WorldWideScience

Sample records for bim-bh3 mimetic therapy

  1. Bcl-2/MDM2 Dual Inhibitors Based on Universal Pyramid-Like α-Helical Mimetics.

    Science.gov (United States)

    Wang, Ziqian; Song, Ting; Feng, Yingang; Guo, Zongwei; Fan, Yudan; Xu, Wenjie; Liu, Lu; Wang, Anhui; Zhang, Zhichao

    2016-04-14

    No α-helical mimetic that exhibits Bcl-2/MDM2 dual inhibition has been rationally designed due to the different helicities of the α-helixes at their binding interfaces. Herein, we extracted a one-turn α-helix-mimicking ortho-triarene unit from o-phenylene foldamers. Linking benzamide substrates with a rotatable C-N bond, we constructed a novel semirigid pyramid-like scaffold that could support its two-turn α-helix mimicry without aromatic stacking interactions and could adopt the different dihedral angles of the key residues of p53 and BH3-only peptides. On the basis of this universal scaffold, a series of substituent groups were installed to capture the key residues of both p53TAD and BimBH3 and balance the differences of the bulks between them. Identified by FP, ITC, and NMR spectroscopy, a compound 6e (zq-1) that directly binds to Mcl-1, Bcl-2, and MDM2 with balanced submicromolar affinities was obtained. Cell-based experiments demonstrated its antitumor ability through Bcl-2/MDM2 dual inhibition simultaneously.

  2. Bio-mimetic Nanostructure Self-assembled from Au@Ag Heterogeneous Nanorods and Phage Fusion Proteins for Targeted Tumor Optical Detection and Photothermal Therapy

    OpenAIRE

    Fei Wang; Pei Liu; Lin Sun; Cuncheng Li; Valery. A. Petrenko; Aihua Liu

    2014-01-01

    Nanomaterials with near-infrared (NIR) absorption have been widely studied in cancer detection and photothermal therapy (PTT), while it remains a great challenge in targeting tumor efficiently with minimal side effects. Herein we report a novel multifunctional phage-mimetic nanostructure, which was prepared by layer-by-layer self-assembly of Au@Ag heterogenous nanorods (NRs) with rhodamine 6G, and specific pVIII fusion proteins. Au@Ag NRs, first being applied for PTT, exhibited excellent stab...

  3. A superoxide dismutase/catalase mimetic nanomedicine for targeted therapy of inflammatory bowel disease.

    Science.gov (United States)

    Zhang, Qixiong; Tao, Hui; Lin, Yongyao; Hu, Ying; An, Huijie; Zhang, Dinglin; Feng, Shibin; Hu, Houyuan; Wang, Ruibing; Li, Xiaohui; Zhang, Jianxiang

    2016-10-01

    Oxidative stress, resulting from excessive generation of reactive oxygen species (ROS), plays a pivotal role in the initiation and progression of inflammatory bowel disease (IBD). To develop an efficacious and safe nanotherapy against IBD, we designed and developed a superoxide dismutase/catalase mimetic nanomedicine comprising a hydrogen peroxide-eliminating nanomatrix and a free radical scavenger Tempol (Tpl). To this end, an oxidation-responsive β-cyclodextrin material (OxbCD) was synthesized, and a Tpl-loaded OxbCD nanoparticle (Tpl/OxbCD NP) was produced. Hydrolysis of OxbCD NP could be triggered by hydrogen peroxide, leading to on-demand release of loaded Tpl molecules from Tpl/OxbCD NP. OxbCD NP was able to efficiently accumulate in the inflamed colon in mice, thereby dramatically reducing nonspecific distribution after oral delivery. In three mouse colitis models, oral administration of Tpl/OxbCD NP notably mitigated manifestations relevant to colitis, and significantly suppressed expression of proinflammatory mediators, with the efficacy superior over free Tpl or a control nanomedicine based on poly(lactide-co-glycolide) (PLGA). Accordingly, by scavenging multiple components of ROS, Tpl/OxbCD NP may effectively reduce ulcerative colitis in mice, and it can be intensively developed as a translational nanomedicine for the management of IBD and other inflammatory diseases. PMID:27525680

  4. A superoxide dismutase/catalase mimetic nanomedicine for targeted therapy of inflammatory bowel disease.

    Science.gov (United States)

    Zhang, Qixiong; Tao, Hui; Lin, Yongyao; Hu, Ying; An, Huijie; Zhang, Dinglin; Feng, Shibin; Hu, Houyuan; Wang, Ruibing; Li, Xiaohui; Zhang, Jianxiang

    2016-10-01

    Oxidative stress, resulting from excessive generation of reactive oxygen species (ROS), plays a pivotal role in the initiation and progression of inflammatory bowel disease (IBD). To develop an efficacious and safe nanotherapy against IBD, we designed and developed a superoxide dismutase/catalase mimetic nanomedicine comprising a hydrogen peroxide-eliminating nanomatrix and a free radical scavenger Tempol (Tpl). To this end, an oxidation-responsive β-cyclodextrin material (OxbCD) was synthesized, and a Tpl-loaded OxbCD nanoparticle (Tpl/OxbCD NP) was produced. Hydrolysis of OxbCD NP could be triggered by hydrogen peroxide, leading to on-demand release of loaded Tpl molecules from Tpl/OxbCD NP. OxbCD NP was able to efficiently accumulate in the inflamed colon in mice, thereby dramatically reducing nonspecific distribution after oral delivery. In three mouse colitis models, oral administration of Tpl/OxbCD NP notably mitigated manifestations relevant to colitis, and significantly suppressed expression of proinflammatory mediators, with the efficacy superior over free Tpl or a control nanomedicine based on poly(lactide-co-glycolide) (PLGA). Accordingly, by scavenging multiple components of ROS, Tpl/OxbCD NP may effectively reduce ulcerative colitis in mice, and it can be intensively developed as a translational nanomedicine for the management of IBD and other inflammatory diseases.

  5. Diabetes-Impaired Wound Healing Is Improved by Matrix Therapy With Heparan Sulfate Glycosaminoglycan Mimetic OTR4120 in Rats

    OpenAIRE

    Tong, Miao; Tuk, Bastiaan; Shang, Peng; Hekking, Ineke M.; Esther M G Fijneman; Guijt, Marnix; Hovius, Steven E. R.; Johan W van Neck

    2012-01-01

    Wound healing in diabetes is frequently impaired, and its treatment remains a challenge. We tested a therapeutic strategy of potentiating intrinsic tissue regeneration by restoring the wound cellular environment using a heparan sulfate glycosaminoglycan mimetic, OTR4120. The effect of OTR4120 on healing of diabetic ulcers was investigated. Experimental diabetes was induced by intraperitoneal injection of streptozotocin. Seven weeks after induction of diabetes, rats were ulcerated by clamping ...

