior to chemotherapy treatment were associated with significantly reduced progression-free (P = 0.014) and overall survival (P = 0.036). HA production in ovarian cancer cells was increased in cancer tissues collected following chemotherapy treatment and at recurrence. Furthermore HA treatment significantly increased the expression of ABC drug transporters (ABCB3, ABCC1, ABCC2, and ABCC3), but only in ovarian cancer cells expressing CD44. The effects of HA and carboplatin on ABC transporter expression in ovarian cancer cells could be abrogated by HA oligomer treatment. Importantly, HA oligomers increased the sensitivity of chemoresistant SKOV3 cells to carboplatin. Our findings indicate that carboplatin chemotherapy induces HA production which can contribute to chemoresistance by regulating ABC

  4. High-molecular-mass hyaluronan mediates the cancer resistance of the naked mole rat.

    Science.gov (United States)

    Tian, Xiao; Azpurua, Jorge; Hine, Christopher; Vaidya, Amita; Myakishev-Rempel, Max; Ablaeva, Julia; Mao, Zhiyong; Nevo, Eviatar; Gorbunova, Vera; Seluanov, Andrei

    2013-07-18

    The naked mole rat (Heterocephalus glaber) displays exceptional longevity, with a maximum lifespan exceeding 30 years. This is the longest reported lifespan for a rodent species and is especially striking considering the small body mass of the naked mole rat. In comparison, a similarly sized house mouse has a maximum lifespan of 4 years. In addition to their longevity, naked mole rats show an unusual resistance to cancer. Multi-year observations of large naked mole-rat colonies did not detect a single incidence of cancer. Here we identify a mechanism responsible for the naked mole rat's cancer resistance. We found that naked mole-rat fibroblasts secrete extremely high-molecular-mass hyaluronan (HA), which is over five times larger than human or mouse HA. This high-molecular-mass HA accumulates abundantly in naked mole-rat tissues owing to the decreased activity of HA-degrading enzymes and a unique sequence of hyaluronan synthase 2 (HAS2). Furthermore, the naked mole-rat cells are more sensitive to HA signalling, as they have a higher affinity to HA compared with mouse or human cells. Perturbation of the signalling pathways sufficient for malignant transformation of mouse fibroblasts fails to transform naked mole-rat cells. However, once high-molecular-mass HA is removed by either knocking down HAS2 or overexpressing the HA-degrading enzyme, HYAL2, naked mole-rat cells become susceptible to malignant transformation and readily form tumours in mice. We speculate that naked mole rats have evolved a higher concentration of HA in the skin to provide skin elasticity needed for life in underground tunnels. This trait may have then been co-opted to provide cancer resistance and longevity to this species.

  5. High molecular weight hyaluronan mediates the cancer resistance of the naked mole-rat

    Science.gov (United States)

    Tian, Xiao; Azpurua, Jorge; Hine, Christopher; Vaidya, Amita; Myakishev-Rempel, Max; Ablaeva, Julia; Mao, Zhiyong; Nevo, Eviatar; Gorbunova, Vera; Seluanov, Andrei

    2013-01-01

    The naked mole-rat displays exceptional longevity, with a maximum lifespan exceeding 30 years1–3. This is the longest reported lifespan for a rodent species and is especially striking considering the small body mass of the naked mole-rat. In comparison, a similarly sized house mouse has a maximum lifespan of 4 years4,5. In addition to their longevity, naked mole-rats show an unusual resistance to cancer. Multi-year observations of large naked mole-rat colonies did not detect a single incidence of cancer2,6. Here we identify a mechanism responsible for the naked mole-rat’s cancer resistance. We found that naked mole-rat fibroblasts secrete extremely high molecular weight hyaluronan (HA), which is over five times larger than human or mouse HA. This high molecular weight HA accumulates abundantly in naked mole rat tissues due to the decreased activity of HA-degrading enzymes and a unique sequence of hyaluronan synthase 2 (HAS2). Furthermore, the naked mole-rat cells are more sensitive to HA signaling, as the naked mole rat cells have a higher affinity to HA than the mouse or human cells. Perturbation of the signaling pathways sufficient for malignant transformation of mouse fibroblasts fails to transform naked mole-rat cells. However, once high molecular weight HA is removed by either knocking down HAS2 or overexpressing the HA-degrading enzyme, Hyal2, naked mole-rat cells become susceptible to malignant transformation and readily form tumors in mice. We speculate that naked mole-rats have evolved a higher concentration of HA in the skin to provide skin elasticity needed for life in underground tunnels. This trait may have then been co-opted to provide cancer resistance and longevity to this species. PMID:23783513

  6. Glucose regulated proteins 78 and 75 bind to the receptor for hyaluronan mediated motility in interphase microtubules

    International Nuclear Information System (INIS)

    Kuwabara, Hiroko; Yoneda, Masahiko; Hayasaki, Hana; Nakamura, Toshiya; Mori, Hiroshi

    2006-01-01

    The receptor for hyaluronan mediated motility (RHAMM), which is a hyaluronan-binding protein, is a centrosomal and microtubal protein. Here, we have identified two RHAMM-binding proteins, glucose regulated protein (GRP) 78 and GRP75, using co-immunoprecipitation analysis. These two proteins directly bound to glutathione-S-transferase-RHAMM fusion proteins. By double immunostaining, GRP78 and GRP75 colocalized with RHAMM in interphase microtubules, but were separated in mitotic spindles. Prevention of microtubule polymerization by TN-16 and vincristine sulfate induced RHAMM overexpression without a significant change in GRP78/75. Taken together, GRP78/75 and RHAMM complexes may stabilize microtubules in the interphase, associated with a downregulation of RHAMM. These results reveal a new biochemical activity of RHAMM

  7. Oral hyaluronan relieves wrinkles: a double-blinded, placebo-controlled study over a 12-week period

    OpenAIRE

    Oe, Mariko; Sakai, Seigo; Yoshida, Hideto; Okado, Nao; Kaneda, Haruna; Masuda, Yasunobu; Urushibata, Osamu

    2017-01-01

    Mariko Oe,1 Seigo Sakai,1 Hideto Yoshida,1 Nao Okado,1 Haruna Kaneda,1 Yasunobu Masuda,1 Osamu Urushibata2 1R&D Division, Kewpie Corporation, Sengawa-cho, Chofu-shi, 2Department of Dermatology, Toho University Ohashi Medical Center, Ohashi, Meguro-ku, Tokyo, Japan Background: Hyaluronan (HA) has critical moisturizing property and high water retention capacity especially for human skin. This study aimed to evaluate the effect of oral intake of HA. Methods: The mean molecular weight (MW...

  8. Hyaluronan-Based Nanohydrogels as Effective Carriers for Transdermal Delivery of Lipophilic Agents: Towards Transdermal Drug Administration in Neurological Disorders

    Directory of Open Access Journals (Sweden)

    Seong Uk Son

    2017-12-01

    Full Text Available We suggest a convenient nanoemulsion fabrication method to create hyaluronan (HA-based nanohydrogels for effective transdermal delivery. First, hyaluronan-conjugated dodecylamine (HA–Do HA-based polymers to load the lipophilic agents were synthesized with hyaluronan (HA and dodecylamine (Do by varying the substitution ratio of Do to HA. The synthetic yield of HA–Do was more than 80% (HA–Do (A: 82.7 ± 4.7%, HA–Do (B: 87.1 ± 3.9% and HA–Do (C: 81.4 ± 4.5%. Subsequently, nanohydrogels were fabricated using the nanoemulsion method. Indocyanine green (ICG simultaneously self-assembled with HA–Do, and the size depended on the substitution ratio of Do in HA–Do (nanohydrogel (A: 118.0 ± 2.2 nm, nanohydrogel (B: 121.9 ± 11.4 nm, and nanohydrogel (C: 142.2 ± 3.8 nm. The nanohydrogels were delivered into cells, and had excellent biocompatibility. Especially, nanohydrogel (A could deliver and permeate ICG into the deep skin layer, the dermis. This suggests that nanohydrogels can be potent transdermal delivery systems.

  9. Gait patterns after intraarticular treatment of patients with osteoarthritis of the Knee - Hyaluronan versus triamcinolone: a prospective, randomized, doubleblind, monocentric study

    Directory of Open Access Journals (Sweden)

    Skwara A

    2009-04-01

    Full Text Available Abstract Objective Evaluation of gait performance and muscle activity patterns as well as clinical efficacy and safety after single intraarticular injection with hyaluronan compared with triamcinolone in patients with knee osteoarthritis. Materials and Methods This trial evaluated the influence of a single injection of hyaluronan or triamcinolone on gait pattern and muscle activity. For clinical evaluation a visual analogue scale for pain, Lequesne index, and Knee Society Score were used. Quality of life was assessed with the SF-36. Results The complete analysis was performed in 50 of 60 patients. 26 patients were treated with triamcinolone and 24 with hyaluronan. Hyaluronan treatment led to significant improvement of range of motion at hip and knee. Significant improvement could be either demonstrated for the pain scale, Lequesne and Knee Society score in both groups. Quality of life showed greater improvement in the triamcinolone group. Conclusion Single application of high-viscosity hyaluronan shows superior range of motion and pain reduction as well as improvement in clinical results. Even if there was a lack of significant differences compared to triamcinolone, this therapy classified as safe and effective in the short follow up.

  10. Green synthesis, characterization, and anticancer activity of hyaluronan/zinc oxide nanocomposites

    Directory of Open Access Journals (Sweden)

    Namvar F

    2016-07-01

    Full Text Available Farideh Namvar,1,2 Susan Azizi,3 Heshu Sulaiman Rahman,4–6 Rosfarizan Mohamad,1,3 Abdullah Rasedee,4 Mozhgan Soltani,2 Raha Abdul Rahim71Institute of Tropical Forestry and Forest Products (INTROP, Universiti Putra Malaysia, UPM Serdang, Selangor, Malaysia; 2Research Center for Animal Development Applied Biology, Mashhad Branch, Islamic Azad University, Mashhad, Iran; 3Department of Bioprocess Technology, Faculty of Biotechnology and Biomolecular Sciences, 4Department of Veterinary Laboratory Diagnosis, Faculty of Veterinary Medicine, Universiti Putra Malaysia, UPM Serdang, Selangor, Malaysia; 5Department of Clinic and Internal Medicine, College of Veterinary Medicine, University of Sulaimani, 6Department of Laboratory Medical Sciences, Komar University of Science and Technology, Sulaimani City, Kurdistan Region, Northern Iraq; 7Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, UPM Serdang, Selangor, Malaysia Abstract: The study describes an in situ green biosynthesis of zinc oxide nanocomposite using the seaweed Sargassum muticum water extract and hyaluronan biopolymer. The morphology and optical properties of the hyaluronan/zinc oxide (HA/ZnO nanocomposite were determined by Fourier transform infrared spectroscopy, X-ray diffraction, field emission scanning electron microscopy, transmission electron microscopy, and ultraviolet–vis analysis. Electron microscopy and X-ray diffraction analysis showed that the zinc oxide nanoparticles were polydispersed with a mean size of 10.2±1.5 nm. The nanoparticles were mostly hexagonal in crystalline form. The HA/ZnO nanocomposite showed the absorption properties in the ultraviolet zone that is ascribed to the band gap of zinc oxide nanocomposite. In the cytotoxicity study, cancer cells, pancreatic adenocarcinoma (PANC-1, ovarian adenocarcinoma (CaOV-3, colonic adenocarcinoma (COLO205, and acute promyelocytic leukemia (HL-60 cells

  11. Ultra-low friction between boundary layers of hyaluronan-phosphatidylcholine complexes.

    Science.gov (United States)

    Zhu, Linyi; Seror, Jasmine; Day, Anthony J; Kampf, Nir; Klein, Jacob

    2017-09-01

    The boundary layers coating articular cartilage in synovial joints constitute unique biomaterials, providing lubricity at levels unmatched by any human-made materials. The underlying molecular mechanism of this lubricity, essential to joint function, is not well understood. Here we study the interactions between surfaces bearing attached hyaluronan (hyaluronic acid, or HA) to which different phosphatidylcholine (PC) lipids had been added, in the form of small unilamellar vesicles (SUVs or liposomes), using a surface force balance, to shed light on possible cartilage boundary lubrication by such complexes. Surface-attached HA was complexed with different PC lipids (hydrogenated soy PC (HSPC), 1,2-dimyristoyl-sn-glycero-3-PC (DMPC) and 1-palmitoyl-2-oleoyl-sn-glycero-3-PC (POPC)), followed by rinsing. Atomic force microscopy (AFM) and cryo-scanning electron microscopy (Cryo-SEM) were used to image the HA-PC surface complexes following addition of the SUVs. HA-HSPC complexes provide very efficient lubrication, with friction coefficients as low as μ∼0.001 at physiological pressures P≈150atm, while HA-DMPC and HA-POPC complexes are efficient only at low P (up to 10-20atm). The friction reduction in all cases is attributed to hydration lubrication by highly-hydrated phosphocholine groups exposed by the PC-HA complexes. The greater robustness at high P of the HSPC (C 16(15%) ,C 18(85%) ) complexes relative to the DMPC ((C 14 ) 2 ) or POPC (C 16 , C 18:1 ) complexes is attributed to the stronger van der Waals attraction between the HSPC acyl tails, relative to the shorter or un-saturated tails of the other two lipids. Our results shed light on possible lubrication mechanisms at the articular cartilage surface in joints. Can designed biomaterials emulate the unique lubrication ability of articular cartilage, and thus provide potential alleviation to friction-related joint diseases? This is the motivation behind the present study. The principles of cartilage lubrication

  12. Intra-articular hyaluronan is without clinical effect in knee osteoarthritis: a multicentre, randomised, placebo-controlled, double-blind study of 337 patients followed for 1 year

    DEFF Research Database (Denmark)

    Jørgensen, Anette; Stengaard-Pedersen, Kristian; Simonsen, Ole

    2010-01-01

    OBJECTIVE: To examine the long-term efficacy and safety of five intra-articular injections with hyaluronan in knee osteoarthritis. METHODS: A multicentre, randomised, placebo-controlled double-blind study of 337 patients fulfilling the American College of Rheumatology (ACR) criteria for knee...... osteoarthritis (clinical and laboratory) and with a Lequesne algofunctional index score (LFI) of 10 or greater. Patients received a hyaluronan product (sodium hyaluronate; Hyalgan) (n=167) or saline (n=170) intra-articularly weekly for 5 weeks and were followed up to 1 year. Time to recurrence was the primary...... the ACR criteria for osteoarthritis of the knee with moderate to severe disease activity (LFI > or = 10), five intra-articular injections of hyaluronan did not improve pain, function, paracetamol consumption or other efficacy parameters 3, 6, 9 and 12 months after the treatment....

  13. MDA-MB-231 breast cancer cell viability, motility and matrix adhesion are regulated by a complex interplay of heparan sulfate, chondroitin-/dermatan sulfate and hyaluronan biosynthesis.

    Science.gov (United States)

    Viola, Manuela; Brüggemann, Kathrin; Karousou, Evgenia; Caon, Ilaria; Caravà, Elena; Vigetti, Davide; Greve, Burkhard; Stock, Christian; De Luca, Giancarlo; Passi, Alberto; Götte, Martin

    2017-06-01

    Proteoglycans and glycosaminoglycans modulate numerous cellular processes relevant to tumour progression, including cell proliferation, cell-matrix interactions, cell motility and invasive growth. Among the glycosaminoglycans with a well-documented role in tumour progression are heparan sulphate, chondroitin/dermatan sulphate and hyaluronic acid/hyaluronan. While the mode of biosynthesis differs for sulphated glycosaminoglycans, which are synthesised in the ER and Golgi compartments, and hyaluronan, which is synthesized at the plasma membrane, these polysaccharides partially compete for common substrates. In this study, we employed a siRNA knockdown approach for heparan sulphate (EXT1) and heparan/chondroitin/dermatan sulphate-biosynthetic enzymes (β4GalT7) in the aggressive human breast cancer cell line MDA-MB-231 to study the impact on cell behaviour and hyaluronan biosynthesis. Knockdown of β4GalT7 expression resulted in a decrease in cell viability, motility and adhesion to fibronectin, while these parameters were unchanged in EXT1-silenced cells. Importantly, these changes were associated with a decreased expression of syndecan-1, decreased signalling response to HGF and an increase in the synthesis of hyaluronan, due to an upregulation of the hyaluronan synthases HAS2 and HAS3. Interestingly, EXT1-depleted cells showed a downregulation of the UDP-sugar transporter SLC35D1, whereas SLC35D2 was downregulated in β4GalT7-depleted cells, indicating an intricate regulatory network that connects all glycosaminoglycans synthesis. The results of our in vitro study suggest that a modulation of breast cancer cell behaviour via interference with heparan sulphate biosynthesis may result in a compensatory upregulation of hyaluronan biosynthesis. These findings have important implications for the development of glycosaminoglycan-targeted therapeutic approaches for malignant diseases.

  14. Elasticity, biodegradability and cell adhesive properties of chitosan/hyaluronan multilayer films

    Energy Technology Data Exchange (ETDEWEB)

    Schneider, Aurore; Richert, Ludovic; Francius, Gregory; Voegel, Jean-Claude; Picart, Catherine [Present address: Universite de Montpellier II, CNRS-UMR 5539, cc107, Place Eugene Bataillon, 34 095 Montpellier Cedex 5 (France)

    2007-03-01

    In the bioengineering field, a recent and promising approach to modifying biomaterial surfaces is the layer-by-layer (LbL) technique used to build thin polyelectrolyte multilayer films. In this work, we focused on polyelectrolyte multilayer films made of two polysaccharides, chitosan (CHI) and hyaluronan (HA), and on the control of their physico-chemical and cell adhesive properties by chemical cross-linking. CHI/HA films were cross-linked using a water soluble carbodiimide and observed by confocal laser scanning microscopy (CLSM) with a fluorescently labeled CHI. Film thicknesses were similar for native and cross-linked films. The film nanometer roughness was measured by atomic force microscopy and was found to be higher for cross-linked films. Cross-linking the films also leads to a drastic change in film stiffness. The elastic modulus of the films (Young's modulus) as measured by AFM nano-indentation was about tenfold increased for cross-linked films as compared to native ones. From a biological point of view, cross-liked films are more resistant to enzymatic degradation by hyaluronidase. Furthermore, the increase in film stiffness has a favorable effect on the adhesion and spreading of chondrosarcoma cells. Thus, the CHI/HA cross-linked films could be used for various applications due to their adhesive properties and to their mechanical properties (including stability in enzymatic media)

  15. Chitosan-hyaluronan/nano chondroitin sulfate ternary composite sponges for medical use.

    Science.gov (United States)

    Anisha, B S; Sankar, Deepthi; Mohandas, Annapoorna; Chennazhi, K P; Nair, Shantikumar V; Jayakumar, R

    2013-02-15

    In this work chitosan-hyaluronan composite sponge incorporated with chondroitin sulfate nanoparticle (nCS) was developed. The fabrication of hydrogel was based on simple ionic cross-linking using EDC, followed by lyophilization to obtain the composite sponge. nCS suspension was characterized using DLS and SEM and showed a size range of 100-150 nm. The composite sponges were characterized using SEM, FT-IR and TG-DTA. Porosity, swelling, biodegradation, blood clotting and platelet activation of the prepared sponges were also evaluated. Nanocomposites showed a porosity of 67% and showed enhanced swelling and blood clotting ability. Cytocompatibility and cell adhesion studies of the sponges were done using human dermal fibroblast (HDF) cells and the nanocomposite sponges showed more than 90% viability. Nanocomposite sponges also showed enhanced proliferation of HDF cells within two days of study. These results indicated that this nanocomposite sponges would be a potential candidate for wound dressing. Copyright © 2012 Elsevier Ltd. All rights reserved.

  16. Composite Alginate-Hyaluronan Sponges for the Delivery of Tranexamic Acid in Postextractive Alveolar Wounds.

    Science.gov (United States)

    Catanzano, Ovidio; D'Esposito, Vittoria; Formisano, Pietro; Boateng, Joshua S; Quaglia, Fabiana

    2018-02-01

    The management of wounds in patients on anticoagulant therapy who require oral surgical procedures is problematic and often results in a nonsatisfactory healing process. Here, we report a method to prepare an advanced dressing able to avoid uncontrolled bleeding by occluding the postextractive alveolar wounds, and simultaneously, capable of a fast release of tranexamic acid (TA). Composite alginate/hyaluronan (ALG/HA) sponge dressings loaded with TA were prepared by a straightforward internal gelation method followed by a freeze-drying step. Both blank and drug-loaded sponges were soft, flexible, and elegant in appearance and nonbrittle in nature. Scanning electron microscopy analysis confirmed the porous nature of these dressings. The integration of HA influenced the microstructure, reducing the porosity, modifying the water uptake kinetic, and increasing the resistance to compression. TA release from ALG/HA sponges showed a controlled release up to 3 h, and it was faster in the presence of HA. Finally, an in vitro clotting test performed on human whole blood confirmed that the TA-loaded sponges significantly reduce the blood clotting index by 30% compared with ALG/HA 20 sponges. These results suggest that, if placed in a socket cavity, these dressings could give a relevant help to the blood hemostasis after dental extractions, especially in patients with coagulation disorders. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  17. Selective in vitro anticancer effect of superparamagnetic iron oxide nanoparticles loaded in hyaluronan polymeric micelles.

    Science.gov (United States)

    Smejkalová, Daniela; Nešporová, Kristina; Huerta-Angeles, Gloria; Syrovátka, Jakub; Jirák, Daniel; Gálisová, Andrea; Velebný, Vladimír

    2014-11-10

    Due to its native origin, excellent biocompatibility and biodegradability, hyaluronan (HA) represents an attractive polymer for superparamagnetic iron oxide nanoparticles (SPION) coating. Herein, we report HA polymeric micelles encapsulating oleic acid coated SPIONs, having a hydrodynamic size of about 100 nm and SPION loading capacity of 1-2 wt %. The HA-SPION polymeric micelles were found to be selectively cytotoxic toward a number of human cancer cell lines, mainly those of colon adenocarcinoma (HT-29). The selective inhibition of cell growth was even observed when the SPION loaded HA polymeric micelles were incubated with a mixture of control and cancer cells. The selective in vitro inhibition could not be connected with an enhanced CD44 uptake or radical oxygen species formation and was rather connected with a different way of SPION intracellular release. While aggregated iron particles were visualized in control cells, nonaggregated solubilized iron oxide particles were detected in cancer cells. In vivo SPION accumulation in intramuscular tumor following an intravenous micelle administration was confirmed by magnetic resonance (MR) imaging and histological analysis. Having a suitable hydrodynamic size, high magnetic relaxivity, and being cancer specific and able to accumulate in vivo in tumors, SPION-loaded HA micelles represent a promising platform for theranostic applications.

  18. Serum inter-alpha-trypsin inhibitor and matrix hyaluronan promote angiogenesis in fibrotic lung injury.

    Science.gov (United States)

    Garantziotis, Stavros; Zudaire, Enrique; Trempus, Carol S; Hollingsworth, John W; Jiang, Dianhua; Lancaster, Lisa H; Richardson, Elizabeth; Zhuo, Lisheng; Cuttitta, Frank; Brown, Kevin K; Noble, Paul W; Kimata, Koji; Schwartz, David A

    2008-11-01

    The etiology and pathogenesis of angiogenesis in idiopathic pulmonary fibrosis (IPF) is poorly understood. Inter-alpha-trypsin inhibitor (IaI) is a serum protein that can bind to hyaluronan (HA) and may contribute to the angiogenic response to tissue injury. To determine whether IaI promotes HA-mediated angiogenesis in tissue injury. An examination was undertaken of angiogenesis in IaI-sufficient and -deficient mice in the bleomycin model of pulmonary fibrosis and in angiogenesis assays in vivo and in vitro. IaI and HA in patients with IPF were examined. IaI significantly enhances the angiogenic response to short-fragment HA in vivo and in vitro. lal deficiency Ieads to decreased angiogenesis in the matrigel model, and decreases lung angiogenesis after bleomycin exposure in mice. IaI is found in fibroblastic foci in IPF, where it colocalizes with HA. The colocalization is particularly strong in vascular areas around fibroblastic foci. Serum levels of IaI and HA are significantly elevated in patients with IPF compared with control subjects. High serum IaI and HA levels are associated with decreased lung diffusing capacity, but not FVC. Our findings indicate that serum IaI interacts with HA, and promotes angiogenesis in lung injury. IaI appears to contribute to the vascular response to lung injury and may lead to aberrant angiogenesis. Clinical trial registered with www.clinicaltrials.gov (NCT00016627).

  19. Serum Inter–α-Trypsin Inhibitor and Matrix Hyaluronan Promote Angiogenesis in Fibrotic Lung Injury

    Science.gov (United States)

    Garantziotis, Stavros; Zudaire, Enrique; Trempus, Carol S.; Hollingsworth, John W.; Jiang, Dianhua; Lancaster, Lisa H.; Richardson, Elizabeth; Zhuo, Lisheng; Cuttitta, Frank; Brown, Kevin K.; Noble, Paul W.; Kimata, Koji; Schwartz, David A.

    2008-01-01

    Rationale: The etiology and pathogenesis of angiogenesis in idiopathic pulmonary fibrosis (IPF) is poorly understood. Inter-α-trypsin inhibitor (IaI) is a serum protein that can bind to hyaluronan (HA) and may contribute to the angiogenic response to tissue injury. Objectives: To determine whether IaI promotes HA-mediated angiogenesis in tissue injury. Methods: An examination was undertaken of angiogenesis in IaI-sufficient and -deficient mice in the bleomycin model of pulmonary fibrosis and in angiogenesis assays in vivo and in vitro. IaI and HA in patients with IPF were examined. Measurements and Main Results: IaI significantly enhances the angiogenic response to short-fragment HA in vivo and in vitro. lal deficiency Ieads to decreased angiogenesis in the matrigel model, and decreases lung angiogenesis after bleomycin exposure in mice. IaI is found in fibroblastic foci in IPF, where it colocalizes with HA. The colocalization is particularly strong in vascular areas around fibroblastic foci. Serum levels of IaI and HA are significantly elevated in patients with IPF compared with control subjects. High serum IaI and HA levels are associated with decreased lung diffusing capacity, but not FVC. Conclusions: Our findings indicate that serum IaI interacts with HA, and promotes angiogenesis in lung injury. IaI appears to contribute to the vascular response to lung injury and may lead to aberrant angiogenesis. Clinical trial registered with www.clinicaltrials.gov (NCT00016627). PMID:18703791

  20. Formulation and Evaluation of Organogels Containing Hyaluronan Microparticles for Topical Delivery of Caffeine.

    Science.gov (United States)

    Simsolo, Erol Eli; Eroğlu, İpek; Tanrıverdi, Sakine Tuncay; Özer, Özgen

    2018-04-01

    Cellulite is a dermal disorder including the extracellular matrix, the lymphatic and microcirculatory systems and the adipose tissue. Caffeine is used as the active moiety depending its preventive effect on localization of fat in the cellular structure. Hyaluronic acid (hyaluronan-HA) is a natural constituent of skin that generates formation and poliferation of new cells having a remarkable moisturizing ability. The aim of this study is to formulate HA microparticles loaded with caffeine via spray-drying method. Resulting microparticle formulations (33.97 ± 0.3 μm, span < 2, 88.56 ± 0.42% encapsulation efficiency) were distributed in lecithin organogels to maintain the proper viscosity for topical application. Following the characterization and cell culture studies, in vitro drug release and ex vivo permeation studies were performed. The accumulated amount of caffeine was twice higher than the aqueous solution for the microparticle-loaded organogels at 24 h (8262,673 μg/cm 2 versus 4676,691 μg/cm 2 ). It was related to the sustained behaviour of caffeine release from the microparticles. As a result, lecithin organogel containing HA-encapsulated microparticles could be considered as suitable candidate formulations for efficient topical drug delivery system of caffeine. In addition to that, synergistic effect of this combination appears as a promising approach for long-acting treatment of cellulite.

  1. Oleyl-hyaluronan micelles loaded with upconverting nanoparticles for bio-imaging

    Energy Technology Data Exchange (ETDEWEB)

    Pospisilova, Martina, E-mail: martina.pospisilova@contipro.com; Mrazek, Jiri; Matuska, Vit; Kettou, Sofiane; Dusikova, Monika; Svozil, Vit; Nesporova, Kristina; Huerta-Angeles, Gloria; Vagnerova, Hana; Velebny, Vladimir [Contipro Biotech (Czech Republic)

    2015-09-15

    Hyaluronan (HA) represents an interesting polymer for nanoparticle coating due to its biocompatibility and enhanced cell interaction via CD44 receptor. Here, we describe incorporation of oleate-capped β–NaYF{sub 4}:Yb{sup 3+}, Er{sup 3+} nanoparticles (UCNP-OA) into amphiphilic HA by microemulsion method. Resulting structures have a spherical, micelle-like appearance with a hydrodynamic diameter of 180 nm. UCNP-OA-loaded HA micelles show a good stability in PBS buffer and cell culture media. The intensity of green emission of UCNP-OA-loaded HA micelles in water is about five times higher than that of ligand-free UCNP, indicating that amphiphilic HA effectively protects UCNP luminescence from quenching by water molecules. We found that UCNP-OA-loaded HA micelles in concentrations up to 50 μg mL{sup −1} increase cell viability of normal human dermal fibroblasts (NHDF), while viability of human breast adenocarcinoma cells MDA–MB–231 is reduced at these concentrations. The utility of UCNP-OA-loaded HA micelles as a bio-imaging probe was demonstrated in vitro by successful labelling of NHDF and MDA–MB–231 cells overexpressing the CD44 receptor.

  2. Hyaluronan/Tween 80-assisted synthesis of silver nanoparticles for biological application

    Science.gov (United States)

    Li, Hui-Jun; Zhang, An-Qi; Sui, Li; Qian, Dong-Jin; Chen, Meng

    2015-02-01

    Water-soluble and well-stabilized silver nanoparticles (NPs) of small size have been synthesized using hyaluronan (HA) and Tween 80 as reducing and stabilizing agents. The effect of reaction conditions on the formation process of silver NPs was studied, and an aggregative growth mechanism of the silver NPs dominated in HA/Tween 80 system at pH 12 has been proposed. The obtained Ag NPs were characterized by UV-Vis spectroscopy, transmission electron microscopy, X-ray powder diffraction, and X-ray photoelectron spectroscopy. Moreover, the stability of the HA-Tween 80-silver NPs in normal saline was also studied, and a flexible blend membrane containing chitosan, gelatin, and the HA-Tween 80-silver NPs was prepared for further biological applications. Due to the high specific surface area and improved stability of silver NPs, the chitosan-gelatin-silver membrane has shown high antibacterial activity for strains of Escherichia coli. The cell viability tests indicate that the polymer membrane is non-cytotoxic to HepG2 cells, which might be attributed to its good biocompatibility.

  3. Hyaluronan/Tween 80-assisted synthesis of silver nanoparticles for biological application

    International Nuclear Information System (INIS)

    Li, Hui-Jun; Zhang, An-Qi; Sui, Li; Qian, Dong-Jin; Chen, Meng

    2015-01-01

    Water-soluble and well-stabilized silver nanoparticles (NPs) of small size have been synthesized using hyaluronan (HA) and Tween 80 as reducing and stabilizing agents. The effect of reaction conditions on the formation process of silver NPs was studied, and an aggregative growth mechanism of the silver NPs dominated in HA/Tween 80 system at pH 12 has been proposed. The obtained Ag NPs were characterized by UV–Vis spectroscopy, transmission electron microscopy, X-ray powder diffraction, and X-ray photoelectron spectroscopy. Moreover, the stability of the HA–Tween 80-silver NPs in normal saline was also studied, and a flexible blend membrane containing chitosan, gelatin, and the HA–Tween 80-silver NPs was prepared for further biological applications. Due to the high specific surface area and improved stability of silver NPs, the chitosan–gelatin-silver membrane has shown high antibacterial activity for strains of Escherichia coli. The cell viability tests indicate that the polymer membrane is non-cytotoxic to HepG2 cells, which might be attributed to its good biocompatibility

  4. Anticancer Effects of Sinulariolide-Conjugated Hyaluronan Nanoparticles on Lung Adenocarcinoma Cells

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    Kuan Yin Hsiao

    2016-03-01

    Full Text Available Lung cancer is one of the most clinically challenging malignant diseases worldwide. Sinulariolide (SNL, extracted from the farmed coral species Sinularia flexibilis, has been used for suppressing malignant cells. For developing anticancer therapeutic agents, we aimed to find an alternative for non-small cell lung cancer treatment by using SNL as the target drug. We investigated the SNL bioactivity on A549 lung cancer cells by conjugating SNL with hyaluronan nanoparticles to form HA/SNL aggregates by using a high-voltage electrostatic field system. SNL was toxic on A549 cells with an IC50 of 75 µg/mL. The anticancer effects of HA/SNL aggregates were assessed through cell viability assay, apoptosis assays, cell cycle analyses, and western blotting. The size of HA/SNL aggregates was approximately 33–77 nm in diameter with a thin continuous layer after aggregating numerous HA nanoparticles. Flow cytometric analysis revealed that the HA/SNL aggregate-induced apoptosis was more effective at a lower SNL dose of 25 µg/mL than pure SNL. Western blotting indicated that caspases-3, -8, and -9 and Bcl-xL and Bax played crucial roles in the apoptotic signal transduction pathway. In summary, HA/SNL aggregates exerted stronger anticancer effects on A549 cells than did pure SNL via mitochondria-related pathways.

  5. Hyaluronan - a functional and structural sweet spot in the tissue microenvironment

    Directory of Open Access Journals (Sweden)

    James eMonslow

    2015-05-01

    Full Text Available Transition from homeostatic to reactive matrix remodeling is a fundamental adaptive tissue response to injury, inflammatory disease, fibrosis and cancer. Alterations in architecture, physical properties and matrix composition result in changes in biomechanical and biochemical cellular signaling. The dynamics of pericellular and extracellular matrices, including matrix protein, proteoglycan and glycosaminoglycan modification are continually emerging as essential regulatory mechanisms underlying cellular and tissue function. Nevertheless, the impact of matrix organization on inflammation and immunity in particular, and the consequent effects on tissue healing and disease outcome are arguably under-studied aspects of adaptive stress responses. Herein, we review how the predominant glycosaminoglycan hyaluronan (HA contributes to the structure and function of the tissue microenvironment. Specifically, we examine the evidence of HA degradation and the generation of biologically-active smaller HA fragments in pathological settings in vivo. We discuss how HA fragments versus nascent HA via alternate receptor-mediated signaling influence inflammatory cell recruitment and differentiation, resident cell activation, as well as tumor growth, survival and metastasis. Finally, we discuss how HA fragmentation impacts restoration of normal tissue function and pathological outcomes in disease.

  6. Novel enzymatically cross-linked hyaluronan hydrogels support the formation of 3D neuronal networks.

    Science.gov (United States)

    Broguiere, Nicolas; Isenmann, Luca; Zenobi-Wong, Marcy

    2016-08-01

    Hyaluronan (HA) is an essential component of the central nervous system's extracellular matrix and its high molecular weight (MW) form has anti-inflammatory and anti-fibrotic properties relevant for regenerative medicine. Here, we introduce a new hydrogel based on high MW HA which is cross-linked using the transglutaminase (TG) activity of the activated blood coagulation factor XIII (FXIIIa). These HA-TG gels have significant advantages for neural tissue engineering compared to previous HA gels. Due to their chemical inertness in the absence of FXIIIa, the material can be stored long-term, is stable in solution, and shows no cytotoxicity. The gelation is completely cell-friendly due to the specificity of the enzyme and the gelation rate can be tuned from seconds to hours at physiological pH and independently of stiffness. The gels are injectable, and attach covalently to fibrinogen and fibrin, two common bioactive components in in vitro tissue engineering, as well as proteins present in vivo, allowing the gels to covalently bind to brain or spinal cord defects. These optimal chemical and bioactive properties of HA-TG gels enabled the formation of 3D neuronal cultures of unprecedented performance, showing fast neurite outgrowth, axonal and dendritic speciation, strong synaptic connectivity in 3D networks, and rapidly-occurring and long-lasting coordinated electrical activity. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Fabrication of Hyaluronan-Poly(vinylphosphonic acid-Chitosan Hydrogel for Wound Healing Application

    Directory of Open Access Journals (Sweden)

    Dang Hoang Phuc

    2016-01-01

    Full Text Available A new hydrogel made of hyaluronan, poly(vinylphosphonic acid, and chitosan (HA/PVPA/CS hydrogel was fabricated and characterized to be used for skin wound healing application. Firstly, the component ratio of hydrogel was studied to optimize the reaction effectiveness. Next, its microstructure was observed by light microscope. The chemical interaction in hydrogel was evaluated by nuclear magnetic resonance spectroscopy and Fourier transform-infrared spectroscopy. Then, a study on its degradation rate was performed. After that, antibacterial activity of the hydrogel was examined by agar diffusion method. Finally, in vivo study was performed to evaluate hydrogel’s biocompatibility. The results showed that the optimized hydrogel had a three-dimensional highly porous structure with the pore size ranging from about 25 µm to less than 125 µm. Besides, with a degradation time of two weeks, it could give enough time for the formation of extracellular matrix framework during remodeling stages. Furthermore, the antibacterial test showed that hydrogel has antimicrobial activity against E. coli. Finally, in vivo study indicated that the hydrogel was not rejected by the immune system and could enhance wound healing process. Overall, HA/PVPA/CS hydrogel was successfully fabricated and results implied its potential for wound healing applications.

  8. Layilin, a cell surface hyaluronan receptor, interacts with merlin and radixin

    International Nuclear Information System (INIS)

    Bono, Petri; Cordero, Etchell; Johnson, Kristen; Borowsky, Mark; Ramesh, Vijaya; Jacks, Tyler; Hynes, Richard O.

    2005-01-01

    Layilin is a widely expressed integral membrane hyaluronan receptor, originally identified as a binding partner of talin located in membrane ruffles. We have identified merlin, the neurofibromatosis type 2 tumor suppressor protein and radixin, as other interactors with the carboxy-terminal domain of layilin. We show that the carboxy-terminal domain of layilin is capable of binding to the amino-terminal domain of radixin. An interdomain interaction between the amino- and the carboxy-terminal domains of radixin inhibits its ability to bind to layilin. In the presence of acidic phospholipids, the interdomain interaction of radixin is inhibited and layilin can bind to full-length radixin. In contrast, layilin binds both full-length and amino-terminal merlin-GST fusion proteins without a requirement for phospholipids. Furthermore, layilin antibody can immunoprecipitate merlin, confirming association in vivo between these two proteins, which also display similar subcellular localizations in ruffling membranes. No interaction was observed between layilin and ezrin or layilin and moesin. These findings expand the known binding partners of layilin to include other members of the talin/band 4.1/ERM (ezrin, radixin, and moesin) family of cytoskeletal-membrane linker molecules. This in turn suggests that layilin may mediate signals from extracellular matrix to the cell cytoskeleton via interaction with different intracellular binding partners and thereby be involved in the modulation of cortical structures in the cell

  9. Specific sizes of hyaluronan oligosaccharides stimulate fibroblast migration and excisional wound repair.

    Directory of Open Access Journals (Sweden)

    Cornelia Tolg

    Full Text Available The extracellular matrix polysaccharide hyaluronan (HA plays a key role in both fibrotic and regenerative tissue repair. Accumulation of high molecular weight HA is typical of regenerative repair, which is associated with minimal inflammation and fibrosis, while fragmentation of HA is typical of postnatal wounds, which heal in the presence of inflammation and transient fibrosis. It is generally considered that HA oligosaccharides and fragments of a wide size range support these processes of adult, fibrotic wound repair yet the consequences of sized HA fragments/oligosaccharides to each repair stage is not well characterized. Here, we compared the effects of native HA, HA oligosaccharide mixtures and individual sizes (4-10 mer oligosaccharides, 5 and, 40 kDa of HA oligosaccharides and fragments, on fibroblast migration in scratch wound assays and on excisional skin wound repair in vivo. We confirm that 4-10 mer mixtures significantly stimulated scratch wound repair and further report that only the 6 and 8 mer oligosaccharides in this mixture are responsible for this effect. The HA 6 mer promoted wound closure, accumulation of wound M1 and M2 macrophages and the M2 cytokine TGFβ1, but did not increase myofibroblast differentiation. The effect of 6 mer HA on wound closure required both RHAMM and CD44 expression. In contrast, The 40 kDa HA fragment inhibited wound closure, increased the number of wound macrophages but had no effect on TGFβ1 accumulation or subsequent fibrosis. These results show that specific sizes of HA polymer have unique effects on postnatal wound repair. The ability of 6 mer HA to promote wound closure and inflammation resolution without increased myofibroblast differentiation suggests that this HA oligosaccharide could be useful for treatment of delayed or inefficient wound repair where minimal fibrosis is advantageous.

  10. Peritoneal Adhesion and Angiogenesis in Ovarian Carcinoma Are Inversely Regulated by Hyaluronan: The Role of Gonadotropins

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    Yael Chagit Tzuman

    2010-01-01

    Full Text Available Ovarian carcinoma is the leading cause of death among gynecologic cancers. Although transformation of the outer ovarian epithelium was linked with ovulation, the disease is significantly more prevalent and severe in postmenopausal women. We postulated that menopause could augment ovarian cancer progression through the effects of gonadotropins on multifocal seeding to the mesothelial layer lining the peritoneum. This seeding is mediated by integrins as well as by CD44 interaction with hyaluronan (HA. Here, we report the effect of gonadotropins on HA synthesis and degradation and on peritoneal adhesion. A significant concentration- and time-dependent induction in expression levels of HA synthases (HASs and hyaluronidases (Hyals was observed in vitro on stimulation of human epithelial ovarian carcinoma cells by gonadotropins. Hormonal regulation of HA-mediated adhesion was manifested in vivo as well, by fluorescence microscopy of stained MLS multicellular tumor spheroids. The number of spheroids adhered to the mesothelium of ovariectomized CD-1 nude mice 9.5 hours after intraperitoneal insertion was significantly higher than in nonovariectomized mice. Inhibition of HA synthesis by 6-diazo-5-oxo-1-norleucine (DON both in spheroids and ovariectomized mice significantly reduced the number of adhered spheroids. Thus, the change in the hormonal environment during menopause assists in HA-dependent adherence of ovarian cancer spheroids onto the peritoneum. However, HA is antiangiogenic and it can significantly suppress tumor progression. Accordingly, angiogenesis of the adhered spheroids was significantly elevated in DON-treated tumors. These results can explain the selective pressure that can lead to simultaneously increased tumor expression of both HASs and Hyals.

  11. Changes in condylar coefficient of friction after osteochondral graft transplantation and modulation with hyaluronan.