  6. Mimetic discretization methods

    CERN Document Server

    Castillo, Jose E

    2013-01-01

    To help solve physical and engineering problems, mimetic or compatible algebraic discretization methods employ discrete constructs to mimic the continuous identities and theorems found in vector calculus. Mimetic Discretization Methods focuses on the recent mimetic discretization method co-developed by the first author. Based on the Castillo-Grone operators, this simple mimetic discretization method is invariably valid for spatial dimensions no greater than three. The book also presents a numerical method for obtaining corresponding discrete operators that mimic the continuum differential and

  7. Bio-mimetic Nanostructure Self-assembled from Au@Ag Heterogeneous Nanorods and Phage Fusion Proteins for Targeted Tumor Optical Detection and Photothermal Therapy

    Science.gov (United States)

    Wang, Fei; Liu, Pei; Sun, Lin; Li, Cuncheng; Petrenko, Valery A.; Liu, Aihua

    2014-10-01

    Nanomaterials with near-infrared (NIR) absorption have been widely studied in cancer detection and photothermal therapy (PTT), while it remains a great challenge in targeting tumor efficiently with minimal side effects. Herein we report a novel multifunctional phage-mimetic nanostructure, which was prepared by layer-by-layer self-assembly of Au@Ag heterogenous nanorods (NRs) with rhodamine 6G, and specific pVIII fusion proteins. Au@Ag NRs, first being applied for PTT, exhibited excellent stability, cost-effectivity, biocompatibility and tunable NIR absorption. The fusion proteins were isolated from phage DDAGNRQP specifically selected from f8/8 landscape phage library against colorectal cancer cells in a high-throughput way. Considering the definite charge distribution and low molecular weight, phage fusion proteins were assembled on the negatively charged NR core by electrostatic interactions, exposing the N-terminus fused with DDAGNRQP peptide on the surface. The fluorescent images showed that assembled phage fusion proteins can direct the nanostructure into cancer cells. The nanostructure was more efficient than gold nanorods and silver nanotriangle-based photothermal agents and was capable of specifically ablating SW620 cells after 10 min illumination with an 808 nm laser in the light intensity of 4 W/cm2. The prepared nanostructure would become an ideal reagent for simutaneously targeted optical imaging and PTT of tumor.

  8. Combination small molecule PPT1 mimetic and CNS-directed gene therapy as a treatment for infantile neuronal ceroid lipofuscinosis

    OpenAIRE

    Roberts, Marie S.; Macauley, Shannon L.; Wong, Andrew M.; Yilmas, Denis; Hohm, Sarah; Cooper, Jonathan D.; Sands, Mark S.

    2012-01-01

    Infantile neuronal ceroid lipofuscinosis (INCL) is a profoundly neurodegenerative disease of children caused by a deficiency in the lysosomal enzyme palmitoyl protein thioesterase-1 (PPT1). There is currently no effective therapy for this invariably fatal disease. To date, preclinical experiments using single treatments have resulted in incremental clinical improvements. Therefore, we determined the efficacy of CNS-directed AAV2/5-mediated gene therapy alone and in combination with the system...

  9. Unimodular-Mimetic Cosmology

    CERN Document Server

    Nojiri, S; Oikonomou, V K

    2016-01-01

    We combine the unimodular gravity and mimetic gravity theories into a unified theoretical framework, which is proposed to solve the cosmological constant problem and the dark matter issue. After providing the formulation of the unimodular mimetic gravity and investigating all the new features that the vacuum unimodular gravity implies, by using the underlying reconstruction method, we realize some well known cosmological evolutions, with some of these being exotic for the ordinary Einstein-Hilbert gravity. Specifically we provide the vacuum unimodular mimetic gravity description of the de Sitter cosmology, of the perfect fluid with constant equation of state cosmology, of the Type IV singular cosmology and of the $R^2$ inflation cosmology. Moreover, we investigate how cosmologically viable cosmologies, which are compatible with the recent observational data, can be realized by the vacuum unimodular mimetic gravity. Since in some cases, the graceful exit from inflation problem might exist, we provide a qualita...

  10. Unimodular-mimetic cosmology

    Science.gov (United States)

    Nojiri, S.; Odintsov, S. D.; Oikonomou, V. K.

    2016-06-01

    We combine the unimodular gravity and mimetic gravity theories into a unified theoretical framework, which is proposed to provide a suggestive proposal for a framework that may assist in the discussion and search for a solution to the cosmological constant problem and the dark matter issue. After providing the formulation of the unimodular mimetic gravity and investigating all the new features that the vacuum unimodular gravity implies, by using the underlying reconstruction method, we realize some well known cosmological evolutions, with some of these being exotic for the ordinary Einstein-Hilbert gravity. Specifically we provide the vacuum unimodular mimetic gravity description of the de Sitter cosmology and of the perfect fluid with constant equation of state cosmology. As we demonstrate, these cosmologies can be realized by vacuum mimetic unimodular gravity, without the existence of any matter fluid source. Moreover, we investigate how cosmologically viable cosmologies, which are compatible with the recent observational data, can be realized by the vacuum unimodular mimetic gravity. Since in some cases, a graceful exit from inflation problem might exist, we provide a qualitative description of the mechanism that can potentially generate the graceful exit from inflation in these theories, by searching for the unstable de Sitter solutions in the context of unimodular mimetic theories of gravity.

  11. Mimetic finite difference method

    Science.gov (United States)

    Lipnikov, Konstantin; Manzini, Gianmarco; Shashkov, Mikhail

    2014-01-01

    The mimetic finite difference (MFD) method mimics fundamental properties of mathematical and physical systems including conservation laws, symmetry and positivity of solutions, duality and self-adjointness of differential operators, and exact mathematical identities of the vector and tensor calculus. This article is the first comprehensive review of the 50-year long history of the mimetic methodology and describes in a systematic way the major mimetic ideas and their relevance to academic and real-life problems. The supporting applications include diffusion, electromagnetics, fluid flow, and Lagrangian hydrodynamics problems. The article provides enough details to build various discrete operators on unstructured polygonal and polyhedral meshes and summarizes the major convergence results for the mimetic approximations. Most of these theoretical results, which are presented here as lemmas, propositions and theorems, are either original or an extension of existing results to a more general formulation using polyhedral meshes. Finally, flexibility and extensibility of the mimetic methodology are shown by deriving higher-order approximations, enforcing discrete maximum principles for diffusion problems, and ensuring the numerical stability for saddle-point systems.

  12. Promises and Challenges of Smac Mimetics as Cancer Therapeutics.

    Science.gov (United States)

    Fulda, Simone

    2015-11-15

    Inhibitor of Apoptosis (IAP) proteins block programmed cell death and are expressed at high levels in various human cancers, thus making them attractive targets for cancer drug development. Second mitochondrial activator of caspases (Smac) mimetics are small-molecule inhibitors that mimic Smac, an endogenous antagonist of IAP proteins. Preclinical studies have shown that Smac mimetics can directly trigger cancer cell death or, even more importantly, sensitize tumor cells for various cytotoxic therapies, including conventional chemotherapy, radiotherapy, or novel agents. Currently, several Smac mimetics are under evaluation in early clinical trials as monotherapy or in rational combinations (i.e., GDC-0917/CUDC-427, LCL161, AT-406/Debio1143, HGS1029, and TL32711/birinapant). This review discusses the promise as well as some challenges at the translational interface of exploiting Smac mimetics as cancer therapeutics.

  13. Mimetic Compact Stars

    CERN Document Server

    Momeni, D; Gholizade, H; Myrzakulov, R

    2015-01-01

    Modified gravity models have been constantly proposed with the purpose of evading some standard gravity shortcomings. Recently proposed by A.H. Chamseddine and V. Mukhanov, the Mimetic Gravity arises as an optimistic alternative. Our purpose in this work is to derive Tolman-Oppenheimer-Volkoff equations and solutions for such a gravity theory. We solve them numerically for quark star and neutron star cases. The results are carefully discussed.

  14. Cylindrical solutions in mimetic gravity

    Energy Technology Data Exchange (ETDEWEB)

    Momeni, Davood; Myrzakulov, Kairat; Myrzakulov, Ratbay [Eurasian National University, Eurasian International Center for Theoretical Physics and Department of General and Theoretical Physics, Astana (Kazakhstan); Raza, Muhammad [COMSATS Institute of Information Technology, Department of Mathematics, Sahiwal (Pakistan)

    2016-06-15

    This paper is devoted to investigate cylindrical solutions in mimetic gravity. The explicit forms of the metric of this theory, namely mimetic-Kasner (say) have been obtained. In this study we have noticed that the Kasner's family of exact solutions needs to be reconsidered under this type of modified gravity. A no-go theorem is proposed for the exact solutions in the presence of a cosmological constant. (orig.)

  15. Effect of chronic antioxidant therapy with superoxide dismutase-mimetic drug, tempol, on progression of renal disease in rats with renal mass reduction.

    Science.gov (United States)

    Quiroz, Yasmir; Ferrebuz, Atilio; Vaziri, Nosratola D; Rodriguez-Iturbe, Bernardo

    2009-01-01

    Oxidative stress and inflammation play a major role in the progression of renal damage and antioxidants are potentially useful therapeutic options in chronic renal disease. We investigated if treatment with tempol, a superoxide dismutase mimetic that has beneficial effects in several experimental models of hypertension and acute kidney injury, ameliorates the chronic renal damage resulting in renal mass reduction. Rats with surgical 5/6 nephrectomy were randomly assigned to receive no treatment (CRF group, n = 10) or tempol, 1 mmol/l in the drinking water (CRF-tempol group, n = 10). Sham-operated rats (n = 10) served as controls. All rats were followed for 12 weeks post-nephrectomy. Tempol treatment reduced plasma malondialdehyde (MDA) levels and halved the number of superoxide-positive cells in the remnant kidney; however, the number of hydrogen peroxide-positive cells increased and the overall renal oxidative stress (MDA and nitrotyrosine abundance) and inflammation (interstitial p65 NF-kappaB, macrophage and lymphocyte infiltration) were unchanged. Proteinuria, renal function and glomerular and tubulointerstitial damage in the remnant kidney were similar in the CRF and CRF-tempol groups. In conclusion, tempol administration, at the dose used in these studies, decreased plasma MDA and heightened superoxide dismutation in the kidney, but was incapable of reducing renal oxidative stress or improving renal function or structure in the remnant kidney model.

  16. Bio-mimetic Flow Control

    Science.gov (United States)

    Choi, Haecheon

    2009-11-01

    Bio-mimetic engineering or bio-mimetics is the application of biological methods and systems found in nature to the study and design of engineering systems and modern technology (from Wikipedia). The concept itself is old, but successful developments have been made recently, especially in the research field of flow control. The objective of flow control based on the bio-mimetic approach is to develop novel concepts for reducing drag, increasing lift and enhancing aerodynamic performance. For skin friction reduction, a few ideas have been suggested such as the riblet from shark, compliant surface from dolphin, microbubble injection and multiple front-body curvature from penguin, and V-shaped protrusion from sailfish. For form drag reduction, several new attempts have been also made recently. Examples include the V-shaped spanwise grooves from saguaro cactus, overall shape of box fish, longitudinal grooves on scallop shell, bill of swordfish, hooked comb on owl wing, trailing-edge protrusion on dragonfly wing, and fillet. For the enhancement of aerodynamic performance, focuses have been made on the birds, fish and insects: e.g., double layered feather of landing bird, leading-edge serration of humpback-whale flipper, pectoral fin of flying fish, long tail on swallowtail-butterfly wing, wing flapping motion of dragonfly, and alula in birds. Living animals adapt their bodies to better performance in multi purposes, but engineering requires single purpose in most cases. Therefore, bio-mimetic approaches often produce excellent results more than expected. However, they are sometimes based on people's wrong understanding of nature and produce unwanted results. Successes and failures from bio-mimetic approaches in flow control will be discussed in the presentation.

  17. Many Faces of Mimetic Gravity

    CERN Document Server

    Hammer, Katrin

    2015-01-01

    We consider the recently introduced mimetic gravity, which is a Weyl-symmetric extension of the General Relativity and which can play a role of an imperfect fluid-like Dark Matter with a small sound speed. In this paper we discuss in details how this higher- derivative scalar-tensor theory goes beyond the construction by Horndeski, keeping only one scalar degree of freedom on top of two standard graviton polarizations. In particular, we consider representations of the theory in different sets of Weyl-invariant variables and connect this framework to the singular Brans-Dicke theory. Further, we find solution of equations of motion for the mimetic gravity in the synchronous reference frame in a general curved spacetime. This solution is exact in the test-field approximation or in the case of a shear-free spacetime without any other matter.

  18. Unimodular mimetic F(R) inflation

    Science.gov (United States)

    Odintsov, S. D.; Oikonomou, V. K.