    Science.gov (United States)

    Lane, John; Healey, Robert; Amiel, David

    2009-12-01

    To better understand the changes in the cartilage coefficient of friction (COF) after an osteochondral repair, an assessment of dynamic loads has been developed using a goat knee model. The application of hyaluronan (HA) was also assessed for its lubricative properties and the resulting COF of the knee after osteochondral repair. A total of 18 caprine knees were dissected and mounted into an Instron load frame (Instron, Norwood, MA) for testing. The COF was measured in 10 knees relative to the normal, unaltered joint and then calibrated to account for friction of the system. These experimental knees were tested in 5 modes: normal; empty 4.5-mm defect; and osteochondral repairs that were elevated, flush, or depressed relative to the cartilage surface. Saline solution lavage kept the knees moist during testing. The effect of HA was evaluated after mechanical testing. Eight knees were used to study the effect of lavage on the joints because of the significant increase in the COF that it produced. Whereas all modes increased the COF from normal levels, the most significant changes occurred when there was proud placement. Increases of 4 times the normal friction levels were measured. Increases in the COF were also associated with saline solution lavage (0.006 to 0.046). There was a significant reduction in friction after HA injection, which reduced the COF to near-normal levels. There is a significant increase in the COF associated with saline solution lavage and an osteochondral plug being left proud, which can be temporarily reduced with a lubricative material such as HA. Dramatic increases in the COF can potentially damage chondrocytes when the patient begins articulating the joint after surgery. Such injuries may affect the ability of the cartilage to heal fully. Reducing the elevated COF with lubricating materials, such as HA, is recommended based on the results of this study.

  12. Regulation of proximal tubular epithelial cell CD44-mediated binding and internalisation of hyaluronan.

    Science.gov (United States)

    Jones, Stuart George; Ito, Takafumi; Phillips, Aled Owain

    2003-09-01

    Increased expression of the connective tissue polysaccharide hyaluronan (HA) in the renal corticointerstitium is associated with progressive renal fibrosis. Numerous studies have demonstrated involvement proximal tubular epithelial cells in the fibrotic process and in the current study we have characterised their expression of the HA receptor, CD44, and examined changes in CD44 expression and function in response to either IL-1beta or glucose. Characterisation of CD44 splice variant expression was carried out in primary cultures of human proximal tubular cells (PTC) and HK2 cells. Binding and internalisation HA was examined by addition of exogenous of fluorescein-HA (fl-HA), and expression of CD44 examined by immunoblot analysis and flow cytometry. Alteration in "functional" CD44 was determined by immunoprecipitation of CD44 following stimulation in the presence of fl-HA. PTC, both primary culture and the PTC cell line, HK2, express at least 5 CD44 splice variants, the expression of which are not altered by addition of either IL-1beta or 25mM D-glucose. Addition of either stimulus increased cell surface binding and internalisation of fl-HA and increased expression of functionally active CD44. Increased binding and internalisation of fl-HA, was blocked by anti-CD44 antibody, and by the inhibition of O-glycosylation. The data demonstrate that stimuli inducing PTC HA synthesis also regulate PTC-HA interactions. Furthermore increased HA binding and internalisation is the result of post-translational modification of CD44 by O-glycosylation, rather than by alteration in expression of CD44 at the cell surface, or by alternate use of CD44 splice variants.

  13. Dietary flavonoid fisetin increases abundance of high-molecular-mass hyaluronan conferring resistance to prostate oncogenesis.

    Science.gov (United States)

    Lall, Rahul K; Syed, Deeba N; Khan, Mohammad Imran; Adhami, Vaqar M; Gong, Yuansheng; Lucey, John A; Mukhtar, Hasan

    2016-09-01

    We and others have shown previously that fisetin, a plant flavonoid, has therapeutic potential against many cancer types. Here, we examined the probable mechanism of its action in prostate cancer (PCa) using a global metabolomics approach. HPLC-ESI-MS analysis of tumor xenografts from fisetin-treated animals identified several metabolic targets with hyaluronan (HA) as the most affected. Efficacy of fisetin on HA was then evaluated in vitro and also in vivo in the transgenic TRAMP mouse model of PCa. Size exclusion chromatography-multiangle laser light scattering (SEC-MALS) was performed to analyze the molar mass (Mw) distribution of HA. Fisetin treatment downregulated intracellular and secreted HA levels both in vitro and in vivo Fisetin inhibited HA synthesis and degradation enzymes, which led to cessation of HA synthesis and also repressed the degradation of the available high-molecular-mass (HMM)-HA. SEC-MALS analysis of intact HA fragment size revealed that cells and animals have more abundance of HMM-HA and less of low-molecular-mass (LMM)-HA upon fisetin treatment. Elevated HA levels have been shown to be associated with disease progression in certain cancer types. Biological responses triggered by HA mainly depend on the HA polymer length where HMM-HA represses mitogenic signaling and has anti-inflammatory properties whereas LMM-HA promotes proliferation and inflammation. Similarly, Mw analysis of secreted HA fragment size revealed less HMM-HA is secreted that allowed more HMM-HA to be retained within the cells and tissues. Our findings establish that fisetin is an effective, non-toxic, potent HA synthesis inhibitor, which increases abundance of antiangiogenic HMM-HA and could be used for the management of PCa. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  14. Microneedle fractional radiofrequency increases epidermal hyaluronan and reverses age-related epidermal dysfunction.

    Science.gov (United States)

    Lee, Hee Jung; Seo, Seong Rak; Yoon, Moon Soo; Song, Ji-Ye; Lee, Eun Young; Lee, Sang Eun

    2016-02-01

    Skin aging results in physiological alterations in keratinocyte activities and epidermal function, as well as dermal changes. Yet, the cellular and molecular mechanisms that cause epidermal dysfunction during skin aging are not well understood. Recently, the role of epidermal hyaluronan (HA) as an active regulator of dynamic cellular processes is getting attention and alterations in HA metabolism are thought to be important in age-related epidermal dysfunction. Microneedle fractional radiofrequency (RF) has shown effects for improving cutaneous aging. However, little is known about the effects of fractional RF on the epidermal HA and epidermal function. We investigated the effect of microneedle fractional RF on the expression of epidermal HA in young and aged mice epidermis. We performed fractional RF on the dorsal skin of 30 8-week-old (young) hairless mice and 15 47-week-old (aged) C57BL/6J mice. Skin samples were collected on day 1, 3, and 7. HA content was measured by ELISA. Gene expressions of CD 44, HABP4, and HAS3 were measured using real time RT-PCR. Immunohistochemistry for detection of HA, CD44, PCNA, and filaggrin were performed. HA content and the mRNA levels of HABP4, CD44, and HAS3 were upregulated in the epidermis of both young and aged mice after microneedle fractional RF treatment. The expression was increased from day 1 after treatment and increased expression persisted on day 7. Fractional RF treatment significantly increased PCNA and filaggrin expression only in the aged mice skin. Microneedle fractional RF increased epidermal HA and CD44 expression in both young and aged mice and reversed age-related epidermal dysfunction especially in aged mice, suggesting a new mechanism involved in the skin rejuvenation effect of microneedle fractional RF. © 2015 Wiley Periodicals, Inc.

  15. Hyaluronan-modified superparamagnetic iron oxide nanoparticles for bimodal breast cancer imaging and photothermal therapy

    Directory of Open Access Journals (Sweden)

    Yang R

    2016-12-01

    Full Text Available Rui-Meng Yang,1,* Chao-Ping Fu,2,* Jin-Zhi Fang,1 Xiang-Dong Xu,1 Xin-Hua Wei,1 Wen-Jie Tang,1 Xin-Qing Jiang,1 Li-Ming Zhang2 1Department of Radiology, Guangzhou First People’s Hospital, Guangzhou Medical University, 2School of Materials Science and Engineering, School of Chemistry, Sun Yat-sen University, Guangzhou, China *These authors contributed equally to this work Abstract: Theranostic nanoparticles with both imaging and therapeutic abilities are highly promising in successful diagnosis and treatment of the most devastating cancers. In this study, the dual-modal imaging and photothermal effect of hyaluronan (HA-modified superparamagnetic iron oxide nanoparticles (HA-SPIONs, which was developed in a previous study, were investigated for CD44 HA receptor-overexpressing breast cancer in both in vitro and in vivo experiments. Heat is found to be rapidly generated by near-infrared laser range irradiation of HA-SPIONs. When incubated with CD44 HA receptor-overexpressing MDA-MB-231 cells in vitro, HA-SPIONs exhibited significant specific cellular uptake and specific accumulation confirmed by Prussian blue staining. The in vitro and in vivo results of magnetic resonance imaging and photothermal ablation demonstrated that HA-SPIONs exhibited significant negative contrast enhancement on T2-weighted magnetic resonance imaging and photothermal effect targeted CD44 HA receptor-overexpressing breast cancer. All these results indicated that HA-SPIONs have great potential for effective diagnosis and treatment of cancer. Keywords: iron oxide nanoparticles, surface functionalization, bioactive glycosaminoglycan, magnetic resonance imaging, cellular uptake, breast carcinoma

  16. The influence of hyaluronan on the structure of a DPPC-bilayer under high pressures.

    Science.gov (United States)

    Zander, Thomas; Wieland, D C Florian; Raj, Akanksha; Wang, Min; Nowak, Benedikt; Krywka, Christina; Dėdinaitė, Andra; Claesson, Per Martin; Garamus, Vasil M; Schreyer, Andreas; Willumeit-Römer, Regine

    2016-06-01

    The superior lubrication properties of synovial joints have inspired many studies aiming at uncovering the molecular mechanisms which give rise to low friction and wear. However, the mechanisms are not fully understood yet, and, in particular, it has not been elucidated how the biolubricants present at the interface of cartilage respond to high pressures, which arise during high loads of joints. In this study we utilize a simple model system composed of two biomolecules that have been implied as being important for joint lubrication. It consists of a solid supported dipalmitoylphosphatidylcholin (DPPC) bilayer, which was formed via vesicles fusion on a flat Si wafer, and the anionic polysaccharide hyaluronan (HA). We first characterized the structure of the HA layer that adsorbed to the DPPC bilayers at ambient pressure and different temperatures using X-ray reflectivity (XRR) measurements. Next, XRR was utilized to evaluate the response of the system to high hydrostatic pressures, up to 2kbar (200MPa), at three different temperatures. By means of fluorescence microscopy images the distribution of DPPC and HA on the surface was visualized. Our data suggest that HA adsorbs to the headgroup region that is oriented towards the water side of the supported bilayer. Phase transitions of the bilayer in response to temperature and pressure changes were also observed in presence and absence of HA. Our results reveal a higher stability against high hydrostatic pressures for DPPC/HA composite layers compared to that of the DPPC bilayer in absence of HA. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. A Novel Eliminase from a Marine Bacterium That Degrades Hyaluronan and Chondroitin Sulfate*

    Science.gov (United States)

    Han, Wenjun; Wang, Wenshuang; Zhao, Mei; Sugahara, Kazuyuki; Li, Fuchuan

    2014-01-01

    Lyases cleave glycosaminoglycans (GAGs) in an eliminative mechanism and are important tools for the structural analysis and oligosaccharide preparation of GAGs. Various GAG lyases have been identified from terrestrial but not marine organisms even though marine animals are rich in GAGs with unique structures and functions. Herein we isolated a novel GAG lyase for the first time from the marine bacterium Vibrio sp. FC509 and then recombinantly expressed and characterized it. It showed strong lyase activity toward hyaluronan (HA) and chondroitin sulfate (CS) and was designated as HA and CS lyase (HCLase). It exhibited the highest activities to both substrates at pH 8.0 and 0.5 m NaCl at 30 °C. Its activity toward HA was less sensitive to pH than its CS lyase activity. As with most other marine enzymes, HCLase is a halophilic enzyme and very stable at temperatures from 0 to 40 °C for up to 24 h, but its activity is independent of divalent metal ions. The specific activity of HCLase against HA and CS reached a markedly high level of hundreds of thousands units/mg of protein under optimum conditions. The HCLase-resistant tetrasaccharide Δ4,5HexUAα1-3GalNAc(6-O-sulfate)β1-4GlcUA(2-O-sulfate)β1-3GalNAc(6-O-sulfate) was isolated from CS-D, the structure of which indicated that HCLase could not cleave the galactosaminidic linkage bound to 2-O-sulfated d-glucuronic acid (GlcUA) in CS chains. Site-directed mutagenesis indicated that HCLase may work via a catalytic mechanism in which Tyr-His acts as the Brønsted base and acid. Thus, the identification of HCLase provides a useful tool for HA- and CS-related research and applications. PMID:25122756

  18. Inhibition of hyaluronan synthesis reduces versican and fibronectin levels in trabecular meshwork cells.

    Directory of Open Access Journals (Sweden)

    Kate E Keller

    Full Text Available Hyaluronan (HA is a major component of the extracellular matrix (ECM and is synthesized by three HA synthases (HAS. Similarities between the HAS2 knockout mouse and the hdf mutant mouse, which has a mutation in the versican gene, suggest that HA and versican expression may be linked. In this study, the relationship between HA synthesis and levels of versican, fibronectin and several other ECM components in trabecular meshwork cells from the anterior segment of the eye was investigated. HA synthesis was inhibited using 4-methylumbelliferone (4MU, or reduced by RNAi silencing of each individual HAS gene. Quantitative RT-PCR and immunoblotting demonstrated a reduction in mRNA and protein levels of versican and fibronectin. Hyaluronidase treatment also reduced versican and fibronectin levels. These effects could not be reversed by addition of excess glucose or glucosamine or exogenous HA to the culture medium. CD44, tenascin C and fibrillin-1 mRNA levels were reduced by 4MU treatment, but SPARC and CSPG6 mRNA levels were unaffected. Immunostaining of trabecular meshwork tissue after exposure to 4MU showed an altered localization pattern of HA-binding protein, versican and fibronectin. Reduction of versican by RNAi silencing did not affect HA concentration as assessed by ELISA. Together, these data imply that HA concentration affects synthesis of certain ECM components. Since precise regulation of the trabecular meshwork ECM composition and organization is required to maintain the aqueous humor outflow resistance and intraocular pressure homeostasis in the eye, coordinated coupling of HA levels and several of its ECM binding partners should facilitate this process.

  19. Three-year clinical outcome after chondrocyte transplantation using a hyaluronan matrix for cartilage repair

    Energy Technology Data Exchange (ETDEWEB)

    Nehrer, S. [Department of Orthopedics, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria)]. E-mail: stefan.nehrer@meduniwien.ac.at; Domayer, S. [Department of Orthopedics, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria); Dorotka, R. [Department of Orthopedics, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria); Schatz, K. [Department of Orthopedics, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria); Bindreiter, U. [Department of Orthopedics, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria); Kotz, R. [Department of Orthopedics, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria)

    2006-01-15

    Repair of articular cartilage represents a significant clinical problem and although various new techniques - including the use of autologous chondrocytes - have been developed within the last century the clinical efficacy of these procedures is still discussed controversially. Although autologous chondrocyte transplantation (ACT) has been widely used with success, it has several inherent limitations, including its invasive nature and problems related to the use of the periosteal flap. To overcome these problems autologous chondrocytes transplantation combined with the use of biodegradable scaffolds has received wide attention. Among these, a hyaluronan-based scaffold has been found useful for inducing hyaline cartilage regeneration. In the present study, we have investigated the mid-term efficacy and safety of Hyalograft[reg] C grafts in a group of 36 patients undergoing surgery for chronic cartilage lesions of the knee. Clinical Outcome was assessed prospectively before and at 12, 24, and 36 months after surgery. No major adverse events have been reported during the 3-year follow-up. Significant improvements of the evaluated scores were observed (P < 0.02) at 1 year and a continued increase of clinical performance was evident at 2 and 3 years follow-up. Patients under 30 years of age with single lesions showed statistically significant improvements at all follow-up visits compared to those over 30 with multiple defects (P < 0.01). Hyalograft[reg] C compares favorably with classic ACT and is particularly indicated in younger patients with single lesions. The graft can be implanted through a miniarthrotomy and needs no additional fixation with sutures except optional fibrin gluing at the defect borders. These results suggest that Hyalograft[reg] C is a valid alternative to ACT.

  20. Hyaluronan and N-ERC/mesothelin as key biomarkers in a specific two-step model to predict pleural malignant mesothelioma.

    Science.gov (United States)

    Mundt, Filip; Nilsonne, Gustav; Arslan, Sertaç; Csürös, Karola; Hillerdal, Gunnar; Yildirim, Huseyin; Metintas, Muzaffer; Dobra, Katalin; Hjerpe, Anders

    2013-01-01

    Diagnosis of malignant mesothelioma is challenging. The first available diagnostic material is often an effusion and biochemical analysis of soluble markers may provide additional diagnostic information. This study aimed to establish a predictive model using biomarkers from pleural effusions, to allow early and accurate diagnosis. Effusions were collected prospectively from 190 consecutive patients at a regional referral centre. Hyaluronan, N-ERC/mesothelin, C-ERC/mesothelin, osteopontin, syndecan-1, syndecan-2, and thioredoxin were measured using ELISA and HPLC. A predictive model was generated and validated using a second prospective set of 375 effusions collected consecutively at a different referral centre. Biochemical markers significantly associated with mesothelioma were hyaluronan (odds ratio, 95% CI: 8.82, 4.82-20.39), N-ERC/mesothelin (4.81, 3.19-7.93), CERC/mesothelin (3.58, 2.43-5.59) and syndecan-1 (1.34, 1.03-1.77). A two-step model using hyaluronan and N-ERC/mesothelin, and combining a threshold decision rule with logistic regression, yielded good discrimination with an area under the ROC curve of 0.99 (95% CI: 0.97-1.00) in the model generation dataset and 0.83 (0.74-0.91) in the validation dataset, respectively. A two-step model using hyaluronan and N-ERC/mesothelin predicts mesothelioma with high specificity. This method can be performed on the first available effusion and could be a useful adjunct to the morphological diagnosis of mesothelioma.

  1. Effects of low molecular weight hyaluronan combined with carprofen on canine osteoarthritis articular chondrocytes and cartilage explants in vitro.

    Science.gov (United States)

    Euppayo, Thippaporn; Siengdee, Puntita; Buddhachat, Kittisak; Pradit, Waranee; Viriyakhasem, Nawarat; Chomdej, Siriwadee; Ongchai, Siriwan; Harada, Yasuji; Nganvongpanit, Korakot

    2015-09-01

    Intra-articular injection with non-steroidal anti-inflammatory drugs (NSAIDs) is used to treat inflammatory joint disease, but the side effects of NSAIDs include chondrotoxicity. Hyaluronan has shown positive effects on chondrocytes by reducing apoptosis and increasing proteoglycan synthesis. The purposes of this study were to evaluate the effects of low molecular weight hyaluronan (low MW HA), carprofen 25 mg/ml, carprofen 12.5 mg/ml, and a combination of HA and carprofen on canine osteoarthritis (OA) articular chondrocytes and a cartilage explant model in terms of cell viability, extracellular matrix remaining, and gene expression after exposure. In chondrocyte culture, MTT assay was used to evaluate the chondrotoxicity of IC50 and IC80 of carprofen with HA. In cartilage explant culture, two kinds of extracellular matrix (uronic acid and collagen) remaining in cartilage were used to evaluate cartilage damage for 14 d after treatment. Expression of COL2A1, AGG, and MMP3 was used to evaluate the synthesis and degradation of the matrix for 7 d after treatment. In chondrocyte culture, low MW HA could preserve OA chondrocyte viability but could not reduce the chondrotoxicity level of carprofen (P carprofen caused less destruction of uronic acid and collagen structure when compared with the control (P carprofen resulted in higher COL2A1 and AGG expression levels than carprofen alone.

  2. The hyaluronan and proteoglycan link proteins: Organizers of the brain extracellular matrix and key molecules for neuronal function and plasticity.

    Science.gov (United States)

    Oohashi, Toshitaka; Edamatsu, Midori; Bekku, Yoko; Carulli, Daniela

    2015-12-01

    The hyaluronan and proteoglycanbinding link protein (Hapln) is a key molecule in the formation and control of hyaluronan-based condensed perineuronal matrix in the adult brain. This review summarizes the recent advances in understanding the role of Haplns in the formation and control of two distinct types of perineuronal matrices, one for "classical" PNN and the other for the specialized extracellular matrix (ECM) at the node of Ranvier in the central nervous system (CNS). We introduce the structural components of each ECM organization including the basic concept of supramolecular structure named "HLT model". We furthermore summarize the developmental and physiological role of perineuronal ECMs from the studies of Haplns and related molecules. Finally, we also discuss the potential mechanism modulating PNNs in the adult CNS. This layer of organized matrices may exert a direct effect via core protein or sugar moiety from the structure or by acting as a binding site for biologically active molecules, which are important for neuronal plasticity and saltatory conduction. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Local delivery of hyaluronan as an adjunct to scaling and root planing in the treatment of chronic periodontitis.

    Science.gov (United States)

    Johannsen, Annsofi; Tellefsen, Monica; Wikesjö, Ulf; Johannsen, Gunnar

    2009-09-01

    The aim of the present study was to evaluate the adjunctive effect of the local application of a hyaluronan gel to scaling and root planing in the treatment of chronic periodontitis. Twelve patients with chronic periodontitis were recruited to participate in a study with a split-mouth design and provided informed consent. Plaque formation and bleeding on probing were evaluated pretreatment (baseline) and at 1, 4, and 12 weeks post-treatment. Probing depths and attachment levels were evaluated at baseline and at 12 weeks. The patients received full-mouth scaling and root planing. A hyaluronan gel was administered subgingivally in the test sites at baseline and after 1 week. Significant differences between test and control were evaluated using the paired t test, repeated-measures analysis of variance (Wilks lambda), and a non-parametric Wilcoxon signed-rank test. A significant reduction in bleeding on probing scores and probing depths was observed in both groups at 12 weeks (P scaling and root planing may have a beneficial effect on periodontal health in patients with chronic periodontitis.

  4. A mast cell secretagogue, compound 48/80, prevents the accumulation of hyaluronan in lung tissue injured by ionizing irradiation

    International Nuclear Information System (INIS)

    Nilsson, K.; Bjermer, L.; Hellstroem, S.H.; Henriksson, R.; Haellgren, R.

    1990-01-01

    Irradiation with a single dose of 30 Grey on the basal regions of the lungs of Sprague-Dawley rats induced a peribronchial and alveolar inflammation. Infiltration of mast cells in the edematous alveolar interstitial tissue and also in the peribronchial tissue were characteristic features of the lesion. The appearance of mast cells was already seen 4 wk after irradiation and by weeks 6 to 8 there was a heavy infiltration. The staining properties suggested that they were connective tissue-type mast cells. The infiltration of mast cells was paralleled by an accumulation of hyaluronan (hyaluronic acid) in the alveolar interstitial tissue 6 and 8 wk after irradiation. The recovery of hyaluronan (HA) during bronchoalveolar lavage (BAL) of the lungs also increased at this time. Treatment with a mast cell secretagogue, compound 48/80, induced a distinct reduction of granulated mast cells in the alveolar tissue. Regular treatment with compound 48/80 from the time of irradiation considerably reduced the HA recovery during BAL and the HA accumulation in the interstitial tissue but did not affect the interstitial infiltration of mononuclear cells and polymorphonuclear leukocytes. By contrast, an accumulation of HA in the alveolar interstitial space was induced when compound 48/80 was given not until mast cell infiltration of the lung had started. The effects of compound 48/80 indicate that the connective tissue response after lung irradiation is dependent on whether or not mast cell degranulation is induced before or after the mast cell infiltration of the alveolar tissue

  5. Chondrogenic differentiation of mesenchymal stem cells in a hydrogel system based on an enzymatically crosslinked tyramine derivative of hyaluronan

    Czech Academy of Sciences Publication Activity Database

    Dvořáková, J.; Kučera, L.; Kučera, J.; Svik, K.; Foglarová, M.; Muthny, T.; Pravda, M.; Němcová, M.; Velebný, V.; Kubala, Lukáš

    2014-01-01

    Roč. 102, č. 10 (2014), s. 3523-3530 ISSN 1549-3296 R&D Projects: GA MŠk(CZ) ED1.100/02/0123 Institutional support: RVO:68081707 Keywords : hyaluronate * tyramine * chondrogenesis Subject RIV: BO - Biophysics Impact factor: 3.369, year: 2014

  6. Hyaluronan-conjugated liposomes encapsulating gemcitabine for breast cancer stem cells

    Directory of Open Access Journals (Sweden)

    Han NK

    2016-04-01

    Full Text Available Na-Kyung Han,1,* Dae Hwan Shin,1,* Jung Seok Kim,1 Kwon Yeon Weon,2 Chang-Young Jang,1 Jin-Seok Kim1 1Research Center for Cell Fate Control (RCCFC and College of Pharmacy, Sookmyung Women’s University, Seoul, 2College of Pharmacy, Catholic University of Daegu, Gyeongbuk, Korea *These authors contributed equally to this work Abstract: Investigation of potential therapeutics for targeting breast cancer stem cells (BCSCs is important because these cells are regarded as culprit of breast cancer relapse. Accomplishing this kind of strategy requires a specific drug-delivery system using the distinct features of liposomes. Studies on targeted liposomal delivery systems have indicated the conjugation of hyaluronan (HA, a primary ligand for CD44 surface markers, as an appropriate method for targeting BCSCs. For this study, enriched BCSCs were obtained by culturing MCF-7 breast cancer cells in nonadherent conditions. The enriched BCSCs were challenged with HA-conjugated liposomes encapsulating gemcitabine (2, 2-difluoro-2-deoxycytidine, GEM. In vitro study showed that the HA-conjugated liposomes significantly enhanced the cytotoxicity, anti-migration, and anti-colony formation abilities of GEM through targeting of CD44 expressed on BCSCs. In pharmacokinetic study, area under the drug concentration vs time curve (AUC of the immunoliposomal GEM was 3.5 times higher than that of free GEM, indicating that the HA-conjugated liposomes enhanced the stability of GEM in the bloodstream and therefore prolonged its half-life time. The antitumor effect of the immunoliposomal GEM was 3.3 times higher than that of free GEM in a xenograft mouse model, probably reflecting the unique targeting of the CD44 receptor by HA and the increased cytotoxicity and stability through the liposomal formulation. Furthermore, marginal change in body weight demonstrated that the use of liposomes considerably reduced the systemic toxicity of GEM on normal healthy cells. Taken together

  7. Hyaluronan microgel as a potential carrier for protein sustained delivery by tailoring the crosslink network

    Energy Technology Data Exchange (ETDEWEB)

    Luo, Chunhong [Department of Materials Science and Engineering, College of Science and Engineering, Jinan University, Guangzhou 510632 (China); Zhao, Jianhao, E-mail: jhzhao@jnu.edu.cn [Department of Materials Science and Engineering, College of Science and Engineering, Jinan University, Guangzhou 510632 (China); Engineering Research Center of Artificial Organs and Materials, Ministry of Education, Guangzhou 510632 (China); Tu, Mei; Zeng, Rong; Rong, Jianhua [Department of Materials Science and Engineering, College of Science and Engineering, Jinan University, Guangzhou 510632 (China); Engineering Research Center of Artificial Organs and Materials, Ministry of Education, Guangzhou 510632 (China)

    2014-03-01

    Hyaluronan (HA) microgels with different crosslink network, i.e. HGPs-1, HGPs-1.5, HGPs-3, HGPs-6 and HGPs-15, were synthesized using divinyl sulfone (DVS) as the crosslinker in an inverse microemulsion system for controlling the sustained delivery of bovine serum albumin (BSA). With increasing the crosslinker content, the average particle size slightly increased from 1.9 ± 0.3 μm to 3.6 ± 0.5 μm by dynamic laser scattering analysis. However, the crosslinker content had no significant effect on the morphology of HA microgels by scanning and transmission electron microscopes. Fourier transform infrared spectroscopy and elemental analysis proved more sulfur participated in the crosslink reaction when raising the crosslinker amount. The water swelling test confirmed the increasing crosslink density with the crosslinker content by calculating the average molecular weight between two crosslink points to be 8.25 ± 2.51 × 10{sup 5}, 1.26 ± 0.43 × 10{sup 5}, 0.96 ± 0.09 × 10{sup 5}, 0.64 ± 0.03 × 10{sup 5}, and 0.11 ± 0.01 × 10{sup 5} respectively. The degradation of HA microgels by hyaluronidase slowed down by enhancing the crosslink density, only about 5% of HGPs-15 was degraded as opposed to over 90% for HGPs-1. BSA loading had no obvious influence on the surface morphology of HA microgels but seemed to induce their aggregation. The increase of crosslink density decreased the BSA loading capacity but facilitated its long-term sustained delivery. When the molar ratio of DVS to repeating unit of HA reached 3 or higher, similar delivery profiles were obtained. Among all these HA microgels, HGPs-3 was the optimal carrier for BSA sustained delivery in this system because it possessed both high BSA loading capacity and long-term delivery profile simultaneously. - Highlights: • HA microgels with different crosslink densities were prepared. • The crosslinker content had little effect on the morphology and size of HA microgels. • The crosslink density

  8. A novel eliminase from a marine bacterium that degrades hyaluronan and chondroitin sulfate.

    Science.gov (United States)

    Han, Wenjun; Wang, Wenshuang; Zhao, Mei; Sugahara, Kazuyuki; Li, Fuchuan

    2014-10-03

    Lyases cleave glycosaminoglycans (GAGs) in an eliminative mechanism and are important tools for the structural analysis and oligosaccharide preparation of GAGs. Various GAG lyases have been identified from terrestrial but not marine organisms even though marine animals are rich in GAGs with unique structures and functions. Herein we isolated a novel GAG lyase for the first time from the marine bacterium Vibrio sp. FC509 and then recombinantly expressed and characterized it. It showed strong lyase activity toward hyaluronan (HA) and chondroitin sulfate (CS) and was designated as HA and CS lyase (HCLase). It exhibited the highest activities to both substrates at pH 8.0 and 0.5 m NaCl at 30 °C. Its activity toward HA was less sensitive to pH than its CS lyase activity. As with most other marine enzymes, HCLase is a halophilic enzyme and very stable at temperatures from 0 to 40 °C for up to 24 h, but its activity is independent of divalent metal ions. The specific activity of HCLase against HA and CS reached a markedly high level of hundreds of thousands units/mg of protein under optimum conditions. The HCLase-resistant tetrasaccharide Δ(4,5)HexUAα1-3GalNAc(6-O-sulfate)β1-4GlcUA(2-O-sulfate)β1-3GalNAc(6-O-sulfate) was isolated from CS-D, the structure of which indicated that HCLase could not cleave the galactosaminidic linkage bound to 2-O-sulfated d-glucuronic acid (GlcUA) in CS chains. Site-directed mutagenesis indicated that HCLase may work via a catalytic mechanism in which Tyr-His acts as the Brønsted base and acid. Thus, the identification of HCLase provides a useful tool for HA- and CS-related research and applications. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  9. Revealing the mechanisms of protein disorder and N-glycosylation in CD44-hyaluronan binding using molecular simulation

    Directory of Open Access Journals (Sweden)

    Olgun eGuvench

    2015-06-01

    Full Text Available The extracellular N-terminal hyaluronan binding domain (HABD of CD44 is a small globular domain that confers hyaluronan (HA binding functionality to this large transmembrane glycoprotein. When recombinantly expressed by itself, HABD exists as a globular water-soluble protein that retains the capacity to bind HA. This has enabled atomic-resolution structural biology experiments that have revealed the structure of HABD and its binding mode with oligomeric HA. Such experiments have also pointed to an order-to-disorder transition in HABD that is associated with HA binding. However, it had remained unclear how this structural transition was involved in binding since it occurs in a region of HABD distant from the HA-binding site. Furthermore, HABD is known to be N-glycosylated, and such glycosylation can diminish HA binding when the associated N-glycans are capped with sialic acid residues. The intrinsic flexibility of disordered proteins and of N-glycans makes it difficult to apply experimental structural biology approaches to probe the molecular mechanisms of how the order-to-disorder transition and N-glycosylation can modulate HA binding by HABD. We review recent results from molecular dynamics simulations that provide atomic-resolution mechanistic understanding of such modulation to help bridge gaps between existing experimental binding and structural biology data. Findings from these simulations include: Tyr42 may function as a molecular switch that converts the HA binding site from a low affinity to a high affinity state; in the partially-disordered form of HABD, basic amino acids in the C-terminal region can gain sufficient mobility to form direct contacts with bound HA to further stabilize binding; and terminal sialic acids on covalently-attached N-glycans can form charge-paired hydrogen bonding interactions with basic amino acids that could otherwise bind to HA, thereby blocking HA binding to glycosylated CD44 HABD.

  10. Altered expression of hyaluronan, HAS1-2, and HYAL1-2 in oral lichen planus.

    Science.gov (United States)

    Siponen, Maria; Kullaa, Arja; Nieminen, Pentti; Salo, Tuula; Pasonen-Seppänen, Sanna

    2015-07-01

    Oral lichen planus (OLP) is an immune-mediated mucosal disease of unclear etiology and of unresolved pathogenesis. Hyaluronan (HA) is an extracellular matrix glycosaminoglycan involved in inflammation and tumor progression. However, its presence in OLP has not been reported. We therefore aimed to study the immunohistochemical expression of HA, its receptor CD44, hyaluronan synthases (HAS1-3), and hyaluronidases (HYAL1-2) in OLP. The presence of HA, CD44, HAS1-3, and HYAL1-2 was studied by immunohistochemical methods in 55 OLP and 23 control oral mucosal specimens (CTR). The localization, intensity, and differences of the epithelial expression between OLP and CTRs were analyzed. HA and CD44 were found on cell membranes in the epithelial basal and intermediate layers in CTR and OLP specimens. The HA staining intensity was stronger in the basal layer of the epithelium in OLP than in CTRs (P < 0.001). HAS1 (P = 0.001) and HAS2 (P < 0.001) showed stronger staining in the basal and weaker staining in the superficial (P < 0.001) epithelial layers in OLP than in CTRs. The immunostaining of HAS3 was low in both OLP and CTRs. Positive HYAL1 and HYAL2 staining were mainly found in the basal and intermediate epithelial layers, and their intensities were significantly increased in OLP, except HYAL 2 in the intermediate epithelial layer. HA, HAS1-2, and HYAL1-2 have altered expression in OLP compared to CTRs and may therefore have a role in OLP pathogenesis. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Intra-articular hyaluronan is without clinical effect in knee osteoarthritis: a multicentre, randomised, placebo-controlled, double-blind study of 337 patients followed for 1 year

    DEFF Research Database (Denmark)

    Jørgensen, Anette; Stengaard-Pedersen, Kristian; Simonsen, Lars Ole

    2010-01-01

    Objective To examine the long-term efficacy and safety of five intra-articular injections with hyaluronan in knee osteoarthritis. Methods A multicentre, randomised, placebo-controlled double-blind study of 337 patients fulfilling the American College of Rheumatology (ACR) criteria for knee...... osteoarthritis (clinical and laboratory) and with a Lequesne algofunctional index score (LFI) of 10 or greater. Patients received a hyaluronan product (sodium hyaluronate; Hyalgan) (n= 167) or saline (n= 170) intra-articularly weekly for 5 weeks and were followed up to 1 year. Time to recurrence was the primary...... efficacy parameter. LFI, pain on walking 50 m based on visual analogue scale (VAS pain 50 m), paracetamol consumption, patients' global assessment, Nottingham health profile, joint effusion and number of responders were secondary efficacy parameters. The efficacy parameters were analysed by intention...

  12. Hyaluronan and N-ERC/mesothelin as key biomarkers in a specific two-step model to predict pleural malignant mesothelioma.

    Directory of Open Access Journals (Sweden)

    Filip Mundt

    Full Text Available PURPOSE: Diagnosis of malignant mesothelioma is challenging. The first available diagnostic material is often an effusion and biochemical analysis of soluble markers may provide additional diagnostic information. This study aimed to establish a predictive model using biomarkers from pleural effusions, to allow early and accurate diagnosis. PATIENTS AND METHODS: Effusions were collected prospectively from 190 consecutive patients at a regional referral centre. Hyaluronan, N-ERC/mesothelin, C-ERC/mesothelin, osteopontin, syndecan-1, syndecan-2, and thioredoxin were measured using ELISA and HPLC. A predictive model was generated and validated using a second prospective set of 375 effusions collected consecutively at a different referral centre. RESULTS: Biochemical markers significantly associated with mesothelioma were hyaluronan (odds ratio, 95% CI: 8.82, 4.82-20.39, N-ERC/mesothelin (4.81, 3.19-7.93, CERC/mesothelin (3.58, 2.43-5.59 and syndecan-1 (1.34, 1.03-1.77. A two-step model using hyaluronan and N-ERC/mesothelin, and combining a threshold decision rule with logistic regression, yielded good discrimination with an area under the ROC curve of 0.99 (95% CI: 0.97-1.00 in the model generation dataset and 0.83 (0.74-0.91 in the validation dataset, respectively. CONCLUSIONS: A two-step model using hyaluronan and N-ERC/mesothelin predicts mesothelioma with high specificity. This method can be performed on the first available effusion and could be a useful adjunct to the morphological diagnosis of mesothelioma.

  13. Sevoflurane mitigates shedding of hyaluronan from the coronary endothelium, also during ischemia/reperfusion: an ex vivo animal study

    Directory of Open Access Journals (Sweden)

    Chen C

    2016-04-01

    Full Text Available Congcong Chen,1,3 Daniel Chappell,2,3 Thorsten Annecke,2,3 Peter Conzen,2 Matthias Jacob,2,3 Ulrich Welsch,4 Bernhard Zwissler,2 Bernhard F Becker3 1Department of Anesthesiology, Second Affiliated Hospital of Zhejiang University, Hangzhou, People's Republic of China; 2Clinic of Anesthesiology, Ludwig-Maximilians-University, Munich, Germany; 3Walter-Brendel-Centre of Experimental Medicine, Ludwig-Maximilians-University, Munich, Germany; 4Institute of Anatomy, Ludwig-Maximilians-University, Munich, Germany Abstract: Glycosaminoglycan hyaluronan (HA, a major constituent of the endothelial glycocalyx, helps to maintain vascular integrity. Preconditioning the heart with volatile anesthetic agents protects against ischemia/reperfusion injury. We investigated a possible protective effect of sevoflurane on the glycocalyx, especially on HA. The effect of pre-ischemic treatment with sevoflurane (15 minutes at 2% vol/vol gas on shedding of HA was evaluated in 28 isolated, beating guinea pig hearts, subjected to warm ischemia (20 minutes at 37°C followed by reperfusion (40 minutes, half with and half without preconditioning by sevoflurane. HA concentration was measured in the coronary effluent. Over the last 20 minutes of reperfusion hydroxyethyl starch (1 g% was continuously infused and the epicardial transudate collected over the last 5 minutes for measuring the colloid extravasation. Additional hearts were fixed by perfusion after the end of reperfusion for immunohistology and electron microscopy. Sevoflurane did not significantly affect post-ischemic oxidative stress, but strongly inhibited shedding of HA during the whole period, surprisingly even prior to ischemia. Immunohistology demonstrated that heparan sulfates and SDC1 of the glycocalyx were also preserved by sevoflurane. Electron microscopy revealed shedding of glycocalyx caused by ischemia and a mostly intact glycocalyx in hearts exposed to sevoflurane. Coronary vascular permeability of the

  14. LIF inhibits osteoblast differentiation at least in part by regulation of HAS2 and its product hyaluronan.

    Science.gov (United States)

    Falconi, Dominic; Aubin, Jane E

    2007-08-01

    LIF arrests osteogenesis in fetal rat calvaria cells in a differentiation stage-specific manner. Differential display identified HAS2 as a LIF-induced gene and its product, HA, modulated osteoblast differentiation similarly to LIF. Our data suggest that LIF arrests osteoblast differentiation by altering HA content of the extracellular matrix. Leukemia inhibitory factor (LIF) elicits both anabolic and catabolic effects on bone. We previously showed in the fetal rat calvaria (RC) cell system that LIF inhibits osteoblast differentiation at the late osteoprogenitor/early osteoblast stage. To uncover potential molecular mediators of this inhibitory activity, we used a positive-negative genome-wide differential display screen to identify LIF-induced changes in the developing osteoblast transcriptome. Although LIF signaling is active throughout the RC cell proliferation-differentiation sequence, only a relatively small number of genes, in several different functional clusters, are modulated by LIF specifically during the LIF-sensitive inhibitory time window. Based on their known and predicted functions, most of the LIF-regulated genes identified are plausible candidates to be involved in the LIF-induced arrest of osteoprogenitor differentiation. To test this hypothesis, we further analyzed the function of one of the genes identified, hyaluronan synthase 2 (HAS2), in the LIF-induced inhibition. Synthesis of hyaluronan (HA), the product of HAS enzymatic activity, was stimulated by LIF and mimicked the HAS2 expression profile, with highest expression in early/proliferative and late/maturing cultures and lowest levels in intermediate/late osteoprogenitor-early osteoblast cultures. Exogenously added high molecular weight HA, the product of HAS2, dose-dependently inhibited osteoblast differentiation, with pulse-treatment effective in the same differentiation stage-specific inhibitory window as seen with LIF. In addition, however, pulse treatment with HA in early cultures

  15. Tissue hyaluronan expression, as reflected in the sputum of lung cancer patients, is an indicator of malignancy

    Energy Technology Data Exchange (ETDEWEB)

    Rangel, M.P.; Sá, V.K. de; Martins, V. [Departamento de Patologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Martins, J.R.M. [Disciplina de Biologia Molecular, Departamento de Bioquímica, Faculdade de Medicina, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Disciplina de Endocrinologia e Metabolismo, Laboratório de Endocrinologia Molecular e Translacional-LEMT, Departamento de Medicina, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Parra, E.R. [Departamento de Patologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Mendes, A. [Disciplina de Biologia Molecular, Departamento de Bioquímica, Faculdade de Medicina, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Andrade, P.C. [Departamento de Patologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Reis, R.M. [Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga (Portugal); ICVS/3B' s - PT Government Associate Laboratory, Guimarães (Portugal); Centro de Pesquisa em Oncologia Molecular, Hospital de Câncer de Barretos, Fundação Pio XII, Barretos, SP (Brazil); Longatto-Filho, A. [Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga (Portugal); ICVS/3B' s - PT Government Associate Laboratory, Guimarães (Portugal); Laboratório de Investigação Médica (LIM 14), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Centro de Pesquisa em Oncologia Molecular, Hospital de Câncer de Barretos, Fundação Pio XII, Barretos, SP (Brazil); Oliveira, C.Z. [Centro de Pesquisa em Oncologia Molecular, Hospital de Câncer de Barretos, Fundação Pio XII, Barretos, SP (Brazil); Takagaki, T. [Divisão de Pneumologia, Instituto do Coração, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Carraro, D.M. [Centro Internacional de Pesquisa/CIPE, AC Camargo Cancer Center, São Paulo, SP (Brazil); Nader, H.B. [Disciplina de Biologia Molecular, Departamento de Bioquímica, Faculdade de Medicina, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Capelozzi, V.L. [Departamento de Patologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil)

    2015-05-08

    Hyaluronan (HA) shows promise for detecting cancerous change in pleural effusion and urine. However, there is uncertainty about the localization of HA in tumor tissue and its relationship with different histological types and other components of the extracellular matrix, such as angiogenesis. We evaluated the association between HA and degree of malignancy through expression in lung tumor tissue and sputum. Tumoral tissue had significantly increased HA compared to normal tissue. Strong HA staining intensity associated with cancer cells was significant in squamous cell carcinoma compared to adenocarcinoma and large cell carcinoma. A significant direct association was found between tumors with a high percentage of HA and MVD (microvessel density) in tumoral stroma. Similarly significant was the direct association between N1 tumors and high levels of HA in cancer cells. Cox multivariate analysis showed significant association between better survival and low HA. HA increased in sputum from lung cancer patients compared to cancer-free and healthy volunteers and a significant correlation was found between HA in sputum and HA in cancer tissue. Localization of HA in tumor tissue was related to malignancy and reflected in sputum, making this an emerging factor for an important diagnostic procedure in patients suspected to have lung cancer. Further study in additional patients in a randomized prospective trial is required to finalize these results and to validate our quantitative assessment of HA, as well as to couple it to gold standard sputum cytology.

  16. Radiation-induced increase in hyaluronan and fibronectin in bronchoalveolar lavage fluid from breast cancer patients is suppressed by smoking

    International Nuclear Information System (INIS)

    Bjermer, L.; Nilsson, K.; Haellgren, R.; Franzen, L.; Henriksson, R.; Sandstroem, T.; Saernstrand, B.

    1992-01-01

    Bronchoalveolar lavage (BAL) fluid was analysed from 21 patients with breast cancer, stage T 1 N 0 M 0 , who had undergone tumour resection and postoperative local irradiation (accumulated dose 56 Gy). The lavage was performed two months after radiotherapy, in the anterior part of the lingula (left side) or of the right middle lobe (right side), depending on which side had been exposed to radiation. The patients had significantly increased concentrations of fibronectin (FN) (p<0.001), hyaluronan (HA) (p<0.01) and albumin (p<0.05) in BAL fluid compared with the healthy controls (n=19). However, when the patients were separated, according to smoking history, it was obvious that the inflammatory reaction occurred entirely in the nonsmoking patient group (n=10), whilst no difference could be found between the smoking patients (n=11) and the controls. In the nonsmoking patient group, there was a sevenfold increase in BAL concentrations of FN and a threefold increase in HA. Moreover, four patients had detectable levels of procollagen III peptide in BAL, all were nonsmokers. The smoking habits of the controls had no influence on the BAL measurements. These findings indicate that smoking interferes with the radiation-induced early inflammatory connective tissue reaction of the lung. Finally, the results justify further investigation of interaction of smoking with cancer treatment, both from the view of therapy effectiveness and reduction of adverse effects. (au)

  17. Chitin-Hyaluronan Nanoparticles: A Multifunctional Carrier to Deliver Anti-Aging Active Ingredients through the Skin

    Directory of Open Access Journals (Sweden)

    Pierfrancesco Morganti

    2014-07-01

    Full Text Available The paper describes the process to produce Chitin Nanofibril-Hyaluronan nanoparticles (CN-HA, showing their ability to easily load active ingredients, facilitate penetration through the skin layers, and increase their effectiveness and safety as an anti-aging agent. Size and characterization of CN-HA nanoparticles were determined by Scanning Electron Microscopy (SEM and Zetasizer, while encapsulation efficiency and loading capacity of the entrapped ingredients were controlled by chromatographic and spectrophotometric methods. Safeness was evidenced on fibroblasts and keratinocytes culture viability by the MTT (Methylthiazol assay; anti-aging activity was evaluated in vitro measuring antioxidant capacity, anti-collagenase activity, and metalloproteinase and pro-inflammatory release; efficacy was shown in vivo by a double-blind vehicle-controlled study for 60 days on 60 women affected by photo-aging. In addition, the CN-HA nanoparticles have shown interesting possibility to be used as active ingredients, for designing and making advanced medication by the electrospinning technology, as well as to produce transparent films for food packaging, by the casting method, and can be used also in their dry form as tissues or films without adding preservatives. These unusual CN-HA nanoparticles obtained from the use of raw materials of waste origin may offer an unprecedented occasion for making innovative products, ameliorating the quality of life, reducing pollution and safeguarding the environment’s integrity.

  18. Tissue hyaluronan expression, as reflected in the sputum of lung cancer patients, is an indicator of malignancy

    International Nuclear Information System (INIS)

    Rangel, M.P.; Sá, V.K. de; Martins, V.; Martins, J.R.M.; Parra, E.R.; Mendes, A.; Andrade, P.C.; Reis, R.M.; Longatto-Filho, A.; Oliveira, C.Z.; Takagaki, T.; Carraro, D.M.; Nader, H.B.; Capelozzi, V.L.

    2015-01-01

    Hyaluronan (HA) shows promise for detecting cancerous change in pleural effusion and urine. However, there is uncertainty about the localization of HA in tumor tissue and its relationship with different histological types and other components of the extracellular matrix, such as angiogenesis. We evaluated the association between HA and degree of malignancy through expression in lung tumor tissue and sputum. Tumoral tissue had significantly increased HA compared to normal tissue. Strong HA staining intensity associated with cancer cells was significant in squamous cell carcinoma compared to adenocarcinoma and large cell carcinoma. A significant direct association was found between tumors with a high percentage of HA and MVD (microvessel density) in tumoral stroma. Similarly significant was the direct association between N1 tumors and high levels of HA in cancer cells. Cox multivariate analysis showed significant association between better survival and low HA. HA increased in sputum from lung cancer patients compared to cancer-free and healthy volunteers and a significant correlation was found between HA in sputum and HA in cancer tissue. Localization of HA in tumor tissue was related to malignancy and reflected in sputum, making this an emerging factor for an important diagnostic procedure in patients suspected to have lung cancer. Further study in additional patients in a randomized prospective trial is required to finalize these results and to validate our quantitative assessment of HA, as well as to couple it to gold standard sputum cytology

  19. Pursuing Intracellular Pathogens with Hyaluronan. From a 'Pro-Infection' Polymer to a Biomaterial for 'Trojan Horse' Systems.

    Science.gov (United States)

    Montanari, Elita; Di Meo, Chiara; Oates, Angela; Coviello, Tommasina; Matricardi, Pietro

    2018-04-18

    Hyaluronan (HA) is among the most important bioactive polymers in mammals, playing a key role in a number of biological functions. In the last decades, it has been increasingly studied as a biomaterial for drug delivery systems, thanks to its physico-chemical features and ability to target and enter certain cells. The most important receptor of HA is ‘Cluster of Differentiation 44’ (CD44), a cell surface glycoprotein over-expressed by a number of cancers and heavily involved in HA endocytosis. Moreover, CD44 is highly expressed by keratinocytes, activated macrophages and fibroblasts, all of which can act as ‘reservoirs’ for intracellular pathogens. Interestingly, both CD44 and HA appear to play a key role for the invasion and persistence of such microorganisms within the cells. As such, HA is increasingly recognised as a potential target for nano-carriers development, to pursuit and target intracellular pathogens, acting as a ‘Trojan Horse’. This review describes the biological relationship between HA, CD44 and the entry and survival of a number of pathogens within the cells and the subsequent development of HA-based nano-carriers for enhancing the intracellular activity of antimicrobials.

  20. A Modified ELISA Accurately Measures Secretion of High Molecular Weight Hyaluronan (HA) by Graves' Disease Orbital Cells

    Science.gov (United States)

    Krieger, Christine C.

    2014-01-01

    Excess production of hyaluronan (hyaluronic acid [HA]) in the retro-orbital space is a major component of Graves' ophthalmopathy, and regulation of HA production by orbital cells is a major research area. In most previous studies, HA was measured by ELISAs that used HA-binding proteins for detection and rooster comb HA as standards. We show that the binding efficiency of HA-binding protein in the ELISA is a function of HA polymer size. Using gel electrophoresis, we show that HA secreted from orbital cells is primarily comprised of polymers more than 500 000. We modified a commercially available ELISA by using 1 million molecular weight HA as standard to accurately measure HA of this size. We demonstrated that IL-1β-stimulated HA secretion is at least 2-fold greater than previously reported, and activation of the TSH receptor by an activating antibody M22 from a patient with Graves' disease led to more than 3-fold increase in HA production in both fibroblasts/preadipocytes and adipocytes. These effects were not consistently detected with the commercial ELISA using rooster comb HA as standard and suggest that fibroblasts/preadipocytes may play a more prominent role in HA remodeling in Graves' ophthalmopathy than previously appreciated. PMID:24302624

  1. Hyaluronan suppresses prostate tumor cell proliferation through diminished expression of N-cadherin and aberrant growth factor receptor signaling

    International Nuclear Information System (INIS)

    Bharadwaj, Alamelu G.; Goodrich, Nathaniel P.; McAtee, Caitlin O.; Haferbier, Katie; Oakley, Gregory G.; Wahl, James K.; Simpson, Melanie A.

    2011-01-01

    Hyaluronan (HA) production has been functionally implicated in prostate tumorigenesis and metastasis. We previously used prostate tumor cells overexpressing the HA synthesizing enzyme HAS3 or the clinically relevant hyaluronidase Hyal1 to show that excess HA production suppresses tumor growth, while HA turnover accelerates spontaneous metastasis from the prostate. Here, we examined pathways responsible for effects of HAS3 and Hyal1 on tumor cell phenotype. Detailed characterization of cell cycle progression revealed that expression of Hyal1 accelerated cell cycle re-entry following synchronization, whereas HAS3 alone delayed entry. Hyal1 expressing cells exhibited a significant reduction in their ability to sustain ERK phosphorylation upon stimulation by growth factors, and in their expression of the cyclin-dependent kinase inhibitor p21. In contrast, HAS3 expressing cells showed prolonged ERK phosphorylation and increased expression of both p21 and p27, in asynchronous and synchronized cultures. Changes in cell cycle regulatory proteins were accompanied by HA-induced suppression of N-cadherin, while E-cadherin expression and β-catenin expression and distribution remained unchanged. Our results are consistent with a model in which excess HA synthesis suppresses cell proliferation by promoting homotypic E-cadherin mediated cell-cell adhesion, consequently signaling to elevate cell cycle inhibitor expression and suppress G1- to S-phase transition.

  2. Effect of Hyaluronan on Developmental Competence and Quality of Oocytes and Obtained Blastocysts from In Vitro Maturation of Bovine Oocytes

    Directory of Open Access Journals (Sweden)

    Jolanta Opiela

    2014-01-01

    Full Text Available The objective of the present study was to evaluate the effect of hyaluronan (HA during IVM on meiotic maturation, embryonic development, and the quality of oocytes, granulosa cells (GC, and obtained blastocysts. COCs were matured in vitro in control medium and medium with additional 0.035% or 0.07% of exogenous HA. The meiotic maturity did not differ between the analysed groups. The best rate and the highest quality of obtained blastocysts were observed when 0.07% HA was used. A highly significant difference (P<0.001 was noted in the mean number of apoptotic nuclei per blastocyst and in the DCI between the 0.07% HA and the control blastocysts (P<0.01. Our results suggest that addition of 0.035% HA and 0.07% HA to oocyte maturation media does not affect oocyte nuclear maturation and DNA fragmentation. However, the addition of 0.07% HA during IVM decreases the level of blastocysts DNA fragmentation. Finally, our results suggest that it may be risky to increase the HA concentration during IVM above 0.07% as we found significantly higher Bax mRNA expression levels in GC cultured with 0.07% HA. The final concentration of HA being supplemented to oocyte maturation media is critical for the success of the IVP procedure.

  3. Fluorescent molecularly imprinted polymers as plastic antibodies for selective labeling and imaging of hyaluronan and sialic acid on fixed and living cells.

    Science.gov (United States)

    Panagiotopoulou, Maria; Kunath, Stephanie; Medina-Rangel, Paulina Ximena; Haupt, Karsten; Tse Sum Bui, Bernadette

    2017-02-15

    Altered glycosylation levels or distribution of sialic acids (SA) or hyaluronan in animal cells are indicators of pathological conditions like infection or malignancy. We applied fluorescently-labeled molecularly imprinted polymer (MIP) particles for bioimaging of fixed and living human keratinocytes, to localize hyaluronan and sialylation sites. MIPs were prepared with the templates D-glucuronic acid (GlcA), a substructure of hyaluronan, and N-acetylneuraminic acid (NANA), the most common member of SA. Both MIPs were found to be highly selective towards their target monosaccharides, as no cross-reactivity was observed with other sugars like N-acetyl-D-glucosamine, N-acetyl-D-galactosamine, D-glucose and D-galactose, present on the cell surface. The dye rhodamine and two InP/ZnS quantum dots (QDs) emitting in the green and in the red regions were used as fluorescent probes. Rhodamine-MIPGlcA and rhodamine-MIPNANA were synthesized as monodispersed 400nm sized particles and were found to bind selectively their targets located in the extracellular region, as imaged by epifluorescence and confocal microscopy. In contrast, when MIP-GlcA and MIP-NANA particles with a smaller size (125nm) were used, the MIPs being synthesized as thin shells around green and red emitting QDs respectively, it was possible to stain the intracellular and pericellular regions as well. In addition, simultaneous dual-color imaging with the two different colored QDs-MIPs was demonstrated. Importantly, the MIPs were not cytotoxic and did not affect cell viability; neither was the cells morphology affected as demonstrated by live cell imaging. These synthetic receptors could offer a new and promising imaging tool to monitor disease progression. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Hyaluronan (HA) interacting proteins RHAMM and hyaluronidase impact prostate cancer cell behavior and invadopodia formation in 3D HA-based hydrogels.

    Science.gov (United States)

    Gurski, Lisa A; Xu, Xian; Labrada, Lyana N; Nguyen, Ngoc T; Xiao, Longxi; van Golen, Kenneth L; Jia, Xinqiao; Farach-Carson, Mary C

    2012-01-01

    To study the individual functions of hyaluronan interacting proteins in prostate cancer (PCa) motility through connective tissues, we developed a novel three-dimensional (3D) hyaluronic acid (HA) hydrogel assay that provides a flexible, quantifiable, and physiologically relevant alternative to current methods. Invasion in this system reflects the prevalence of HA in connective tissues and its role in the promotion of cancer cell motility and tissue invasion, making the system ideal to study invasion through bone marrow or other HA-rich connective tissues. The bio-compatible cross-linking process we used allows for direct encapsulation of cancer cells within the gel where they adopt a distinct, cluster-like morphology. Metastatic PCa cells in these hydrogels develop fingerlike structures, "invadopodia", consistent with their invasive properties. The number of invadopodia, as well as cluster size, shape, and convergence, can provide a quantifiable measure of invasive potential. Among candidate hyaluronan interacting proteins that could be responsible for the behavior we observed, we found that culture in the HA hydrogel triggers invasive PCa cells to differentially express and localize receptor for hyaluronan mediated motility (RHAMM)/CD168 which, in the absence of CD44, appears to contribute to PCa motility and invasion by interacting with the HA hydrogel components. PCa cell invasion through the HA hydrogel also was found to depend on the activity of hyaluronidases. Studies shown here reveal that while hyaluronidase activity is necessary for invadopodia and inter-connecting cluster formation, activity alone is not sufficient for acquisition of invasiveness to occur. We therefore suggest that development of invasive behavior in 3D HA-based systems requires development of additional cellular features, such as activation of motility associated pathways that regulate formation of invadopodia. Thus, we report development of a 3D system amenable to dissection of

  5. Hypochlorite and superoxide radicals can act synergistically to induce fragmentation of hyaluronan and chondroitin sulphates

    DEFF Research Database (Denmark)

    Rees, Martin D; Hawkins, Clare Louise; Davies, Michael Jonathan

    2004-01-01

    at pH 7.4). Exposure of glycosaminoglycans to a MPO-H2O2-Cl- system or reagent HOCl generates long-lived chloramides [R-NCl-C(O)-R'] derived from the glycosamine N-acetyl functions. Decomposition of these species by transition metal ions gives polymer-derived amidyl (nitrogen-centred) radicals [R......-carboxybenzyl)hyponitrite] was demonstrated to be entirely chloramide dependent as no fragmentation occurred with the native polymers or when the chloramides were quenched by prior treatment with methionine. EPR spin-trapping experiments using 5,5-dimethyl1-pyrroline-N-oxide and 2-methyl-2-nitrosopropane have...

  6. Hyaluronan activates Hyal-2/WWOX/Smad4 signaling and causes bubbling cell death when the signaling complex is overexpressed

    Science.gov (United States)

    Hsu, Li-Jin; Hong, Qunying; Chen, Shur-Tzu; Kuo, Hsiang-Lin; Schultz, Lori; Heath, John; Lin, Sing-Ru; Lee, Ming-Hui; Li, Dong-Zhang; Li, Zih-Ling; Cheng, Hui-Ching; Armand, Gerard; Chang, Nan-Shan

    2017-01-01

    Malignant cancer cells frequently secrete significant amounts of transforming growth factor beta (TGF-β), hyaluronan (HA) and hyaluronidases to facilitate metastasizing to target organs. In a non-canonical signaling, TGF-β binds membrane hyaluronidase Hyal-2 for recruiting tumor suppressors WWOX and Smad4, and the resulting Hyal-2/WWOX/Smad4 complex is accumulated in the nucleus to enhance SMAD-promoter dependent transcriptional activity. Yeast two-hybrid analysis showed that WWOX acts as a bridge to bind both Hyal-2 and Smad4. When WWOX-expressing cells were stimulated with high molecular weight HA, an increased formation of endogenous Hyal-2/WWOX/Smad4 complex occurred rapidly, followed by relocating to the nuclei in 20-40 min. In WWOX-deficient cells, HA failed to induce Smad2/3/4 relocation to the nucleus. To prove the signaling event, we designed a real time tri-molecular FRET analysis and revealed that HA induces the signaling pathway from ectopic Smad4 to WWOX and finally to p53, as well as from Smad4 to Hyal-2 and then to WWOX. An increased binding of the Smad4/Hyal-2/WWOX complex occurs with time in the nucleus that leads to bubbling cell death. In contrast, HA increases the binding of Smad4/WWOX/p53, which causes membrane blebbing but without cell death. In traumatic brain injury-induced neuronal death, the Hyal-2/WWOX complex was accumulated in the apoptotic nuclei of neurons in the rat brains in 24 hr post injury, as determined by immunoelectron microscopy. Together, HA activates the Hyal-2/WWOX/Smad4 signaling and causes bubbling cell death when the signaling complex is overexpressed. PMID:27845895

  7. Oral hyaluronan relieves wrinkles: a double-blinded, placebo-controlled study over a 12-week period

    Directory of Open Access Journals (Sweden)

    Oe M

    2017-07-01

    Full Text Available Mariko Oe,1 Seigo Sakai,1 Hideto Yoshida,1 Nao Okado,1 Haruna Kaneda,1 Yasunobu Masuda,1 Osamu Urushibata2 1R&D Division, Kewpie Corporation, Sengawa-cho, Chofu-shi, 2Department of Dermatology, Toho University Ohashi Medical Center, Ohashi, Meguro-ku, Tokyo, Japan Background: Hyaluronan (HA has critical moisturizing property and high water retention capacity especially for human skin. This study aimed to evaluate the effect of oral intake of HA. Methods: The mean molecular weight (MW of HA is 2 k and 300 k. Sixty Japanese male and female subjects aged 22–59 years who presented with crow’s feet wrinkles were randomly assigned to the HA 2 k or HA 300 k at 120 mg/day or the placebo group. The subjects were administered HA at a rate of 120 mg/day or a placebo for 12 weeks. The skin wrinkles were evaluated by image analysis of skin wrinkle replicas, and their skin condition was evaluated using a questionnaire survey. Results: During the study period, the HA groups showed better level of the whole sulcus ­volume ratio, wrinkle area ratio, and wrinkle volume ratio than the placebo group. After 8 weeks of ingestion, the HA 300 k group showed significantly diminished wrinkles compared with the placebo group. Skin luster and suppleness significantly improved after 12 weeks in all groups compared with the baseline. Conclusion: The results suggest that oral HA (both HA 2 k and HA 300 k inhibits skin wrinkles and improves skin condition. Keywords: hyaluronic acid, dietary supplement, skin, wrinkle volume, molecular weight

  8. Hyaluronan activates Hyal-2/WWOX/Smad4 signaling and causes bubbling cell death when the signaling complex is overexpressed.

    Science.gov (United States)

    Hsu, Li-Jin; Hong, Qunying; Chen, Shur-Tzu; Kuo, Hsiang-Lin; Schultz, Lori; Heath, John; Lin, Sing-Ru; Lee, Ming-Hui; Li, Dong-Zhang; Li, Zih-Ling; Cheng, Hui-Ching; Armand, Gerard; Chang, Nan-Shan

    2017-03-21

    Malignant cancer cells frequently secrete significant amounts of transforming growth factor beta (TGF-β), hyaluronan (HA) and hyaluronidases to facilitate metastasizing to target organs. In a non-canonical signaling, TGF-β binds membrane hyaluronidase Hyal-2 for recruiting tumor suppressors WWOX and Smad4, and the resulting Hyal-2/WWOX/Smad4 complex is accumulated in the nucleus to enhance SMAD-promoter dependent transcriptional activity. Yeast two-hybrid analysis showed that WWOX acts as a bridge to bind both Hyal-2 and Smad4. When WWOX-expressing cells were stimulated with high molecular weight HA, an increased formation of endogenous Hyal-2/WWOX/Smad4 complex occurred rapidly, followed by relocating to the nuclei in 20-40 min. In WWOX-deficient cells, HA failed to induce Smad2/3/4 relocation to the nucleus. To prove the signaling event, we designed a real time tri-molecular FRET analysis and revealed that HA induces the signaling pathway from ectopic Smad4 to WWOX and finally to p53, as well as from Smad4 to Hyal-2 and then to WWOX. An increased binding of the Smad4/Hyal-2/WWOX complex occurs with time in the nucleus that leads to bubbling cell death. In contrast, HA increases the binding of Smad4/WWOX/p53, which causes membrane blebbing but without cell death. In traumatic brain injury-induced neuronal death, the Hyal-2/WWOX complex was accumulated in the apoptotic nuclei of neurons in the rat brains in 24 hr post injury, as determined by immunoelectron microscopy. Together, HA activates the Hyal-2/WWOX/Smad4 signaling and causes bubbling cell death when the signaling complex is overexpressed.

  9. Evaluation of hyaluronan from different sources: Streptococcus zooepidemicus, rooster comb, bovine vitreous, and human umbilical cord.

    Science.gov (United States)

    Shiedlin, Aviva; Bigelow, Russell; Christopher, William; Arbabi, Saman; Yang, Laura; Maier, Ronald V; Wainwright, Norman; Childs, Alice; Miller, Robert J

    2004-01-01

    Sodium hyaluronate (HA) is widely distributed in extracellular matrixes and can play a role in orchestrating cell function. Consequently, many investigators have looked at the effect of exogenous HA on cell behavior in vitro. HA can be isolated from several sources (e.g., bacterial, rooster comb, umbilical cord) and therefore can possess diverse impurities. This current study compares the measured impurities and the differences in biological activity between HA preparations from these sources. It was demonstrated that nucleic acid and protein content was highest in human umbilical cord and bovine vitreous HA and was low in bacterial and rooster comb HA. Macrophages exposed to human umbilical cord HA produced significantly higher amounts of TNF-alpha relative to control or bacterial-derived HA. These results indicate that the source of HA should be considered due to differences in the amounts and types of contaminants that could lead to widely different behaviors in vitro and in vivo.

  10. Chitosan-hyaluronan based 3D co-culture platform for studying the crosstalk of lung cancer cells and mesenchymal stem cells.

    Science.gov (United States)

    Han, Hao-Wei; Hsu, Shan-Hui

    2016-09-15

    The controversial roles of mesenchymal stem cells (MSCs) in lung cancer development are not yet resolved because of the lack of an extracellular environment that mimics the tumor microenvironment. Three-dimensional (3D) culture system is an emerging research tool for biomedical applications such as drug screening. In this study, MSCs and human non-small cell lung carcinoma cells (A549) were co-cultured on a thin biomaterial-based substratum (hyaluronan-grafted chitosan, CS-HA; ∼2μm), and they were self-organized into the 3D tumor co-spheroids with core-shell structure. The gene expression levels of tumorigenicity markers in cancer cells associated with cancer stemness, epithelial-mesenchymal transition (EMT) property, and cell mobility were up-regulated for more than twofold in the MSC-tumor co-spheroids, through the promoted expression of certain tumor enhancers and the direct cell-cell interaction. To verify the different extents of tumorigenicity, A549 cells or those co-cultured with MSCs were transplanted into zebrafish embryos for evaluation in vivo. The tumorigenicity obtained from the zebrafish xenotransplantation model was consistent with that observed in vitro. These evidences suggest that the CS-HA substrate-based 3D co-culture platform for cancer cells and MSCs may be a convenient tool for studying the cell-cell interaction in a tumor-like microenvironment and potentially for cancer drug testing. Mesenchymal stem cells (MSCs) have been found in several types of tumor tissues. However, the controversial roles of MSCs in cancer development are still unsolved. Chitosan and hyaluronan are commonly used materials in the biomedical field. In the current study, we co-cultured lung cancer cells and MSCs on the planar hyaluronan-grafted chitosan (CS-HA) hybrid substrates, and discovered that lung cancer cells and MSCs were rapidly self-assembled into 3D tumor spheroids with core-shell structure on the substrates after only two days in culture. Therefore, CS

  11. Immunohistochemical analysis of EGFR and hyaluronan in tongue cancer and the development of regional recurrence in patients initially diagnosed N0.

    Science.gov (United States)

    Lindell Jonsson, Eva; Nylander, Karin; Hallén, Lars; Laurell, Göran

    2017-08-01

    To investigate whether the extent of expression of hyaluronan (HA) and epidermal growth factor receptor (EGFR) in squamous cell carcinoma of the mobile tongue can predict the risk of cervical metastasis and survival. Retrospective histopathologic study. Surgical specimens from 64 patients who had undergone surgery for squamous cell carcinoma of the mobile tongue were assessed using immunohistochemistry to investigate the expression of HA and EGFR in the primary tumours, and the data were then correlated to cervical metastasis and survival. There was a significant correlation between the intensity of HA staining and patient survival (p .024), and a weak correlation between the staining proportion of EGFR and the risk for regional recurrence (AUC 66). This study indicates that immunoscoring using HA could be used to provide prognostic tools for tongue cancer, and that it might be of interest to study the prognostic properties of EGFR further concerning the risk for regional recurrence after the primary treatment.

  12. Hyaluronan-CD44v3 Interaction with Oct4-Sox2-Nanog Promotes miR-302 Expression Leading to Self-renewal, Clonal Formation, and Cisplatin Resistance in Cancer Stem Cells from Head and Neck Squamous Cell Carcinoma*

    Science.gov (United States)

    Bourguignon, Lilly Y. W.; Wong, Gabriel; Earle, Christine; Chen, Liqun

    2012-01-01

    Human head and neck squamous cell carcinoma (HNSCC) is a highly malignant cancer associated with major morbidity and mortality. In this study, we determined that human HNSCC-derived HSC-3 cells contain a subpopulation of cancer stem cells (CSCs) characterized by high levels of CD44v3 and aldehyde dehydrogenase-1 (ALDH1) expression. These tumor cells also express several stem cell markers (the transcription factors Oct4, Sox2, and Nanog) and display the hallmark CSC properties of self-renewal/clonal formation and the ability to generate heterogeneous cell populations. Importantly, hyaluronan (HA) stimulates the CD44v3 (an HA receptor) interaction with Oct4-Sox2-Nanog leading to both a complex formation and the nuclear translocation of three CSC transcription factors. Further analysis reveals that microRNA-302 (miR-302) is controlled by an upstream promoter containing Oct4-Sox2-Nanog-binding sites, whereas chromatin immunoprecipitation (ChIP) assays demonstrate that stimulation of miR-302 expression by HA-CD44 is Oct4-Sox2-Nanog-dependent in HNSCC-specific CSCs. This process results in suppression of several epigenetic regulators (AOF1/AOF2 and DNMT1) and the up-regulation of several survival proteins (cIAP-1, cIAP-2, and XIAP) leading to self-renewal, clonal formation, and cisplatin resistance. These CSCs were transfected with a specific anti-miR-302 inhibitor to silence miR-302 expression and block its target functions. Our results demonstrate that the anti-miR-302 inhibitor not only enhances the expression of AOF1/AOF2 and DNMT1 but also abrogates the production of cIAP-1, cIAP-2, and XIAP and HA-CD44v3-mediated cancer stem cell functions. Taken together, these findings strongly support the contention that the HA-induced CD44v3 interaction with Oct4-Sox2-Nanog signaling plays a pivotal role in miR-302 production leading to AOF1/AOF2/DNMT1 down-regulation and survival of protein activation. All of these events are critically important for the acquisition of cancer

  13. Hyaluronan-CD44v3 interaction with Oct4-Sox2-Nanog promotes miR-302 expression leading to self-renewal, clonal formation, and cisplatin resistance in cancer stem cells from head and neck squamous cell carcinoma.

    Science.gov (United States)

    Bourguignon, Lilly Y W; Wong, Gabriel; Earle, Christine; Chen, Liqun

    2012-09-21

    Human head and neck squamous cell carcinoma (HNSCC) is a highly malignant cancer associated with major morbidity and mortality. In this study, we determined that human HNSCC-derived HSC-3 cells contain a subpopulation of cancer stem cells (CSCs) characterized by high levels of CD44v3 and aldehyde dehydrogenase-1 (ALDH1) expression. These tumor cells also express several stem cell markers (the transcription factors Oct4, Sox2, and Nanog) and display the hallmark CSC properties of self-renewal/clonal formation and the ability to generate heterogeneous cell populations. Importantly, hyaluronan (HA) stimulates the CD44v3 (an HA receptor) interaction with Oct4-Sox2-Nanog leading to both a complex formation and the nuclear translocation of three CSC transcription factors. Further analysis reveals that microRNA-302 (miR-302) is controlled by an upstream promoter containing Oct4-Sox2-Nanog-binding sites, whereas chromatin immunoprecipitation (ChIP) assays demonstrate that stimulation of miR-302 expression by HA-CD44 is Oct4-Sox2-Nanog-dependent in HNSCC-specific CSCs. This process results in suppression of several epigenetic regulators (AOF1/AOF2 and DNMT1) and the up-regulation of several survival proteins (cIAP-1, cIAP-2, and XIAP) leading to self-renewal, clonal formation, and cisplatin resistance. These CSCs were transfected with a specific anti-miR-302 inhibitor to silence miR-302 expression and block its target functions. Our results demonstrate that the anti-miR-302 inhibitor not only enhances the expression of AOF1/AOF2 and DNMT1 but also abrogates the production of cIAP-1, cIAP-2, and XIAP and HA-CD44v3-mediated cancer stem cell functions. Taken together, these findings strongly support the contention that the HA-induced CD44v3 interaction with Oct4-Sox2-Nanog signaling plays a pivotal role in miR-302 production leading to AOF1/AOF2/DNMT1 down-regulation and survival of protein activation. All of these events are critically important for the acquisition of cancer

  14. Evaluation of long-term antinociceptive properties of stabilized hyaluronic acid preparation (NASHA) in an animal model of repetitive joint pain

    Science.gov (United States)

    2011-01-01

    Introduction Clinical trials provided controversial results on whether the injection of hyaluronan preparations into osteoarthritic joints reduces pain. Problems of clinical studies may be the substantial placebo effects of intra-articular injections, different severity and rate of progression of the disease and others. We hypothesize that the use of preclinical pain models may help to clarify whether a certain hyaluronan exerts antinociceptive effects upon intra-articular injection. In the present study we tested in the bradykinin/prostaglandin E2 (PGE2) model primarily the putative antinociceptive effect of stabilized hyaluronic acid from a non animal source (NASHA), a stabilized hyaluronic acid based gel for intra-articular treatment of OA. We established a dose-response relationship for NASHA and we compared NASHA to other hyaluronans with different formulations that are in clinical use. Methods To induce transient joint pain episodes bradykinin and PGE2 were repetitively administered intra-articularly and unilaterally into rat knee joints during short anaesthesia. After establishment of the predrug nociceptive responses, a single intra-articular injection of saline or NASHA at different concentrations was administered and pain responses to further bradykinin/PGE2 injections were monitored up to 56 days after NASHA. Furthermore, the obtained effective dose was compared to clinically defined concentrations of Hylan GF20 and sodium hyaluronate. The primary outcome measures were primary mechanical hyperalgesia at the knee joint and pain-induced weight bearing. Results On day 1 after injection, all tested hyaluronan preparations showed an antinociceptive effect >50% compared to saline. Single injections of higher doses of NASHA (50, 75 and 100 μl) were antinociceptive up to 56 days. When injection volumes in rat knee joints were adapted to clinical injection volumes in humans, the antinociceptive effects of the cross-linked NASHA and Hylan GF20 had a longer

  15. Global Derivatives

    DEFF Research Database (Denmark)

    Andersen, Torben Juul

    approaches to dealing in the global business environment." - Sharon Brown-Hruska, Commissioner, Commodity Futures Trading Commission, USA. "This comprehensive survey of modern risk management using derivative securities is a fine demonstration of the practical relevance of modern derivatives theory to risk......" provides comprehensive coverage of different types of derivatives, including exchange traded contracts and over-the-counter instruments as well as real options. There is an equal emphasis on the practical application of derivatives and their actual uses in business transactions and corporate risk...... management situations. Its key features include: derivatives are introduced in a global market perspective; describes major derivative pricing models for practical use, extending these principles to valuation of real options; practical applications of derivative instruments are richly illustrated...

  16. Biomechanical and histologic evaluation of tissue engineered ligaments using chitosan and hyaluronan hybrid polymer fibers: a rabbit medial collateral ligament reconstruction model.

    Science.gov (United States)

    Irie, Toru; Majima, Tokifumi; Sawaguchi, Naohiro; Funakoshi, Tadanao; Nishimura, Shin-Ichiro; Minami, Akio

    2011-05-01

    In this study, we used a rabbit medial collateral ligament reconstruction model to evaluate a novel chitosan-based hyaluronan hybrid polymer fiber scaffold for ligament tissue engineering and to examine whether mechanical forces exerted in an in vivo model increased extracellular matrix production by seeded fibroblasts. Scaffolds were used 2 weeks after incubation with fibroblasts obtained from the same rabbit in a cell-seeded scaffold (CSS) group and without cells in a noncell-seeded scaffold (NCSS) group. At 3, 6, and 12 weeks after surgery, the failure loads of the engineered ligaments in the CSS groups were significantly greater than those in the NCSS groups. At 6 weeks after surgery, the reconstructed tissue of the CSS group was positive for type I collagen, whereas that in the NCSS group was negative for type I collagen. At 12 weeks after surgery, the reconstructed tissue stained positive for type I collagen in the CSS group, but negative in the NCSS group. Our results indicate that the scaffold material enhanced the production of type I collagen and led to improved mechanical strength in the engineered ligament in vivo. Copyright © 2011 Wiley Periodicals, Inc.

  17. Corneal protection with high-molecular-weight hyaluronan against in vitro and in vivo sodium lauryl sulfate-induced toxic effects.

    Science.gov (United States)

    Pauloin, Thierry; Dutot, Mélody; Liang, Hong; Chavinier, Emilie; Warnet, Jean-Michel; Rat, Patrice

    2009-10-01

    The aim of this study was to investigate high-molecular-weight hyaluronan (HA-HMW) corneal protection against sodium lauryl sulfate (SLS)-induced toxic effects with in vitro and in vivo experimental approaches. In vitro experiments consisted of a human corneal epithelial cell line incubated with HA-HMW, rinsed, and incubated with SLS. Cell viability, oxidative stress, chromatin condensation, caspase-3, -8, -9, and P2X7 cell death receptor activation, interleukin-6, and interleukin-8 production were investigated. In vivo experiments consisted of 36 New Zealand white rabbits treated for 3 days, 3 times per day, with HA-HMW or phosphate-buffered salt solution. At day 4, eyes were treated with SLS. Clinical observation and in vivo confocal microscopy using the Rostock Cornea Module of the Heidelberg Retina Tomograph-II were performed to evaluate and to compare SLS-induced toxicity between eyes treated with HA-HMW and eyes treated with phosphate-buffered salt solution. In vitro data indicate that exposure of human corneal epithelial cells to HA-HMW significantly decreased SLS-induced oxidative stress, apoptosis, and inflammation cytokine production. In vivo data indicate that SLS cornea injuries, characterized by damaged corneal epithelium, damaged anterior stroma, and inflammatory infiltrations, were attenuated with HA-HMW treatment. A good correlation was seen between in vitro and in vivo findings showing that HA-HMW decreases SLS-induced toxic effects and protects cornea.

  18. A single molecule assay to probe monovalent and multivalent bonds between hyaluronan and its key leukocyte receptor CD44 under force

    Science.gov (United States)

    Bano, Fouzia; Banerji, Suneale; Howarth, Mark; Jackson, David G.; Richter, Ralf P.

    2016-09-01

    Glycosaminoglycans (GAGs), a category of linear, anionic polysaccharides, are ubiquitous in the extracellular space, and important extrinsic regulators of cell function. Despite the recognized significance of mechanical stimuli in cellular communication, however, only few single molecule methods are currently available to study how monovalent and multivalent GAG·protein bonds respond to directed mechanical forces. Here, we have devised such a method, by combining purpose-designed surfaces that afford immobilization of GAGs and receptors at controlled nanoscale organizations with single molecule force spectroscopy (SMFS). We apply the method to study the interaction of the GAG polymer hyaluronan (HA) with CD44, its receptor in vascular endothelium. Individual bonds between HA and CD44 are remarkably resistant to rupture under force in comparison to their low binding affinity. Multiple bonds along a single HA chain rupture sequentially and independently under load. We also demonstrate how strong non-covalent bonds, which are versatile for controlled protein and GAG immobilization, can be effectively used as molecular anchors in SMFS. We thus establish a versatile method for analyzing the nanomechanics of GAG·protein interactions at the level of single GAG chains, which provides new molecular-level insight into the role of mechanical forces in the assembly and function of GAG-rich extracellular matrices.

  19. Quantitative proteomics reveals altered expression of extracellular matrix related proteins of human primary dermal fibroblasts in response to sulfated hyaluronan and collagen applied as artificial extracellular matrix.

    Science.gov (United States)

    Müller, Stephan A; van der Smissen, Anja; von Feilitzsch, Margarete; Anderegg, Ulf; Kalkhof, Stefan; von Bergen, Martin

    2012-12-01

    Fibroblasts are the main matrix producing cells of the dermis and are also strongly regulated by their matrix environment which can be used to improve and guide skin wound healing processes. Here, we systematically investigated the molecular effects on primary dermal fibroblasts in response to high-sulfated hyaluronan [HA] (hsHA) by quantitative proteomics. The comparison of non- and high-sulfated HA revealed regulation of 84 of more than 1,200 quantified proteins. Based on gene enrichment we found that sulfation of HA alters extracellular matrix remodeling. The collagen degrading enzymes cathepsin K, matrix metalloproteinases-2 and -14 were found to be down-regulated on hsHA. Additionally protein expression of thrombospondin-1, decorin, collagen types I and XII were reduced, whereas the expression of trophoblast glycoprotein and collagen type VI were slightly increased. This study demonstrates that global proteomics provides a valuable tool for revealing proteins involved in molecular effects of growth substrates for further material optimization.

  20. Dual pH/redox responsive and CD44 receptor targeting hybrid nano-chrysalis based on new oligosaccharides of hyaluronan conjugates.

    Science.gov (United States)

    Chen, Daquan; Dong, Xue; Qi, Mengjiao; Song, Xiaoyan; Sun, Jingfang

    2017-02-10

    A smart hybrid microenvironment-mediated dual pH/redox-responsive polymeric nanoparticles combined with inorganic calcium phosphate (CaP) was fabricated, which we term as armored nano-chrysalis inspired by butterfly pupa. The nano-chrysalis has an inner core composed of specially designed oligosaccharides of hyaluronan (oHA) targeting CD44 receptor. The inner core has two functions, i.e., the dual pH/redox responsive polymeric conjugate and the fluorescent curcumin-prodrug function. The prepared nano-chrysalis possessed a smaller size (102.5±4.6nm) than the unarmored nano-chrysalis (122.5±6.6nm). Interestingly, while the nano-chrysalis were stable under pH 7.4, when incubated under the tumor acidic conditions (pH 6.5) the outer CaP armor would dissolve in a pH-dependent, sustained manner. Moreover, nano-chrysalis was demonstrated to present the most effective antitumor efficacy than other formulations. This study provides a promising smart nano-carrier platform to enhance the stability, decrease the side effects, and improve the therapeutic efficacy of anticancer drugs. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Financial Derivatives

    DEFF Research Database (Denmark)

    Wigan, Duncan

    2013-01-01

    Contemporary derivatives mark the development of capital and constitute a novel form of ownership. By reconfiguring the temporal, spatial and legal character of ownership derivatives present a substantive challenge to the tax collecting state. While fiscal systems are nationally bounded...... and inherently static, capital itself is unprecedentedly mobile, fluid and fungible. As such derivatives raise the specter of ‘financial weapons of mass destruction’....

  2. Financial Derivatives

    OpenAIRE

    Janečková, Alena

    2011-01-01

    1 Abstract/ Financial derivatives The purpose of this thesis is to provide an introduction to financial derivatives which has been, from the legal perspective, described in a not satisfactory manner as quite little literature that can be found about this topic. The main objectives of this thesis are to define the term "financial derivatives" and its particular types and to analyse legal nature of these financial instruments. The last objective is to try to draft future law regulation of finan...

  3. The interaction between LYVE-1 with hyaluronan on the cell surface may play a role in the diversity of adhesion to cancer cells.

    Science.gov (United States)

    Du, Yan; Liu, Hua; He, Yiqing; Liu, Yiwen; Yang, Cuixia; Zhou, Muqing; Wang, Wenjuan; Cui, Lian; Hu, Jiajie; Gao, Feng

    2013-01-01

    Hyaluronan (HA), a simple disaccharide unit, can polymerize and is considered a primary component of the extracellular matrix, which has a wide range of biological functions. In recent years, HA was found on the surface of tumor cells. According to previous reports, differing HA content on the cell surface of tumor cells is closely related to lymph node metastases, but the mechanisms mediating this process remained unclear. This research intended to study the surface content of HA on tumor cells and analyze cell adhesive changes caused by the interaction between HA and its lymphatic endothelial receptor (LYVE-1). We screened and observed high HA content on HS-578T breast cells and low HA content on MCF-7 breast cells through particle exclusion, immunofluorescence and flow cytometry experiments. The expression of LYVE-1, the lymph-vessel specific HA receptor, was consistent with our previous report and enhanced the adhesion of HA(high)-HS-578T cells to COS-7(LYVE-1(+)) through HA in cell static adhesion and dynamic parallel plate flow chamber experiments. MCF-7 breast cells contain little HA on the surface; however, our results showed little adhesion difference between MCF-7 cells and COS-7(LYVE-1(+)) and COS-7(LYVE-1(-)) cells. Similar results were observed concerning the adhesion of HS-578T cells or MCF-7 cells to SVEC4-10 cells. Furthermore, we observed for the first time that the cell surface HA content of high transfer tumor cells was rich, and we visualized the cross-linking of HA cable structures, which may activate LYVE-1 on lymphatic endothelial cells, promoting tumor adhesion. In summary, high-low cell surface HA content of tumor cells through the interaction with LYVE-1 leads to adhesion differences.