    2016-07-01

    We propose the unimodular-mimetic F(R) gravity theory, to resolve cosmological constant problem and dark matter problem in a unified geometric manner. We demonstrate that such a theory naturally admits accelerating universe evolution. Furthermore, we construct unimodular-mimetic F(R) inflationary cosmological scenarios compatible with the Planck and BICEP2/Keck-Array observational data. We also address the graceful exit issue, which is guaranteed by the existence of unstable de Sitter vacua.

  19. Cosmological perturbations in mimetic matter model

    CERN Document Server

    Matsumoto, Jiro; Sushkov, Sergey V

    2015-01-01

    We investigate the cosmological evolution of mimetic matter model with arbitrary scalar potential. The cosmological reconstruction is explicitly done for different choices of potential. The cases that mimetic matter model shows the evolution as Cold Dark Matter(CDM), wCDM model, dark matter and dark energy with dynamical $Om(z)$ or phantom dark energy with phantom-non-phantom crossing are presented in detail. The cosmological perturbations for such evolution are studied in mimetic matter model. For instance, the evolution behavior of the matter density contrast which is different from usual one, i.e. $\\ddot \\delta + 2 H \\dot \\delta - \\kappa ^2 \\rho \\delta /2 = 0$ is investigated. The possibility of peculiar evolution of $\\delta$ in the model under consideration is shown. Special attention is paid to the behavior of matter density contrast near to future singularity where decay of perturbations may occur much earlier the singularity.

  20. Mimetic desire and scapegoat mechanism in sport

    Directory of Open Access Journals (Sweden)

    Jernej Pisk

    2012-12-01

    Full Text Available BACKGROUND: The most fundamental question about sport is what is sport, what is its origin and its essence? Because sport is connected with the human being (there is no sport without human beings different anthropological visions of human being result in different understandings of sport. OBJECTIVE: The objective of this paper is to present and explain an anthropological vision of the human being and society as was developed by René Girard. In his view mimetic desire and the scapegoat mechanism have a central role in any culture, religion or other secular institutions. The explanatory power of his theory is presented when it is applied to the world of sport. METHODS: Our methodology is philosophical, involving conceptual analysis and the application of the outcomes to sport. RESULTS: In the paper we show that mimetic desire can be recognized as one of the important origins of recreational and competitive sports. When people recognize what other people are able to do or accomplish in sport this invokes the mimetic desire as a result of which motivation for sport and competiveness can arise. But mimetic rivalry leads to an unstable situation. Therefore a second element is needed: Scapegoating in sport is presented as a mean to preserve the good reputation of sport, to keep peace in sport as well as in society as a whole. Finally, the attempt to overcome mimetic desire and scapegoating in sport is presented and the question if this is worth trying at all is opened. CONCLUSIONS: The theories of mimetic desire and scapegoat mechanism have great explanatory power when they are applied to the field of sport. They could reveal us some hidden motives and forces which drive athletes and sport as a whole. Moreover, they exceed the world of sport and reveal the influence of sport on the whole of society.

  1. Mimetic dark matter, ghost instability and a mimetic tensor-vector-scalar gravity

    OpenAIRE

    Chaichian, Masud; Klusoň, Josef; Oksanen, Markku; Tureanu, Anca

    2014-01-01

    Recently modified gravitational theories which mimic the behaviour of dark matter, the so-called "Mimetic Dark Matter", have been proposed. We study the consistency of such theories with respect to the absence of ghost instability and propose a new tensor-vector-scalar theory of gravity, which is a generalization of the previous models of mimetic dark matter with additional desirable features. The original model proposed by Chamseddine and Mukhanov [JHEP 1311 (2013) 135, arXiv:1308.5410] is c...

  2. Antibody mimetics: promising complementary agents to animal-sourced antibodies.

    Science.gov (United States)

    Baloch, Abdul Rasheed; Baloch, Abdul Wahid; Sutton, Brian J; Zhang, Xiaoying

    2016-01-01

    Despite their wide use as therapeutic, diagnostic and detection agents, the limitations of polyclonal and monoclonal antibodies have inspired scientists to design the next generation biomedical agents, so-called antibody mimetics that offer many advantages over conventional antibodies. Antibody mimetics can be constructed by protein-directed evolution or fusion of complementarity-determining regions through intervening framework regions. Substantial progress in exploiting human, butterfly (Pieris brassicae) and bacterial systems to design and select mimetics using display technologies has been made in the past 10 years, and one of these mimetics [Kalbitor® (Dyax)] has made its way to market. Many challenges lie ahead to develop mimetics for various biomedical applications, especially those for which conventional antibodies are ineffective, and this review describes the current characteristics, construction and applications of antibody mimetics compared to animal-sourced antibodies. The possible limitations of mimetics and future perspectives are also discussed. PMID:25264572

  3. Oestrogene mimetic isoflavones’ pharmacokinetics and pharmacodynamics

    Directory of Open Access Journals (Sweden)

    Anca Dragomirescu,

    2008-12-01

    Full Text Available Genisteine is the most abundant and the most studied estrogen-mimetic izoflavone. It's chemical formula is 4',5,7 – trihidroxyisoflavone. It has also estrogen-modulated properties by its binding ability to the beta type estrogen receptor. Genisteine presents the following farmacodinamic effects: antiaterogen effect, prevention of estrogen-dependent cancers, especially breast cancer, prevention of skin aging body, osteoprogen effect, prevention of osteoporosis at the menopauses women. Despite all these real benefits, there are also many adverse effects, registered both in humans and animals. Thus, the sheep feeding with some Fabaceae species, containing estrogen-mimetic isoflavones were stopped their reproductive function(isoflavones acted as an oral contraceptive. In humans, phytoestroges influence is still under evaluation, being suspected effects such as cerebral involution - via abusive apoptosis - or disturbance in hormonal status, in male children. All these are added to already known allergies, caused by soy proteins.

  4. A note on a mimetic scalar-tensor cosmological model

    Energy Technology Data Exchange (ETDEWEB)

    Rabochaya, Yevgeniya; Zerbini, Sergio [Universita di Trento, Dipartimento di Fisica, Povo, Trento (Italy); TIFPA-INFN, Povo, Trento (Italy)

    2016-02-15

    A specific Hordenski scalar-gravity mimetic model is investigated within a FLWR space-time. The mimetic scalar field is implemented via a Lagrangian multiplier, and it is shown that the model has equations of motion formally similar to the original simpler mimetic matter model of Chamseddine-Mukhanov-Vikman. Several exact solutions describing inflation, bounces, and future-time singularities are presented and discussed. (orig.)

  5. Cosmological perturbations in a mimetic matter model

    Science.gov (United States)

    Matsumoto, Jiro; Odintsov, Sergei D.; Sushkov, Sergey V.