  4. pH-Amplified multilayer films based on hyaluronan: influence of HA molecular weight and concentration on film growth and stability.

    Science.gov (United States)

    Shen, Liyan; Chaudouet, Patrick; Ji, Jian; Picart, Catherine

    2011-04-11

    In this study, we investigate the growth and internal properties of polyelectrolyte multilayer films made of poly(l-lysine) and hyaluronan (PLL/HA) under pH-amplified conditions, that is, by alternate deposition of PLL at high pH and HA at low pH. We focus especially on the influence of the molecular weight of HA in this process as well as on its concentration in solution. Film growth was followed by quartz crystal microbalance and by infrared spectroscopy to quantify the deposited mass and to characterize the internal properties of the films, including the presence of hydrogen bonds and the ionization degree of HA in the films. Film growth was significantly faster for HA of high molecular weight (1300 kDa) as compared with 400 and 200 kDa. PLL was found to exhibit a random structure once deposited in the films. Furthermore, we found that PLL-ending films are more stable when they are placed in PBS than their HA counterparts. This was explained on the basis of more cohesive interactions in the films for PLL-ending films. Finally, we quantified PLL(FITC) diffusion into the films and observed that PLL diffusion is enhanced when PLL is paired with the HA of high MW. All together, these results suggest that besides purely physicochemical parameters such as variation in pH, the molecular weight of HA, its concentration in solution, and the possibility to form intermolecular HA association play important roles in film growth, internal cohesion, and stability.

  5. Effect of long-term culture of mouse embryonic stem cells under low oxygen concentration as well as on glycosaminoglycan hyaluronan on cell proliferation and differentiation.

    Science.gov (United States)

    Ramírez, M Á; Pericuesta, E; Yáñez-Mó, M; Palasz, A; Gutiérrez-Adán, A

    2011-02-01

    Maintaining undifferentiated stem cells in defined conditions is of critical importance to improve their in vitro culture. We have evaluated the effects of culturing mouse stem (mES) cells under physiological oxygen concentration as well as by replacing fibroblast feeder layer (mEF) with gelatin or glycosaminoglycan hyaluronan (HA), on cell proliferation and differentiation. After 3 days culture or after long-term cell culture under different conditions, levels of apoptotic cell death were determined by cell cycle and TUNEL (TdT-mediated dUTP nick end labelling) assays and levels of cell proliferation by CFSE (5-(and-6)-carboxyfluorescein diacetate succinimidyl ester) labelling. We assessed spontaneous differentiation into cardiomyocytes and mRNA expression of pluripotency and differentiation biomarkers. After 3 days culture under hypoxic conditions, levels of proliferation and apoptosis of mES cells were higher, in correlation with increase in intracellular reactive oxygen species. However, when cells were continuously grown for 1 month under those conditions, the level of apoptosis was, in all cases, under 4%. Hypoxia reduced spontaneous differentiation of mES into cardiomyocytes. Long-term culture on HA was more effective in maintaining the pluripotent state of the mES cells when compared to that on gelatin. Level of terminal differentiation was highest on mEF, intermediate on HA and lowest on gelatin. Our data suggest that hypoxia is not necessary for maintaining pluripotency of mES cells and appeared to be detrimental during ES differentiation. Moreover, HA may offer a valuable alternative for long-term culture of mES cells in vitro. © 2010 Blackwell Publishing Ltd.

  6. Sequencing of chondroitin sulfate oligosaccharides using a novel exolyase from a marine bacterium that degrades hyaluronan and chondroitin sulfate/dermatan sulfate.

    Science.gov (United States)

    Wang, Wenshuang; Cai, Xiaojuan; Han, Naihan; Han, Wenjun; Sugahara, Kazuyuki; Li, Fuchuan

    2017-11-09

    Glycosaminoglycans (GAGs) are a family of chemically heterogeneous polysaccharides that play important roles in physiological and pathological processes. Owing to the structural complexity of GAGs, their sophisticated chemical structures and biological functions have not been extensively studied. Lyases that cleave GAGs are important tools for structural analysis. Although various GAG lyases have been identified, exolytic lyases with unique enzymatic property are urgently needed for GAG sequencing. In the present study, a putative exolytic GAG lyase from a marine bacterium was recombinantly expressed and characterized in detail. Since it showed exolytic lyase activity toward hyaluronan (HA), chondroitin sulfate (CS), and dermatan sulfate (DS), it was designated as HCDLase. This novel exolyase exhibited the highest activity in Tris-HCl buffer (pH 7.0) at 30°C. Especially, it showed a specific activity that released 2-aminobenzamide (2-AB)-labeled disaccharides from the reducing end of 2-AB-labeled CS oligosaccharides, which suggest that HCDLase is not only a novel exolytic lyase that can split disaccharide residues from the reducing termini of sugar chains but also a useful tool for the sequencing of CS chains. Notably, HCDLase could not digest 2-AB-labeled oligosaccharides from HA, DS, or unsulfated chondroitin, which indicated that sulfates and bond types affect the catalytic activity of HCDLase. Finally, this enzyme combined with CSase ABC was successfully applied for the sequencing of several CS hexa- and octasaccharides with complex structures. The identification of HCDLase provides a useful tool for CS-related research and applications. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  7. Derivative chameleons

    International Nuclear Information System (INIS)

    Noller, Johannes

    2012-01-01

    We consider generalized chameleon models where the conformal coupling between matter and gravitational geometries is not only a function of the chameleon field φ, but also of its derivatives via higher order co-ordinate invariants (such as ∂ μ φ∂ μ φ,□φ,...). Specifically we consider the first such non-trivial conformal factor A(φ,∂ μ φ∂ μ φ). The associated phenomenology is investigated and we show that such theories have a new generic mass-altering mechanism, potentially assisting the generation of a sufficiently large chameleon mass in dense environments. The most general effective potential is derived for such derivative chameleon setups and explicit examples are given. Interestingly this points us to the existence of a purely derivative chameleon protected by a shift symmetry for φ → φ+c. We also discuss potential ghost-like instabilities associated with mass-lifting mechanisms and find another, mass-lowering and instability-free, branch of solutions. This suggests that, barring fine-tuning, stable derivative models are in fact typically anti-chameleons that suppress the field's mass in dense environments. Furthermore we investigate modifications to the thin-shell regime and prove a no-go theorem for chameleon effects in non-conformal geometries of the disformal type

  8. Derivative chameleons

    Energy Technology Data Exchange (ETDEWEB)

    Noller, Johannes, E-mail: johannes.noller08@imperial.ac.uk [Theoretical Physics, Blackett Laboratory, Imperial College London, Prince Consort Road, London, SW7 2BZ (United Kingdom)

    2012-07-01

    We consider generalized chameleon models where the conformal coupling between matter and gravitational geometries is not only a function of the chameleon field φ, but also of its derivatives via higher order co-ordinate invariants (such as ∂{sub μ}φ∂{sup μ}φ,□φ,...). Specifically we consider the first such non-trivial conformal factor A(φ,∂{sub μ}φ∂{sup μ}φ). The associated phenomenology is investigated and we show that such theories have a new generic mass-altering mechanism, potentially assisting the generation of a sufficiently large chameleon mass in dense environments. The most general effective potential is derived for such derivative chameleon setups and explicit examples are given. Interestingly this points us to the existence of a purely derivative chameleon protected by a shift symmetry for φ → φ+c. We also discuss potential ghost-like instabilities associated with mass-lifting mechanisms and find another, mass-lowering and instability-free, branch of solutions. This suggests that, barring fine-tuning, stable derivative models are in fact typically anti-chameleons that suppress the field's mass in dense environments. Furthermore we investigate modifications to the thin-shell regime and prove a no-go theorem for chameleon effects in non-conformal geometries of the disformal type.

  9. Electricity derivatives

    CERN Document Server

    Aïd, René

    2015-01-01

    Offering a concise but complete survey of the common features of the microstructure of electricity markets, this book describes the state of the art in the different proposed electricity price models for pricing derivatives and in the numerical methods used to price and hedge the most prominent derivatives in electricity markets, namely power plants and swings. The mathematical content of the book has intentionally been made light in order to concentrate on the main subject matter, avoiding fastidious computations. Wherever possible, the models are illustrated by diagrams. The book should allow prospective researchers in the field of electricity derivatives to focus on the actual difficulties associated with the subject. It should also offer a brief but exhaustive overview of the latest techniques used by financial engineers in energy utilities and energy trading desks.

  10. A Randomized Controlled Trial on the Efficacy and Safety of a New Crosslinked Hyaluronan Gel in Reducing Adhesions after Gynecologic Laparoscopic Surgeries.

    Science.gov (United States)

    Liu, Chongdong; Lu, Qi; Zhang, Zhiqiang; Xue, Min; Zhang, Youzhong; Zhang, Yi; Wang, Huilan; Li, Huajun; Zhou, Yingfang; Zhang, Zhenyu; Li, Wei

    2015-01-01

    To evaluate the safety and efficacy of a new crosslinked hyaluronan (NCH) gel in reducing postoperative adhesions. Randomized controlled trial (Canadian Task Force classification I). Seven departments of obstetrics and gynecology in China. A total of 216 women scheduled for gynecologic laparoscopic surgery for primary removal of adhesions, myomas, ovarian cysts, or endometriotic cysts. Patients were randomized to receive either NCH gel or saline with 1:1 allocation. All patients were evaluated using a modified American Fertility Society (mAFS) scoring system for the incidence, extent, and severity of pre-existing and postoperative adhesions at the 10 anatomic sites of ovaries/tubes and at the expanded 23 or 24 anatomic sites throughout the abdominopelvic cavity by laparoscopy. A total of 215 randomized patients were treated with either saline solution (108 of 108) or NCH gel (107 of 108), composing the full analysis set (FAS), and 196 patients (94 of 108 in the saline control group and 102 of 108 in the NCH gel group) completed the entire study, composing the per protocol set (PPS). The postoperative incidence of moderate or severe adhesions evaluated at the 10 sites (the primary endpoint for efficacy) was 27.7% in the control group and 9.8% in the NCH gel group, a difference of 14.4% (95% confidence interval [CI], 2.6%-20.6%) in the PPS, and 37.0% in the control group and 14.0% in the NCH gel group, a difference of 20.0% (95% CI, 8.9%-26.8%) in the FAS. The postoperative incidence of moderate or severe adhesions evaluated at the 24 sites was also significantly lower in the NCH gel group compared with the control group (5.9% vs 14.9%; p = .036) in the PPS. Also in the PPS, the NCH gel group had significantly lower postoperative adhesion scores of severity, extent, and mAFS: 60.0%, 50.8%, and 76.9%, respectively (median scores of the 10 sites; p = .002) and 48.5%, 50.0%, and 72.2% (median scores of the 24 sites; p = .001) lower than those recorded in the control

  11. Highly versatile nanohydrogel platform based on riboflavin-polysaccharide derivatives useful in the development of intrinsically fluorescent and cytocompatible drug carriers.

    Science.gov (United States)

    Di Meo, Chiara; Montanari, Elita; Manzi, Lucio; Villani, Claudio; Coviello, Tommasina; Matricardi, Pietro

    2015-01-22

    In this work we describe a new nanohydrogel platform, based on polysaccharides modified with the hydrophobic and fluorescent molecule riboflavin tetrabutyrate, which leads to innovative structures useful for drug delivery applications. Hyaluronic acid and pullulan were chosen as representative of anionic and neutral polysaccharides, respectively, and the bromohexyl derivative of riboflavin tetrabutyrate was chemically linked to these polymer chains. Because of such derivatization, polymer chains were able to self-assemble in aqueous environment thus forming nanohydrogels, with mean diameters of about 312 and 210 nm, for hyaluronan and pullulan, respectively. These new nanohydrogels showed low polydispersity index, and negative ζ-potential. Moreover, the nanohydrogels, which can be easily loaded with model drugs, showed long-term stability in water and physiological conditions and excellent cytocompatibility. All these properties allow to consider these intrinsically fluorescent nanohydrogels suitable for the formulation of innovative drug dosage forms. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. The ligand-binding profile of HARE: hyaluronan and chondroitin sulfates A, C, and D bind to overlapping sites distinct from the sites for heparin, acetylated low-density lipoprotein, dermatan sulfate, and CS-E.

    Science.gov (United States)

    Harris, Edward N; Weigel, Paul H

    2008-08-01

    The hyaluronic acid receptor for endocytosis (HARE)/ Stabilin-2 is the primary systemic scavenger receptor for hyaluronan (HA), the chondroitin sulfates (CS), dermatan sulfate (DS), and nonglycosaminoglycan (GAG) ligands such as acetylated low-density lipoprotein (AcLDL), pro-collagen propeptides, and advanced glycation end products. We recently discovered that HARE is also a systemic scavenger receptor for heparin (Hep) (Harris EN, Weigel JA, Weigel PH. 2008. The human hyaluronan receptor for endocytosis [HARE/Stabilin-2] is a systemic clearance receptor for heparin. J Biol Chem. 283:17341-17350). Our goal was to map the binding sites of eight different ligands within HARE. We used biotinylated GAGs and radio-iodinated streptavidin or AcLDL to assess the binding activities of ligands directly or indirectly (by competition with unlabeled ligands) in endocytosis assays using stable cell lines expressing the 315 or 190 kDa HA receptor for endocytosis (315- or 190-HARE) isoforms, and ELISA-like assays, with purified recombinant soluble 190-HARE ecto-domain. For example, Hep binding to HARE was competed by DS, CS-E, AcLDL, and dextran sulfate, but not by other CS types, HA, dextran, or heparosan. (125)I-AcLDL binding to HARE was partially competed by Hep and dextran sulfate, but not competed by HA. Two ligands, DS and CS-E, competed with both Hep and HA to some degree. Hep and HA binding or endocytosis is mutually inclusive; binding of these two GAGs occurs with functionally separate, noncompetitive, and apparently noninteracting domains. Thus, HARE binds to HA and Hep simultaneously. Although the domain(s) responsible for Hep binding remains unknown, the Link domain was required for HARE binding to HA, CS-A, CS-C, and CS-D. These results enable us to outline, for the first time, a binding activity map for multiple ligands of HARE.

  13. Simultaneous analysis of heparan sulfate, chondroitin/dermatan sulfates, and hyaluronan disaccharides by glycoblotting-assisted sample preparation followed by single-step zwitter-ionic-hydrophilic interaction chromatography.

    Science.gov (United States)

    Takegawa, Yasuhiro; Araki, Kayo; Fujitani, Naoki; Furukawa, Jun-ichi; Sugiyama, Hiroaki; Sakai, Hideaki; Shinohara, Yasuro

    2011-12-15

    Glycosaminoglycans (GAGs) play important roles in cell adhesion and growth, maintenance of extracellular matrix (ECM) integrity, and signal transduction. To fully understand the biological functions of GAGs, there is a growing need for sensitive, rapid, and quantitative analysis of GAGs. The present work describes a novel analytical technique that enables high throughput cellular/tissue glycosaminoglycomics for all three families of uronic acid-containing GAGs, hyaluronan (HA), chondroitin sulfate (CS)/dermatan sulfate (DS), and heparan sulfate (HS). A one-pot purification and labeling procedure for GAG Δ-disaccharides was established by chemo-selective ligation of disaccharides onto high density hydrazide beads (glycoblotting) and subsequent labeling by fluorescence. The 17 most common disaccharides (eight comprising HS, eight CS/DS, and one comprising HA) could be separated with a single chromatography for the first time by employing a zwitter-ionic type of hydrophilic-interaction chromatography column. These novel analytical techniques were able to precisely characterize the glycosaminoglycome in various cell types including embryonal carcinoma cells and ocular epithelial tissues (cornea, conjunctiva, and limbus).

  14. Interest rate derivatives

    DEFF Research Database (Denmark)

    Svenstrup, Mikkel

    This Ph.D. thesis consists of four self-contained essays on valuation of interest rate derivatives. In particular derivatives related to management of interest rate risk care are considered.......This Ph.D. thesis consists of four self-contained essays on valuation of interest rate derivatives. In particular derivatives related to management of interest rate risk care are considered....

  15. Hydrogel-based 3D model of patient-derived prostate xenograft tumors suitable for drug screening.

    Science.gov (United States)

    Fong, Eliza L S; Martinez, Mariane; Yang, Jun; Mikos, Antonios G; Navone, Nora M; Harrington, Daniel A; Farach-Carson, Mary C

    2014-07-07

    The lack of effective therapies for bone metastatic prostate cancer (PCa) underscores the need for accurate models of the disease to enable the discovery of new therapeutic targets and to test drug sensitivities of individual tumors. To this end, the patient-derived xenograft (PDX) PCa model using immunocompromised mice was established to model the disease with greater fidelity than is possible with currently employed cell lines grown on tissue culture plastic. However, poorly adherent PDX tumor cells exhibit low viability in standard culture, making it difficult to manipulate these cells for subsequent controlled mechanistic studies. To overcome this challenge, we encapsulated PDX tumor cells within a three-dimensional hyaluronan-based hydrogel and demonstrated that the hydrogel maintains PDX cell viability with continued native androgen receptor expression. Furthermore, a differential sensitivity to docetaxel, a chemotherapeutic drug, was observed as compared to a traditional PCa cell line. These findings underscore the potential impact of this novel 3D PDX PCa model as a diagnostic platform for rapid drug evaluation and ultimately push personalized medicine toward clinical reality.

  16. Derivatives in emerging markets

    OpenAIRE

    Dubravko Mihaljek; Frank Packer

    2010-01-01

    Turnover of derivatives has grown more rapidly in emerging markets than in developed countries. Foreign exchange derivatives are the most commonly traded of all risk categories, with increasingly frequent turnover in emerging market currencies and a growing share of cross-border transactions. As the global reach of the financial centres in emerging Asia has expanded, the offshore trading of many emerging market currency derivatives has risen as well. Growth in derivatives turnover is positive...

  17. Global Derivatives Market

    Directory of Open Access Journals (Sweden)

    Stankovska Aleksandra

    2017-06-01

    Full Text Available Globalization of financial markets led to the enormous growth of volume and diversification of financial transactions. Financial derivatives were the basic elements of this growth. Derivatives play a useful and important role in hedging and risk management, but they also pose several dangers to the stability of financial markets and thereby the overall economy. Derivatives are used to hedge and speculate the risk associated with commerce and finance.

  18. Three dimensional culture of fresh and vitrified mouse pre-antral follicles in a hyaluronan-based hydrogel: a preliminary investigation of a novel biomaterial for in vitro follicle maturation

    Directory of Open Access Journals (Sweden)

    Desai Nina

    2012-06-01

    Full Text Available Abstract Background Folliculogenesis within the ovary requires interaction between somatic cell components and the oocyte. Maintenance of 3-dimensional (3-D architecture and granulosa-oocyte interaction may be critical for successful in vitro maturation of follicles. Testing of novel biomaterials for the 3-D culture of follicles may ultimately lead to a culture model that can support the longer in vitro culture intervals needed for in vitro maturation of human oocytes from ovarian tissue biopsies. Methods A novel tyramine-based hyaluronan (HA hydrogel was tested for its biocompatibility with ovarian follicles. The HA was prepared at concentrations from 2 to 5 mg/ml. HA hydrogel was also formulated and tested with matrix proteins (ECM. Enzymatically isolated pre-antral follicles from the ovaries of 10–12 day SJL pups were divided amongst control (CT and HA treatments. The growth of both fresh and vitrified follicles was assessed after encapsulation in the hydrogel. The basal culture medium was MEM alpha supplemented with FSH, LH, ITS and 5% FBS. Maturation was triggered by addition of hCG and EGF after in vitro culture (IVC. Outcome parameters monitored were follicle morphology, survival after IVC, antrum formation, GVBD and MII formation. Differences between treatments were analyzed. Results HA and ECM-HA encapsulated follicles looked healthy and maintained their 3-D architecture during IVC. In control cultures, the follicles flattened and granulosa:oocyte connections appeared fragile. Estradiol secretion per follicle was significantly higher by Day 12 in ECM-HA compared to HA or CT (4119, 703 and 1080 pg/ml, respectively. HA and ECM-HA cultured follicles had similar survival rates (62% and 54%, respectively, percent GV breakdown (96–97%, MII formation (47–48% and oocyte diameters at the end of IVC. Control cultures differed significantly in percent GVBD (85% and MII formation (67% . Vitrified-warmed follicles encapsulated in HA had

  19. Alteration of introns in a hyaluronan synthase 1 (HAS1 minigene convert Pre-mRNA [corrected] splicing to the aberrant pattern in multiple myeloma (MM: MM patients harbor similar changes.

    Directory of Open Access Journals (Sweden)

    Jitra Kriangkum

    Full Text Available Aberrant pre-mRNA splice variants of hyaluronan synthase 1 (HAS1 have been identified in malignant cells from cancer patients. Bioinformatic analysis suggests that intronic sequence changes can underlie aberrant splicing. Deletions and mutations were introduced into HAS1 minigene constructs to identify regions that can influence aberrant intronic splicing, comparing the splicing pattern in transfectants with that in multiple myeloma (MM patients. Introduced genetic variations in introns 3 and 4 of HAS1 as shown here can promote aberrant splicing of the type detected in malignant cells from MM patients. HAS1Vd is a novel intronic splice variant first identified here. HAS1Vb, an intronic splice variant previously identified in patients, skips exon 4 and utilizes the same intron 4 alternative 3'splice site as HAS1Vd. For transfected constructs with unaltered introns 3 and 4, HAS1Vd transcripts are readily detectable, frequently to the exclusion of HAS1Vb. In contrast, in MM patients, HAS1Vb is more frequent than HAS1Vd. In the HAS1 minigene, combining deletion in intron 4 with mutations in intron 3 leads to a shift from HAS1Vd expression to HAS1Vb expression. The upregulation of aberrant splicing, exemplified here by the expression of HAS1Vb, is shown here to be influenced by multiple genetic changes in intronic sequences. For HAS1Vb, this includes enhanced exon 4 skipping and increased usage of alternative 3' splice sites. Thus, the combination of introduced mutations in HAS1 intron3 with introduced deletions in HAS1 intron 4 promoted a shift to an aberrant splicing pattern previously shown to be clinically significant. Most MM patients harbor genetic variations in intron 4, and as shown here, nearly half harbor recurrent mutations in HAS1 intron 3. Our work suggests that aberrant intronic HAS1 splicing in MM patients may rely on intronic HAS1 deletions and mutations that are frequent in MM patients but absent from healthy donors.

  20. Risk and Derivative Price

    OpenAIRE

    Yusuke Osaki

    2007-01-01

    We consider an asset market traded three types of assets: the risk–free asset, the market portfolio and derivatives written on the market portfolio return. We determine a sufficient condition to guarantee that noise risk monotonically changes their derivatives. The condition is that Arrow–Pratt absolute risk aversion is decreasing and convex.

  1. Financial Derivatives in China

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Francis Repka sees bright prospects for the future development of the financial derivatives market in China. Repka,Vice President of the Asian Bond Finance Department of Societe Generale, says the situation in France just after the birth of derivatives was very similar to the situation in China today.

  2. Vitamin D derivatives

    International Nuclear Information System (INIS)

    Deluca, H.F.; Schnoes, H.K.; Napoli, J.L.; Fivizzani, M.A.

    1982-01-01

    The chemical preparation of 26,27-isotopically labelled vitamin D 3 derivatives of high specific activity is described. These labelled vitamin D derivatives are useful in the determination of vitamin D metabolite levels in the blood and tissues of man and animals. (U.K.)

  3. Taxation of Derivatives

    DEFF Research Database (Denmark)

    Dyppel, Katja Joo

    2013-01-01

    The main objective for this thesis is to analyse and systematise the Danish legislation on taxation of derivatives. According to financial terminology, a derivative is a financial instrument. Its value is derived from changes in the value of one or more underlying assets.The most common derivatives...... in the Danish tax legislation. However, contracts known as forwards (terminskontrakter) and options (aftaler om køberetter og salgsretter) are generally included in the term financials contracts covered by the Danish Act on Taxation of Gains and Losses on Claims and Debt. The main part of the analysis deals...... with the scope of sections 29-33 of the Danish Act on Taxation of Gains and Losses on Claims and Debt and the tax consequences for the covered financial contracts. In the analysis of taxation of derivatives, the fundamental issues of qualification and tax treatment of the instruments are dealt with....

  4. Superstability of Generalized Derivations

    Directory of Open Access Journals (Sweden)

    Ansari-Piri Esmaeil

    2010-01-01

    Full Text Available We investigate the superstability of the functional equation , where and are the mappings on Banach algebra . We have also proved the superstability of generalized derivations associated to the linear functional equation , where .

  5. Amphetamine derivative related deaths.

    Science.gov (United States)

    Lora-Tamayo, C; Tena, T; Rodríguez, A

    1997-02-28

    Amphetamine its methylendioxy (methylendioxyamphetamine methylenedioxymethylamphetamine, methylenedioxyethylamphetamine) and methoxy derivatives (p-methoxyamphetamine and p-methoxymethylamphetamine) are widely abused in Spanish society. We present here the results of a systematic study of all cases of deaths brought to the attention of the Madrid department of the Instituto Nacional de Toxicologia from 1993 to 1995 in which some of these drugs have been found in the cadaveric blood. The cases were divided into three categories: amphetamine and derivatives, amphetamines and alcohol, amphetamines and other drugs. Data on age, sex, clinical symptoms, morphological findings, circumstances of death, when known, and concentration of amphetamine derivatives, alcohol and other drugs in blood are given for each group. The information provided here may prove to be useful for the forensic interpretation of deaths which are directly or indirectly related to abuse of amphetamine derivatives.

  6. Investigation - Derived Waste Program

    International Nuclear Information System (INIS)

    Beardsley, C.; Anderson, R.

    1998-06-01

    The Investigation-Derived Waste Program is a software application that was developed to identify the groundwater monitoring wells at the Savannah River Site that require containerization and treatment for purge water generated during sampling

  7. Development of Derivatives Reporting

    OpenAIRE

    Pejčochová, Kristina

    2012-01-01

    This thesis aims to summarise the theoretical principles, concepts and considerations pertaining to accounting for and reporting of derivatives and to describe and analyse the development of major accounting standards dealing with related issues. Sections 1 and 2 provide a basic overview of derivative instruments'categorisation, mechanics, valuation and uses. Section 3 studies the principles that ensure the provision of useful financial information, with specific focus on financial instrument...

  8. On higher derivative gravity

    International Nuclear Information System (INIS)

    Accioly, A.J.

    1987-01-01

    A possible classical route conducting towards a general relativity theory with higher-derivatives starting, in a sense, from first principles, is analysed. A completely causal vacuum solution with the symmetries of the Goedel universe is obtained in the framework of this higher-derivative gravity. This very peculiar and rare result is the first known vcuum solution of the fourth-order gravity theory that is not a solution of the corresponding Einstein's equations.(Author) [pt

  9. Brain derived neurotrophic factor

    DEFF Research Database (Denmark)

    Mitchelmore, Cathy; Gede, Lene

    2014-01-01

    Brain Derived Neurotrophic Factor (BDNF) is a neurotrophin with important functions in neuronal development and neuroplasticity. Accumulating evidence suggests that alterations in BDNF expression levels underlie a variety of psychiatric and neurological disorders. Indeed, BDNF therapies are curre......Brain Derived Neurotrophic Factor (BDNF) is a neurotrophin with important functions in neuronal development and neuroplasticity. Accumulating evidence suggests that alterations in BDNF expression levels underlie a variety of psychiatric and neurological disorders. Indeed, BDNF therapies...

  10. Gorenstein derived functions

    DEFF Research Database (Denmark)

    Holm, Henrik Granau

    2004-01-01

    Over any associative ring R it is standard to derive HomR(􀀀;􀀀) using projective resolutions in the rst variable, or injective resolutions in the second variable, and doing this, one obtains Extn R(􀀀;􀀀) in both cases. We examine the situation where projective...... and injective modules are replaced by Gorenstein projective and Gorenstein injective ones, respectively. Furthermore, we derive the tensor product 􀀀 R 􀀀 using Gorenstein at modules....

  11. Asia Pacific energy derivatives

    International Nuclear Information System (INIS)

    Fusaro, P.C.

    1997-09-01

    Asia Pacific Energy Derivatives, from FT Energy, is the first report of its kind to examine the growth of energy derivatives within Asia Pacific and their increasing importance within this region. It provides a comprehensive overview of the subject, including analysis of: deregulation as a market driver; the impact of privatisation; the future for energy risk management tools; the unique characteristics of the Asia Pacific energy market; the role of futures exchanges in Asia; existing indexes and their performance; the differences between the Asia Pacific markets and their more mature counterparts in London and New York; non-oil derivatives, project finance and cross commodity arbitrage; the thriving Pacific Rim Over the Counter (OTC) markets. (author)

  12. 4-Aminoquinoline derivatives

    DEFF Research Database (Denmark)

    Singh, Shailja; Agarwal, Drishti; Sharma, Kumkum

    2016-01-01

    and found them to be effective against Plasmodium falciparum under in vitro conditions. Further, we selected four most active derivatives 1m, 1o, 2c and 2j and evaluated their antimalarial potential against Plasmodium berghei in vivo. These 4-aminoquinolines cured BALB/c mice infected with P. berghei......Synthetic quinoline derivatives continue to be considered as candidates for new drug discovery if they act against CQ-resistant strains of malaria even after the widespread emergence of resistance to CQ. In this study, we explored the activities of two series of new 4-aminoquinoline derivatives...... for structure activity relationship to find lead molecules for treating multidrug-resistant Plasmodium falciparum and Plasmodium vivax....

  13. Essays on Derivatives Pricing

    DEFF Research Database (Denmark)

    Kokholm, Thomas

    . With the existence of a liquid market for derivatives with variance as underlying, such as VIX options, VIX futures and a well-developed over-the-counter market for options on variance swaps, it is important to consider models that are able to fit these markets while consistently pricing vanilla options...... financial models, and most importantly, to be aware of their limitations. Following that belief, this thesis consists of three independent and self-contained papers, all dealing with topics in derivatives pricing. The first paper considers the pricing of traffic light options, which are appropriate...... the market for multivariate credit instruments, we take a step back and focus on single-name default modeling and introduce two new model classes for modeling of the default time of a company. Finally, in the third paper we propose a consistent pricing model for index and volatility derivatives...

  14. The combinatorial derivation

    Directory of Open Access Journals (Sweden)

    Igor V. Protasov

    2013-09-01

    $\\Delta(A=\\{g\\in G:|gA\\cap A|=\\infty\\}$. The mapping $\\Delta:\\mathcal{P}_G\\rightarrow\\mathcal{P}_G$, $A\\mapsto\\Delta(A$, is called a combinatorial derivation and can be considered as an analogue of the topological derivation $d:\\mathcal{P}_X\\rightarrow\\mathcal{P}_X$, $A\\mapsto A^d$, where $X$ is a topological space and $A^d$ is the set of all limit points of $A$. Content: elementary properties, thin and almost thin subsets, partitions, inverse construction and $\\Delta$-trajectories,  $\\Delta$ and $d$.

  15. Quinazolin-4-one derivatives

    DEFF Research Database (Denmark)

    Mosley, Cara A; Acker, Timothy M; Hansen, Kasper Bø

    2010-01-01

    We describe a new class of subunit-selective antagonists of N-methyl D-aspartate (NMDA)-selective ionotropic glutamate receptors that contain the (E)-3-phenyl-2-styrylquinazolin-4(3H)-one backbone. The inhibition of recombinant NMDA receptor function induced by these quinazolin-4-one derivatives...

  16. Metal borohydrides and derivatives

    DEFF Research Database (Denmark)

    Paskevicius, Mark; Haarh Jepsen, Lars; Schouwink, Pascal

    2017-01-01

    major classes of metal borohydride derivatives have also been discovered: anion-substituted compounds where the complex borohydride anion, BH4 -, is replaced by another anion, i.e. a halide or amide ion; and metal borohydrides modified with neutral molecules, such as NH3, NH3BH3, N2H4, etc. Here, we...

  17. 78 FR 32191 - Derivatives

    Science.gov (United States)

    2013-05-29

    ... rate risk. This proposed rule applies to federal credit unions and any federally insured, state... risk to the National Credit Union Share Insurance Fund (NCUSIF). \\1\\ A derivative is an instrument... degrees of risk to a credit union. Accordingly, this risk calls for a more robust asset/ liability...

  18. Superstability of Generalized Derivations

    Directory of Open Access Journals (Sweden)

    Esmaeil Ansari-Piri

    2010-01-01

    Full Text Available We investigate the superstability of the functional equation f(xy=xf(y+g(xy, where f and g are the mappings on Banach algebra A. We have also proved the superstability of generalized derivations associated to the linear functional equation f(γx+βy=γf(x+βf(y, where γ,β∈ℂ.

  19. Approximate *-derivations and approximate quadratic *-derivations on C*-algebras

    Directory of Open Access Journals (Sweden)

    Park Choonkil

    2011-01-01

    Full Text Available Abstract In this paper, we prove the stability of *-derivations and of quadratic *-derivations on Banach *-algebras. We moreover prove the superstability of *-derivations and of quadratic *-derivations on C*-algebras. 2000 Mathematics Subject Classification: 39B52; 47B47; 46L05; 39B72.

  20. Hyaluronan and phospholipid association in biolubrication

    DEFF Research Database (Denmark)

    Wang, Min; Liu, Chao; Thormann, Esben

    2013-01-01

    It is becoming increasingly clear that the outstanding lubrication of synovial joints is achieved by a sophisticated hierarchical structure of cartilage combined with synergistic actions of surface-active components present in the synovial fluid. In this work we focus on the association of two co...

  1. The Ability of Human Nasal Inferior Turbinate-Derived Mesenchymal Stem Cells to Repair Vocal Fold Injuries.

    Science.gov (United States)

    Kim, Choung-Soo; Choi, Hyunsu; Park, Ki Cheol; Kim, Sung Won; Sun, Dong-Il

    2018-03-01

    Objective This study investigated the ability of implanted human nasal inferior turbinate-derived mesenchymal stem cells (hTMSCs) to repair injured vocal folds. To this end, we used quantitative real-time polymerase chain reaction (PCR) to analyze the early phase of wound healing and histopathological analysis to explore the late phase of wound healing in xenograft animal models. Study Design Prospective animal study. Setting Research laboratory. Subjects and Methods The right-side lamina propria of the vocal fold was injured in 20 rabbits and 30 rats. Next, hTMSCs were implanted into half of the injured vocal folds (hTMSC groups). As a control, phosphate-buffered saline (PBS) was injected into the other half of the injured vocal folds (PBS groups). Rat vocal folds were harvested for polymerase chain reaction (PCR) at 1 week after injury. Rabbit vocal folds were evaluated endoscopically and the larynges harvested for histological and immunohistochemical examination at 2 and 8 weeks after injury. Results In the hTMSC group, PCR showed that hyaluronan synthase ( HAS) 1, HAS 2, and transforming growth factor ( TGF)-β1 were significantly upregulated compared with the PBS group. Procollagen type III ( COL III) messenger RNA expression was significantly upregulated in the PBS group compared with the normal group. Histological analyses showed that hTMSC administration afforded more favorable collagen and hyaluronic acid deposition than was evident in the controls. Implanted hTMSCs were observed in injured vocal folds 2 weeks after implantation. Conclusions Our results show that hTMSCs implantation into injured vocal folds facilitated vocal fold regeneration, with presenting antifibrotic effects.

  2. Derived enriched uranium market

    International Nuclear Information System (INIS)

    Rutkowski, E.

    1996-01-01

    The potential impact on the uranium market of highly enriched uranium from nuclear weapons dismantling in the Russian Federation and the USA is analyzed. Uranium supply, conversion, and enrichment factors are outlined for each country; inventories are also listed. The enrichment component and conversion components are expected to cause little disruption to uranium markets. The uranium component of Russian derived enriched uranium hexafluoride is unresolved; US legislation places constraints on its introduction into the US market

  3. Computation of Mie derivatives.

    Science.gov (United States)

    Li, Yang; Bowler, Nicola

    2013-07-10

    Analytical expressions are obtained for the derivatives of Mie scattering coefficients with respect to the electrical radius of the spherical scattering particle, and to the relative permittivity and permeability of both the particle and the surrounding medium. Their corresponding approximate expressions are developed to avoid numerical overflow based on the logarithmic derivative of Riccati-Bessel functions. The analytical expressions have been verified by comparing their results with those calculated by analytical expressions developed by Mathematica. Compared with the numerical derivative, the analytical expressions and approximate expressions show a higher accuracy and are 2.0 and 2.8 times, respectively, faster in the case of a single magnetodielectric sphere. Generally, for spheres with an electrical radius in a large range, the approximate expressions can yield acceptable accuracy and computation time up to a high order. This work can be used in the design of nonmetallic metamaterials, and in the retrieval of aerosol properties from remote sensing data. An example calculation is given for the design of an optical, all-dielectric, mu-negative metamaterial consisting of a simple cubic array of tellurium nanoparticles.

  4. Carnitine derivatives: clinical usefulness.

    Science.gov (United States)

    Malaguarnera, Mariano

    2012-03-01

    Carnitine and its derivatives are natural substances involved in both carbohydrate and lipid metabolism. This review summarizes the recent progress in the field in relation to the molecular mechanisms. The pool of different carnitine derivatives is formed by acetyl-L-carnitine (ALC), propionyl-L-carnitine (PLC), and isovaleryl-carnitine. ALC may have a preferential effect on the brain tissue. ALC represents a compound of great interest for its wide clinical application in various neurological disorders: it may be of benefit in treating Alzheimer's dementia, depression in the elderly, HIV infection, chronic fatigue syndrome, peripheral neuropathies, ischemia and reperfusion of the brain, and cognitive impairment associated with various conditions. PLC has been demonstrated to replenish the intermediates of the tricarboxylic acid cycle by the propionyl-CoA moiety, a greater affinity for the sarcolemmal carrier, peripheral vasodilator activity, a greater positive inotropism, and more rapid entry into myocytes. Most studies of the therapeutic use of PLC are focused on the prevention and treatment of ischemic heart disease, congestive heart failure, hypertrophic heart disease, and peripheral arterial disease. ALC and PLC are considered well tolerated without significant side-effects. A number of therapeutic effects possibly come from the interaction of carnitine and its derivatives with the elements of cellular membranes.

  5. Multifunctional Cinnamic Acid Derivatives

    Directory of Open Access Journals (Sweden)

    Aikaterini Peperidou

    2017-07-01

    Full Text Available Our research to discover potential new multitarget agents led to the synthesis of 10 novel derivatives of cinnamic acids and propranolol, atenolol, 1-adamantanol, naphth-1-ol, and (benzylamino ethan-1-ol. The synthesized molecules were evaluated as trypsin, lipoxygenase and lipid peroxidation inhibitors and for their cytotoxicity. Compound 2b derived from phenoxyphenyl cinnamic acid and propranolol showed the highest lipoxygenase (LOX inhibition (IC50 = 6 μΜ and antiproteolytic activity (IC50 = 0.425 μΜ. The conjugate 1a of simple cinnamic acid with propranolol showed the higher antiproteolytic activity (IC50 = 0.315 μΜ and good LOX inhibitory activity (IC50 = 66 μΜ. Compounds 3a and 3b, derived from methoxylated caffeic acid present a promising combination of in vitro inhibitory and antioxidative activities. The S isomer of 2b also presented an interesting multitarget biological profile in vitro. Molecular docking studies point to the fact that the theoretical results for LOX-inhibitor binding are identical to those from preliminary in vitro study.

  6. Credit derivatives and risk management

    OpenAIRE

    Michael S. Gibson

    2007-01-01

    The striking growth of credit derivatives suggests that market participants find them to be useful tools for risk management. I illustrate the value of credit derivatives with three examples. A commercial bank can use credit derivatives to manage the risk of its loan portfolio. An investment bank can use credit derivatives to manage the risks it incurs when underwriting securities. An investor, such as an insurance company, asset manager, or hedge fund, can use credit derivatives to align its...

  7. Credit derivatives in emerging markets

    OpenAIRE

    Romain Rancière

    2002-01-01

    Credit Derivatives are securities that offer protection against credit or default risk of bonds or loans. The credit derivatives emerging market has grown rapidly and credit derivatives are widely used. This paper describes the emerging credit derivatives market structure. The current market activity is analyzed through elementary pricing dynamics and the study of the term structure of default risk. Focusing on the performance of credit derivatives in stress situation, including legal and mar...

  8. In defense of derivations

    Science.gov (United States)

    Mungan, Carl E.

    2016-05-01

    At the 2015 AAPT Summer Meeting, I presented four derivations of the formula for motional emf. Such physics derivations involve the construction of explanatory frameworks involving diagrams and mathematical models. Although textbooks devote considerable space to such explanations, many teachers and students spend their time on worksheets, end-of-chapter problems, and the like. The book is reduced to a bank of solved (i.e., example) and unsolved (i.e., homework) questions, along with equations in colored boxes that presumably are to be used to answer those questions. Such an approach encourages fragmentation of knowledge, the view that there is only one right answer to a problem with the goal of physics being to find that answer (neatly boxed of course), and the inability to reason about even a slightly different (much less a novel) situation. If we are to develop scientific literacy, significant course time must be devoted to explaining the structure of and support for the models and equations we use.

  9. 6-Bromocholesterol derivatives

    International Nuclear Information System (INIS)

    Flanagan, R.J.

    1984-01-01

    Novel 6-bromo derivatives of cholesterol have the formula 3-(R-O-),6-BR,17-((H3C-)2-HC-H2C-H2C-H2C-HC(-CH3)-)-ESTR-5-ENE Such compounds are prepared from the known 6-iodocholesterol by treatment with cuprous bromide. These compounds, labelled with radioisotopes of Br-82 or Br-77, are localized in the adrenal, mammary and ovary tissue of female mammals and in the adrenal or prostate tissue of males when administered to such individuals. This provides a method for imaging adrenal, ovary or prostate tissue which is superior to use of the prior art 6-iodo-cholesterol

  10. Algae Derived Biofuel

    Energy Technology Data Exchange (ETDEWEB)

    Jahan, Kauser [Rowan Univ., Glassboro, NJ (United States)

    2015-03-31

    One of the most promising fuel alternatives is algae biodiesel. Algae reproduce quickly, produce oils more efficiently than crop plants, and require relatively few nutrients for growth. These nutrients can potentially be derived from inexpensive waste sources such as flue gas and wastewater, providing a mutual benefit of helping to mitigate carbon dioxide waste. Algae can also be grown on land unsuitable for agricultural purposes, eliminating competition with food sources. This project focused on cultivating select algae species under various environmental conditions to optimize oil yield. Membrane studies were also conducted to transfer carbon di-oxide more efficiently. An LCA study was also conducted to investigate the energy intensive steps in algae cultivation.

  11. SEMANTIC DERIVATION OF BORROWINGS

    Directory of Open Access Journals (Sweden)

    Shigapova, F.F.