    2015-03-01

    We investigate the cosmological evolution of a mimetic matter model with arbitrary scalar potential. The cosmological reconstruction—which is the method for constructing a model for an arbitrary evolution of the scale factor—is explicitly performed for different choices of potential. The cases where the mimetic matter model shows the evolution as cold dark matter (CDM), the w CDM model, dark matter and dark energy with a dynamical O m (z ) [where O m (z )≡[(H (z )/H0)2-1 ]/[(1 +z )3-1 ] ], and phantom dark energy with a phantom-nonphantom crossing are presented in detail. The cosmological perturbations for such evolutions are studied in the mimetic matter model. For instance, the evolution behavior of the matter density contrast (which is different than the usual one, i.e., δ ¨+2 H δ ˙-κ2ρ δ /2 =0 ) is investigated. The possibility of a peculiar evolution of δ in the model under consideration is shown. Special attention is paid to the behavior of the matter density contrast near the future singularity, where the decay of perturbations may occur much earlier than the singularity.

  6. NEC violation in mimetic cosmology revisited

    Directory of Open Access Journals (Sweden)

    Anna Ijjas

    2016-09-01

    Full Text Available In the context of Einstein gravity, if the null energy condition (NEC is satisfied, the energy density in expanding space–times always decreases while in contracting space–times the energy density grows and the universe eventually collapses into a singularity. In particular, no non-singular bounce is possible. It is, though, an open question if this energy condition can be violated in a controlled way, i.e., without introducing pathologies, such as unstable negative-energy states or an imaginary speed of sound. In this letter, we will re-examine the claim that the recently proposed mimetic scenario can violate the NEC without pathologies. We show that mimetic cosmology is prone to gradient instabilities even in cases when the NEC is satisfied (except for trivial examples. Most interestingly, the source of the instability is always the Einstein–Hilbert term in the action. The matter stress-energy component does not contribute spatial gradient terms but instead makes the problematic curvature modes dynamical. We also show that mimetic cosmology can be understood as a singular limit of known, well-behaved theories involving higher-derivative kinetic terms and discuss ways of removing the instability.

  7. NEC violation in mimetic cosmology revisited

    Science.gov (United States)

    Ijjas, Anna; Ripley, Justin; Steinhardt, Paul J.

    2016-09-01

    In the context of Einstein gravity, if the null energy condition (NEC) is satisfied, the energy density in expanding space-times always decreases while in contracting space-times the energy density grows and the universe eventually collapses into a singularity. In particular, no non-singular bounce is possible. It is, though, an open question if this energy condition can be violated in a controlled way, i.e., without introducing pathologies, such as unstable negative-energy states or an imaginary speed of sound. In this letter, we will re-examine the claim that the recently proposed mimetic scenario can violate the NEC without pathologies. We show that mimetic cosmology is prone to gradient instabilities even in cases when the NEC is satisfied (except for trivial examples). Most interestingly, the source of the instability is always the Einstein-Hilbert term in the action. The matter stress-energy component does not contribute spatial gradient terms but instead makes the problematic curvature modes dynamical. We also show that mimetic cosmology can be understood as a singular limit of known, well-behaved theories involving higher-derivative kinetic terms and discuss ways of removing the instability.

  8. From neutron stars to quark stars in mimetic gravity

    Science.gov (United States)

    Astashenok, Artyom V.; Odintsov, Sergei D.

    2016-09-01

    Realistic models of neutron and quark stars in the framework of mimetic gravity with a Lagrange multiplier constraint are presented. We discuss the effect of a mimetic scalar aiming to describe dark matter on the mass-radius relation and the moment of inertia for slowly rotating relativistic stars. The mass-radius relation and moment of inertia depend on the value of the mimetic scalar in the center of the star. This fact leads to the ambiguity in the mass-radius relation for a given equation of state. Such ambiguity allows us to explain some observational facts better than in standard general relativity. The case of mimetic potential V (ϕ )˜A eC ϕ2 is considered in detail. The relative deviation of the maximal moment of inertia is approximately twice as large as the relative deviation of the maximal stellar mass. We also briefly discuss the mimetic f (R ) gravity. In the case of f (R )=R +a R2 mimetic gravity, it is expected that the increase of maximal mass and maximal moment of inertia due to the mimetic scalar becomes much stronger with bigger parameter a . The influence of the scalar field in mimetic gravity can lead to the possible existence of extreme neutron stars with large masses.

  9. Disformal transformations, veiled General Relativity and Mimetic Gravity

    Energy Technology Data Exchange (ETDEWEB)

    Deruelle, Nathalie [APC, CNRS-Université Paris 7, 75205 Paris CEDEX 13 (France); Rua, Josephine, E-mail: deruelle@ihes.fr, E-mail: rua@cbpf.br [Instituto de Cosmologia, Relatividade e Astrofísica—ICRA/CBPF, Rua Dr. Xavier Sigaud 150, 22290-180 Rio de Janeiro (Brazil)

    2014-09-01

    In this Note we show that Einstein's equations for gravity are generically invariant under ''disformations''. We also show that the particular subclass when this is not true yields the equations of motion of ''Mimetic Gravity''. Finally we give the ''mimetic'' generalization of the Schwarzschild solution.

  10. SuperMimic – Fitting peptide mimetics into protein structures

    Directory of Open Access Journals (Sweden)

    Schmidt Ulrike

    2006-01-01

    Full Text Available Abstract Background Various experimental techniques yield peptides that are biologically active but have unfavourable pharmacological properties. The design of structurally similar organic compounds, i.e. peptide mimetics, is a challenging field in medicinal chemistry. Results SuperMimic identifies compounds that mimic parts of a protein, or positions in proteins that are suitable for inserting mimetics. The application provides libraries that contain peptidomimetic building blocks on the one hand and protein structures on the other. The search for promising peptidomimetic linkers for a given peptide is based on the superposition of the peptide with several conformers of the mimetic. New synthetic elements or proteins can be imported and used for searching. Conclusion We present a graphical user interface for finding peptide mimetics that can be inserted into a protein or for fitting small molecules into a protein. Using SuperMimic, promising locations in proteins for the insertion of mimetics can be found quickly and conveniently.

  11. SuperMimic – Fitting peptide mimetics into protein structures

    Science.gov (United States)

    Goede, Andrean; Michalsky, Elke; Schmidt, Ulrike; Preissner, Robert

    2006-01-01

    Background Various experimental techniques yield peptides that are biologically active but have unfavourable pharmacological properties. The design of structurally similar organic compounds, i.e. peptide mimetics, is a challenging field in medicinal chemistry. Results SuperMimic identifies compounds that mimic parts of a protein, or positions in proteins that are suitable for inserting mimetics. The application provides libraries that contain peptidomimetic building blocks on the one hand and protein structures on the other. The search for promising peptidomimetic linkers for a given peptide is based on the superposition of the peptide with several conformers of the mimetic. New synthetic elements or proteins can be imported and used for searching. Conclusion We present a graphical user interface for finding peptide mimetics that can be inserted into a protein or for fitting small molecules into a protein. Using SuperMimic, promising locations in proteins for the insertion of mimetics can be found quickly and conveniently. PMID:16403211

  12. A cosmological solution to mimetic dark matter

    Energy Technology Data Exchange (ETDEWEB)

    Saadi, Hassan [American University of Beirut, Physics Department, Beirut (Lebanon)

    2016-01-15

    In this paper, a cosmological solution to Mimetic Dark Matter (MDM) for an exponential potential is provided. Then a solution for the 0 - i perturbed Einstein differential equation of MDM is obtained based on an exponential potential that satisfies inflation for some initial conditions. Another general potential is suggested that incorporates inflation too. Then quantum perturbations are included. The constants in the model can be tuned to be in agreement with the fluctuation amplitude of the cosmic microwave background (CMB) radiation. Finally, the spectral index is calculated for the suggested potentials. Moreover, MDM is shown to be a viable model to produce dark matter, inflation, and CMB's fluctuation. (orig.)

  13. A cosmological solution to mimetic dark matter

    Energy Technology Data Exchange (ETDEWEB)

    Saadi, Hassan, E-mail: hls01@mail.aub.edu [Physics Department, American University of Beirut, Beirut (Lebanon)

    2016-01-11

    In this paper, a cosmological solution to Mimetic Dark Matter (MDM) for an exponential potential is provided. Then a solution for the 0-i perturbed Einstein differential equation of MDM is obtained based on an exponential potential that satisfies inflation for some initial conditions. Another general potential is suggested that incorporates inflation too. Then quantum perturbations are included. The constants in the model can be tuned to be in agreement with the fluctuation amplitude of the cosmic microwave background (CMB) radiation. Finally, the spectral index is calculated for the suggested potentials. Moreover, MDM is shown to be a viable model to produce dark matter, inflation, and CMB’s fluctuation.

  14. Smac mimetic-derived augmentation of chemotherapeutic response in experimental pancreatic cancer

    International Nuclear Information System (INIS)

    Pancreatic ductal adenocarcinoma (PDAC) is highly resistant to conventional chemotherapy, in part due to the overexpression of inhibitors of apoptosis proteins (IAPs). Smac is an endogenous IAP-antagonist, which renders synthetic Smac mimetics attractive anticancer agents. We evaluated the benefits of combining a Smac mimetic, JP1201 (JP), with conventional chemotherapy agents used for PDAC management. Cell viability assays and protein expression analysis were performed using WST-1 reagent and Western blotting, respectively. Apoptosis was detected by annexin V/propidium iodide staining. In vivo tumor growth and survival studies were performed in murine PDAC xenografts. JP and gemcitabine (Gem) inhibited PDAC cell proliferation with additive effects in combination. The percentage of early apoptotic cells in controls, JP, Gem and JP + Gem was 17%, 26%, 26% and 38%, respectively. JP-induced apoptosis was accompanied by PARP-1 cleavage. Similar additive anti-proliferative effects were seen for combinations of JP with doxorubicin (Dox) and docetaxel (DT). The JP + Gem combination caused a 30% decrease in tumor size in vivo compared to controls. Median animal survival was improved significantly in mice treated with JP + Gem (38 d) compared to controls (22 d), JP (28 d) or Gem (32 d) (p = 0.01). Animal survival was also improved with JP + DT treatment (32 d) compared to controls (16 d), JP (21 d) or DT alone (27 d). These results warrant further exploration of strategies that promote chemotherapy-induced apoptosis of tumors and highlight the potential of Smac mimetics in clinical PDAC therapy

  15. NEC violation in mimetic cosmology revisited

    CERN Document Server

    Ijjas, Anna; Steinhardt, Paul J

    2016-01-01

    In the context of Einstein gravity, if the null energy condition (NEC) is satisfied, the energy density in expanding space-times always decreases while in contracting space-times the energy density grows and the universe eventually collapses into a singularity. In particular, no non-singular bounce is possible. It is, though, an open question if this energy condition can be violated in a controlled way, i.e., without introducing pathologies, such as unstable negative-energy states or an imaginary speed of sound. In this paper, we will re-examine the claim that the recently proposed mimetic scenario can violate the NEC without pathologies. We show that mimetic cosmology is prone to gradient instabilities even in cases when the NEC is satisfied (except for trivial examples). Most interestingly, the source of the instability is always the Einstein-Hilbert term in the action. The matter stress-energy component does not contribute spatial gradient terms but instead makes the problematic curvature modes dynamical. ...

  16. The testosterone mimetic properties of icariin

    Institute of Scientific and Technical Information of China (English)

    Zhen-Bao Zhang; Qing-Tao Yang

    2006-01-01

    Aim: To evaluate the testosterone mimetic properties of icariin. Methods: Forty-eight healthy male Sprague-Dawley rats at the age of 15 months were randomly divided into four groups with 12 rats each: the control group (C), the model group (M), the icariin group (ICA) and the testosterone group (T). The reproductive system was damaged by cyclogroup for 7 consecutive days, respectively. The levels of serum testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH), serum bone Gla-protein (BGP) and tartrate-resistant acid phosphatase activity in serum (StrACP) were determined. The histological changes of the testis and the penis were observed by microscope with hematoxylin-eosin (HE) staining and terminal deoxynucleotidyl transferase biotin-dUTP-X nick end labeling (TUNEL),respectively. Results: (1) Icariin improved the condition of reproductive organs and increased the circulating levels of testosterone. (2) Icariin treatment also improved the steady-state serum BGP and might have promoted bone formation. At the same time, it decreased the serum levels of StrACP and might have reduced the bone resorption. (3)Icarrin suppressed the extent of apoptosis of penile cavernosal smooth muscle cells. Conclusion: Icariin has testosterone mimetic properties and has therapeutic potential in the management of hypoandrogenism.