    2017-09-01

    Full Text Available The author carried out the contrastive analysis of the word спикер borrowed into Russian from English and the English word speaker. The findings of the analysis include confirm (1 different derivational abilities and functions of the borrowed word and the native word; (2 distinctive features in the definitions, i.e. semantic structures, registered in monolingual non-abridged dictionaries; (3 heterogeneous parameters of frequencies recorded in the National Corpus of the Russian language and the British National Corpus; (4 absence of bilingual equivalent collocations with words спикер and speaker. The collocations with words studied revealed new lexical and connotative senses in the meaning of the word. Relevance of the study conducted is justified by the new facts revealed about the semantic adaptation of the borrowed word in the system of the Russian language and its paradigmatic and syntagmatic connections in the system of the recipient language.

  12. Original and Derived Judgment

    DEFF Research Database (Denmark)

    Foss, Kirsten; Foss, Nicolai Juul; Klein, Peter G.

    2007-01-01

    Recent work links entrepreneurship to the economic theory of the firm, using the concept of entrepreneurship as judgment introduced by Frank Knight. When judgment is complementary to other assets, it makes sense for entrepreneurs to hire labour and to own assets. The entrepreneur's role, then...... to subordinates, who exercise derived judgment. We call these employees `proxy-entrepreneurs', and ask how the firm's organizational structure - its formal and informal systems of rewards and punishments, rules for settling disputes and renegotiating agreements, means of evaluating performance and so on - can...... be designed to encourage forms of proxy entrepreneurship that increase firm value while discouraging actions that destroy value. Building on key ideas from the entrepreneurship literature, Austrian economics and the economic theory of the firm, we develop a framework for analysing the trade-off between...

  13. Thermosensitive hydrogel based on chitosan and its derivatives containing medicated nanoparticles for transcorneal administration of 5-fluorouracil

    Directory of Open Access Journals (Sweden)

    Fabiano A

    2017-01-01

    Full Text Available Angela Fabiano,1 Ranieri Bizzarri,2 Ylenia Zambito1 1Department of Pharmacy, University of Pisa, 2NEST, Istituto Nanoscienze CNR (CNR-NANO and Scuola Normale Superiore, Pisa, Italy Abstract: A thermosensitive ophthalmic hydrogel (TSOH – fluid at 4°C (instillation temperature, semisolid at 35°C (eye temperature, which coupled the dosing accuracy and administration ease of eyedrops with the increased ocular bioavailability of a hydrogel – was prepared by gelling a chitosan hydrochloride (ChHCl solution (27.8 mg/mL medicated with 1.25 mg/mL 5-fluorouracil (5-FU with β-glycerophosphate 0.8 mg/mL. Polymer mixtures, where Ch was partially (10%, 15%, or 20% replaced by quaternary ammonium–chitosan conjugates (QA-Ch or thiolated derivatives thereof, were also used to modulate 5-FU-release properties of TSOH. Also, Ch-based nanoparticles (NPs; size after lyophilization and redispersion 341.5±15.2 nm, polydispersity 0.315±0.45, ζ-potential 10.21 mV medicated with 1.25 mg/mL 5-FU prepared by ionotropic cross-linking of Ch with hyaluronan were introduced into TSOH. The 5-FU binding by TSOH polymers in the sol state was maximum with plain Ch (31.4% and tended to decrease with increasing QA presence in polymer mixture. 5-FU release from TSOH with or without NPs was diffusion-controlled and linear in √t. The different TSOH polymers were compared on a diffusivity basis by comparing the slopes of √t plots. These showed a general decrease with NP-containing TSOH, which was the most marked with the TSOH, where Ch was 20% replaced by the derivative QA-Ch50. This formulation and that not containing NP were instilled in rabbits and the 5-FU transcorneal penetration was measured by analyzing the aqueous humor. Both TSOH solutions increased the area under the curve (0–8 hours 3.5 times compared with the plain eyedrops, but maximum concentration for the NP-free TSOH was about 0.65 µg/mL, followed by a slow decline, while the NP-containing one showed a

  14. Piroxicam derivatives THz classification

    Science.gov (United States)

    Sterczewski, Lukasz A.; Grzelczak, Michal P.; Nowak, Kacper; Szlachetko, Bogusław; Plinska, Stanislawa; Szczesniak-Siega, Berenika; Malinka, Wieslaw; Plinski, Edward F.

    2016-02-01

    In this paper we report a new approach to linking the terahertz spectral shapes of drug candidates having a similar molecular structure to their chemical and physical parameters. We examined 27 newly-synthesized derivatives of a well-known nonsteroidal anti-inflammatory drug Piroxicam used for treatment of inflammatory arthritis and chemoprevention of colon cancer. The testing was carried out by means of terahertz pulsed spectroscopy (TPS). Using chemometric techniques we evaluated their spectral similarity in the terahertz range and attempted to link the position on the principal component analysis (PCA) score map to the similarity of molecular descriptors. A simplified spectral model preserved 75% and 85.1% of the variance in 2 and 3 dimensions respectively, compared to the input 1137. We have found that in 85% of the investigated samples a similarity of the physical and chemical parameters corresponds to a similarity in the terahertz spectra. The effects of data preprocessing on the generated maps are also discussed. The technique presented can support the choice of the most promising drug candidates for clinical trials in pharmacological research.

  15. Experts' understanding of partial derivatives using the Partial Derivative Machine

    OpenAIRE

    Roundy, David; Dorko, Allison; Dray, Tevian; Manogue, Corinne A.; Weber, Eric

    2014-01-01

    Partial derivatives are used in a variety of different ways within physics. Most notably, thermodynamics uses partial derivatives in ways that students often find confusing. As part of a collaboration with mathematics faculty, we are at the beginning of a study of the teaching of partial derivatives, a goal of better aligning the teaching of multivariable calculus with the needs of students in STEM disciplines. As a part of this project, we have performed a pilot study of expert understanding...

  16. Derivative spectrophotometry of cobalt alloys

    International Nuclear Information System (INIS)

    Spitsyn, P.K.

    1985-01-01

    The method of derivative spectrophotometry is briefly described, and derivative absorption spectra are presented for samarium, cobalt, and commercial Sm-Co alloys. It is shown that the use of derivative spectrophotometry not only improves the accuracy and selectivity of element determinations but also simplifies the analysis of alloys. Results of a statistical evaluation of the metrological characteristics of the analytical procedure described here are presented. 8 references

  17. Central Clearing of OTC Derivatives

    DEFF Research Database (Denmark)

    Cont, Rama; Kokholm, Thomas

    2014-01-01

    netting agreements. When a CCP exists for interest rate derivatives, adding a CCP for credit derivatives is shown to decrease overall exposures. These findings are shown to be robust to the statistical assumptions of the model as well as the choice of risk measure used to quantify exposures....

  18. Chemistry of aliphatic sulfurpentafluoride derivatives

    International Nuclear Information System (INIS)

    Bissell, E.R.

    1975-01-01

    This report summarizes the literature through 1974 on aliphatic sulfurpentafluoride compounds. Methods of preparation and methods of transforming one pentafluorothio compound into another are briefly discussed. The physical properties of all known derivatives are tabulated

  19. Higher derivatives in gauge transformations

    International Nuclear Information System (INIS)

    Gogilidze, S.A.; Sanadze, V.V.; Tkebuchava, F.G.

    1992-01-01

    The mechanism of appearance of highher derivatives of coordinates in the symmetry transformation law of the second Noether's theorem is established. It is shown that the corresponding transformations are canonical in the extended phase space. 15 refs

  20. Push-outs of derivations

    Indian Academy of Sciences (India)

    extension as a limit of operators b ↦→ D(ba) − b.D(a), a ∈ A in an appropriate operator topology, the main point in the proof being to show that the limit map is in fact a derivation. In this paper we make clear which part of this approach is analytic and which algebraic by presenting an algebraic scheme that gives derivations ...

  1. Elementary derivation of Kepler's laws

    International Nuclear Information System (INIS)

    Vogt, E.

    1995-02-01

    A simple derivation of all three so-called Kepler Laws is presented in which the orbits, bound and unbound, follow directly and immediately from conservation of energy and angular momentum. The intent is to make this crowning achievement of Newtonian Mechanics easily accessible to students in introductory physics courses. The method is also extended to simplify the derivation of the Rutherford Scattering Law. (author). 4 refs., 3 figs

  2. Derivatives Trading and Negative Voting

    OpenAIRE

    Spamann, Holger

    2012-01-01

    This paper exposits a model of parallel trading of corporate securities (shares, bonds) and derivatives in which a large trader can sometimes profitably acquire securities with their corporate control rights for the sole purpose of reducing the corporations value and gaining on a net short position created through off-setting derivatives. At other times, the large trader profitably takes a net long position. The large trader requires no private information beyond its own trades. The problem i...

  3. Quinazoline derivatives: synthesis and bioactivities

    OpenAIRE

    Wang, Dan; Gao, Feng

    2013-01-01

    Owing to the significant biological activities, quinazoline derivatives have drawn more and more attention in the synthesis and bioactivities research. This review summarizes the recent advances in the synthesis and biological activities investigations of quinazoline derivatives. According to the main method the authors adopted in their research design, those synthetic methods were divided into five main classifications, including Aza-reaction, Microwave-assisted reaction, Metal-mediated reac...

  4. Anisotropic inflation with derivative couplings

    Science.gov (United States)

    Holland, Jonathan; Kanno, Sugumi; Zavala, Ivonne

    2018-05-01

    We study anisotropic power-law inflationary solutions when the inflaton and its derivative couple to a vector field. This type of coupling is motivated by D-brane inflationary models, in which the inflaton, and a vector field living on the D-brane, couple disformally (derivatively). We start by studying a phenomenological model where we show the existence of anisotropic solutions and demonstrate their stability via a dynamical system analysis. Compared to the case without a derivative coupling, the anisotropy is reduced and thus can be made consistent with current limits, while the value of the slow-roll parameter remains almost unchanged. We also discuss solutions for more general cases, including D-brane-like couplings.

  5. Sol-gel derived sorbents

    Science.gov (United States)

    Sigman, Michael E.; Dindal, Amy B.

    2003-11-11

    Described is a method for producing copolymerized sol-gel derived sorbent particles for the production of copolymerized sol-gel derived sorbent material. The method for producing copolymerized sol-gel derived sorbent particles comprises adding a basic solution to an aqueous metal alkoxide mixture for a pH.ltoreq.8 to hydrolyze the metal alkoxides. Then, allowing the mixture to react at room temperature for a precalculated period of time for the mixture to undergo an increased in viscosity to obtain a desired pore size and surface area. The copolymerized mixture is then added to an immiscible, nonpolar solvent that has been heated to a sufficient temperature wherein the copolymerized mixture forms a solid upon the addition. The solid is recovered from the mixture, and is ready for use in an active sampling trap or activated for use in a passive sampling trap.

  6. Synthesis of 2-phosphaadamantane derivatives

    International Nuclear Information System (INIS)

    Zemlyanoi, V.N.; Aleksandrov, A.M.; Kukhar', V.P.

    1986-01-01

    The authors describe the synthesis and properties of 2-phosphadamantane derivatives. For the synthesis of 2-phosphaadamantane derivatives they decided to use the methodology of the synthesis of 2-thiaadamantane. The IR spectra were determined on CHCl 3 solutions with a Specord 711R spectrometer, the PMR spectra were determined on Tesla BS-467 (60 MHz) and Bruker WP-200 (200 MHz) spectrometers, external standard hexamethyldisiloxane, the 31 P NMR spectra were determined on Tesla BS-487 C (30 MHz) and Bruker WP-200 (81 MHz) spectrometers, external standard 85% phosphoric acid, and the mass spectra were determined on an MS-1302 spectrometer

  7. Bounded Densities and Their Derivatives

    DEFF Research Database (Denmark)

    Kozine, Igor; Krymsky, V.

    2009-01-01

    This paper describes how one can compute interval-valued statistical measures given limited information about the underlying distribution. The particular focus is on a bounded derivative of a probability density function and its combination with other available statistical evidence for computing ...... quantities of interest. To be able to utilise the evidence about the derivative it is suggested to adapt the ‘conventional’ problem statement to variational calculus and the way to do so is demonstrated. A number of examples are given throughout the paper....

  8. Risk Factors in Derivatives Markets

    Directory of Open Access Journals (Sweden)

    Raimonda Martinkutė-Kaulienė

    2015-02-01

    Full Text Available The objective of the article is to analyse and present the classification of risks actual to derivative securities. The analysis is based on classical and modern literature findings and analysis of newest statistical data. The analysis led to the conclusion, that the main risks typical for derivatives contracts and their traders are market risk, liquidity risk, credit and counterparty risk, legal risk and transactions risk. Pricing risk and systemic risk is also quite important. The analysis showed that market risk is the most important kind of risk that in many situations influences the level of remaining risks.

  9. Analytical application of derivative spectrophotometry

    Directory of Open Access Journals (Sweden)

    VIOLETA M. STEFANOVIC

    2000-07-01

    Full Text Available 1. Introduction 2. Basic characteristics of derivative spectrophotometry 2.1. Increase of spectra resolution 2.2. Elimination of the influence of baseline shift and matrix interferences 2.3. Enhancement of the detectability of minor spectral features 2.4. Precise determination of the positions of absorption maxima 2.5. Signal-to-noise ratio (SNR 2.6. Quantitative analysis 3. Analytical applications 3.1. Inorganic analysis 3.2. Organic and pharmaceutical analysis 3.3. Analysis of food and water 3.4. Application of derivative spectrophotometry for the determination of equilibrium constants

  10. Derived equivalences for group rings

    CERN Document Server

    König, Steffen

    1998-01-01

    A self-contained introduction is given to J. Rickard's Morita theory for derived module categories and its recent applications in representation theory of finite groups. In particular, Broué's conjecture is discussed, giving a structural explanation for relations between the p-modular character table of a finite group and that of its "p-local structure". The book is addressed to researchers or graduate students and can serve as material for a seminar. It surveys the current state of the field, and it also provides a "user's guide" to derived equivalences and tilting complexes. Results and proofs are presented in the generality needed for group theoretic applications.

  11. derivatives: Synthesis and antimicrobial evaluation

    Indian Academy of Sciences (India)

    cal activity study revealed that all compounds showed promising activities and bis-(1H-2-benzopyran-1-one) derivatives (5) ...... A and Galvez J 2004 Planta Med. 70 315. 6. ... Ante N, Erik De C, Jan B and Mladen M 2011 Molecules. 16 6023.

  12. Second derivative spectrophotometric determination of ...

    African Journals Online (AJOL)

    A new, simple, rapid, wide applicable range and reliable second derivative spectrophotometric method has been developed for determination of cyclophosphamide (CP) in bulk and pharmaceutical dosage forms. Calibration graph is linear in the concentration range of 25 - 200 μg/ml of CP with 10 μg/ml of detection limit and ...

  13. Hypoxanthine Derivatives in Experimental Infections

    Directory of Open Access Journals (Sweden)

    Claudio De Simone

    1992-01-01

    ability of ST 789 to increase interleukin-6 production, suggest that monocyte/macrophages are likely to be the main cellular target of the immunomodulating activity of ST 789. Finally, in the presentln vivo study, hypoxanthine derivatives did not enhance the mean survival time of tumour-bearing immunosuppressed mice.

  14. Radiological protection optimization using derivatives

    International Nuclear Information System (INIS)

    Freitas Acosta Perez, C. de; Sordi, G.M.A.A.

    2006-01-01

    The aim of this paper is to provide a different approach related to the integral cost-benefit and extended cost-benefit analysis used in the decision-aiding techniques. In the ICRP publication 55 the annual protection cost is envisaged as a set of points, each of them representing an option, linked by a straight line. The detriment cost function is considered a linear function whose angular coefficient is determined by the alpha value. In this paper the uranium mine example considered in the ICRP publication 55 was used. But the potential curve was introduced both in the integral cost benefit analysis and in the extended cost-benefit analysis, which the individual dose distribution attribute is added. The result was obtained using derivatives. The detriment cost, Y, is not necessary because the alpha value is known. The Y derivative dS/dY is the alpha value itself and so, the attention is directed to the derivative -dX/dS on the points that, along with the alpha value, present the optimum option. The results makes clear that the prevailing factor in the optimum option selection is the alpha value imputed, and those a single alpha value, as suggested now, probably as little efficiency on the optimization process. Obtaining a curve for the alpha value and using the derivative technique introduced in this paper, the analytical solution is more convenient and reliable compared to the one used now. (authors)

  15. Alchemical derivatives of reaction energetics

    Science.gov (United States)

    Sheppard, Daniel; Henkelman, Graeme; von Lilienfeld, O. Anatole

    2010-08-01

    Based on molecular grand canonical ensemble density functional theory, we present a theoretical description of how reaction barriers and enthalpies change as atoms in the system are subjected to alchemical transformations, from one element into another. The change in the energy barrier for the umbrella inversion of ammonia is calculated along an alchemical path in which the molecule is transformed into water, and the change in the enthalpy of protonation for methane is calculated as the molecule is transformed into a neon atom via ammonia, water, and hydrogen fluoride. Alchemical derivatives are calculated analytically from the electrostatic potential in the unperturbed system, and compared to numerical derivatives calculated with finite difference interpolation of the pseudopotentials for the atoms being transformed. Good agreement is found between the analytical and numerical derivatives. Alchemical derivatives are also shown to be predictive for integer changes in atomic numbers for oxygen binding to a 79 atom palladium nanoparticle, illustrating their potential use in gradient-based optimization algorithms for the rational design of catalysts.

  16. Radiolabeled derivatives of folic acid

    International Nuclear Information System (INIS)

    1980-01-01

    Derivatives of folic acid are described, in which the α-carboxyl group is substituted with an amino compound having an aromatic or heterocyclic ring substituent which is capable of being radiolabelled. Particularly mentioned as a radiolabel is 125 I. (author)

  17. Second derivative spectrophotometric determination of ...

    African Journals Online (AJOL)

    Hemn

    2013-11-13

    Nov 13, 2013 ... olanzapine in pharmaceutical formulation.Int.J.ChemTech. Res.2(1):756-761. Stanisz B, Paszun S, Lesniak M (2009). Validation of UV derivative spectrophotometric method for determination of benazepril hydrochloride in tablets and evaluation of its stability.ActaPoloniaePharmaceutica-Drug Research.

  18. Novel bisstyryl derivatives of bakuchiol

    DEFF Research Database (Denmark)

    Reddy, Mallepally V; Thota, Niranjan; Sangwan, Payare L

    2010-01-01

    Novel bisstyryl derivatives of bakuchiol using Heck coupling reaction as the key step were synthesized and screened against a panel of six oral cavity pathogens for their antimicrobial activity. Four compounds (9-12) showed two to fourfold and four to eightfold better activity (MIC 0.25-16 microg...

  19. Push-outs of derivations

    DEFF Research Database (Denmark)

    Grønbæk, Niels

    2008-01-01

    Let A be a Banach algebra and let X be a Banach A-bimodule. In studying H¹(A,X) it is often useful to extend a given derivation D: A->X to a Banach algebra B containing A as an ideal, thereby exploiting (or establishing) hereditary properties. This is usually done using (bounded/unbounded) approx...

  20. Asymptotic aspect of derivations in Banach algebras

    Directory of Open Access Journals (Sweden)

    Jaiok Roh

    2017-02-01

    Full Text Available Abstract We prove that every approximate linear left derivation on a semisimple Banach algebra is continuous. Also, we consider linear derivations on Banach algebras and we first study the conditions for a linear derivation on a Banach algebra. Then we examine the functional inequalities related to a linear derivation and their stability. We finally take central linear derivations with radical ranges on semiprime Banach algebras and a continuous linear generalized left derivation on a semisimple Banach algebra.

  1. Higher-derivative generalization of conformal mechanics

    Science.gov (United States)

    Baranovsky, Oleg

    2017-08-01

    Higher-derivative analogs of multidimensional conformal particle and many-body conformal mechanics are constructed. Their Newton-Hooke counterparts are derived by applying appropriate coordinate transformations.

  2. Variation in primary and culture-expanded cells derived from connective tissue progenitors in human bone marrow space, bone trabecular surface and adipose tissue.

    Science.gov (United States)

    Qadan, Maha A; Piuzzi, Nicolas S; Boehm, Cynthia; Bova, Wesley; Moos, Malcolm; Midura, Ronald J; Hascall, Vincent C; Malcuit, Christopher; Muschler, George F

    2018-03-01

    Connective tissue progenitors (CTPs) embody the heterogeneous stem and progenitor cell populations present in native tissue. CTPs are essential to the formation and remodeling of connective tissue and represent key targets for tissue-engineering and cell-based therapies. To better understand and characterize CTPs, we aimed to compare the (i) concentration and prevalence, (ii) early in vitro biological behavior and (iii) expression of surface-markers and transcription factors among cells derived from marrow space (MS), trabecular surface (TS), and adipose tissues (AT). Cancellous-bone and subcutaneous-adipose tissues were collected from 8 patients. Cells were isolated and cultured. Colony formation was assayed using Colonyze software based on ASTM standards. Cell concentration ([Cell]), CTP concentration ([CTP]) and CTP prevalence (P CTP ) were determined. Attributes of culture-expanded cells were compared based on (i) effective proliferation rate and (ii) expression of surface-markers CD73, CD90, CD105, SSEA-4, SSEA-3, SSEA-1/CD15, Cripto-1, E-Cadherin/CD324, Ep-CAM/CD326, CD146, hyaluronan and transcription factors Oct3/4, Sox-2 and Nanog using flow cytometry. Mean [Cell], [CTP] and P CTP were significantly different between MS and TS samples (P = 0.03, P = 0.008 and P= 0.0003), respectively. AT-derived cells generated the highest mean total cell yield at day 6 of culture-4-fold greater than TS and more than 40-fold greater than MS per million cells plated. TS colonies grew with higher mean density than MS colonies (290 ± 11 versus 150 ± 11 cell per mm 2 ; P = 0.0002). Expression of classical-mesenchymal stromal cell (MSC) markers was consistently recorded (>95%) from all tissue sources, whereas all the other markers were highly variable. The prevalence and biological potential of CTPs are different between patients and tissue sources and lack variation in classical MSC markers. Other markers are more likely to discriminate differences

  3. Derivatives in energy project finance

    International Nuclear Information System (INIS)

    Spencer, Lloyd

    1999-01-01

    This chapter focuses on risk management of merchant power generation projects and describes project finance as balancing risk and reward over time. The historical background to risk management is traced, and the case for derivatives in energy project finance is put forward with the hedging of forward output, and forwards and power purchase agreements discussed. Current and prospective usage, and the implementation issues of market liquidity, margin calls, letters of credit, derivative counterparty credit risk, and accounting policy are considered. A detailed example of a gas-fired plant in the US is presented with details given of the distribution of project earnings before tax. Oil field operating cashflows are examined, with reserved flow models, leverage effects, and price hedging addressed

  4. Diagnostic radio labelled polysaccharide derivatives

    International Nuclear Information System (INIS)

    Milbrath, D.S.; Ferber, R.H.; Barnett, W.E.

    1982-01-01

    A radiopharmaceutical compound for diagnosing blood clots is claimed. It is the reaction product of a compound characterized by a water-soluble polysaccharide moiety having an average of at least 0.25 anionic group per monosaccharide unit, and at least one chelating group derived from the group consisting of amino acids, substituted cyclic acid anhydrides, and carbon disulfide; and a radioactive tracer metal compound selected from In-111, Tc-99m, Cr-51, Ga-68, and a reduced pertechnetate compound

  5. Derivation of Hamiltonians for accelerators

    Energy Technology Data Exchange (ETDEWEB)

    Symon, K.R.

    1997-09-12

    In this report various forms of the Hamiltonian for particle motion in an accelerator will be derived. Except where noted, the treatment will apply generally to linear and circular accelerators, storage rings, and beamlines. The generic term accelerator will be used to refer to any of these devices. The author will use the usual accelerator coordinate system, which will be introduced first, along with a list of handy formulas. He then starts from the general Hamiltonian for a particle in an electromagnetic field, using the accelerator coordinate system, with time t as independent variable. He switches to a form more convenient for most purposes using the distance s along the reference orbit as independent variable. In section 2, formulas will be derived for the vector potentials that describe the various lattice components. In sections 3, 4, and 5, special forms of the Hamiltonian will be derived for transverse horizontal and vertical motion, for longitudinal motion, and for synchrobetatron coupling of horizontal and longitudinal motions. Hamiltonians will be expanded to fourth order in the variables.

  6. Financial Derivatives (Based on Two Supports Evaluation

    Directory of Open Access Journals (Sweden)

    Tiberiu Socaciu

    2016-07-01

    Full Text Available In this paper we build a PDE like Black-Scholes equation in hypothesis of a financial derivative that is dependent on two supports (usual is dependent only on one support, like amoption based on gold, when national currency has a great float.Keywords: Financial derivatives, derivatives evaluation, derivatives based on two supports, extended Itō like lemma.

  7. 12 CFR 403.4 - Derivative classification.

    Science.gov (United States)

    2010-01-01

    ... SAFEGUARDING OF NATIONAL SECURITY INFORMATION § 403.4 Derivative classification. (a) Use of derivative classification. (1) Unlike original classification which is an initial determination, derivative classification... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Derivative classification. 403.4 Section 403.4...

  8. Clearing and settlement of exchange traded derivatives

    OpenAIRE

    John McPartland

    2009-01-01

    Derivatives are a class of financial instruments that derive their value from some underlying commodity, security, index, or other asset. Futures and options are common forms of derivatives. This article explains how clearing and settlement systems for exchange traded derivatives work.

  9. Development trends of the international derivatives market

    OpenAIRE

    Motorniuk, U.; Terebukh, M.; Kharchuk, V.

    2016-01-01

    The factors forming international derivatives market trends are researched in this article. The history of the formation of the global derivatives market was analyzed, in particular, events which have led to the growth of the derivatives market. Global derivatives market has revealed major changes in its trends and witnessed the gradual transformation of its structure, observed in recent years. Global derivatives market has revealed major changes in its trends and witnessed the gradual transf...

  10. Iron and iron derived radicals

    International Nuclear Information System (INIS)

    Borg, D.C.; Schaich, K.M.

    1987-04-01

    We have discussed some reactions of iron and iron-derived oxygen radicals that may be important in the production or treatment of tissue injury. Our conclusions challenge, to some extent, the usual lines of thought in this field of research. Insofar as they are born out by subsequent developments, the lessons they teach are two: Think fast! Think small! In other words, think of the many fast reactions that can rapidly alter the production and fate of highly reactive intermediates, and when considering the impact of competitive reactions on such species, think how they affect the microenvironment (on the molecular scale) ''seen'' by each reactive molecule. 21 refs., 3 figs., 1 tab

  11. Resorcinol derivatives from Ardisia maculosa.

    Science.gov (United States)

    Zheng, Ying; Wu, Feng-E

    2007-01-01

    Besides a series of known sterols and triterpenoids, a new resorcinol (1) and a known resorcinol (2) have been isolated from ethanol extract of Ardisia maculosa for the first time. The structures of these resorcinol derivatives were elucidated as 2-methyl-5-(Z-heptadec-8-enyl) resorcinol and 5-Z-heptadec-8-enyl) resorcinol by HRESI-MS, NMR ((1)H, (13)C, HSQC, HMBC) experiments. In our in vitro assay, compounds 1 and 2 showed no antimicrobial activities, however, compound 2 exhibited cytotoxity activity against human cancer cell line with GI(50) value of 2.14 x 10(- 4) mmol/ml.

  12. Topological Derivatives in Shape Optimization

    CERN Document Server

    Novotny, Antonio André

    2013-01-01

    The topological derivative is defined as the first term (correction) of the asymptotic expansion of a given shape functional with respect to a small parameter that measures the size of singular domain perturbations, such as holes, inclusions, defects, source-terms and cracks. Over the last decade, topological asymptotic analysis has become a broad, rich and fascinating research area from both theoretical and numerical standpoints. It has applications in many different fields such as shape and topology optimization, inverse problems, imaging processing and mechanical modeling including synthesis and/or optimal design of microstructures, sensitivity analysis in fracture mechanics and damage evolution modeling. Since there is no monograph on the subject at present, the authors provide here the first account of the theory which combines classical sensitivity analysis in shape optimization with asymptotic analysis by means of compound asymptotic expansions for elliptic boundary value problems. This book is intende...

  13. Antioxidant capacity of eugenol derivatives

    Directory of Open Access Journals (Sweden)

    María E. Hidalgo

    2009-01-01

    Full Text Available Toxicity and antioxidant capacity of eugenol derivatives (E2 = 2-Methoxy-4-[1-propenylphenyl]acetate, E3 = 4-Allyl-2-methoxyphenylacetate, E4 = 4-Allyl-2-methoxy-4-nitrophenol, E5 = 5-Allyl-3-nitrobenzene-1,2-diol, E6 = 4-Allyl-2-methoxy-5-nitrophenyl acetate were evaluated in order to determine the influence of the sustituents. E2-E6 were synthesized from eugenol (E1. E1 was extracted from cloves oil, and E2-E6 were obtained through acetylation and nitration reactions. Antioxidant capacity evaluated by DPPH (1, 1-Diphenyl-2-picrylhydrazil and ORAC fluorescein demonstrated that E1 and E5 have a higher capacity and the minor toxicity evaluated by red blood cells haemolysis and the Artemia saline test. In accordance with our results, the compound's (E1-E5 use in the pharmaceutical, cosmetic and or food industries could be suggested.

  14. Cytotoxicity study of pyrazole derivatives

    Directory of Open Access Journals (Sweden)

    Nusrat Binta Ahasan

    2007-06-01

    Full Text Available Pyrazolone heterocyclic compound, 3-methyl-1-phenyl-2-pyrazoline-5-one 2(a was synthesized by condensation reaction between ethyl acetoacetate and phenyl hydrazine and was converted into their corresponding heterocyclic derivatives 2(b to 2(f2 . Their cytotoxicity effects were measured by brine shrimp lethality bioassay. Among them the compounds 2(b , 2(f1 , and 2(f2 were highly active according to IC50 values 19.50, 19.50 and 20 ppm respectively. The rest of compounds 2(a , 2(c , 2(d1 , and 2(d2 having IC50 values 38, 33.50, 37.50, 36, 37.50 and 36 ppm in that order, were moderately active.

  15. Cytotoxicity study of pyrazole derivatives

    Directory of Open Access Journals (Sweden)

    Nusrat Binta Ahasan and Md. Rabiul Islam

    2007-12-01

    Full Text Available Pyrazolone heterocyclic compound, 3-methyl-1-phenyl-2-pyrazoline-5-one 2(a was synthesized by condensation reaction between ethyl acetoacetate and phenyl hydrazine and was converted into their corresponding heterocyclic derivatives 2(b to 2(f2. Their cytotoxicity effects were measured by brine shrimp lethality bioassay. Among them the compounds 2(b, 2(f1, and 2(f2 were highly active according to IC50 values 19.50, 19.50 and 20 ppm respectively. The rest of compounds 2(a, 2(c, 2(d1, and 2(d2 having IC50 values 38, 33.50, 37.50, 36, 37.50 and 36 ppm in that order, were moderately active.

  16. Silsesquioxane-derived ceramic fibres

    Science.gov (United States)

    Hurwitz, F. I.; Farmer, S. C.; Terepka, F. M.; Leonhardt, T. A.

    1991-01-01

    Fibers formed from blends of silsesquioxane polymers were characterized to study the pyrolytic conversion of these precursors to ceramics. The morphology of fibers pyrolyzed to 1400 C revealed primarily amorphous glasses whose conversion to beta-SiC is a function of both blend composition and pyrolysis conditions. Formation of beta-SiC crystallites within the glassy phase is favored by higher than stoichiometric C/Si ratios, while carbothermal reduction of Si-O bonds to form SiC with loss of SiO and CO occurs at higher methyl/phenylpropyl silsesquioxane (lower C/Si) ratios. As the carbothermal reduction is assumed to be diffusion controlled, the fibers can serve as model systems to gain understanding of the silsesquioxane pyrolysis behavior, and therefore are useful in the development of polysilsesquioxane-derived ceramic matrices and coatings as well.

  17. Radiation processing of polysaccharide derivatives

    International Nuclear Information System (INIS)

    Yoshii, Fumio

    2004-01-01

    Carboxymethylcellulose (CMC), carboxymethylstarch (CMS), carboxymethylchitin (CM-chitin) and carboxymethylchitosan (CM-chitosan) form gels when irradiated at paste-like condition. Bedsore prevention mat filled up CMC hydrogel crosslinked by irradiation at paste-like condition was practical applied as a health care products. It was found that CM-chitosan hydrogels have anti-microbial activity and effective as absorbents to remove metal ions. When crosslinked gel sheets of CM-chitin and CM-chitosan were immersed in copper (II) aqueous solution, absorption of Cu (II) were 161 mg/g and 172 mg/g, respectively. Radiation crosslinking of cellulose derivative such as hydroxypropyl methylcellulose phthalate, (HPMCP) kneaded with aqueous alkali solution and methanol was achieved with EB-irradiation at paste-like condition. The HPMCP gel absorbed organic solvents such as chloroform and pyridine. (author)

  18. Derived limits for surface contamination

    CERN Document Server

    Wrixon, A D; Linsley, G S; White, D F

    1979-01-01

    Derived limits (DLs) for surface contamination were first established for use in the nuclear energy industry where a wide variety of radionuclides is encountered. They were later used in factories, hospitals, and universities, where the radionuclides used are normally fewer in number, either known or readily identifiable, and often of low toxicity. In these situations the current limits are frequently over-restrictive. This report describes a reassessment of the values in the light of more recent information on the possible pathways of exposure and the dose equivalent limits given in ICRP Publication 26. The reassessment is prompted also by the introduction of SI units. The results of the reassessment are used to produce a classification of DLs for all radionuclides for active and inactive area surfaces and for skin.

  19. Derivation of the dipole map

    International Nuclear Information System (INIS)

    Ali, Halima; Punjabi, Alkesh; Boozer, Allen

    2004-01-01

    In our method of maps [Punjabi et al., Phy. Rev. Lett. 69, 3322 (1992), and Punjabi et al., J. Plasma Phys. 52, 91 (1994)], symplectic maps are used to calculate the trajectories of magnetic field lines in divertor tokamaks. Effects of the magnetic perturbations are calculated using the low MN map [Ali et al., Phys. Plasmas 11, 1908 (2004)] and the dipole map [Punjabi et al., Phys. Plasmas 10, 3992 (2003)]. The dipole map is used to calculate the effects of externally located current carrying coils on the trajectories of the field lines, the stochastic layer, the magnetic footprint, and the heat load distribution on the collector plates in divertor tokamaks [Punjabi et al., Phys. Plasmas 10, 3992 (2003)]. Symplectic maps are general, efficient, and preserve and respect the Hamiltonian nature of the dynamics. In this brief communication, a rigorous mathematical derivation of the dipole map is given

  20. Landslide in claystone derived soil

    Energy Technology Data Exchange (ETDEWEB)

    Richardson, A M

    1979-07-01

    This article describes a landslide that occured in the Pittsburgh area in a soil deposit derived from the Pittsburgh Redbed Claystone when a cut was made at the toe. (The Pittsburgh Redbed Claystone is the parent of much of the soil material involved in the Pittsburgh area and occurs about mid way between the base of Pittsburgh Coal and the top of the Upper Freepost Coal). The topography before the slide was known and the geometry of the slide mass was established. Slope stability analysis indicated that the landslide could have been predicted using effective stress-shear-strength parameters of s of 12 to 13 and c is 0, where s is angle of shearing resistance and c is cohesion intercept in terms of effective stresses.

  1. THE SPECIFICITY OF KERATEINE DERIVATIVES.

    Science.gov (United States)

    Pillemer, L; Ecker, E E; Martiensen, E W

    1939-09-30

    Carboxymethyl, alpha-carboxyethyl-, alpha-carboxy-n-propyl-, alpha-carboxyisopropyl-, alpha-carboxy-n-butyl, alpha-carboxyisobutyl, alpha-carboxyamyl-, benzyl-, and beta-phenylethylkeratemes were prepared from the parent protein, reduced keratin or kerateine. Chemical analysis disclosed that the various compounds differed in their isoelectric points and solubilities depending on the nature of the substituent group introduced. In general, it was found that in so far as could be determined, nearly all of the available sulfhydryl groups were substituted, while no detectable substitution of the free amino groups of the proteins occurred. The results of the serologic studies revealed that the kerateine derivatives acquired a new immunologie character dependent on the nature of the introduced determinant group. Inhibition tests confirmed the results obtained. Evidence was also produced to show that the grouping See PDF for structure may play a rôle in some of the reactions observed.

  2. Penetratin and derivatives acting as antifungal agents

    NARCIS (Netherlands)

    Masman, Marcelo F.; Rodriguez, Ana M.; Raimondi, Marcela; Zacchino, Susana A.; Luiten, Paul G. M.; Somlai, Csaba; Kortvelyesi, Tamas; Penke, Botond; Enriz, Ricardo D.

    The synthesis, in vitro evaluation, and conformational study of RQIKTWFQNRRMKWKK-NH(2) (penetratin) and related derivatives acting as antifungal agents are reported. Penetratin and some of its derivatives displayed antifungal activity against the human opportunistic pathogenic standardized ATCC

  3. Nature of the basic financial derivatives

    OpenAIRE

    Kats, Svetlana

    2014-01-01

    The article reveals the essence of basic derivatives. Studied by various authors approaches to defining derivatives and their definitions in the legislation and proposed his own definition of the most appropriate for use in accounting practice.

  4. fq-Derivations of G-Algebra

    Directory of Open Access Journals (Sweden)

    Deena Al-Kadi

    2016-01-01

    Full Text Available We introduce the notion of fq-derivation as a new derivation of G-algebra. For an endomorphism map f of any G-algebra X, we show that at least one fq-derivation of X exists. Moreover, for such a map, we show that a self-map dqf of X is fq-derivation of X if X is an associative medial G-algebra. For a medial G-algebra X, dqf is fq-derivation of X if dqf is an outside fq-derivation of X. Finally, we show that if f is the identity endomorphism of X then the composition of two fq-derivations of X is a fq-derivation. Moreover, we give a condition to get a commutative composition.

  5. Polymer-Derived Ceramic Fibers

    Science.gov (United States)

    Ichikawa, Hiroshi

    2016-07-01

    SiC-based ceramic fibers are derived from polycarbosilane or polymetallocarbosilane precursors and are classified into three groups according to their chemical composition, oxygen content, and C/Si atomic ratio. The first-generation fibers are Si-C-O (Nicalon) fibers and Si-Ti-C-O (Tyranno Lox M) fibers. Both fibers contain more than 10-wt% oxygen owing to oxidation during curing and lead to degradation in strength at temperatures exceeding 1,300°C. The maximum use temperature is 1,100°C. The second-generation fibers are SiC (Hi-Nicalon) fibers and Si-Zr-C-O (Tyranno ZMI) fibers. The oxygen content of these fibers is reduced to less than 1 wt% by electron beam irradiation curing in He. The thermal stability of these fibers is improved (they are stable up to 1,500°C), but their creep resistance is limited to a maximum of 1,150°C because their C/Si atomic ratio results in excess carbon. The third-generation fibers are stoichiometric SiC fibers, i.e., Hi-Nicalon Type S (hereafter Type S), Tyranno SA, and Sylramic™ fibers. They exhibit improved thermal stability and creep resistance up to 1,400°C. Stoichiometric SiC fibers meet many of the requirements for the use of ceramic matrix composites for high-temperature structural application. SiBN3C fibers derived from polyborosilazane also show promise for structural applications, remain in the amorphous state up to 1,800°C, and have good high-temperature creep resistance.

  6. Effect of Cyclic Dynamic Compressive Loading on Chondrocytes and Adipose-Derived Stem Cells Co-Cultured in Highly Elastic Cryogel Scaffolds

    Directory of Open Access Journals (Sweden)

    Chih-Hao Chen

    2018-01-01

    Full Text Available In this study, we first used gelatin/chondroitin-6-sulfate/hyaluronan/chitosan highly elastic cryogels, which showed total recovery from large strains during repeated compression cycles, as 3D scaffolds to study the effects of cyclic dynamic compressive loading on chondrocyte gene expression and extracellular matrix (ECM production. Dynamic culture of porcine chondrocytes was studied at 1 Hz, 10% to 40% strain and 1 to 9 h/day stimulation duration, in a mechanical-driven multi-chamber bioreactor for 14 days. From the experimental results, we could identify the optimum dynamic culture condition (20% and 3 h/day to enhance the chondrocytic phenotype of chondrocytes from the expression of marker (Col I, Col II, Col X, TNF-α, TGF-β1 and IGF-1 genes by quantitative real-time polymerase chain reactions (qRT-PCR and production of ECM (GAGs and Col II by biochemical analysis and immunofluorescence staining. With up-regulated growth factor (TGF-β1 and IGF-1 genes, co-culture of chondrocytes with porcine adipose-derived stem cells (ASCs was employed to facilitate chondrogenic differentiation of ASCs during dynamic culture in cryogel scaffolds. By replacing half of the chondrocytes with ASCs during co-culture, we could obtain similar production of ECM (GAGs and Col II and expression of Col II, but reduced expression of Col I, Col X and TNF-α. Subcutaneous implantation of cells/scaffold constructs in nude mice after mono-culture (chondrocytes or ASCs or co-culture (chondrocytes + ASCs and subject to static or dynamic culture condition in vitro for 14 days was tested for tissue-engineering applications. The constructs were retrieved 8 weeks post-implantation for histological analysis by Alcian blue, Safranin O and Col II immunohistochemical staining. The most abundant ectopic cartilage tissue was found for the chondrocytes and chondrocytes + ASCs groups using dynamic culture, which showed similar neo-cartilage formation capability with half of the

  7. 40 CFR 721.1820 - Bisphenol derivative.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Bisphenol derivative. 721.1820 Section... Substances § 721.1820 Bisphenol derivative. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as bisphenol derivative (PMN No. P-92-509) is...

  8. 45 CFR 601.5 - Derivative classification.

    Science.gov (United States)

    2010-10-01

    ... CLASSIFICATION AND DECLASSIFICATION OF NATIONAL SECURITY INFORMATION § 601.5 Derivative classification. Distinct... 45 Public Welfare 3 2010-10-01 2010-10-01 false Derivative classification. 601.5 Section 601.5... classification guide, need not possess original classification authority. (a) If a person who applies derivative...

  9. 5 CFR 1312.7 - Derivative classification.

    Science.gov (United States)

    2010-01-01

    ..., DOWNGRADING, DECLASSIFICATION AND SAFEGUARDING OF NATIONAL SECURITY INFORMATION Classification and Declassification of National Security Information § 1312.7 Derivative classification. A derivative classification... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Derivative classification. 1312.7 Section...

  10. 6 CFR 7.26 - Derivative classification.

    Science.gov (United States)

    2010-01-01

    ... 6 Domestic Security 1 2010-01-01 2010-01-01 false Derivative classification. 7.26 Section 7.26 Domestic Security DEPARTMENT OF HOMELAND SECURITY, OFFICE OF THE SECRETARY CLASSIFIED NATIONAL SECURITY INFORMATION Classified Information § 7.26 Derivative classification. (a) Derivative classification is defined...

  11. 22 CFR 9.6 - Derivative classification.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Derivative classification. 9.6 Section 9.6 Foreign Relations DEPARTMENT OF STATE GENERAL SECURITY INFORMATION REGULATIONS § 9.6 Derivative classification. (a) Definition. Derivative classification is the incorporating, paraphrasing, restating or...