  17. Iron oxide superparamagnetic nanoparticles conjugated with a conformationally blocked α-Tn antigen mimetic for macrophage activation

    Science.gov (United States)

    Manuelli, Massimo; Fallarini, Silvia; Lombardi, Grazia; Sangregorio, Claudio; Nativi, Cristina; Richichi, Barbara

    2014-06-01

    Among new therapies to fight tumors, immunotherapy is still one of the most promising and intriguing. Thanks to the ongoing structural elucidation of several tumor antigens and the development of innovative antigen carriers, immunotherapy is in constant evolution and it is largely used either alone or in synergy with chemotherapy/radiotherapy. With the aim to develop fully synthetic immunostimulants we have recently developed a mimetic of the α-Tn mucin antigen, a relevant tumor antigen. The 4C1 blocked mimetic 1, unique example of an α-Tn mimetic antigen, was functionalized with an ω-phosphonate linker and used to decorate iron oxide superparamagnetic nanoparticles (MNPs), employed as multivalent carriers. MNPs, largely exploited for supporting and carrying biomolecules, like antibodies, drugs or antigens, consent to combine in the same nanometric system the main features of an inorganic magnetic core with a bioactive organic coating. The superparamagnetic glyconanoparticles obtained, named GMNPs, are indeed biocompatible and immunoactive, and they preserve suitable characteristics for use as heat mediators in the magnetic fluid hyperthermia (MFH) treatment of tumors. All together these properties make GMNPs attracting devices for innovative tumor treatment.Among new therapies to fight tumors, immunotherapy is still one of the most promising and intriguing. Thanks to the ongoing structural elucidation of several tumor antigens and the development of innovative antigen carriers, immunotherapy is in constant evolution and it is largely used either alone or in synergy with chemotherapy/radiotherapy. With the aim to develop fully synthetic immunostimulants we have recently developed a mimetic of the α-Tn mucin antigen, a relevant tumor antigen. The 4C1 blocked mimetic 1, unique example of an α-Tn mimetic antigen, was functionalized with an ω-phosphonate linker and used to decorate iron oxide superparamagnetic nanoparticles (MNPs), employed as multivalent

  18. Synthetic oligosaccharides as heparin-mimetics displaying anticoagulant properties.

    Science.gov (United States)

    Avci, Fikri Y; Karst, Nathalie A; Linhardt, Robert J

    2003-01-01

    Heparin and low molecular weight heparins are major clinical anticoagulants and the drugs of choice for the treatment of deep venous thrombosis. The discovery of an antithrombin binding domain in heparin focused interest on understanding the mechanism of heparin's antithrombotic/ anticoagulant activity. Various heparin-mimetic oligosaccharides have been prepared in an effort to replace polydisperse heparin and low molecular weight heparins with a structurally-defined anticoagulant. The goal of attaining a heparin-mimetic with no unwanted side-effects has also provided motivation for these efforts. This article reviews structure-activity relationship (SAR) of structurally-defined heparin-mimetic oligosaccharides. PMID:14529394

  19. Caloric Restriction Mimetics Enhance Anticancer Immunosurveillance.

    Science.gov (United States)

    Pietrocola, Federico; Pol, Jonathan; Vacchelli, Erika; Rao, Shuan; Enot, David P; Baracco, Elisa E; Levesque, Sarah; Castoldi, Francesca; Jacquelot, Nicolas; Yamazaki, Takahiro; Senovilla, Laura; Marino, Guillermo; Aranda, Fernando; Durand, Sylvère; Sica, Valentina; Chery, Alexis; Lachkar, Sylvie; Sigl, Verena; Bloy, Norma; Buque, Aitziber; Falzoni, Simonetta; Ryffel, Bernhard; Apetoh, Lionel; Di Virgilio, Francesco; Madeo, Frank; Maiuri, Maria Chiara; Zitvogel, Laurence; Levine, Beth; Penninger, Josef M; Kroemer, Guido

    2016-07-11

    Caloric restriction mimetics (CRMs) mimic the biochemical effects of nutrient deprivation by reducing lysine acetylation of cellular proteins, thus triggering autophagy. Treatment with the CRM hydroxycitrate, an inhibitor of ATP citrate lyase, induced the depletion of regulatory T cells (which dampen anticancer immunity) from autophagy-competent, but not autophagy-deficient, mutant KRAS-induced lung cancers in mice, thereby improving anticancer immunosurveillance and reducing tumor mass. Short-term fasting or treatment with several chemically unrelated autophagy-inducing CRMs, including hydroxycitrate and spermidine, improved the inhibition of tumor growth by chemotherapy in vivo. This effect was only observed for autophagy-competent tumors, depended on the presence of T lymphocytes, and was accompanied by the depletion of regulatory T cells from the tumor bed. PMID:27411589

  20. The Mimetic Principle in the Underground Economy

    Directory of Open Access Journals (Sweden)

    Cristina Voicu

    2009-08-01

    Full Text Available There has been in the recent years an increased preoccupation at international level for the research of the mechanism of development of the underground economy. The numerous vain attempts to measure the dimension of the underground economy persuaded us to embark on a qualitative research of this economic phenomenon. In our investigation on the roots of the underground economy we drew very close to the psychological and sociological aspects of the phenomenon itself. The process of humanizing that has at its origin components of the mimetic principle, like acquisitive mimesis, prompt us to ponder over J.M. Keynes’ words: „The avoidance of taxes is the only intellectual ambition that one feels rewarded for.”

  1. The mimetic finite difference method for elliptic problems

    CERN Document Server

    Veiga, Lourenço Beirão; Manzini, Gianmarco

    2014-01-01

    This book describes the theoretical and computational aspects of the mimetic finite difference method for a wide class of multidimensional elliptic problems, which includes diffusion, advection-diffusion, Stokes, elasticity, magnetostatics and plate bending problems. The modern mimetic discretization technology developed in part by the Authors allows one to solve these equations on unstructured polygonal, polyhedral and generalized polyhedral meshes. The book provides a practical guide for those scientists and engineers that are interested in the computational properties of the mimetic finite difference method such as the accuracy, stability, robustness, and efficiency. Many examples are provided to help the reader to understand and implement this method. This monograph also provides the essential background material and describes basic mathematical tools required to develop further the mimetic discretization technology and to extend it to various applications.

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

    Institute of Scientific and Technical Information of China (English)

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

    2014-01-01

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

  3. A Finite Element Framework for Some Mimetic Finite Difference Discretizations

    OpenAIRE

    Rodrigo, Carmen; Gaspar, Francisco; Hu, Xiaozhe; Zikatanov, Ludmil

    2015-01-01

    In this work we derive equivalence relations between mimetic finite difference schemes on simplicial grids and modified N\\'ed\\'elec-Raviart-Thomas finite element methods for model problems in $\\mathbf{H}(\\operatorname{\\mathbf{curl}})$ and $H(\\operatorname{div})$. This provides a simple and transparent way to analyze such mimetic finite difference discretizations using the well-known results from finite element theory. The finite element framework that we develop is also crucial for the design...