  12. Quantum derivatives and the Schroedinger equation

    International Nuclear Information System (INIS)

    Ben Adda, Faycal; Cresson, Jacky

    2004-01-01

    We define a scale derivative for non-differentiable functions. It is constructed via quantum derivatives which take into account non-differentiability and the existence of a minimal resolution for mean representation. This justify heuristic computations made by Nottale in scale-relativity. In particular, the Schroedinger equation is derived via the scale-relativity principle and Newton's fundamental equation of dynamics

  13. 12 CFR 563.172 - Financial derivatives.

    Science.gov (United States)

    2010-01-01

    ... underlying assets, indices, or reference rates. The most common types of financial derivatives are futures, forward commitments, options, and swaps. A mortgage derivative security, such as a collateralized mortgage... 12 Banks and Banking 5 2010-01-01 2010-01-01 false Financial derivatives. 563.172 Section 563.172...

  14. Deriving the bond pricing equation

    Directory of Open Access Journals (Sweden)

    Kožul Nataša

    2014-01-01

    Full Text Available Given the recent focus on Eurozone debt crisis and the credit rating downgrade not only of US debt, but that of other countries and many UK major banking institutions, this paper aims to explain the concept of bond yield, its different measures and bond pricing equation. Yields on capital market instruments are rarely quoted on the same basis, which makes direct comparison between different as investment choices impossible. Some debt instruments are quoted on discount basis, whilst coupon-bearing ones accrue interest differently, offer different compounding opportunities, have different coupon payment frequencies, and manage non-business day maturity dates differently. Moreover, rules governing debt vary across countries, markets and currencies, making yield calculation and comparison a rather complex issue. Thus, some fundamental concepts applicable to debt instrument yield measurement, with focus on bond equation, are presented here. In addition, bond equation expressed in annuity form and used to apply Newton-Raphson algorithm to derive true bond yield is also shown.

  15. Classical gravity with higher derivatives

    International Nuclear Information System (INIS)

    Stelle, K.S.

    1978-01-01

    Inclusion of the four-derivative terms ∫Rsub(μν) Rsup(μν)(-g)sup(1/2) and ∫R 2 (-g)sup(1/2) into the gravitational action gives a class of effectively multimass models of gravity. In addition to the usual massless excitations of the field, there are now, for general amounts of the two new terms, massive spin-two and massive scalar excitations, with a total of eight degrees of freedom. The massive spin-two part of the field has negative energy. Specific ration of the two new terms give models with either the massive tensor or the massive scalar missing, with correspondingly fewer degrees of freedom. The static, linearized solutions of the field equations are combinations of Newtonian and Yukawa potentials. Owing to the Yukawa form of the corrections, observational evidence sets only very weak restrictions on the new masses. The acceptable static metric solutions in the full nonlinear theory are regular at the origin. The dynamical content of the linearized field is analyzed by reducing the fourth-order field equations to separated second-order equations, related by coupling to external sources in a fixed ratio. This analysis is carried out into the various helicity components using the transverse-traceless decomposition of the metric. (author)

  16. The estimation of derived limits

    International Nuclear Information System (INIS)

    Harrison, N.T.; Bryant, P.M.; Clarke, R.H.; Morley, F.

    1979-08-01

    In practical radiation protection, it is often necessary to calculate limits of intake of radionuclides associated with various quantities; such limits are needed, for example, to assess the adequacy of the control of environmental contamination. In publication 26 of the International Commission on Radiological Protection (ICRP), these limits, when related to the basic limits of dose-equivalent by a defined model, are referred to as Derived Limits (DLs). In the present report the principles to be adopted by the Board in calculating DLs to be recommended for general application within the United Kingdom are outlined. DLs will be recommended for a wide range of radionuclides and for circumstances relevant to the workplace, and, more frequently, the general environment. The latter will include DLs in foodstuffs and associated environmental materials, such as soil and grass, and DLs for discharges from stacks. DLs will be related to dose equivalents for workers or members of the public for stochastic or non-stochastic effects as appropriate. Consideration will be given to relevant data on radiosensitivity, metabolism and dosimetry for children and to the physicochemical forms of radionuclides. (author)

  17. Option Derivatives in Electricity Hedging

    Directory of Open Access Journals (Sweden)

    P. Pavlátka

    2010-01-01

    Full Text Available Despite the high volatility of electricity prices, there is still little demand for electricity power options, and the liquidity on the power exchanges of these power derivatives is quite low. One of the reasons is the uncertainty about how to evaluate these electricity options and about finding the right fair value of this product. Hedging of electricity is associated mainly with products such as futures and forwards. However, due to new trends in electricity trading and hedging, it is also useful to think more about options and the principles for working with them in hedging various portfolio positions and counterparties. We can quite often encounter a situation when we need to have a perfect hedge for our customer’s (end user consuming electricity portfolio, or we have to evaluate the volumetric risk (inability of a customer to predict consumption, which is very similar to selling options. Now comes the moment to compare the effects of using options or futures to hedge these open positions. From a practical viewpoint, the Black-Scholes prices appear to be the best available and the simplest method for evaluating option premiums, but there are some limitations that we have to consider.

  18. 21 CFR 184.1685 - Rennet (animal-derived) and chymosin preparation (fermentation-derived).

    Science.gov (United States)

    2010-04-01

    ... (fermentation-derived). 184.1685 Section 184.1685 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... (animal-derived) and chymosin preparation (fermentation-derived). (a)(1) Rennet and bovine rennet are... clear solution containing the active enzyme chymosin (E.C. 3.4.23.4). It is derived, via fermentation...

  19. Mucoadhesive nanoparticles made of thiolated quaternary chitosan crosslinked with hyaluronan.

    Science.gov (United States)

    Zambito, Ylenia; Felice, Francesca; Fabiano, Angela; Di Stefano, Rossella; Di Colo, Giacomo

    2013-01-30

    Mucoadhesive polymeric nanoparticles intended for drug transport across the gastrointestinal mucosa were prepared from quaternary ammonium-chitosan conjugates synthesised from reduced-MW chitosan (32 kDa). Conjugates contained pendant moieties of 2-4 adjacent diethyl-dimethylene-ammonium groups substituted on repeating units (26-55%). Conjugates were thiolated via amide bonds with thioglycolic acid to yield products with thiol content in the 35-87 μmol/g range. Nanoparticles with mean size in the 270-370 nm range and positive zeta-potential (+3.7 to +12.5 mV) resulted from ionotropic gelation of the thiolated conjugates with de-polymerised hyaluronic acid (470 kDa). The nanoparticles were fairly stable in size and thiol content and showed a significant mucoadhesivity, matching and even exceeding that of the constituent polymers. Nanoparticles were internalised by endothelial progenitor cells in direct relation to their surface charge intensity. Nanoparticle uptake significantly improved cell viability and resistance to oxidation. The lyophilised nanoparticles were re-dispersible and could make a manageable formulation for oral use. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. Desmosine-Inspired Cross-Linkers for Hyaluronan Hydrogels

    Science.gov (United States)

    Hagel, Valentin; Mateescu, Markus; Southan, Alexander; Wegner, Seraphine V.; Nuss, Isabell; Haraszti, Tamás; Kleinhans, Claudia; Schuh, Christian; Spatz, Joachim P.; Kluger, Petra J.; Bach, Monika; Tussetschläger, Stefan; Tovar, Günter E. M.; Laschat, Sabine; Boehm, Heike

    2013-06-01

    We designed bioinspired cross-linkers based on desmosine, the cross-linker in natural elastin, to prepare hydrogels with thiolated hyaluronic acid. These short, rigid cross-linkers are based on pyridinium salts (as in desmosine) and can connect two polymer backbones. Generally, the obtained semi-synthetic hydrogels are form-stable, can withstand repeated stress, have a large linear-elastic range, and show strain stiffening behavior typical for biopolymer networks. In addition, it is possible to introduce a positive charge to the core of the cross-linker without affecting the gelation efficiency, or consequently the network connectivity. However, the mechanical properties strongly depend on the charge of the cross-linker. The properties of the presented hydrogels can thus be tuned in a range important for engineering of soft tissues by controlling the cross-linking density and the charge of the cross-linker.

  1. Hyaluronan Oligosaccharides for the Promotion of Remyelination (Revised)

    Science.gov (United States)

    2012-10-01

    would be both safe and efficacious as a therapy or co- therapy to promote remyelination. REFERENCES Botzki  A,  Rigden  DJ,  Braun...with reduced brightness and contrast, demonstrating the morphology within lesions. Arrows in C and D indicate regions of persistent lyso- lecithin ... therapies for the promotion of remyelination. Acknowledgment This work was supported by NIH (NINDS) grants NS056234 (L.S.S.), NS054044, and NS045737-06S1

  2. Atomistic fingerprint of hyaluronan-CD44 binding

    Czech Academy of Sciences Publication Activity Database

    Vuorio, J.; Vattulainen, I.; Martinez-Seara, Hector

    2017-01-01

    Roč. 13, č. 7 (2017), č. článku e1005663. ISSN 1553-734X R&D Projects: GA ČR(CZ) GBP208/12/G016 Institutional support: RVO:61388963 Keywords : molecular simulations * protein interaction * N-glycosylation Subject RIV: CF - Physical ; Theoretical Chemistry OBOR OECD: Physical chemistry Impact factor: 4.542, year: 2016 http://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1005663

  3. Targeted Delivery of Hyaluronan-Immobilized Magnetic Ceramic Nanocrystals.

    Science.gov (United States)

    Wu, Hsi-Chin; Wang, Tzu-Wei; Hsieh, Shun-Yu; Sun, Jui-Sheng; Kang, Pei-Leun

    2016-01-01

    Effective cancer therapy relies on delivering the therapeutic agent precisely to the target site to improve the treatment outcome and to minimize side effects. Although surgery, chemotherapy, and radiotherapy are the standard methods commonly used in clinics, hyperthermia has been developed as a new and promising strategy for cancer therapy. In this study, magnetic bioceramic hydroxyapatite (mHAP) nanocrystals have been developed as heat mediator for intracellular hyperthermia. Hyaluronic acid (HA) modified mHAP nanocrystals are synthesized by a wet chemical precipitation process to achieve active targeting. The results demonstrate that the HA targeting moiety conjugated by a poly(ethylene glycol) (PEG) spacer arm is successfully immobilized on the surface of mHAP. The HA-modified mHAP possesses relatively good biocompatibility, an adequate biodegradation rate and superparamagnetic properties. The HA-modified mHAP could be localized and internalized into HA receptor-overexpressed malignant cells (e.g., MDA-MB-231 cell) and used as the heat generating agent for intracellular hyperthermia. The results from this study indicate that biocompatible HA-modified mHAP shows promise as a novel heat mediator and a specific targeting nanoagent for intracellular hyperthermia cancer therapy.

  4. Hyaluronan-Based Therapy for Metastatic Prostate Cancer

    Science.gov (United States)

    2016-09-01

    Importantly, the system can target CD44+ prostate cancer stem cells through intrinsic HA-CD44 receptor interactions and deliver drugs directly to...be released by enzymatic degradation via HYAL1. Importantly, the system can target CD44+ prostate cancer stem cells through intrinsic HA-CD44...In Situ DNA Strand Break Labeling (TUNEL assay)—Tumor tissues were recovered from euthanized animals. Sections (5 μm) were cut from 10% neutral

  5. Effect of hyaluronan on periodontitis: A clinical and histological study

    Directory of Open Access Journals (Sweden)

    Gauri Gontiya

    2012-01-01

    Full Text Available Background: Conventional, non-surgical periodontal therapy consists of supra- and subgingival tooth debridement. However, it is a technically demanding procedure and is not always efficient at eradicating all periodontal pathogens and in reducing inflammation. Therefore, local subgingival application of other chemotherapeutic agents may be used as an adjunct to non-surgical therapy. The aim of this study was to investigate the clinical and histological outcomes of local subgingival application of 0.2% hyaluronic acid gel (GENGIGEL® as an adjunct to scaling and root planing (SRP in chronic periodontitis patients. Materials and Methods: One hundred and twenty sites were chosen from 26 patients with chronic periodontitis (criteria being periodontal pockets ≥5mm. Experimental sites additionally received HA gel subgingivally at baseline, 1 st , 2 nd , and 3 rd week. Clinical parameters were re-assessed at 4 th , 6 th , and 12 th week. At 4 th week recall, a gingival biopsy was obtained from test and control site for histologic examination. Results: Intra-group analysis of all the clinical parameters at all sites from baseline to 4 th , 6 th , and 12 th week showed statistically significant changes. Experimental sites showed statistically significant improvement in Gingival index and Bleeding index at 6 th and 12 th week when compared with control sites. However, no statistically significant differences were observed in the PPD and RAL between control and experimental sites at 4 th , 6 th , and 12 th week time interval. No statistically significant association was found between the histological grading of the sites that received HA treatment. Conclusion: Subgingival placement of 0.2% HA gel along with SRP provided a significant improvement in gingival parameters. However, no additional benefit was found in periodontal parameters. Histologically, experimental sites showed reduced inflammatory infiltrate, but it was not statistically significant.

  6. Drug Nanoparticle Formulation Using Ascorbic Acid Derivatives

    Directory of Open Access Journals (Sweden)

    Kunikazu Moribe

    2011-01-01

    Full Text Available Drug nanoparticle formulation using ascorbic acid derivatives and its therapeutic uses have recently been introduced. Hydrophilic ascorbic acid derivatives such as ascorbyl glycoside have been used not only as antioxidants but also as food and pharmaceutical excipients. In addition to drug solubilization, drug nanoparticle formation was observed using ascorbyl glycoside. Hydrophobic ascorbic acid derivatives such as ascorbyl mono- and di-n-alkyl fatty acid derivatives are used either as drugs or carrier components. Ascorbyl n-alkyl fatty acid derivatives have been formulated as antioxidants or anticancer drugs for nanoparticle formulations such as micelles, microemulsions, and liposomes. ASC-P vesicles called aspasomes are submicron-sized particles that can encapsulate hydrophilic drugs. Several transdermal and injectable formulations of ascorbyl n-alkyl fatty acid derivatives were used, including ascorbyl palmitate.

  7. Perturbative reduction of derivative order in EFT

    Science.gov (United States)

    Glavan, Dražen

    2018-02-01

    Higher derivative corrections are ubiquitous in effective field theories, which seemingly introduces new degrees of freedom at successive orders. This is actually an artefact of the implicit local derivative expansion defining effective field theories. We argue that higher derivative corrections that introduce additional degrees of freedom should be removed and their effects captured either by lower derivative corrections, or special combinations of higher derivative corrections not propagating extra degrees of freedom. Three methods adapted for this task are examined and field redefinitions are found to be most appropriate. First order higher derivative corrections in a scalar tensor theory are removed by field redefinition and it is found that their effects are captured by a subset of Horndeski theories. A case is made for restricting the effective field theory expansions in principle to only terms not introducing additional degrees of freedom.

  8. Weather Derivatives – Origin, Types and Application

    Directory of Open Access Journals (Sweden)

    Piotr Binkowski

    2008-01-01

    Full Text Available The number of companies that are exposed to the revenues loss risk caused by weather variability is still increasing. The businesses that are mostly exposed to weather risk are following: energy, agriculture, constructions and transport. That situation has initiated dynamic growth of weather derivatives markets as well as the awareness of the weather risk among the market participants. Presently, the weather derivatives markets evaluate rapidly in all the mature economies: USA, Asia and Europe. Constructing weather derivatives relies on qu- antifying climate factors in the form of indexes, what is quite simple task, more difficultly can be gathering precise historical data of required climate factors. Taking into consideration so far development of derivatives especially the financial derivatives based on different types of indexes financial market has at disposal wide range of different types of proved derivatives (futures, forward, options, swaps, which can be successfully utilised on the weather-driven markets both for hedging weather risk and speculating.

  9. Derivative pricing based on local utility maximization

    OpenAIRE

    Jan Kallsen

    2002-01-01

    This paper discusses a new approach to contingent claim valuation in general incomplete market models. We determine the neutral derivative price which occurs if investors maximize their local utility and if derivative demand and supply are balanced. We also introduce the sensitivity process of a contingent claim. This process quantifies the reliability of the neutral derivative price and it can be used to construct price bounds. Moreover, it allows to calibrate market models in order to be co...

  10. Chromatic Derivatives, Chromatic Expansions and Associated Spaces

    OpenAIRE

    Ignjatovic, Aleksandar

    2009-01-01

    This paper presents the basic properties of chromatic derivatives and chromatic expansions and provides an appropriate motivation for introducing these notions. Chromatic derivatives are special, numerically robust linear differential operators which correspond to certain families of orthogonal polynomials. Chromatic expansions are series of the corresponding special functions, which possess the best features of both the Taylor and the Shannon expansions. This makes chromatic derivatives and ...

  11. Quantile driven identification of structural derivatives

    OpenAIRE

    Andrew Chesher

    2001-01-01

    Conditions are derived under which there is local nonparametric identification of derivatives of structural equations in nonlinear triangular simultaneous equations systems. The attack on this problem is via conditional quantile functions and exploits local quantile independence conditions. The identification conditions include local analogues of the order and rank conditions familiar in the analysis of linear simultaneous equations models. The objects whose identification is sought are deriv...

  12. Isotope-labelled folic acid derivatives

    International Nuclear Information System (INIS)

    Lewin, N.; Wong, E.T.

    1976-01-01

    The suggestion deals with the production of folic acid derivatives suitable as indicators or tracers for analyses of serum folates. These folic acid derivatives contain folic acid which is bound by one or both carboxyl groups to the amino nitrogen of compounds such as, e.g., tyramine, glycyl tyrosine, tyrosine, or the methyl ester of tyrosine. The derivative obtained can be substituted by a gamma emitter, e.g. the iodine isotope I 125. The radioactive derivative is used in the method for the competitive protein bonding to determine endogenic folates in the serum. (UWI) [de

  13. Superstability for Generalized Module Left Derivations and Generalized Module Derivations on a Banach Module (I

    Directory of Open Access Journals (Sweden)

    Rassias JM

    2009-01-01

    Full Text Available We discuss the superstability of generalized module left derivations and generalized module derivations on a Banach module. Let be a Banach algebra and a Banach -module, and . The mappings , and are defined and it is proved that if (resp., is dominated by then is a generalized (resp., linear module- left derivation and is a (resp., linear module- left derivation. It is also shown that if (resp., is dominated by then is a generalized (resp., linear module- derivation and is a (resp., linear module- derivation.

  14. Derivative analyticity relations and asymptotic energies

    International Nuclear Information System (INIS)

    Fischer, J.

    1976-01-01

    On the basis of general principles of the S-matrix theory theorems are derived showing that derivative analyticity relations analogous to those of Bronzen, Kane and Sukhatme hold at asymptotic energies if the high-energy limits of certain physical quantities exist

  15. 28 CFR 17.26 - Derivative classification.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Derivative classification. 17.26 Section 17.26 Judicial Administration DEPARTMENT OF JUSTICE CLASSIFIED NATIONAL SECURITY INFORMATION AND ACCESS TO CLASSIFIED INFORMATION Classified Information § 17.26 Derivative classification. (a) Persons...

  16. 5 CFR 2500.5 - Derivative classification.

    Science.gov (United States)

    2010-01-01

    ... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Derivative classification. 2500.5 Section 2500.5 Administrative Personnel OFFICE OF ADMINISTRATION, EXECUTIVE OFFICE OF THE PRESIDENT INFORMATION SECURITY REGULATION § 2500.5 Derivative classification. The Office of Administration serves only as the...

  17. Derivative Securities and Financial Crisis in Romania

    OpenAIRE

    Gogoncea Ramona

    2012-01-01

    This paper aims to investigate the impact of the global financial crisis on the young Romanian market of derivative securities. It also describes the recent developments within Romanian capital market, in general, with focus on innovation in the field of derivative products.

  18. 46 CFR 503.55 - Derivative classification.

    Science.gov (United States)

    2010-10-01

    ... Security Program § 503.55 Derivative classification. (a) In accordance with Part 2 of Executive Order 12958 and directives of the Information Security Oversight Office, the incorporation, paraphrasing... 46 Shipping 9 2010-10-01 2010-10-01 false Derivative classification. 503.55 Section 503.55...

  19. Synthesis and Cytotoxicity of Novel Hexahydrothienocycloheptapyridazinone Derivatives

    Directory of Open Access Journals (Sweden)

    Irene Marchesi

    2009-09-01

    Full Text Available Designed as a new group of tricyclic molecules containing the thienocycloheptapyridazinone ring system, a number of 2N-substituted-hexahydrothienocycloheptapyridazinone derivatives were synthesized and their biological activity evaluated. Among the synthesized compounds, derivatives 7d and 7h were found to possess cytotoxic activity against non-small cell lung cancer and central nervous system cancer cell lines, respectively.

  20. "Nonmorphological Derivations" and the Four Main English ...

    African Journals Online (AJOL)

    This article addresses the problem of "nonmorphological derivations" in English and its consequences for pedagogical lexicography, i.e. learner's dictionaries. The term "nonmorphological derivation" refers to cases such as sun — solar, moon — lunar, cat — feline, and in general to all cases where instead of, or in addition ...

  1. Mesogenic benzothiazole derivatives with methoxy substituents

    Indian Academy of Sciences (India)

    Unknown

    2003-10-11

    Oct 11, 2003 ... literature. Barbera et al14 have synthesized 2-pyr- azoline derivatives and also studied the optical,. NLO and mesogenic properties of such materials. Highly polar thiophene-based liquid crystals have also been reported15 in the literature. However, fused ring heterocyclic derivatives which are two conden-.

  2. Deriving force field parameters for coordination complexes

    DEFF Research Database (Denmark)

    Norrby, Per-Ola; Brandt, Peter

    2001-01-01

    The process of deriving molecular mechanics force fields for coordination complexes is outlined. Force field basics are introduced with an emphasis on special requirements for metal complexes. The review is then focused on how to set up the initial model, define the target, refine the parameters......, and validate the final force field, Alternatives to force field derivation are discussed briefly....

  3. Weyl and Marchaud Derivatives: A Forgotten History

    Directory of Open Access Journals (Sweden)

    Fausto Ferrari

    2018-01-01

    Full Text Available In this paper, we recall the contribution given by Hermann Weyl and André Marchaud to the notion of fractional derivative. In addition, we discuss some relationships between the fractional Laplace operator and Marchaud derivative in the perspective to generalize these objects to different fields of the mathematics.

  4. Weyl and Marchaud derivatives: a forgotten history

    OpenAIRE

    Ferrari, Fausto

    2017-01-01

    In this paper, we recall the contribution given by Hermann Weyl and André Marchaud to the notion of fractional derivative. In addition, we discuss some relationships between the fractional Laplace operator and Marchaud derivative in the perspective to generalize these objects to different fields of the mathematics.

  5. New uracil derivatives and their biological activity

    International Nuclear Information System (INIS)

    Hudecova, D.; Striganova, J.; Chovanec, P.; Uher, M.

    1998-01-01

    Present study is concentrated to the research of antimicrobial activity of some derivatives of the uracil and 1,3-dimethyluracyl. The antimicrobial effects of these compounds have been tested on various strains of bacteria, yeasts, and filamentous fungi. The highest antimicrobial effects were found with dithiocarbamato-derivatives, which were effective against pathogenic and non-pathogenic bacteria (IC 50 = 7-25 μg cm -3 ), yeasts (IC 50 = 9-60 μg cm -3 ) and filamentous fungi.The most sensitive fungus to dithiocarbamato-derivatives was Botritis cinerea. It seems to be apparent that the presence of the -NH-C(S)-S- group in molecules of derivatives of uracil and and 1,3-dimethyluracyl influencing the incorporation rate [ 14 ]-adenine and 14 ]-leucine into the biomolecules and also markedly inhibits oxygen consumption (IC 50 = 58 μg cm -3 ). The same derivative demonstrated no mutagenic activity. (authors)

  6. Generalized Fractional Derivative Anisotropic Viscoelastic Characterization

    Directory of Open Access Journals (Sweden)

    Harry H. Hilton

    2012-01-01

    Full Text Available Isotropic linear and nonlinear fractional derivative constitutive relations are formulated and examined in terms of many parameter generalized Kelvin models and are analytically extended to cover general anisotropic homogeneous or non-homogeneous as well as functionally graded viscoelastic material behavior. Equivalent integral constitutive relations, which are computationally more powerful, are derived from fractional differential ones and the associated anisotropic temperature-moisture-degree-of-cure shift functions and reduced times are established. Approximate Fourier transform inversions for fractional derivative relations are formulated and their accuracy is evaluated. The efficacy of integer and fractional derivative constitutive relations is compared and the preferential use of either characterization in analyzing isotropic and anisotropic real materials must be examined on a case-by-case basis. Approximate protocols for curve fitting analytical fractional derivative results to experimental data are formulated and evaluated.

  7. Risk management, derivatives and shariah compliance

    Science.gov (United States)

    Bacha, Obiyathulla Ismath

    2013-04-01

    Despite the impressive growth of Islamic Banking and Finance (IBF), a number of weaknesses remain. The most important of this is perhaps the lack of shariah compliant risk management tools. While the risk sharing philosophy of Islamic Finance requires the acceptance of risk to justify returns, the shariah also requires adherents to avoid unnecessary risk-maysir. The requirement to avoid maysir is in essence a call for the prudent management of risk. Contemporary risk management revolves around financial engineering, the building blocks of which are financial derivatives. Despite the proven efficacy of derivatives in the management of risk in the conventional space, shariah scholars appear to be suspicious and uneasy with their use in IBF. Some have imposed outright prohibition of their use. This paper re-examines the issue of contemporary derivative instruments and shariah compliance. The shariah compatibility of derivatives is shown in a number of ways. First, by way of qualitative evaluation of whether derivatives can be made to comply with the key prohibitions of the sharia. Second, by way of comparing the payoff profiles of derivatives with risk sharing finance and Bai Salam contracts. Finally, the equivalence between shariah compliant derivatives like the IPRS and Islamic FX Currency Forwards with conventional ones is presented.

  8. On derived groups of division rings II

    International Nuclear Information System (INIS)

    Mahdavi Hezavehi, M.; Akbari Feyzaabaadi, S.; Mehraabaadi, M.; Hajie Abolhassan, H.

    1995-05-01

    Let D be a division ring with centre F and denote by D' the derived group (commutator subgroup) of D * = D - {0}. It is shown that if each element of D' is algebraic over F, then D is algebraic over F. It is also proved that each finite separable extension of F in D is of the form F(c) for some element c in the derived group D'. Using these results, it is shown that if each element of the derived group D' is of bounded degree over F, then D is finite dimensional over F. (author). 5 refs

  9. Derivation of GFDM Based on OFDM Principles

    Energy Technology Data Exchange (ETDEWEB)

    Hussein Moradi; Behrouz Farhang-Boroujeny

    2015-06-01

    This paper starts with discussing the principle based on which the celebrated orthogonal frequency division multiplexing (OFDM) signals are constructed. It then extends the same principle to construct the newly introduced generalized frequency division multiplexing (GFDM) signals. This novel derivation sheds light on some interesting properties of GFDM. In particular, our derivation seamlessly leads to an implementation of GFDM transmitter which has significantly lower complexity than what has been reported so far. Our derivation also facilitates a trivial understanding of how GFDM (similar to OFDM) can be applied in MIMO channels.

  10. Mechanism of Platinum Derivatives Induced Kidney Injury

    Directory of Open Access Journals (Sweden)

    Feifei YAN

    2015-09-01

    Full Text Available Platinum derivatives are the most widely used chemotherapeutic agents to treat solid tumors including ovarian, head and neck, and testicular germ cell tumors, lung cancer, and colorectal cancer. Two major problems exist, however, in the clinic use of platinum derivatives. One is the development of tumor resistance to the drug during therapy, leading to treatment failure. The other is the drug’s toxicity such as the cisplatin’s nephrotoxicity, which limits the dose that can be administered. This paper describes the mechanism of platinum derivatives induced kidney injury.

  11. MANGROVE-DERIVED NUTRIENTS AND CORAL REEFS

    Science.gov (United States)

    Understanding the consequences of the declining global cover of mangroves due to anthropogenic disturbance necessitates consideration of how mangrove-derived nutrients contribute to threatened coral reef systems. We sampled potential sources of organic matter and a suite of sessi...

  12. Preparation of 7-substituted ginkgolide derivatives

    DEFF Research Database (Denmark)

    Vogensen, Stine Byskov; Strømgaard, Kristian; Shindou, Hideo

    2003-01-01

    alpha-fluoro ginkgolide B was equipotent to ginkgolide B underlining the critical importance of the 7-position of ginkgolides for PAF receptor activity. Herein we describe the synthesis of a series of ginkgolide B derivatives with modifications at the 7-position and the pharmacological evaluation...... of these derivatives as assayed by cloned PAF receptors. In two cases nucleophilic attack on a 7beta-O-triflate ginkgolide B did not lead to the expected products, but gave rise to two unprecedented ginkgolide derivatives, one with a novel rearranged skeleton. Furthermore, standard reduction of 7alpha-azido ginkgolide......-chloro ginkgolide B, the most potent nonaromatic ginkgolide derivative described to date with a K(i) value of 110 nM....

  13. Patient-Derived Antibody Targets Tumor Cells

    Science.gov (United States)

    An NCI Cancer Currents blog on an antibody derived from patients that killed tumor cells in cell lines of several cancer types and slowed tumor growth in mouse models of brain and lung cancer without evidence of side effects.

  14. Overtone spectroscopy of some benzaldehyde derivatives

    Indian Academy of Sciences (India)

    internuclear distances for the aryl CH bond in the different molecules. The small variation observed in these distances is ..... [6] D N Singh, Vibrational spectra and force fields for some benzaldehyde derivatives, Ph.D. Thesis. (Banaras Hindu ...

  15. SYNTHESIS OF SUBSTITUTED FLAVONE DERIVATIVES AS ...

    African Journals Online (AJOL)

    Preferred Customer

    Flavone (2-phenylchromone) derivatives are naturally occurring heterocyclic compound belongs to the flavanoid group. It showed significant role in pharmaceutical effects [1] including leishmanicidal activity, oviposter stimulant phytoalexins, anti-HIV, vasodilator, antiviral, anti- oxidants, bactericidal, DNA cleavage, ...

  16. Synthesis of Lipophilic Guanine N-9 Derivatives

    DEFF Research Database (Denmark)

    Wamberg, Michael C; Pedersen, Pernille L; Löffler, Philipp M G

    2017-01-01

    the synthesis of five new guanine-N9 derivatives bearing alkyl chains with different attachment chemistries, exploiting a synthesis pathway that allows a flexible choice of hydrophobic anchor moiety. In this study, these guanine derivatives were functionalized with C10 chains for insertion into decanoic acid...... bilayer structures, in which both alkyl chain length and attachment chemistry determined their interaction with the membrane. Incubation of these guanine conjugates, as solids, with a decanoic acid vesicle suspension, showed that ether- and triazole-linked C10 anchors yielded an increased partitioning...... of the guanine derivative into the membranous phase compared to directly N-9-linked saturated alkyl anchors. Decanoic acid vesicle membranes could be loaded with up to 5.5 mol % guanine derivative, a 6-fold increase over previous limits. Thus, anchor chemistries exhibiting favorable interactions with a bilayer...

  17. Particle production in higher derivative theory

    Indian Academy of Sciences (India)

    Lemaitre–Robertson–Walker cosmological model during the early stages of the universe is analysed in the framework of higher derivative theory. The universe has been considered as an open thermodynamic system where particle production ...

  18. Langmuir-Blodgett Films of Graphene Derivatives

    DEFF Research Database (Denmark)

    Petersen, Søren Vermehren

    The work presented in this PhD thesis can be divided into two main categories: 1) Syn-thesis and Langmuir-Blodgett assembly of graphene derivatives and 2) Application and characterization of graphene derivatives as an interface material in molecular electron-ics. While the first category could...... be divided further, the synthesis and Langmuir-Blodgett results are intertwined in such a way that it would be more confusing to pre-sent them separately. The Langmuir-Blodgett deposition also played a crucial, but more isolated, part in the investigation of graphene derivatives as interface material....... Solution processable graphene in the form of chemically derived graphene has been synthesized through the modified Hummers method with subsequent reduction into reduced graphene oxide with hydrazine. The completeness of oxidation, the effect of the refinement steps and the reduction of the graphene oxide...

  19. 76 FR 4751 - Position Limits for Derivatives

    Science.gov (United States)

    2011-01-26

    ... saleable by long traders at its market value in normal cash marketing channels at the derivative contract's... Association, Futures Industry Association, GDF Suez Energy, Morgan Stanley, and NextEra Energy Power Marketing...

  20. Second derivative parallel block backward differentiation type ...

    African Journals Online (AJOL)

    Second derivative parallel block backward differentiation type formulas for Stiff ODEs. ... Log in or Register to get access to full text downloads. ... and the methods are inherently parallel and can be distributed over parallel processors. They are ...

  1. Novel hydroquinone derivatives alleviate algesia, inflammation and ...

    African Journals Online (AJOL)

    derivatives were synthesized and their structures were confirmed by .... to water. The baseline rectal temperature of all mice was noted by inserting a lubricated digital thermometer ... (PDB) and the binding site residues of the receptors were ...

  2. Plant-derived nanostructures: types and applications

    Science.gov (United States)

    Plant-derived nanostructures and nanoparticles (NPs) have functional applications in numerous disciplines such as health care, food and feed, cosmetics, biomedical science, energy science, drug-gene delivery, environmental health, and so on. Consequently, it is imperative for res...

  3. Anodic selective functionalization of cyclic amine derivatives

    OpenAIRE

    Onomura, Osamu

    2012-01-01

    Anodic reactions are desirable methods from the viewpoint of Green Chemistry, since no toxic oxidants are necessary for the oxidation of organic molecules. This review introduces usefulness of anodic oxidation and successive reaction for selective functionalization of cyclic amine derivatives.

  4. Regional Ecological Corridors - MLCCS derived 2008

    Data.gov (United States)

    Minnesota Department of Natural Resources — Identification of potential ecological corridors between the MLCCS derived ecological patches (ear_eco08py3). This was generated using cost / distance analysis,...

  5. MEAN OF MEDIAN ABSOLUTE DERIVATION TECHNIQUE MEAN ...

    African Journals Online (AJOL)

    eobe

    development of mean of median absolute derivation technique based on the based on the based on .... of noise mean to estimate the speckle noise variance. Noise mean property ..... Foraging Optimization,” International Journal of. Advanced ...

  6. An alternative to the flutter derivatives

    DEFF Research Database (Denmark)

    Andersen, Michael Styrk; Brandt, Anders

    A new simplified framework to study flutter and assess the full scale flutter wind speed is suggested. The flutter instability problem is reduced from a problem involving 8 flutter derivatives to only 4 coefficients. With this method it is possible to estimate the self-excited forces with increased...... precision by using stability diagrams. Furthermore, the physical transparency of the aerodynamic damping and stiffness terms is increased because the development in vertical and torsional damping and stiffness is analysed instead of flutter derivatives....

  7. Higher-derivative Lee-Wick unification

    International Nuclear Information System (INIS)

    Carone, Christopher D.

    2009-01-01

    We consider gauge coupling unification in Lee-Wick extensions of the Standard Model that include higher-derivative quadratic terms beyond the minimally required set. We determine how the beta functions are modified when some Standard Model particles have two Lee-Wick partners. We show that gauge coupling unification can be achieved in such models without requiring the introduction of additional fields in the higher-derivative theory and we comment on possible ultraviolet completions.

  8. Financial derivatives in power marketing: The basics

    International Nuclear Information System (INIS)

    Ramesh, V.C.; Ghosh, K.

    1996-01-01

    With the ongoing changes in the power industry worldwide, electricity is beginning to be traded like other commodities. The use of financial derivative instruments in power markets is on the rise. The purpose of this paper is to explain the role of these derivatives in risk management which is vital for survival in the increasingly competitive industry. Starting with the familiar cash markets, the paper discusses the basics of futures, options, and swap markets as applied to electric energy trading

  9. Higher derivative regularization and chiral anomaly

    International Nuclear Information System (INIS)

    Nagahama, Yoshinori.

    1985-02-01

    A higher derivative regularization which automatically leads to the consistent chiral anomaly is analyzed in detail. It explicitly breaks all the local gauge symmetry but preserves global chiral symmetry and leads to the chirally symmetric consistent anomaly. This regularization thus clarifies the physics content contained in the consistent anomaly. We also briefly comment on the application of this higher derivative regularization to massless QED. (author)

  10. Complexes of salicylic acid and its derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Tel' zhenskaya, P N; Shvarts, E M [AN Latvijskoj SSR, Riga. Inst. Neorganicheskoj Khimii

    1977-01-01

    A generalization and systematization have been made of literature data on complexing of various elements, including beryllium, cadmium, boron, indium, rare-earth elements, actinides, and transition elements with salicylic acid and it derivatives (amino-, nitro- and halosalicylic acids). The effect of the position and nature of the substitute, in the case of salicylic acid derivatives, on the complexing process is discussed. Certain physicochemical properties of the complexes under consideration are described along with data indicative of their stability.

  11. On computing Laplace's coefficients and their derivatives.

    Science.gov (United States)

    Gerasimov, I. A.; Vinnikov, E. L.

    The algorithm of computing Laplace's coefficients and their derivatives is proposed with application of recurrent relations. The A.G.M.-method is used for the calculation of values L0(0), L0(1). The FORTRAN-program corresponding to the algorithm is given. The precision control was provided with numerical integrating by Simpsons method. The behavior of Laplace's coefficients and their third derivatives whith varying indices K, n for fixed values of the α-parameter is presented graphically.

  12. Weather Derivatives – Origin, Types and Application

    OpenAIRE

    Piotr Binkowski

    2008-01-01

    The number of companies that are exposed to the revenues loss risk caused by weather variability is still increasing. The businesses that are mostly exposed to weather risk are following: energy, agriculture, constructions and transport. That situation has initiated dynamic growth of weather derivatives markets as well as the awareness of the weather risk among the market participants. Presently, the weather derivatives markets evaluate rapidly in all the mature economies: USA, Asia and Europ...

  13. A note on derivations in semiprime rings

    Directory of Open Access Journals (Sweden)

    Joso Vukman

    2005-01-01

    Full Text Available We prove in this note the following result. Let n>1 be an integer and let R be an n!-torsion-free semiprime ring with identity element. Suppose that there exists an additive mapping D:R→R such that D(xn=∑j=1nxn−jD(xxj−1 is fulfilled for all x∈R. In this case, D is a derivation. This research is motivated by the work of Bridges and Bergen (1984. Throughout, R will represent an associative ring with center Z(R. Given an integer n>1, a ring R is said to be n-torsion-free if for x∈R, nx=0 implies that x=0. Recall that a ring R is prime if for a,b∈R, aRb=(0 implies that either a=0 or b=0, and is semiprime in case aRa=(0 implies that a=0. An additive mapping D:R→R is called a derivation if D(xy=D(xy+xD(y holds for all pairs x,y∈R and is called a Jordan derivation in case D(x2=D(xx+xD(x is fulfilled for all x∈R. Every derivation is a Jordan derivation. The converse is in general not true. A classical result of Herstein (1957 asserts that any Jordan derivation on a prime ring with characteristic different from two is a derivation. A brief proof of Herstein's result can be found in 1988 by Brešar and Vukman. Cusack (1975 generalized Herstein's result to 2-torsion-free semiprime rings (see also Brešar (1988 for an alternative proof. For some other results concerning derivations on prime and semiprime rings, we refer to Brešar (1989, Vukman (2005, Vukman and Kosi-Ulbl (2005.

  14. Introduction of Credit Derivatives and Valuation of Credit Default Swap

    OpenAIRE

    Han, Lu

    2006-01-01

    The credit derivative market was established at the beginning of the 1990s since the emergence of credit derivatives fits the rapid development of the whole derivatives market. However, compare to other derivative market, this market is still small and incomplete. As with other derivatives, credit derivatives can be used to either take more risk or hedge it, hence various credit derivatives instruments are accepted and widely used by market participants such as banks, insurance companies, etc...

  15. Multiscale analysis of the CMB temperature derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Marcos-Caballero, A.; Martínez-González, E.; Vielva, P., E-mail: marcos@ifca.unican.es, E-mail: martinez@ifca.unican.es, E-mail: vielva@ifca.unican.es [Instituto de Física de Cantabria, CSIC-Universidad de Cantabria, Avda. de los Castros s/n, 39005 Santander, Spain. (Spain)

    2017-02-01

    We study the Planck CMB temperature at different scales through its derivatives up to second order, which allows one to characterize the local shape and isotropy of the field. The problem of having an incomplete sky in the calculation and statistical characterization of the derivatives is addressed in the paper. The analysis confirms the existence of a low variance in the CMB at large scales, which is also noticeable in the derivatives. Moreover, deviations from the standard model in the gradient, curvature and the eccentricity tensor are studied in terms of extreme values on the data. As it is expected, the Cold Spot is detected as one of the most prominent peaks in terms of curvature, but additionally, when the information of the temperature and its Laplacian are combined, another feature with similar probability at the scale of 10{sup o} is also observed. However, the p -value of these two deviations increase above the 6% when they are referred to the variance calculated from the theoretical fiducial model, indicating that these deviations can be associated to the low variance anomaly. Finally, an estimator of the directional anisotropy for spinorial quantities is introduced, which is applied to the spinors derived from the field derivatives. An anisotropic direction whose probability is <1% is detected in the eccentricity tensor.

  16. Structure Activity Relationship of Brevenal Hydrazide Derivatives

    Directory of Open Access Journals (Sweden)

    Allan Goodman

    2014-03-01

    Full Text Available Brevenal is a ladder frame polyether produced by the dinoflagellate Karenia brevis. This organism is also responsible for the production of the neurotoxic compounds known as brevetoxins. Ingestion or inhalation of the brevetoxins leads to adverse effects such as gastrointestinal maladies and bronchoconstriction. Brevenal shows antagonistic behavior to the brevetoxins and shows beneficial attributes when administered alone. For example, in an asthmatic sheep model, brevenal has been shown to increase tracheal mucosal velocity, an attribute which has led to its development as a potential treatment for Cystic Fibrosis. The mechanism of action of brevenal is poorly understood and the exact binding site has not been elucidated. In an attempt to further understand the mechanism of action of brevenal and potentially develop a second generation drug candidate, a series of brevenal derivatives were prepared through modification of the aldehyde moiety. These derivatives include aliphatic, aromatic and heteroaromatic hydrazide derivatives. The brevenal derivatives were tested using in vitro synaptosome binding assays to determine the ability of the compounds to displace brevetoxin and brevenal from their native receptors. A sheep inhalation model was used to determine if instillation of the brevenal derivatives resulted in bronchoconstriction. Only small modifications were tolerated, with larger moieties leading to loss of affinity for the brevenal receptor and bronchoconstriction in the sheep model.

  17. PROCEDURES FOR THE DERIVATION OF EQUILIBRIUM ...

    Science.gov (United States)

    This equilibrium partitioning sediment benchmark (ESB) document describes procedures to derive concentrations for 32 nonionic organic chemicals in sediment which are protective of the presence of freshwater and marine benthic organisms. The equilibrium partitioning (EqP) approach was chosen because it accounts for the varying biological availability of chemicals in different sediments and allows for the incorporation of the appropriate biological effects concentration. This provides for the derivation of benchmarks that are causally linked to the specific chemical, applicable across sediments, and appropriately protective of benthic organisms. EqP can be used to calculate ESBs for any toxicity endpoint for which there are water-only toxicity data; it is not limited to any single effect endpoint. For the purposes of this document, ESBs for 32 nonionic organic chemicals, including several low molecular weight aliphatic and aromatic compounds, pesticides, and phthalates, were derived using Final Chronic Values (FCV) from Water Quality Criteria (WQC) or Secondary Chronic Values (SCV) derived from existing toxicological data using the Great Lakes Water Quality Initiative (GLI) or narcosis theory approaches. These values are intended to be the concentration of each chemical in water that is protective of the presence of aquatic life. For nonionic organic chemicals demonstrating a narcotic mode of action, ESBs derived using the GLI approach specifically for fres

  18. Studies on Synthesis of Some Novel Heterocyclic Azlactone Derivatives and Imidazolinone Derivatives and their Antimicrobial Activity

    Directory of Open Access Journals (Sweden)

    Rakesh N. Mistry

    2005-01-01

    Full Text Available p - Methyl benzoic acid on reaction with phosphorus pentachloride gives p - methyl benzoyl chloride derivative which on condensation with glycine gives p - methyl benzoyl glycine derivative. Now, this p - methyl benzoyl glycine derivative on condensation with various substituted aldehydes gives corresponding substituted 4 - [aryl methylidine] - 2 - [p - methyl phenyl] - oxazole - 5 - one derivatives [1(a-j]. Further, these derivatives [1(a-j] on condensation with 4 , 4’ - diamino diphenyl sulphone gives corresponding substituted imidazolinone - dibenzsulphone derivatives [2(a-j], on condensation with 4 , 4’ - diamino diphenyl methane gives corresponding substituted imidazolinone - dibenzmethane derivatives [3(a-j], on condensation with 4,4’- diamino benzanilide gives corresponding substituted imidazolinone - benzanilide derivatives [4(a-j] and on condensation with 2 - amino pyridine gives corresponding substituted imidazolinone - pyridine derivatives [5(a-j] respectively. Structure elucidation of synthesised compounds has been made on the basis of elemental analysis, I.R. spectral studies and 1H N.M.R. spectral studies. The antimicrobial activity of the synthesised compounds has been studied against the cultures “Staphylococcus aureus”, “Escherichia coli” and “Candela albicans”.

  19. Adaptive synchronization of the complex dynamical network with non-derivative and derivative coupling

    Energy Technology Data Exchange (ETDEWEB)

    Xu Yuhua, E-mail: yuhuaxu2004@163.co [College of Information Science and Technology, Donghua University, Shanghai 201620 (China) and Department of Maths, Yunyang Teachers' College, Hubei 442000 (China); Zhou Wuneng, E-mail: wnzhou@163.co [College of Information Science and Technology, Donghua University, Shanghai 201620 (China); Fang Jian' an [College of Information Science and Technology, Donghua University, Shanghai 201620 (China); Sun Wen [School of Mathematics and Information, Yangtze University, Hubei Jingzhou 434023 (China)

    2010-04-05

    This Letter investigates the synchronization of a general complex dynamical network with non-derivative and derivative coupling. Based on LaSalle's invariance principle, adaptive synchronization criteria are obtained. Analytical result shows that under the designed adaptive controllers, a general complex dynamical network with non-derivative and derivative coupling can asymptotically synchronize to a given trajectory, and several useful criteria for synchronization are given. What is more, the coupling matrix is not assumed to be symmetric or irreducible. Finally, simulations results show the method is effective.

  20. 32 CFR 2400.14 - Use of derivative classification.

    Science.gov (United States)

    2010-07-01

    ... SECURITY PROGRAM Derivative Classification § 2400.14 Use of derivative classification. (a) Derivative... 32 National Defense 6 2010-07-01 2010-07-01 false Use of derivative classification. 2400.14... person who applies derivative classification markings believes that the paraphrasing, restating, or...

  1. Contact allergy to isoeugenol and its derivatives

    DEFF Research Database (Denmark)

    Tanaka, Susumu; Royds, C; Buckley, Christopher D

    2004-01-01

    A total of 2261 (808 male, 1453 female) consecutive patients attending contact dermatitis clinics were patch tested to isoeugenol and its derivatives listed in the EU Inventory of Fragrance Ingredients. Positive reactions were found to isoeugenol in 40, transisoeugenol in 40, isoeugenyl acetate...... and 15/16 of those to isoeugenyl phenylacetate but in none of those 6 positive to isoeugenyl methyl ether and in neither of those 2 positive to benzyl isoeugenyl ether. Concomitant contact allergy between isoeugenol and its derivatives may occur through chemical cross-reactivity or local skin metabolism...... of the derivatives. It is more commonly observed with the esters rather than the ethers. Isoeugenyl acetate has been proposed as an alternative to isoeugenol, but there is a high degree of concomitant reactivity with isoeugenol....

  2. Funding climate adaptation strategies with climate derivatives

    Directory of Open Access Journals (Sweden)

    L. Richard Little

    2015-01-01

    Full Text Available Climate adaptation requires large capital investments that could be provided not only by traditional sources like governments and banks, but also by derivatives markets. Such markets would allow two parties with different tolerances and expectations about climate risks to transact for their mutual benefit and, in so doing, finance climate adaptation. Here we calculate the price of a derivative called a European put option, based on future sea surface temperature (SST in Tasmania, Australia, with an 18 °C strike threshold. This price represents a quantifiable indicator of climate risk, and forms the basis for aquaculture industries exposed to the risk of higher SST to finance adaptation strategies through the sale of derivative contracts. Such contracts provide a real incentive to parties with different climate outlooks, or risk exposure to take a market assessment of climate change.

  3. Structure-activity relationships of bumetanide derivatives

    DEFF Research Database (Denmark)

    Pedersen, Kasper Lykke; Töllner, Kathrin; Römermann, Kerstin

    2015-01-01

    of diuretics such as bumetanide. Bumetanide was discovered by screening ∼5000 3-amino-5-sulfamoylbenzoic acid derivatives, long before NKCC2 was identified in the kidney. Therefore, structure-activity studies on effects of bumetanide derivatives on NKCC2 are not available. EXPERIMENTAL APPROACH: In this study......, the effect of a series of diuretically active bumetanide derivatives was investigated on human NKCC2 variant A (hNKCC2A) expressed in Xenopus laevis oocytes. KEY RESULTS: Bumetanide blocked hNKCC2A transport with an IC50 of 4 μM. There was good correlation between the diuretic potency of bumetanide and its...... of the structural requirements that determine relative potency of loop diuretics on human NKCC2 splice variants, and may lead to the discovery of novel high-ceiling diuretics....

  4. FINANCIAL DERIVATIVES - MEANINGS BEYOND SUBPRIME CRISIS STIGMA

    Directory of Open Access Journals (Sweden)

    FELICIA RAMONA BIRĂU

    2012-12-01

    Full Text Available Derivatives are designed as complex financial instruments and their main aim is to manage the risk associated with the underlying asset, in order to ensure against fluctuations in value, or to profit from periods of inactivity, instability or decline. In recent years financial derivatives have experienced a fulminant development and also they have been perceived as an effective lever of the modern economy. The subprime crisis was triggered by a quite significant financial infrastructure glitch, which coalesced around certain factors influence, such as : highly permissive regulation of financial markets, speculative bubbles, underperforming risk management, liquidity injections and structural imbalances. Despite the fact that is a innovative segment and quite difficult affordable as understanding level of the operation mechanisms, financial derivatives were only the tool triggering this global dimension crisis.

  5. Deriving Trading Rules Using Gene Expression Programming

    Directory of Open Access Journals (Sweden)

    Adrian VISOIU

    2011-01-01

    Full Text Available This paper presents how buy and sell trading rules are generated using gene expression programming with special setup. Market concepts are presented and market analysis is discussed with emphasis on technical analysis and quantitative methods. The use of genetic algorithms in deriving trading rules is presented. Gene expression programming is applied in a form where multiple types of operators and operands are used. This gives birth to multiple gene contexts and references between genes in order to keep the linear structure of the gene expression programming chromosome. The setup of multiple gene contexts is presented. The case study shows how to use the proposed gene setup to derive trading rules encoded by Boolean expressions, using a dataset with the reference exchange rates between the Euro and the Romanian leu. The conclusions highlight the positive results obtained in deriving useful trading rules.

  6. Additive derivations on algebras of measurable operators

    International Nuclear Information System (INIS)

    Ayupov, Sh.A.; Kudaybergenov, K.K.

    2009-08-01

    Given a von Neumann algebra M we introduce the so-called central extension mix(M) of M. We show that mix(M) is a *-subalgebra in the algebra LS(M) of all locally measurable operators with respect to M, and this algebra coincides with LS(M) if and only if M does not admit type II direct summands. We prove that if M is a properly infinite von Neumann algebra then every additive derivation on the algebra mix(M) is inner. This implies that on the algebra LS(M), where M is a type I ∞ or a type III von Neumann algebra, all additive derivations are inner derivations. (author)

  7. 5-Nitroimidazole Derivatives and their Antimicrobial Activity

    International Nuclear Information System (INIS)

    Khan, K.M.; Salar, U.; Yousuf, S.; Naz, F.

    2016-01-01

    5-Nitroimidazole derivatives 2-8 were synthesized from secnidazole. The syntheses were accomplished in two steps which start from the oxidation of secnidazole to the secnidazolone 1. Secnidazolone 1 was converted into its hydrazone derivative 2-8 by treating with different substituted acid hydrazide. Compounds 2-8 were evaluated for their antimicrobial activity against Gram-positive and Gram-negative bacteria, compounds 3 and 4 showed the significant activity against Staphylococcus epidermidis, however, compound 2 showed good inhibitions against Corynebacterium diphtheria when compared with the standard. Compound 3 showed good inhibitory potential against tested Gram-negative bacterial strains i.e. Enterobacter aerogene, Escherichia coli, Salmonella typhi, Salmonella paratyphi A, Shigella flexeneri and Vibrio choleriae. All synthetic derivatives were also tested against eight fungal stains, however, they were weekly active against Aspergillus flavus and Candida albican. The synthesized compounds were characterized by different spectroscopy techniques. (author)

  8. Structural studies of 4-aminoantipyrine derivatives

    Science.gov (United States)

    Cunha, Silvio; Oliveira, Shana M.; Rodrigues, Manoel T.; Bastos, Rodrigo M.; Ferrari, Jailton; de Oliveira, Cecília M. A.; Kato, Lucília; Napolitano, Hamilton B.; Vencato, Ivo; Lariucci, Carlito

    2005-10-01

    Reaction of 4-aminoantipyrine with acetylacetone, ethyl acetoacetate, benzoyl isothiocyanate, phenyl isothiocyanate, maleic anhydride and methoxymethylene Meldrum's acid afforded a series of new antipyrine derivatives. The antibacterial activity of the synthesized compounds against Micrococcus luteus ATCC 9341, Staphilococcus aureus ATCC 29737, and Escherichia coli ATCC 8739 was evaluated and the minimal inhibitory concentration determined. Modest activity was found only to the maleamic acid obtained from the reaction of 4-aminoantipyrine and maleic anhydride. 1H NMR investigation of this maleamic acid showed that it is slowly converted to the corresponding toxic maleimide. The structures of three derivatives were determined by X-ray diffraction analysis.

  9. Ethanolamine derivatives of dysprosium and holmium

    International Nuclear Information System (INIS)

    Gharia, K.S.; Singh, M.; Mathur, S.; Sankhla, B.S.

    1981-01-01

    The preparation and properties of dysprosium and holmium derivatives of mono-, di- and tri-ethanolamine derivatives are described. Compounds of general formulae: Ln(OPrsup(i)) 2 (mea), Ln(OPrsup(i))(mea) 2 , Ln(mea) 3 , Ln(OPrsup(i))(dea), Ln 2 (dea) 3 , Ln(dea)(deaH) and Ln(tea) (where Ln = Dy or Ho and mea, dea and tea are the anions of respective ethanolamine) were obtained and characterized by elemental analysis and IR spectra. (author)

  10. Geometric derivation of the quantum speed limit

    International Nuclear Information System (INIS)

    Jones, Philip J.; Kok, Pieter

    2010-01-01

    The Mandelstam-Tamm and Margolus-Levitin inequalities play an important role in the study of quantum-mechanical processes in nature since they provide general limits on the speed of dynamical evolution. However, to date there has been only one derivation of the Margolus-Levitin inequality. In this paper, alternative geometric derivations for both inequalities are obtained from the statistical distance between quantum states. The inequalities are shown to hold for unitary evolution of pure and mixed states, and a counterexample to the inequalities is given for evolution described by completely positive trace-preserving maps. The counterexample shows that there is no quantum speed limit for nonunitary evolution.

  11. A 'simple' hybrid model for power derivatives

    International Nuclear Information System (INIS)

    Lyle, Matthew R.; Elliott, Robert J.

    2009-01-01

    This paper presents a method for valuing power derivatives using a supply-demand approach. Our method extends work in the field by incorporating randomness into the base load portion of the supply stack function and equating it with a noisy demand process. We obtain closed form solutions for European option prices written on average spot prices considering two different supply models: a mean-reverting model and a Markov chain model. The results are extensions of the classic Black-Scholes equation. The model provides a relatively simple approach to describe the complicated price behaviour observed in electricity spot markets and also allows for computationally efficient derivatives pricing. (author)

  12. Novel Aflatoxin Derivatives and Protein Conjugates

    Directory of Open Access Journals (Sweden)

    Reinhard Niessner

    2007-03-01

    Full Text Available Aflatoxins, a group of structurally related mycotoxins, are well known for their toxic and carcinogenic effects in humans and animals. Aflatoxin derivatives and protein conjugates are needed for diverse analytical applications. This work describes a reliable and fast synthesis of novel aflatoxin derivatives, purification by preparative HPLC and characterisation by ESI-MS and one- and two-dimensional NMR. Novel aflatoxin bovine serum albumin conjugates were prepared and characterised by UV absorption and MALDI-MS. These aflatoxin protein conjugates are potentially interesting as immunogens for the generation of aflatoxin selective antibodies with novel specificities.

  13. Derived limits and their practical applications

    International Nuclear Information System (INIS)

    Minarik, F.

    1982-01-01

    Attention is devoted to the approach and methodological procedure in determining derived limits for surface contamination with special regard to external exposure of hands, inhalation of resuspended activity, contamination of the skin and with regard to ingestion of radioactive material from the skin. In the practical part of the article, results are given of measuring contamination by radionuclides 134 Cs, 133 Cs and 60 Co, and the resulting annual equivalent dose rates and their comparison with derived air contamination in the sense of ICRP Publ. No. 30. (author)

  14. Development of chitosan derivatives with anhydride maleic

    International Nuclear Information System (INIS)

    Silva, Solranny C.C.C.; Braz, Elton Marks de A.; Brito, Carla Adriana R. de S.; Silva, Durcilene A. da; Junior, Luiz de S.S.; Silva Filho, Edson C. da

    2015-01-01

    Chitosan was chemically modified with maleic anhydride in ratios of 1/2, 1/5 and 1/10 in the absence of solvents. The obtained derivatives were characterized by elemental analysis, FTIR, thermal analysis (TGA / DTG) and XRD where it was possible to prove the chemical modification. Elemental analysis showed an increase of the relation C / N with the increasing of the proportion of anhydrides. The FTIR showed the incorporation of the anhydride in the biopolymer structure. The thermal stability of the derivatives was lower in comparison to the polysaccharide and by XRD the modified materials were less crystalline. (author)

  15. High ethanol producing derivatives of Thermoanaerobacter ethanolicus

    Science.gov (United States)

    Ljungdahl, L.G.; Carriera, L.H.

    1983-05-24

    Derivatives of the newly discovered microorganism Thermoanaerobacter ethanolicus which under anaerobic and thermophilic conditions continuously ferment substrates such as starch, cellobiose, glucose, xylose and other sugars to produce recoverable amounts of ethanol solving the problem of fermentations yielding low concentrations of ethanol using the parent strain of the microorganism Thermoanaerobacter ethanolicus are disclosed. These new derivatives are ethanol tolerant up to 10% (v/v) ethanol during fermentation. The process includes the use of an aqueous fermentation medium, containing the substrate at a substrate concentration greater than 1% (w/v).

  16. Derivation of Mayer Series from Canonical Ensemble

    International Nuclear Information System (INIS)

    Wang Xian-Zhi

    2016-01-01

    Mayer derived the Mayer series from both the canonical ensemble and the grand canonical ensemble by use of the cluster expansion method. In 2002, we conjectured a recursion formula of the canonical partition function of a fluid (X.Z. Wang, Phys. Rev. E 66 (2002) 056102). In this paper we give a proof for this formula by developing an appropriate expansion of the integrand of the canonical partition function. We further derive the Mayer series solely from the canonical ensemble by use of this recursion formula. (paper)

  17. Derivation of Mayer Series from Canonical Ensemble

    Science.gov (United States)

    Wang, Xian-Zhi

    2016-02-01

    Mayer derived the Mayer series from both the canonical ensemble and the grand canonical ensemble by use of the cluster expansion method. In 2002, we conjectured a recursion formula of the canonical partition function of a fluid (X.Z. Wang, Phys. Rev. E 66 (2002) 056102). In this paper we give a proof for this formula by developing an appropriate expansion of the integrand of the canonical partition function. We further derive the Mayer series solely from the canonical ensemble by use of this recursion formula.

  18. Special relativity derived from spacetime magma.

    Science.gov (United States)

    Greensite, Fred

    2014-01-01

    We present a derivation of relativistic spacetime largely untethered from specific physical considerations, in constrast to the many physically-based derivations that have appeared in the last few decades. The argument proceeds from the inherent magma (groupoid) existing on the union of spacetime frame components [Formula: see text] and Euclidean [Formula: see text] which is consistent with an "inversion symmetry" constraint from which the Minkowski norm results. In this context, the latter is also characterized as one member of a class of "inverse norms" which play major roles with respect to various unital [Formula: see text]-algebras more generally.

  19. Special relativity derived from spacetime magma.

    Directory of Open Access Journals (Sweden)

    Fred Greensite

    Full Text Available We present a derivation of relativistic spacetime largely untethered from specific physical considerations, in constrast to the many physically-based derivations that have appeared in the last few decades. The argument proceeds from the inherent magma (groupoid existing on the union of spacetime frame components [Formula: see text] and Euclidean [Formula: see text] which is consistent with an "inversion symmetry" constraint from which the Minkowski norm results. In this context, the latter is also characterized as one member of a class of "inverse norms" which play major roles with respect to various unital [Formula: see text]-algebras more generally.

  20. Scale up of proteoliposome derived Cochleate production.

    Science.gov (United States)

    Zayas, Caridad; Bracho, Gustavo; Lastre, Miriam; González, Domingo; Gil, Danay; Acevedo, Reinaldo; del Campo, Judith; Taboada, Carlos; Solís, Rosa L; Barberá, Ramón; Pérez, Oliver

    2006-04-12

    Cochleate are highly stable structures with promising immunological features. Cochleate structures are usually obtaining from commercial lipids. Proteoliposome derived Cochleate are derived from an outer membrane vesicles of Neisseria meningitidis B. Previously, we obtained Cochleates using dialysis procedures. In order to increase the production process, we used a crossflow system (CFS) that allows easy scale up to obtain large batches in an aseptic environment. The raw material and solutions used in the production process are already approved for human application. This work demonstrates that CFS is very efficient process to obtain Cochleate structures with a yield of more than 80% and the immunogenicity comparable to that obtained by dialysis membrane.

  1. Urinary Derivations: Radiological Anatomy and Complications

    International Nuclear Information System (INIS)

    Rodriguez, A.; Escartin, I.; Zapater, C.; Riazuelo, G.; Canon, R.; Solanas, S.; Garcia de Jalon, A.

    2003-01-01

    Cystectomy with urine derivation is a common procedure in the treatment of transition cell carcinoma of the bladder. We present radiological findings (ultrasound scan, computerized tomography (CT) and urography) from the surgical reconstruction techniques most often performed by the Urology staff of our hospital as well as some of the complications which occur. The above-mentioned techniques are basically divided into two types: incontinent derivations, of which we highlight the Bicker-Wallace technique and continent ones. The latter can either be ortho topic, with urethral anastomosis (Hauptmann's technique), or heterotopic, with urine excretion through the anus (Mains II technique) or employing a self-catheter (Mainz I technique). (Author) 7 refs

  2. Derivation and characterization of a pig embryonic stem cell-derived exocrine pancreatic cell line

    Science.gov (United States)

    The establishment and initial characterization of a pig embryonic stem cell-derived pancreatic cell line, PICM-31, and a colony-cloned derivative cell line, PICM-31A, is described. The cell lines were propagated for several months at split ratios of 1:3 or 1:5 at each passage on STO feeder cells af...

  3. A class of constitutive relations with internal variable derivatives. Derivation from homogenization and initial value problem

    International Nuclear Information System (INIS)

    Andrieux, S.; Joussemet, M.; Lorentz, E.

    1996-01-01

    A general framework for deriving and using a class of constitutive laws incorporating spatial gradients of internal variables is presented. It uses two basic ingredients: a derivation of such models by homogenization techniques and a reformulation of the evolution equation at the scale of the whole structure. (orig.)

  4. 18 CFR 367.2440 - Account 244, Derivative instrument liabilities.

    Science.gov (United States)

    2010-04-01

    ..., Derivative instrument liabilities. This account must include the change in the fair value of all derivative instrument liabilities not designated as cash flow or fair value hedges. Account 426.5, Other deductions... the fair value of the derivative instrument. ...

  5. Optimal economic order quantity for buyer-distributor-vendor supply chain with backlogging derived without derivatives

    Science.gov (United States)

    Teng, Jinn-Tsair; Cárdenas-Barrón, Leopoldo Eduardo; Lou, Kuo-Ren; Wee, Hui Ming

    2013-05-01

    In this article, we first complement an inappropriate mathematical error on the total cost in the previously published paper by Chung and Wee [2007, 'Optimal the Economic Lot Size of a Three-stage Supply Chain With Backlogging Derived Without Derivatives', European Journal of Operational Research, 183, 933-943] related to buyer-distributor-vendor three-stage supply chain with backlogging derived without derivatives. Then, an arithmetic-geometric inequality method is proposed not only to simplify the algebraic method of completing prefect squares, but also to complement their shortcomings. In addition, we provide a closed-form solution to integral number of deliveries for the distributor and the vendor without using complex derivatives. Furthermore, our method can solve many cases in which their method cannot, because they did not consider that a squared root of a negative number does not exist. Finally, we use some numerical examples to show that our proposed optimal solution is cheaper to operate than theirs.

  6. Energy derivatives, experiences in derivative trading from the natural gas industry : back to basics

    International Nuclear Information System (INIS)

    Dittmer, G.; Coyle, T.

    1998-01-01

    Some basic facts regarding derivatives in the electric power industry were discussed based on experiences in the natural gas industry. Derivatives were described as financial instruments that have no value of their own but derive their value from other assets, such as commodities. Futures and Options are the two forms of derivatives. Electricity as a commodity was characterized, and a historical parallel was drawn between deregulation in the natural gas and electric power industry. Short term and long term factors impacting the market and market dynamics impacting derivatives were identified. The latter include: (1) volatility, (2) liquidity, (3) correlations, and (4) price discovery. In contrast to the natural gas market, the electricity market is considered as lacking liquidity and in need of moving farther along the maturity timeline. The question of natural gas/ electricity convergence was also addressed refs., tabs., figs

  7. Viscosupplementation for treatment of osteoarthritis: from initial discovery to current status and results.

    Science.gov (United States)

    Balazs, Endre A

    2004-01-01

    was introduced, the same highly elastoviscous hyaluronan solutions also were applied in ophthalmic surgery as viscosurgical tools to protect sensitive tissues in the eye during surgery and to be used as soft instruments for tissue manipulation. Modified hyaluronan products (gels) also were introduced for augmentation of the intercellular matrix in tissues (viscoaugmentation) and for separating tissues to prevent adhesions and excessive scar formation (viscoseparation). Hyaluronan and its derivatives (gels) also have been used for drug delivery. The therapeutic use of highly elastoviscous solutions and gels of hyaluronan and its derivatives to build intercellular matrices for supplementation, regeneration, and developing new tissues introduced the concept of matrix engineering into medical practice.

  8. Deriving simulators for hybrid Chi models

    NARCIS (Netherlands)

    Beek, van D.A.; Man, K.L.; Reniers, M.A.; Rooda, J.E.; Schiffelers, R.R.H.

    2006-01-01

    The hybrid Chi language is formalism for modeling, simulation and verification of hybrid systems. The formal semantics of hybrid Chi allows the definition of provably correct implementations for simulation, verification and realtime control. This paper discusses the principles of deriving an

  9. Unedoside derivatives in Nuxia and their biosynthesis

    DEFF Research Database (Denmark)

    Jensen, Søren Rosendal; Ravnkilde, Lene; Schripsema, Jan

    1998-01-01

    An investigation of two species of Nuxia showed that this genus is characterized by the presence of the eight-carbon iridoid glucoside unedoside and/or its derivatives. From N. floribunda unedoside, nuxioside (6-O-alpha-L-rhamnopyranosyl-unedoside) and 2 "-acetyl-3 "-cinnamoyl-nuxioside were...

  10. Significant exposures to isoeugenol derivatives in perfumes

    DEFF Research Database (Denmark)

    Rastogi, S.C.; Johansen, Jeanne Duus

    2008-01-01

    Background: Isoeugenol, an important fragrance allergen in consumers, has been restricted to 200 p.p.m. since 1998 according to guidelines issued by the fragrance industry. However, no decline in contact allergy to isoeugnol has been detected. It has been speculated that isoeugenol derivatives...

  11. Structural Studies of Some Binaphthyl Derivatives

    DEFF Research Database (Denmark)

    Thorup, Niels; Bjørnholm, T.; Bechgaard, K.

    1996-01-01

    Crystal structures of several 1,1'-binaphthyl derivatives have been determined. In particular compounds which at the 2,2' positions have either identical ethoxy groups or a closed bridged ether and furthermore have identical substitution at the 6,6' positions. The latter groups may be Br, CHO, CN...

  12. Generalized Jackknife Estimators of Weighted Average Derivatives

    DEFF Research Database (Denmark)

    Cattaneo, Matias D.; Crump, Richard K.; Jansson, Michael

    With the aim of improving the quality of asymptotic distributional approximations for nonlinear functionals of nonparametric estimators, this paper revisits the large-sample properties of an important member of that class, namely a kernel-based weighted average derivative estimator. Asymptotic...

  13. Synthesis and characterization of novel sulfonamides derivatives

    African Journals Online (AJOL)

    3Department of Chemistry, Comsat Institute of Information & Technology Riawind road. Lahore ... Newer sulfonamides and their derivatives has obtained great attention in pharmaceutical field in ... MS data was recorded on Finnigan MAT 112 mass ..... potent and orally active sulfonamide ETB selective antagonists. Bioorg.

  14. 17 CFR 200.506 - Derivative classification.

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 2 2010-04-01 2010-04-01 false Derivative classification. 200.506 Section 200.506 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION ORGANIZATION; CONDUCT AND ETHICS; AND INFORMATION AND REQUESTS Classification and Declassification of National Security...

  15. Fundamentals of futures, options, basis and derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Jones, D. [TD Securities Inc., Toronto, ON (Canada)

    1997-08-01

    Characteristic features of futures and options contracts, basis differentials and derivatives were defined and explained. A futures contract refers to an exchange-traded supply contract between a buyer and a seller where the buyer is obligated to take delivery and the seller is obligated to provide delivery of a fixed amount of a commodity at a predetermined price at a specified location. In contrast, an option contract gives the purchaser the right, but not the obligation, to buy or sell the underlying commodity at a certain price on or before an agreed date. Basis differential refers to the discount between two distinct delivery points to reflect the relative value of a commodity, such as natural gas, at those points. Advantages and disadvantages of futures and options contacts, the factors affecting options pricing, and basis differentials, and the methods of calculating basis differentials were described. The nature and intricacies of derivatives, their benefits, in particular their use as a tool for the effective management of the volatilities associated with the oil and gas industry were explained. Their shortcomings such as the high liquidity risk, were also described. Examples of derivative transactions were provided to illustrate the interrelationships of futures/options/derivatives, and their role in financial risk management.

  16. 32 CFR 2001.22 - Derivative classification.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 6 2010-07-01 2010-07-01 false Derivative classification. 2001.22 Section 2001.22 National Defense Other Regulations Relating to National Defense INFORMATION SECURITY OVERSIGHT OFFICE, NATIONAL ARCHIVES AND RECORDS ADMINISTRATION CLASSIFIED NATIONAL SECURITY INFORMATION...

  17. Interest Rate Derivative Pricing with Stochastic Volatility

    NARCIS (Netherlands)

    Chen, B.

    2012-01-01

    One purpose of exotic derivative pricing models is to enable financial institutions to quantify and manage their financial risk, arising from large books of portfolios. These portfolios consist of many non-standard exotic financial products. Risk is managed by means of the evaluation of sensitivity

  18. Microscopically derived free energy of dislocations

    NARCIS (Netherlands)

    Kooiman, M.; Hütter, M.; Geers, M.G.D.

    2015-01-01

    The dynamics of large amounts of dislocations is the governing mechanism in metal plasticity. The free energy of a continuous dislocation density profile plays a crucial role in the description of the dynamics of dislocations, as free energy derivatives act as the driving forces of dislocation

  19. Econometric Analysis of Financial Derivatives : An overview

    NARCIS (Netherlands)

    C-L. Chang (Chia-Lin); M.J. McAleer (Michael)

    2014-01-01

    markdownabstract__Abstract__ One of the fastest growing areas in empirical finance, and also one of the least rigorously analyzed, especially from a financial econometrics perspective, is the econometric analysis of financial derivatives, which are typically complicated and difficult to analyze.

  20. Econometric Analysis of Financial Derivatives: An Overview

    NARCIS (Netherlands)

    C-L. Chang (Chia-Lin); M.J. McAleer (Michael)

    2014-01-01

    markdownabstract__Abstract__ One of the fastest growing areas in empirical finance, and also one of the least rigorously analyzed, especially from a financial econometrics perspective, is the econometric analysis of financial derivatives, which are typically complicated and difficult to analyze.

  1. Nitration of Thiacalix[4]arene Derivatives

    Czech Academy of Sciences Publication Activity Database

    Lhoták, P.; Svoboda, J.; Stibor, I.; Sýkora, Jan

    2002-01-01

    Roč. 43, č. 41 (2002), s. 7413-7417 ISSN 0040-4039 R&D Projects: GA ČR GA104/00/1722 Keywords : derivatives * nitation of thiacalix[4]arene Subject RIV: CI - Industrial Chemistry, Chemical Engineering Impact factor: 2.357, year: 2002

  2. Deriving GENERIC from a generalized fluctuation symmetry

    NARCIS (Netherlands)

    Kraaij, R.; Lazarescu, A.; Maes, C.; Peletier, M.A.

    2018-01-01

    Much of the structure of macroscopic evolution equations for relaxation to equilibrium can be derived from symmetries in the dynamical fluctuations around the most typical trajectory. For example, detailed balance as expressed in terms of the Lagrangian for the path-space action leads to gradient

  3. Enabling quaternion derivatives: the generalized HR calculus

    Science.gov (United States)

    Xu, Dongpo; Jahanchahi, Cyrus; Took, Clive C.; Mandic, Danilo P.

    2015-01-01

    Quaternion derivatives exist only for a very restricted class of analytic (regular) functions; however, in many applications, functions of interest are real-valued and hence not analytic, a typical case being the standard real mean square error objective function. The recent HR calculus is a step forward and provides a way to calculate derivatives and gradients of both analytic and non-analytic functions of quaternion variables; however, the HR calculus can become cumbersome in complex optimization problems due to the lack of rigorous product and chain rules, a consequence of the non-commutativity of quaternion algebra. To address this issue, we introduce the generalized HR (GHR) derivatives which employ quaternion rotations in a general orthogonal system and provide the left- and right-hand versions of the quaternion derivative of general functions. The GHR calculus also solves the long-standing problems of product and chain rules, mean-value theorem and Taylor's theorem in the quaternion field. At the core of the proposed GHR calculus is quaternion rotation, which makes it possible to extend the principle to other functional calculi in non-commutative settings. Examples in statistical learning theory and adaptive signal processing support the analysis. PMID:26361555

  4. Initial value formulation of higher derivative gravity

    International Nuclear Information System (INIS)

    Noakes, D.R.

    1983-01-01

    The initial value problem is considered for the conformally coupled scalar field and higher derivative gravity, by expressing the equations of each theory in harmonic coordinates. For each theory it is shown that the (vacuum) equations can take the form of a diagonal hyperbolic system with constraints on the initial data. Consequently these theories possess well-posed initial value formulations

  5. Orchard navigation using derivative free Kalman filtering

    DEFF Research Database (Denmark)

    Hansen, Søren; Bayramoglu, Enis; Andersen, Jens Christian

    2011-01-01

    This paper describes the use of derivative free filters for mobile robot localization and navigation in an orchard. The localization algorithm fuses odometry and gyro measurements with line features representing the surrounding fruit trees of the orchard. The line features are created on basis of 2...

  6. Curcumin derivatives as HIV-1 protease inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Sui, Z.; Li, J.; Craik, C.S.; Ortiz de Montellano, P.R. [Univ. of California, San Francisco, CA (United States)

    1993-12-31

    Curcumin, a non-toxic natural compound from Curcuma longa, has been found to be an HIV-1 protease inhibitor. Some of its derivatives were synthesized and their inhibitory activity against the HIV-1 protease was tested. Curcumin analogues containing boron enhanced the inhibitory activity. At least of the the synthesized compounds irreversibly inhibits the HIV-1 protease.

  7. Genetic enrichment of cardiomyocytes derived from mouse ...

    African Journals Online (AJOL)

    Genetic enrichment of cardiomyocytes derived from mouse embryonic stem cells. WJ He, SC Li, LL Ye, H Liu, QW Wang, WD Han, XB Fu, ZL Chen. Abstract. Pluripotent embryonic stem cells (ESC) have the ability to differentiate into a variety of cell lineages in vitro, including cardiomyocytes. Successful applications of ...

  8. Cocktail : a tool for deriving correct programs

    NARCIS (Netherlands)

    Franssen, M.G.J.; Swart, de H.C.M.

    2004-01-01

    Cocktail is a tool for deriving correct programs from their specifications. The present version is powerful enough for educational purposes. The tool yields support for many sorted first order predicate logic, formulated in a pure type system with parametric constants (CPTS), as the specification

  9. A new pyrrolidone derivative from Pistacia chinensis

    Institute of Scientific and Technical Information of China (English)

    Jian Jun Liu; Chang An Geng; Xi Kui Liu

    2008-01-01

    A new N-phenyl-pyrrolidone derivative had been isolated from Pistacia chinesis Bunge. Its structure was elucidated as4-hydroxy-5-(2-oxo-1-pyrrolidinyl)-benzoic acid, named pistaciamide on the basis of the 1D-NMR, DEPT, HMQC and HMBCspectroscopic techniques.

  10. Particle production in higher derivative theory

    Indian Academy of Sciences (India)

    Cosmological models; particle production; higher derivative theory of gravitation. PACS No. 98.80. 1. ... is of singular models where the cosmic expansion is driven by the big-bang impulse; all ... According to Gibbs integrability condition, one cannot independently specify an equa- .... [3] B Hartle and S W Hawking Phys. Rev.

  11. morphological characteristics and classification of soils derived

    African Journals Online (AJOL)

    Prof. Ekwueme

    MORPHOLOGICAL CHARACTERISTICS AND CLASSIFICATION OF. SOILS DERIVED FROM DIVERSE PARENT MATERIALS IN CENTRAL. CROSS RIVER STATE, NIGERIA. 271. M. E. NSOR and I. J. IBANGA. (Received 5 October 2007; Revision Accepted 5 December 2007). ABSTRACT. Variation in soil characteristics ...

  12. Novel hydroquinone derivatives alleviate algesia, inflammation and ...

    African Journals Online (AJOL)

    The in silico studies predicted high binding affinity of the hydroquinone derivatives to the active site of the cyclooxygenase 2 (COX-2) enzyme. Conclusion: The synthesized hydroquinone compounds possess analgesic, antipyretic and antiinflammatory properties with low gastric-ulcerogenic potential. This may be credited to ...

  13. OPINION Is the repo a derivative?

    African Journals Online (AJOL)

    Introduction. The literature on the derivative markets and the spot (cash) financial markets ... value of R9 450 000, and the interest factor for the period of the repo is R35 000 ... mathematics is simple and in the case of bonds a little less simple.

  14. Characterization of sugar beet pulp derived oligosaccharides

    NARCIS (Netherlands)

    Leijdekkers, M.

    2015-01-01

    Abstract

    This thesis aimed at characterizing complex mixtures of sugar beet pulp derived oligosaccharides, in order to be able to monitor and optimize the enzymatic saccharification of sugar beet pulp.

    Hydrophilic interaction chromatography with on-line evaporative

  15. Nanomaterials derived from metal-organic frameworks

    Science.gov (United States)

    Dang, Song; Zhu, Qi-Long; Xu, Qiang

    2018-01-01

    The thermal transformation of metal-organic frameworks (MOFs) generates a variety of nanostructured materials, including carbon-based materials, metal oxides, metal chalcogenides, metal phosphides and metal carbides. These derivatives of MOFs have characteristics such as high surface areas, permanent porosities and controllable functionalities that enable their good performance in sensing, gas storage, catalysis and energy-related applications. Although progress has been made to tune the morphologies of MOF-derived structures at the nanometre scale, it remains crucial to further our knowledge of the relationship between morphology and performance. In this Review, we summarize the synthetic strategies and optimized methods that enable control over the size, morphology, composition and structure of the derived nanomaterials. In addition, we compare the performance of materials prepared by the MOF-templated strategy and other synthetic methods. Our aim is to reveal the relationship between the morphology and the physico-chemical properties of MOF-derived nanostructures to optimize their performance for applications such as sensing, catalysis, and energy storage and conversion.

  16. Actuarial risk measures for financial derivative pricing

    NARCIS (Netherlands)

    Goovaerts, M.J.; Laeven, R.J.A.

    2008-01-01

    We present an axiomatic characterization of price measures that are superadditive and comonotonic additive for normally distributed random variables. The price representation derived involves a probability measure transform that is closely related to the Esscher transform, and we call it the

  17. Immunochemical analysis of apamin and its derivatives

    International Nuclear Information System (INIS)

    Vasilenko, S.V.; Kolesnikova, I.N.; Miroshnikov, A.I.; Komissarenko, S.V.

    1981-01-01

    The radioimmunologic analysis of apamin (neurotoxin of the venom of Apis mellifica honey bee) is carried out using its derivatives which have modifications of various aminoacidic remnants and antibodies against apamin. The curves of 125 J apamin binding with antiserum against apamin and the curves of inhibition with various nonlabelled binding effectors of 125 J-apamin with antiserum are obtained

  18. Derivation of the Ideal Gas Law

    Science.gov (United States)

    Laugier, Alexander; Garai, Jozsef

    2007-01-01

    Undergraduate and graduate physics and chemistry books usually state that combining the gas laws results in the ideal gas law. Leaving the derivation to the students implies that this should be a simple task, most likely a substitution. Boyle's law, Charles's law, and the Avogadro's principle are given under certain conditions; therefore, direct…

  19. Cinnamic Acid Derivatives as Antidiabetics Agents

    Directory of Open Access Journals (Sweden)

    Teni Ernawati

    2017-04-01

    Full Text Available Diabetes mellitus is a metabolic disorder of carbohydrate metabolism. Treatment of type II diabetes is usually done by prescribing diet and exercise for the patient however it can also be treated with antidiabetic drugs. The purpose of this paper is to illustrate some cinnamic acid derivative compounds which are either isolated from natural materials or the results of the chemical synthesis. In addition, their biological activities as an agent of α-glucosidase inhibitors have also been evaluated. Chemically, cinnamic acid has three main functional groups:  first is the substitution on the phenyl group, second is the additive reaction into the α-β unsaturated, and third is the chemical reaction with carboxylic acid functional groups. Chemical aspects of cinnamic acid derivative compounds have received much attention in the research and development of drugs, especially modifications within three functional groups are very influential. In the last 10 years, a lot of research and development of cinnamic acid derivatives as inhibitors of the α-glucosidase enzyme has been done. One example of the research done in this field is the modification of para position in the structure of cinnamic acid and addition of alkyl groups in the carboxylic group which would increase the activity of the α-glucosidase enzyme therefore the level of inhibition is 100 times higher than that of cinnamic acid compound itself. The novelty of this review article is to focus on the antidiabetic activity of cinnamic acid derivatives.

  20. On pricing of interest rate derivatives

    OpenAIRE

    Di Matteo, T.; Airoldi, M.; Scalas, E.

    2004-01-01

    At present, there is an explosion of practical interest in the pricing of interest rate (IR) derivatives. Textbook pricing methods do not take into account the leptokurticity of the underlying IR process. In this paper, such a leptokurtic behaviour is illustrated using LIBOR data, and a possible martingale pricing scheme is discussed.

  1. Antimutagenic activity of dextran gammaphos derivatives

    International Nuclear Information System (INIS)

    Bakhitova, L.M.; Pashin, O.V.; Drobchenko, S.N.; Bondarev, G.I.

    1991-01-01

    In experiments with V-79 Chinese hamster cell culture the influence of dextran gammaphos derivatives on the mutagenic effects of γ-radiation was studied by the number of cells with micronuclei and fragmented nuclei. Products of interaction between gammaphos and dialdehyde dextran were shown to a higher antimutagenic activity than gammaphos

  2. Sol-Gel Derived Hafnia Coatings

    Science.gov (United States)

    Feldman, Jay D.; Stackpoole, Mairead; Blum, Yigal; Sacks, Michael; Ellerby, Don; Johnson, Sylvia M.; Venkatapathy, Ethiras (Technical Monitor)

    2002-01-01

    Sol-gel derived hafnia coatings are being developed to provide an oxidation protection layer on ultra-high temperature ceramics for potential use in turbine engines (ultra-efficient engine technology being developed by NASA). Coatings using hafnia sol hafnia filler particles will be discussed along with sol synthesis and characterization.

  3. Undesired Plant-Derived Components in Food

    NARCIS (Netherlands)

    Dusemund, Birgit; Rietjens, Ivonne M.C.M.; Abraham, Klaus; Cartus, Alexander; Schrenk, Dieter

    2017-01-01

    Among the various chemical compounds, the class of natural plant-derived substances in the modern food chain is generating increasing concern. Adverse effects encountered may be various and pose risks of acute, subchronic, or chronic toxicity. The underlying mechanisms of toxicity may be

  4. Knot invariants derived from quandles and racks

    OpenAIRE

    Kamada, Seiichi

    2002-01-01

    The homology and cohomology of quandles and racks are used in knot theory: given a finite quandle and a cocycle, we can construct a knot invariant. This is a quick introductory survey to the invariants of knots derived from quandles and racks.

  5. Supersymmetric higher derivative couplings and their applications

    NARCIS (Netherlands)

    Lodato, I.

    2014-01-01

    After an elementary introduction on black hole physics, supersymmetry and effective theories, which motivates the importance of higher derivative couplings in supergravity, we give an exhaustive treatment of the covariant phase space formalism with many examples explicitly worked out. This sets the

  6. Synthesis of hydroxy derivatives of limonene

    International Nuclear Information System (INIS)

    Ardashov, O V; Volcho, K P; Salakhutdinov, N F

    2014-01-01

    Synthetic routes to mono-, di- and trihydroxy derivatives of limonene are presented. Emphasis is given to the problems of regio- and stereoselectivity of transformations. Data on the isolation from natural sources and on the biological activities of the title compounds are given. The bibliography includes 107 references

  7. Approximate methods for derivation of covariance data

    International Nuclear Information System (INIS)

    Tagesen, S.

    1992-01-01

    Several approaches for the derivation of covariance information for evaluated nuclear data files (EFF2 and ENDF/B-VI) have been developed and used at IRK and ORNL respectively. Considerations, governing the choice of a distinct method depending on the quantity and quality of available data are presented, advantages/disadvantages are discussed and examples of results are given

  8. Waste-wood-derived fillers for plastics

    Science.gov (United States)

    Brent English; Craig M. Clemons; Nicole Stark; James P. Schneider

    1996-01-01

    Filled thermoplastic composites are stiffer, stronger, and more dimensionally stable than their unfilled counterparts. Such thermoplastics are usually provided to the end-user as a precompounded, pelletized feedstock. Typical reinforcing fillers are inorganic materials like talc or fiberglass, but materials derived from waste wood, such as wood flour and recycled paper...

  9. Deriving Process Congruences from Reaction Rules

    DEFF Research Database (Denmark)

    Sobocinski, Pawel

    This thesis is concerned with the development of a theory which, given a formalism with a reduction semantics, allows the derivation of a canonical labelled transition system on which bisimilarity as well as other other equiv� alences are congruences; provided that the contexts of the formalism f...

  10. Formula-derived prostate volume determination

    NARCIS (Netherlands)

    Aarnink, R. G.; de la Rosette, J. J.; Debruyne, F. M.; Wijkstra, H.

    1996-01-01

    OBJECTIVES: Despite disadvantages such as time-consuming and tedious to the user, planimetric volumetry is considered to be the most accurate method for prostate volume determination. This study investigates the possibilities of formula-derived volume determination and reveals the best alternative

  11. Surface tree languages and parallel derivation trees

    NARCIS (Netherlands)

    Engelfriet, Joost

    1976-01-01

    The surface tree languages obtained by top-down finite state transformation of monadic trees are exactly the frontier-preserving homomorphic images of sets of derivation trees of ETOL systems. The corresponding class of tree transformation languages is therefore equal to the class of ETOL languages.

  12. Higher-Derivative Supergravity and Moduli Stabilization

    International Nuclear Information System (INIS)

    Ciupke, David; Westphal, Alexander; Louis, Jan; Hamburg Univ.

    2015-05-01

    We review the ghost-free four-derivative terms for chiral superfields in N=1 supersymmetry and supergravity. These terms induce cubic polynomial equations of motion for the chiral auxiliary fields and correct the scalar potential. We discuss the different solutions and argue that only one of them is consistent with the principles of effective field theory. Special attention is paid to the corrections along flat directions which can be stabilized or destabilized by the higher-derivative terms. We then compute these higher-derivative terms explicitly for the type IIB string compactified on a Calabi-Yau orientifold with fluxes via Kaluza-Klein reducing the (α') 3 R 4 corrections in ten dimensions for the respective N=1 Kaehler moduli sector. We prove that together with flux and the known (α') 3 -corrections the higher-derivative term stabilizes all Calabi-Yau manifolds with positive Euler number, provided the sign of the new correction is negative.

  13. INVESTIGATION OF ANTIFUNGAL ACTIVITY OF QUINOLINIUM DERIVATIVES

    Directory of Open Access Journals (Sweden)

    G. A. Alexandrova

    2013-01-01

    Full Text Available Abstract. Antifungal activity (Candida albicans, Candida krusei of some substituted quinolinium derivatives has been investigated. It was established that the most perspective compound for detail investigation of antifungal activity by labeled biomarkers method was N-phenylbenzoquinaldinium tetrafluoroborate.

  14. Ineffective higher derivative black hole hair

    Science.gov (United States)

    Goldstein, Kevin; Mashiyane, James Junior

    2018-01-01

    Inspired by the possibility that the Schwarzschild black hole may not be the unique spherically symmetric vacuum solution to generalizations of general relativity, we consider black holes in pure fourth order higher derivative gravity treated as an effective theory. Such solutions may be of interest in addressing the issue of higher derivative hair or during the later stages of black hole evaporation. Non-Schwarzschild solutions have been studied but we have put earlier results on a firmer footing by finding a systematic asymptotic expansion for the black holes and matching them with known numerical solutions obtained by integrating out from the near-horizon region. These asymptotic expansions can be cast in the form of trans-series expansions which we conjecture will be a generic feature of non-Schwarzschild higher derivative black holes. Excitingly we find a new branch of solutions with lower free energy than the Schwarzschild solution, but as found in earlier work, solutions only seem to exist for black holes with large curvatures, meaning that one should not generically neglect even higher derivative corrections. This suggests that one effectively recovers the nonhair theorems in this context.

  15. Simulation of chemical reactions using fractional derivatives

    International Nuclear Information System (INIS)

    Zabadal, J.; Vilhena, M.; Livotto, P.

    2001-01-01

    In this work a new approach to solve time-dependant Schroedinger equation for molecular systems is proposed. The method employs functional derivatives to describe the time evolution of the wave functions in reactive systems, in order to establish the mechanisms and products of the reaction. A numerical simulation is reported

  16. Inequalities for a Polynomial and its Derivative

    Indian Academy of Sciences (India)

    Annual Meetings · Mid Year Meetings · Discussion Meetings · Public Lectures · Lecture Workshops · Refresher Courses · Symposia · Live Streaming. Home; Journals; Proceedings – Mathematical Sciences; Volume 110; Issue 2. Inequalities for a Polynomial and its Derivative. V K Jain. Volume 110 Issue 2 May 2000 pp 137- ...

  17. Derivation of the fine-structure constant

    International Nuclear Information System (INIS)

    Samec, A.

    1980-01-01

    The fine-structure constant is derived as a dynamical property of quantum electrodynamics. Single-particle solutions of the coupled Maxwell and Dirac equations have a physical charge spectrum. The solutions are used to construct lepton-and quark-like particles. The strong, weak, electromagnetic, and gravitational forces are described as the interactions of complex charges in multiple combinations

  18. Fundamentals of futures, options, basis and derivatives

    International Nuclear Information System (INIS)

    Jones, D.

    1997-01-01

    Characteristic features of futures and options contracts, basis differentials and derivatives were defined and explained. A futures contract refers to an exchange-traded supply contract between a buyer and a seller where the buyer is obligated to take delivery and the seller is obligated to provide delivery of a fixed amount of a commodity at a predetermined price at a specified location. In contrast, an option contract gives the purchaser the right, but not the obligation, to buy or sell the underlying commodity at a certain price on or before an agreed date. Basis differential refers to the discount between two distinct delivery points to reflect the relative value of a commodity, such as natural gas, at those points. Advantages and disadvantages of futures and options contacts, the factors affecting options pricing, and basis differentials, and the methods of calculating basis differentials were described. The nature and intricacies of derivatives, their benefits, in particular their use as a tool for the effective management of the volatilities associated with the oil and gas industry were explained. Their shortcomings such as the high liquidity risk, were also described. Examples of derivative transactions were provided to illustrate the interrelationships of futures/options/derivatives, and their role in financial risk management

  19. Risk Management and Financial Derivatives: An Overview

    NARCIS (Netherlands)

    S.M. Hammoudeh (Shawkat); M.J. McAleer (Michael)

    2012-01-01

    textabstractRisk management is crucial for optimal portfolio management. One of the fastest growing areas in empirical finance is the expansion of financial derivatives. The purpose of this special issue on “Risk Management and Financial Derivatives” is to highlight some areas in which novel

  20. WEATHER INDEX- THE BASIS OF WEATHER DERIVATIVES

    Directory of Open Access Journals (Sweden)

    Botos Horia Mircea

    2011-07-01

    Full Text Available This paper approaches the subject of Weather Derivatives, more exactly their basic element the weather index. The weather index has two forms, the Heating Degree Day (HDD and the Cooling Degree Day (CDD. We will try to explain their origin, use and the relationship between the two forms of the index. In our research we started from the analysis of the weather derivatives and what they are based on. After finding out about weather index, we were interested in understanding exactly how they work and how they influence the value of the contract. On the national level the research in the field is scares, but foreign materials available. The study for this paper was based firstly on reading about Weather Derivative, and then going in the meteorogical field and determining the way by which the indices were determined. After this, we went to the field with interest in the indices, such as the energy and gas industries, and figured out how they determined the weather index. For the examples we obtained data from the weather index database, and calculated the value for the period. The study is made on a period of five years, in 8 cities of the European Union. The result of this research is that we can now understand better the importance of the way the indices work and how they influence the value of the Weather Derivatives. This research has an implication on the field of insurance, because of the fact that weather derivative are at the convergence point of the stock markets and the insurance market. The originality of the paper comes from the personal touch given to the theoretical aspect and through the analysis of the HDD and CDD index in order to show their general behaviour and relationship.

  1. Derivative based sensitivity analysis of gamma index

    Directory of Open Access Journals (Sweden)

    Biplab Sarkar

    2015-01-01

    Full Text Available Originally developed as a tool for patient-specific quality assurance in advanced treatment delivery methods to compare between measured and calculated dose distributions, the gamma index (γ concept was later extended to compare between any two dose distributions. It takes into effect both the dose difference (DD and distance-to-agreement (DTA measurements in the comparison. Its strength lies in its capability to give a quantitative value for the analysis, unlike other methods. For every point on the reference curve, if there is at least one point in the evaluated curve that satisfies the pass criteria (e.g., δDD = 1%, δDTA = 1 mm, the point is included in the quantitative score as "pass." Gamma analysis does not account for the gradient of the evaluated curve - it looks at only the minimum gamma value, and if it is <1, then the point passes, no matter what the gradient of evaluated curve is. In this work, an attempt has been made to present a derivative-based method for the identification of dose gradient. A mathematically derived reference profile (RP representing the penumbral region of 6 MV 10 cm × 10 cm field was generated from an error function. A general test profile (GTP was created from this RP by introducing 1 mm distance error and 1% dose error at each point. This was considered as the first of the two evaluated curves. By its nature, this curve is a smooth curve and would satisfy the pass criteria for all points in it. The second evaluated profile was generated as a sawtooth test profile (STTP which again would satisfy the pass criteria for every point on the RP. However, being a sawtooth curve, it is not a smooth one and would be obviously poor when compared with the smooth profile. Considering the smooth GTP as an acceptable profile when it passed the gamma pass criteria (1% DD and 1 mm DTA against the RP, the first and second order derivatives of the DDs (δD', δD" between these two curves were derived and used as the

  2. A New Grünwald-Letnikov Derivative Derived from a Second-Order Scheme

    Directory of Open Access Journals (Sweden)

    B. A. Jacobs

    2015-01-01

    Full Text Available A novel derivation of a second-order accurate Grünwald-Letnikov-type approximation to the fractional derivative of a function is presented. This scheme is shown to be second-order accurate under certain modifications to account for poor accuracy in approximating the asymptotic behavior near the lower limit of differentiation. Some example functions are chosen and numerical results are presented to illustrate the efficacy of this new method over some other popular choices for discretizing fractional derivatives.

  3. Arbitrage-free valuation of energy derivatives

    International Nuclear Information System (INIS)

    Amin, K.; Ng, V.; Pirrong, C.

    1999-01-01

    This chapter focuses on techniques available for valuing energy-contingent claims and develops an arbitrage-free framework to value energy derivatives. The relationship between the spot, forward and futures prices is explained. Option valuation with deterministic convenience yields is discussed using an extension of the Black (1976) framework, and details of the risk-neutral valuation of European options, and valuation of American and European-style options are given. Option valuations with stochastic convenience yields, the evolution of the term structure of convenience yield, and a tree approach to valuing American and other options are discussed. Applications and limitations of the models for pricing energy derivative products are considered. The stochastic differential equation for the futures prices when the convenience yields are stochastic is presented in an appendix

  4. Fundamentals and advanced techniques in derivatives hedging

    CERN Document Server

    Bouchard, Bruno

    2016-01-01

    This book covers the theory of derivatives pricing and hedging as well as techniques used in mathematical finance. The authors use a top-down approach, starting with fundamentals before moving to applications, and present theoretical developments alongside various exercises, providing many examples of practical interest. A large spectrum of concepts and mathematical tools that are usually found in separate monographs are presented here. In addition to the no-arbitrage theory in full generality, this book also explores models and practical hedging and pricing issues. Fundamentals and Advanced Techniques in Derivatives Hedging further introduces advanced methods in probability and analysis, including Malliavin calculus and the theory of viscosity solutions, as well as the recent theory of stochastic targets and its use in risk management, making it the first textbook covering this topic. Graduate students in applied mathematics with an understanding of probability theory and stochastic calculus will find this b...

  5. Higher derivatives and renormalization in quantum cosmology

    International Nuclear Information System (INIS)

    Mazzitelli, F.D.

    1991-10-01

    In the framework of the canonical quantization of general relativity, quantum field theory on a fixed background formally arises in an expansion in powers of the Planck length. In order to renormalize the theory, quadratic terms in the curvature must be included in the gravitational action from the beginning. These terms contain higher derivatives which change the Hamiltonian structure of the theory completely, making the relation between the renormalized-theory and the original one not clear. We show that it is possible to avoid this problem. We replace the higher derivative theory by a second order one. The classical solutions of the latter are also solutions of the former. We quantize the theory, renormalize the infinities and show that there is a smooth limit between the classical and the renormalized theories. We work in a Robertson Walker minisuperspace with a quantum scalar field. (author). 32 refs

  6. Renminbi Derivatives: Recent Development and Issues

    Institute of Scientific and Technical Information of China (English)

    Wensheng Peng; Chang Shu; Raymond Yip

    2007-01-01

    This study reviews the developments in the onshore and offshore renminbi derivatives markets. The onshore market has seen a rapid build-up in the market infrastructure and price discovery mechanism in the past year, with empirical evidence suggesting that its pricing is increasingly determined by financial fundamentals, such as the covered interest rate parity. However, the growth of the market has been restrained by restrictions on the participant base, limited variations in the RMB/US$ exchange rate, market participants'lack of technical capacity and experience, and inadequate supporting financial market infrastructure. The non-deliverable forward (NDF) market, concentrated in Hong Kong and Singapore, is more developed, but has the drawback that its pricing is not tied to financial fundamentals. The comparison between onshore and offshore markets suggests that two issues are of particular importance for future derivatives market development in China: the balance between regulation and development, and the relationship between onshore and offshore markets.

  7. Electrochemical Behavior of Biologically Important Indole Derivatives

    Directory of Open Access Journals (Sweden)

    Cigdem Karaaslan

    2011-01-01

    Full Text Available Voltammetric techniques are most suitable to investigate the redox properties of a new drug. Use of electrochemistry is an important approach in drug discovery and research as well as quality control, drug stability, and determination of physiological activity. The indole nucleus is an essential element of a number of natural and synthetic products with significant biological activity. Indole derivatives are the well-known electroactive compounds that are readily oxidized at carbon-based electrodes, and thus analytical procedures, such as electrochemical detection and voltammetry, have been developed for the determination of biologically important indoles. This paper explains some of the relevant and recent achievements in the electrochemistry processes and parameters mainly related to biologically important indole derivatives in view of drug discovery and analysis.

  8. Algebraic theory of locally nilpotent derivations

    CERN Document Server

    Freudenburg, Gene

    2017-01-01

    This book explores the theory and application of locally nilpotent derivations, a subject motivated by questions in affine algebraic geometry and having fundamental connections to areas such as commutative algebra, representation theory, Lie algebras and differential equations. The author provides a unified treatment of the subject, beginning with 16 First Principles on which the theory is based. These are used to establish classical results, such as Rentschler's Theorem for the plane and the Cancellation Theorem for Curves. More recent results, such as Makar-Limanov's theorem for locally nilpotent derivations of polynomial rings, are also discussed. Topics of special interest include progress in classifying additive actions on three-dimensional affine space, finiteness questions (Hilbert's 14th Problem), algorithms, the Makar-Limanov invariant, and connections to the Cancellation Problem and the Embedding Problem. A lot of new material is included in this expanded second edition, such as canonical factoriza...

  9. Feynman graph derivation of Einstein quadrupole formula

    International Nuclear Information System (INIS)

    Dass, N.D.H.; Soni, V.

    1980-11-01

    The one graviton transition operator, and consequently, the classical energy loss formula for gravitational radiation are derived from the Feynman graphs of helicity +- 2 theories of gravitation. The calculations are done both for the case of electromagnetic and gravitational scattering. The departure of the in and out states from plane waves owing to the long range nature of gravitation is taken into account to improve the Born approximation calculations. This also includes a long range modification of the graviton wave function which is shown to be equivalent to the classical problem of the true light cones deviating logarithmically at large distances from the flat space light cones. The transition from the S-matrix elements calculated graphically to the graviton transition operator is done by using complimentarity of space-time and momentum descriptions. The energy loss formula derived originally by Einstein is shown to be correct. (Auth.)

  10. Biodegradation of polyurethane derived from castor oil

    Directory of Open Access Journals (Sweden)

    José M. Cangemi

    2008-09-01

    Full Text Available The aim of this research was to study the biodegradation of a polymer derived from castor oil, which is a renewable, natural material that is a practical alternative for the replacement of traditional polyurethane foams. Due to its molecular structure, which contains polyester segments derived from vegetable oil, the polymeric surface is susceptible to microorganism attack. This study tested the biological degrading agent that was in contact with the microorganisms resulting from microbiological grease degrading agents, when foam was inoculated. Solid-media agar-plate tests were conducted for their potential to evaluate the biodegradation of polymeric particles by specific strains of microorganisms during 216 hours. The growth rate was defined. This technique provides a way of distinguishing the degradation abilities of microorganisms from the degradability of materials.

  11. Phloroglucinol derivatives and flavones from Helichrysum paronychioides

    Directory of Open Access Journals (Sweden)

    J. Mutanyatta-Comar

    2006-06-01

    Full Text Available Investigation of Helichrysum paronychioides afforded a total of nine compounds: 4 phloroglucinol derivatives, 2 of which are novel natural products, and 5 flavone derivatives. Structures were established by various spectroscopic techniques (NMR, MS, UV, IR, CD and by comparison with literature data for the known compounds. The four phloroglucinols, trans-(2R,3R-5,7-dihydroxy-2,3-dimethyl-4-chromanone (1, 2-butanoyl-4-prenyl-1-methoxy phloroglucinol (2, 2-(2-methylpropanoyl-4-prenylphloroglucinol (3 and 2-(2-methyl- butanoyl-4-prenylphloroglucinol (4 were screened for antioxidant activity against Cu-induced LDL oxidation. Compound 4 was found to be the most active inhibiting LDL oxidation at all concentrations (0.5-10 μM while the other three showed moderate to no activity.

  12. Inconsistency of Minkowski higher-derivative theories

    Energy Technology Data Exchange (ETDEWEB)

    Aglietti, Ugo G. [Universita di Roma ' ' La Sapienza' ' , Dipartimento di Fisica, Rome (Italy); Anselmi, Damiano [Universita di Pisa, Dipartimento di Fisica ' ' Enrico Fermi' ' , Pisa (Italy); INFN, Sezione di Pisa, Pisa (Italy)

    2017-02-15

    We show that Minkowski higher-derivative quantum field theories are generically inconsistent, because they generate nonlocal, non-hermitian ultraviolet divergences, which cannot be removed by means of standard renormalization procedures. By ''Minkowski theories'' we mean theories that are defined directly in Minkowski spacetime. The problems occur when the propagators have complex poles, so that the correlation functions cannot be obtained as the analytic continuations of their Euclidean versions. The usual power counting rules fail and are replaced by much weaker ones. Self-energies generate complex divergences proportional to inverse powers of D'Alembertians. Three-point functions give more involved nonlocal divergences, which couple to infrared effects. We illustrate the violations of the locality and hermiticity of counterterms in scalar models and higher-derivative gravity. (orig.)

  13. Evaluation of antiproliferative activity of pyrazolothiazolopyrimidine derivatives

    Directory of Open Access Journals (Sweden)

    N. S. Finiuk

    2018-04-01

    Full Text Available The research aim was to test cytotoxic effects in vitro of seven novel pyrazolothiazolopyrimidine derivatives in targeting several lines of tumor and pseudo-normal mammalian cells. We demonstrated that cytotoxic effects of these derivatives depended on the tissue origin of targeted cells. Leukemia cells were found to be the most sensitive to the action of compounds 2 and 7. Compound 2 demonstrated approximately two times higher toxicity towards the multidrug-resistant sub-line of HL-60/ADR cells compared to the Doxorubicin effect. Antiproliferative action of compounds 2 and 7 dropped in the order: leukemia > melanoma > hepatocarcinoma > glioblastoma > colon carcinoma > breast and ovarian carcinoma cells. These compounds were less toxic than Doxorubicin towards the non-tumor cells. The novel pyrazolothiazolopyrimidine, compound 2, demonstrated high toxicity towards human leukemia and, of special importance, towards multidrug-resistant leukemia cells, and low toxicity towards pseudo-normal cells.

  14. A generalization of the Lie derivative

    International Nuclear Information System (INIS)

    Dolan, P.

    1984-01-01

    If X=xisup(i)deltasub(i) and Y=etasup(i)deltasub(i) are vector fields then it is well-known that the Lie derivative Poundsub(X)Y equivalent to [X,Y] (xisup(s)deltasub(s) etasup(s)deltasub(s)xisup(i))deltasub(i) is also a vector field under general coordinate transformations. A generalization of this result, due to previous workers, allows a definition of Poundsub(F)G, where F,G are arbitrary contravariant tensor fields. The formulae are linear in the first partial derivatives of F and G. An application to the theory of Killing-Yano tensor fields on Riemannian manifolds is given. (author)

  15. Folic acid derivatives for use in radioimmunoassay

    International Nuclear Information System (INIS)

    Ali, A.

    1981-01-01

    The chemical preparation of two folic acid derivatives, labelled with 125 I or 131 I, is described for use in radioimmunoassay of folic acid and its metabolites in biological fluids such as blood serum. Labelled compounds of the present invention more closely resemble folic acid in that they have glutamic acid in the terminal position. Examples of the use of these compounds in three different assays are given. (U.K.)

  16. Parallel Aircraft Trajectory Optimization with Analytic Derivatives

    Science.gov (United States)

    Falck, Robert D.; Gray, Justin S.; Naylor, Bret

    2016-01-01

    Trajectory optimization is an integral component for the design of aerospace vehicles, but emerging aircraft technologies have introduced new demands on trajectory analysis that current tools are not well suited to address. Designing aircraft with technologies such as hybrid electric propulsion and morphing wings requires consideration of the operational behavior as well as the physical design characteristics of the aircraft. The addition of operational variables can dramatically increase the number of design variables which motivates the use of gradient based optimization with analytic derivatives to solve the larger optimization problems. In this work we develop an aircraft trajectory analysis tool using a Legendre-Gauss-Lobatto based collocation scheme, providing analytic derivatives via the OpenMDAO multidisciplinary optimization framework. This collocation method uses an implicit time integration scheme that provides a high degree of sparsity and thus several potential options for parallelization. The performance of the new implementation was investigated via a series of single and multi-trajectory optimizations using a combination of parallel computing and constraint aggregation. The computational performance results show that in order to take full advantage of the sparsity in the problem it is vital to parallelize both the non-linear analysis evaluations and the derivative computations themselves. The constraint aggregation results showed a significant numerical challenge due to difficulty in achieving tight convergence tolerances. Overall, the results demonstrate the value of applying analytic derivatives to trajectory optimization problems and lay the foundation for future application of this collocation based method to the design of aircraft with where operational scheduling of technologies is key to achieving good performance.

  17. Cholestane derivatives as antitumor and antiangiogenic drugs

    Czech Academy of Sciences Publication Activity Database

    Hoffmannová, L.; Steigerová, J.; Oklešťková, J.; Kohout, Ladislav; Chodounská, Hana; Hniličková, Jaroslava; Kasal, Alexander; Černý, Ivan; Kolář, Z.; Strnad, M.

    2010-01-01

    Roč. 35, SA (2010), s. 205-205 ISSN 0377-8282. [EFMC-ISMC 2010. International Symposium on Medicinal Chemistry /21./. 05.09.2010-09.09.2010, Brussels] R&D Projects: GA MŠk(CZ) LC06077; GA AV ČR KAN200200651 Institutional research plan: CEZ:AV0Z40550506 Keywords : cholestane derivatives * anticancer drugs Subject RIV: CC - Organic Chemistry

  18. On the Feasibility of Decentralized Derivatives Markets

    OpenAIRE

    Eskandari, Shayan; Clark, Jeremy; Sundaresan, Vignesh; Adham, Moe

    2018-01-01

    In this paper, we present Velocity, a decentralized market deployed on Ethereum for trading a custom type of derivative option. To enable the smart contract to work, we also implement a price fetching tool called PriceGeth. We present this as a case study, noting challenges in development of the system that might be of independent interest to whose working on smart contract implementations. We also apply recent academic results on the security of the Solidity smart contract language in valida...

  19. The Brain Derived Neurotrophic Factor and Personality

    OpenAIRE

    Christian Montag

    2014-01-01

    The study of the biological basis of personality is a timely research endeavor, with the aim of deepening our understanding of human nature. In recent years, a growing body of research has investigated the role of the brain derived neurotrophic factor (BDNF) in the context of individual differences across human beings, with a focus on personality traits. A large number of different approaches have been chosen to illuminate the role of BDNF for personality, ranging from the measurement of BDNF...

  20. Alkylation of Zwitterionic Thiooxalic Acid Derivatives

    Directory of Open Access Journals (Sweden)

    Manfred Michalik

    2001-05-01

    Full Text Available The new S-alkyl thiooxal-1-hydrazono-2-amidrazonium halides 2-4 were synthesized by reaction of the corresponding zwitterionic thiooxalic acid derivatives 1 with alkyl halides in methanol. The structures of compounds 4b and 4d were proven by X-ray structural analysis. Both compounds form an interesting intermolecular network of hydrogen bonds in the solid state.

  1. Coronary CT Angiography Derived Fractional Flow Reserve

    DEFF Research Database (Denmark)

    Nørgaard, Bjarne Linde; Jensen, Jesper Møller; Blanke, Philipp

    2017-01-01

    Purpose of Review: To summarize the scientific basis of CT derived fractional flow reserve (FFRCT) and present an updated review on the evidence from clinical trials and real-world observational data Recent Findings: In prospective multicenter studies of patients with stable coronary artery disea...... of patients with stable CAD. The optimal FFRCT testing interpretation strategy, as well as the relative cost-efficiency of FFRCT against standard noninvasive functional testing, need further investigation....

  2. Eisenhart lift for higher derivative systems

    Energy Technology Data Exchange (ETDEWEB)

    Galajinsky, Anton, E-mail: galajin@tpu.ru; Masterov, Ivan, E-mail: masterov@tpu.ru

    2017-02-10

    The Eisenhart lift provides an elegant geometric description of a dynamical system of second order in terms of null geodesics of the Brinkmann-type metric. In this work, we attempt to generalize the Eisenhart method so as to encompass higher derivative models. The analysis relies upon Ostrogradsky's Hamiltonian. A consistent geometric description seems feasible only for a particular class of potentials. The scheme is exemplified by the Pais–Uhlenbeck oscillator.

  3. Strong commutativity preserving generalized derivations on ...

    African Journals Online (AJOL)

    Let R be a non-commutative prime ring of characteristic different from 2, with right Utumi quotient ring U and extended centroid C and let F and G be generalized derivations of R such that F(x)G(y)-F(y)G(x) = [x; y], for all x; y ∈ S, where S is a subset of R. Here we will discuss the following cases: (a) S = [R;R];. b) S = L, where ...

  4. Covariant derivatives of the Berezin transform

    Czech Academy of Sciences Publication Activity Database

    Engliš, Miroslav; Otáhalová, R.

    2011-01-01

    Roč. 363, č. 10 (2011), s. 5111-5129 ISSN 0002-9947 R&D Projects: GA AV ČR IAA100190802 Keywords : Berezin transform * Berezin symbol * covariant derivative Subject RIV: BA - General Mathematics Impact factor: 1.093, year: 2011 http://www.ams.org/journals/tran/2011-363-10/S0002-9947-2011-05111-1/home.html

  5. Derivation of plutonium-239 materials disposition categories

    International Nuclear Information System (INIS)

    Brough, W.G.

    1995-01-01

    At this time, the Office of Fissile Materials Disposition within the DOE, is assessing alternatives for the disposition of excess fissile materials. To facilitate the assessment, the Plutonium-Bearing Materials Feed Report for the DOE Fissile Materials Disposition Program Alternatives report was written. The development of the material categories and the derivation of the inventory quantities associated with those categories is documented in this report

  6. On butterfly effect in higher derivative gravities

    Energy Technology Data Exchange (ETDEWEB)

    Alishahiha, Mohsen [School of Physics, Institute for Research in Fundamental Sciences (IPM),P.O. Box 19395-5531, Tehran (Iran, Islamic Republic of); Davody, Ali; Naseh, Ali; Taghavi, Seyed Farid [School of Particles and Accelerators, Institute for Research in Fundamental Sciences (IPM),P.O. Box 19395-5531, Tehran (Iran, Islamic Republic of)

    2016-11-07

    We study butterfly effect in D-dimensional gravitational theories containing terms quadratic in Ricci scalar and Ricci tensor. One observes that due to higher order derivatives in the corresponding equations of motion there are two butterfly velocities. The velocities are determined by the dimension of operators whose sources are provided by the metric. The three dimensional TMG model is also studied where we get two butterfly velocities at generic point of the moduli space of parameters. At critical point two velocities coincide.

  7. On butterfly effect in higher derivative gravities

    International Nuclear Information System (INIS)

    Alishahiha, Mohsen; Davody, Ali; Naseh, Ali; Taghavi, Seyed Farid

    2016-01-01

    We study butterfly effect in D-dimensional gravitational theories containing terms quadratic in Ricci scalar and Ricci tensor. One observes that due to higher order derivatives in the corresponding equations of motion there are two butterfly velocities. The velocities are determined by the dimension of operators whose sources are provided by the metric. The three dimensional TMG model is also studied where we get two butterfly velocities at generic point of the moduli space of parameters. At critical point two velocities coincide.

  8. Literature Review of Polymer Derived Ceramics

    Energy Technology Data Exchange (ETDEWEB)

    Peterson, Reuben James [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-05-25

    Polymer Derived Ceramics (PDCs), also known as preceramic polymers, are valuable coating agents that are used to produce surface barriers on substrates such as stainless steel. These barriers protect against a multitude of environmental threats, and have been used since their research and development in 19772. This paper seeks to review and demonstrate the remarkable properties and versatility that PDCs have to offer, while also giving a brief overview of the processing techniques used today.

  9. Photoinactivation of HIV by benzoporphyrin derivative

    International Nuclear Information System (INIS)

    North, J.; Levy, J.; Coombs, R.

    1992-01-01

    Using both the feline leukemia virus and human immunodeficiency virus it is shown that the photosensitizer benzoporphyrin derivative when activated by narrow band red light is effective in eliminating both free virus and virally infected leukocytes from spiked blood products and whole blood drawn from either virally infected animals or humans, under conditions which appear to spare red cell and uninfected leukocytes. (author). 14 refs., 7 figs

  10. Derivatives of the Incomplete Beta Function

    Directory of Open Access Journals (Sweden)

    Robert J. Boik

    1998-03-01

    Full Text Available The incomplete beta function is defined as where Beta(p, q is the beta function. Dutka (1981 gave a history of the development and numerical evaluation of this function. In this article, an algorithm for computing first and second derivatives of Ix,p,q with respect to p and q is described. The algorithm is useful, for example, when fitting parameters to a censored beta, truncated beta, or a truncated beta-binomial model.

  11. Detectability in a derivative Moessbauer spectroscopy

    International Nuclear Information System (INIS)

    Yoshimura, Takeaki; Miyamoto, Masashi; Wakabayashi, Nobuo

    1978-01-01

    In Moessbauer spectrometry, a criterion for detecting a faint peak under the condition that the peak is superimposed onto a tail of a large and broad peak is discussed. By adopting a derivative method, it is found that the criterion is improved in comparison with a usual method, and that the condition for determining the modulation amplitude W/2 is 1.5 GAMMA 1 1 where GAMMA 1 is the spectral linewidth of the faint peak. (auth.)

  12. Bio-Detergent oil derivative used frying

    Directory of Open Access Journals (Sweden)

    Alfonso Jesús Torres Ortega

    2011-04-01

    Full Text Available Currently, the global trend towards sustainable development for environmental friendly products such as biosurfactants shows an excellent performance. Anionic surface active agents can be produced from renewable natural raw materials such as vegetable oils mainly derived from palm oil. Methyl ester sulfonate is an active component of highly biodegradable detergents, one advantage compared with detergents derived from petrochemicals which generate a high pollutant load. This paper proposes the study of sulfonation with sulfur trioxide of esters derived from waste cooking oil which main component is palm oil. The falling film reactor allows determining the conditions of the process at pilot scale. The experimentation allowed an enhancement of empirical equations in the equipment implemented for this purpose and to determine some physicochemical properties. The comparison obtained for this same process with petrochemicals compounds indicates that the model could be applied to any film sulfonation but adjusting the parameters and specific conditions, such as the physicochemical properties of the compounds used, since the sulfonation process described in this work is one of the more complicated cases. The technological development presented here seeks to contribute with the industrial needs to promote green chemical industry for the production of biosurfactant from waste frying oil.

  13. 7-oxygenated Derivatives of Dehydroepiandrosterone and Obesity

    Directory of Open Access Journals (Sweden)

    B. Sedláčková

    2012-01-01

    Full Text Available 7-hydroxy/oxo derivatives of dehydroepiandrosterone are potential regulators of the local cortisol activity due to their competition in the cortisolcortisone balance mediated by 11β-hydroxysteroid dehydrogenase. 7-hydroxydehydroepiandrosterone is marketed as anti-obesity medication, though no clinical study aimed at the benefit of administering 7-oxygenated derivatives of dehydroepiandrosterone has appeared until now. We tried to show whether there exist differences in levels of circulating 7-hydroxy/oxo-dehydroepiandrosterone derivatives between lean and obese boys and girls. From a cohort of adolescents investigated within the frame of anti-obesity programme 10 obese boys and 10 obese girls were compared with age-matched lean boys and girls in their anthropometric data, and concentrations of both epimers of 7-hydroxydehydroepiandrosterone and 7-oxo-dehydroepiandrosterone were determined by the RIA method. The basal levels of 7α-hydroxy-dehydroepiandrosterone were significantly higher in obese boys than in lean boys but not in girls. The association was found for anthropometric parameters and 7α-hydroxy-dehydroepiandrosterone, however again only in boys and not in girls. Higher levels of 7α-hydroxydehydroepiandrosterone its positive association with anthropometric data in obese boys may serve as a sign that, at least in boys, 7-oxygenated 5-ene-steroids may take part in regulating the hormonal signal for fat formation or distribution.

  14. Metal complex derivatives of hydrogen uranyl phosphate

    International Nuclear Information System (INIS)

    Grohol, D.; Blinn, E.L.

    1994-01-01

    Derivatives of hydrogen uranyl phosphate were prepared by incorporating transition metal complexes into the uranyl phosphate matrix. The transition metal complexes employed include bis(ethylenediamine)copper(II), bis(1,3-propanediamine)copper(II) chloride, (triethylenetetramine)copper(II), (1,4,8,11-tetraazacyclotetradecane)copper(II), (1,4,8,12-tetraazacyclopentadecane)copper(II), (1,4,8,11-tetraazacyclotetradecane)nickel(II) chloride, (triethylenetetramine)nickel(II) and others. The chemical analyses of these derivatives indicated that the incorporation of the transition metal complexes into the uranyl phosphate matrix via ion exchange was not stoichiometric. The extent of ion exchange is dependent on the size and structure of the transition metal complex. All complexes were characterized by X-ray powder diffractometry, electronic and infrared spectra, thermal analyses and chemical analysis. An attempt was made to correlate the degree of quenching of the luminescence of the uranyl ion to the spacing between the uranyl phosphate layers in the derivatives

  15. Price models for oil derivates in Slovenia

    International Nuclear Information System (INIS)

    Nemac, F.; Saver, A.

    1995-01-01

    In Slovenia, a law is currently applied according to which any change in the price of oil derivatives is subject to the Governmental approval. Following the target of getting closer to the European Union, the necessity has arisen of finding ways for the introduction of liberalization or automated approach to price modifications depending on oscillations of oil derivative prices on the world market and the rate of exchange of the American dollar. It is for this reason that at the Agency for Energy Restructuring we made a study for the Ministry of Economic Affairs and Development regarding this issue. We analysed the possible models for the formation of oil derivative prices for Slovenia. Based on the assessment of experiences of primarily the west European countries, we proposed three models for the price formation for Slovenia. In future, it is expected that the Government of the Republic of Slovenia will make a selection of one of the proposed models to be followed by enforcement of price liberalization. The paper presents two representative models for price formation as used in Austria and Portugal. In the continuation the authors analyse the application of three models that they find suitable for the use in Slovenia. (author)

  16. Surface spectral emissivity derived from MODIS data

    Science.gov (United States)

    Chen, Yan; Sun-Mack, Sunny; Minnis, Patrick; Smith, William L.; Young, David F.

    2003-04-01

    Surface emissivity is essential for many remote sensing applications including the retrieval of the surface skin temperature from satellite-based infrared measurements, determining thresholds for cloud detection and for estimating the emission of longwave radiation from the surface, an important component of the energy budget of the surface-atmosphere interface. In this paper, data from the Terra MODIS (MODerate-resolution Imaging Spectroradiometer) taken at 3.7, 8.5, 10.8, 12.0 micron are used to simultaneously derive the skin temperature and the surface emissivities at the same wavelengths. The methodology uses separate measurements of the clear-sky temperatures that are determined by the CERES (Clouds and Earth's Radiant Energy System) scene classification in each channel during the daytime and at night. The relationships between the various channels at night are used during the day when solar reflectance affects the 3.7 micron data. A set of simultaneous equations is then solved to derive the emissivities. Global results are derived from MODIS. Numerical weather analyses are used to provide soundings for correcting the observed radiances for atmospheric absorption. These results are verified and will be available for remote sensing applications.

  17. Modeling of heat conduction via fractional derivatives

    Science.gov (United States)

    Fabrizio, Mauro; Giorgi, Claudio; Morro, Angelo

    2017-09-01

    The modeling of heat conduction is considered by letting the time derivative, in the Cattaneo-Maxwell equation, be replaced by a derivative of fractional order. The purpose of this new approach is to overcome some drawbacks of the Cattaneo-Maxwell equation, for instance possible fluctuations which violate the non-negativity of the absolute temperature. Consistency with thermodynamics is shown to hold for a suitable free energy potential, that is in fact a functional of the summed history of the heat flux, subject to a suitable restriction on the set of admissible histories. Compatibility with wave propagation at a finite speed is investigated in connection with temperature-rate waves. It follows that though, as expected, this is the case for the Cattaneo-Maxwell equation, the model involving the fractional derivative does not allow the propagation at a finite speed. Nevertheless, this new model provides a good description of wave-like profiles in thermal propagation phenomena, whereas Fourier's law does not.

  18. FOREST AREA DERIVATION FROM SENTINEL-1 DATA

    Directory of Open Access Journals (Sweden)

    A. Dostálová

    2016-06-01

    Full Text Available The recently launched Sentinel-1A provides the high resolution Synthetic Aperture Radar (SAR data with very high temporal coverage over large parts of European continent. Short revisit time and dual polarization availability supports its usability for forestry applications. The following study presents an analysis of the potential of the multi-temporal dual-polarization Sentinel-1A data for the forest area derivation using the standard methods based on Otsu thresholding and K-means clustering. Sentinel-1 data collected in winter season 2014-2015 over a test area in eastern Austria were used to derive forest area mask with spatial resolution of 10m and minimum mapping unit of 500 m2. The validation with reference forest mask derived from airborne full-waveform laser scanning data revealed overall accuracy of 92 % and kappa statistics of 0.81. Even better results can be achieved when using external mask for urban areas, which might be misclassified as forests when using the introduced approach based on SAR data only. The Sentinel-1 data and the described methods are well suited for forest change detection between consecutive years.

  19. P-Splines Using Derivative Information

    KAUST Repository

    Calderon, Christopher P.

    2010-01-01

    Time series associated with single-molecule experiments and/or simulations contain a wealth of multiscale information about complex biomolecular systems. We demonstrate how a collection of Penalized-splines (P-splines) can be useful in quantitatively summarizing such data. In this work, functions estimated using P-splines are associated with stochastic differential equations (SDEs). It is shown how quantities estimated in a single SDE summarize fast-scale phenomena, whereas variation between curves associated with different SDEs partially reflects noise induced by motion evolving on a slower time scale. P-splines assist in "semiparametrically" estimating nonlinear SDEs in situations where a time-dependent external force is applied to a single-molecule system. The P-splines introduced simultaneously use function and derivative scatterplot information to refine curve estimates. We refer to the approach as the PuDI (P-splines using Derivative Information) method. It is shown how generalized least squares ideas fit seamlessly into the PuDI method. Applications demonstrating how utilizing uncertainty information/approximations along with generalized least squares techniques improve PuDI fits are presented. Although the primary application here is in estimating nonlinear SDEs, the PuDI method is applicable to situations where both unbiased function and derivative estimates are available.

  20. Generalised derived limits for radioisotopes of iodine

    International Nuclear Information System (INIS)

    Hughes, J.S.; Haywood, S.M.; Simmonds, J.R.

    1984-04-01

    Generalised Derived Limits (GDLs) are evaluated for iodine-125,129,131,132,133,134,135 in selected materials from the terrestrial and aquatic environments and for discharge to atmosphere. They are intended for use as convenient reference levels against which the results of environmental monitoring can be compared and atmospheric discharges assessed. GDLs are intended for use when the environmental contamination or discharge to atmosphere is less than about 5% of the GDL. If the level of environmental contamination or discharge to the atmosphere exceeds this percentage of the GDL it does not necessarily mean that the dose equivalents to members of the public are approaching the dose equivalent limit. It is rather an indication that it may be appropriate to obtain a more specific derived limit for the particular situation by reviewing the values of the parameters involved in the calculation. GDL values are specified for iodine radionuclides in water, soil, grass, sediments and various foodstuffs derived from the terrestrial and aquatic environments. GDLs are also given for iodine radionuclides on terrestrial surfaces and for their discharge to atmosphere. (author)