  4. From neutron stars to quark stars in mimetic gravity

    CERN Document Server

    Astashenok, A V

    2015-01-01

    Realistic models of neutron and quark stars in the framework of mimetic gravity with Lagrange multiplier constraint are presented. We discuss the effect of mimetic scalar aiming to describe dark matter on mass-radius relation and the moment of inertia for slowly rotating relativistic stars. The mass-radius relation and moment of inertia depend on the value of mimetic scalar in the center of star. This fact leads to the ambiguity in the mass-radius relation for a given equation of state. {Such ambiguity allows to explain some observational facts better than in standard General Relativity}. The case of two mimetic potentials namely $V(\\phi)\\sim A\\phi^{-2}$ and $V(\\phi)\\sim Ae^{B\\phi^{2}}$ is considered in detail. The relative deviation of maximal moment of inertia is approximately twice larger than the relative deviation of maximal stellar mass. We also briefly discuss the mimetic $f(R)$ gravity. In the case of $f(R)=R+aR^2$ mimetic gravity it is expected that increase of maximal mass and maximal moment of iner...

  5. Towards Protein-Based Viral Mimetics for Cancer Therapies

    OpenAIRE

    Unzueta Elorza, Ugutz; Céspedes, María Virtudes; Vázquez Gómez, Esther; Ferrer Miralles, Neus; Mangues, Ramón; Villaverde Corrales, Antonio

    2015-01-01

    The authors acknowledge the financial support on the development of nano-therapeutics in cancer granted to E.V. (PI12/00327) and R.M. (PI12/01861) from the Fund for Health of Spain (FIS) to E.V. (TV32013-133930), and to R.M. and A.V. (TV32013-132031) from La Marató de TV3 (416/C/2013), to A.V. from MINECO (BIO2013-41019-P), and from the Centro de Investigación Biomédica en Red (CIBER) de Bioingeniería, Biomateriales y Nanomedicina (NANOPROTHER and NANOCOMETS projects), financed by the Institu...

  6. Incretin-based therapy and type 2 diabetes

    DEFF Research Database (Denmark)

    Hare, Kristine J; Knop, Filip Krag

    2010-01-01

    . Two new drug classes based on the actions of the incretin hormones have been approved for therapy of type 2 diabetes: injectable long-acting stable analogs of GLP-1, incretin mimetics, and orally available inhibitors of dipeptidyl peptidase 4 (DPP4; the enzyme responsible for the rapid degradation...... of incretin mimetics and incretin enhancers, review clinical experience gathered so far, and discuss future expectations for incretin-based therapy....

  7. BSA-boronic acid conjugate as lectin mimetics.

    Science.gov (United States)

    Narla, Satya Nandana; Pinnamaneni, Poornima; Nie, Huan; Li, Yu; Sun, Xue-Long

    2014-01-10

    We report bovine serum albumin (BSA)-boronic acid (BA) conjugates as lectin mimetics and their glyco-capturing capacity. The BSA-BA conjugates were synthesized by amidation of carboxylic acid groups in BSA with aminophenyl boronic acid in the presence of EDC, and were characterized by Alizarin Red S (ARS) assay and SDS-PAGE gel. The BSA-BA conjugates were immobilized onto maleimide-functionalized silica beads and their sugar capturing capacity and specificity were confirmed by ARS displacement assay. Further, surface plasmon resonance (SPR) analysis of the glyco-capturing activity of the BSA-BA conjugates was conducted by immobilizing BSA-BA onto SPR gold chip. Overall, we demonstrated a BSA-BA-based lectin mimetics for glyco-capturing applications. These lectin mimetics are expected to provide an important tool for glycomics and biosensor research and applications.

  8. Static spherically symmetric solutions in mimetic gravity: rotation curves & wormholes

    CERN Document Server

    Myrzakulov, Ratbay; Vagnozzi, Sunny; Zerbini, Sergio

    2015-01-01

    In this work, we analyse static spherically symmetric solutions in the framework of mimetic gravity, an extension of general relativity where the conformal degree of freedom of gravity is isolated in a covariant fashion. Here we extend previous works by considering in addition a potential for the mimetic field. An appropriate choice of such potential allows for the reconstruction of a number of interesting cosmological and astrophysical scenarios. We explicitly show how to reconstruct such a potential for a general static spherically symmetric space-time. A number of applications and scenarios are then explored, among which traversable wormholes. Finally, we analytically reconstruct potentials which leads to solutions to the equations of motion featuring polynomial corrections to the Schwarzschild spacetime. Accurate choices for such corrections could provide an explanation for the inferred flat rotation curves of spiral galaxies within the mimetic gravity framework, without the need for particle dark matter.

  9. (Pseudoamide-linked oligosaccharide mimetics: molecular recognition and supramolecular properties

    Directory of Open Access Journals (Sweden)

    José L. Jiménez Blanco

    2010-02-01

    Full Text Available Oligosaccharides are currently recognised as having functions that influence the entire spectrum of cell activities. However, a distinct disadvantage of naturally occurring oligosaccharides is their metabolic instability in biological systems. Therefore, much effort has been spent in the past two decades on the development of feasible routes to carbohydrate mimetics which can compete with their O-glycosidic counterparts in cell surface adhesion, inhibit carbohydrate processing enzymes, and interfere in the biosynthesis of specific cell surface carbohydrates. Such oligosaccharide mimetics are potential therapeutic agents against HIV and other infections, against cancer, diabetes and other metabolic diseases. An efficient strategy to access this type of compounds is the replacement of the glycosidic linkage by amide or pseudoamide functions such as thiourea, urea and guanidine. In this review we summarise the advances over the last decade in the synthesis of oligosaccharide mimetics that possess amide and pseudoamide linkages, as well as studies focussing on their supramolecular and recognition properties.

  10. Bio-Mimetic Sensors Based on Molecularly Imprinted Membranes

    Directory of Open Access Journals (Sweden)

    Catia Algieri

    2014-07-01

    Full Text Available An important challenge for scientific research is the production of artificial systems able to mimic the recognition mechanisms occurring at the molecular level in living systems. A valid contribution in this direction resulted from the development of molecular imprinting. By means of this technology, selective molecular recognition sites are introduced in a polymer, thus conferring it bio-mimetic properties. The potential applications of these systems include affinity separations, medical diagnostics, drug delivery, catalysis, etc. Recently, bio-sensing systems using molecularly imprinted membranes, a special form of imprinted polymers, have received the attention of scientists in various fields. In these systems imprinted membranes are used as bio-mimetic recognition elements which are integrated with a transducer component. The direct and rapid determination of an interaction between the recognition element and the target analyte (template was an encouraging factor for the development of such systems as alternatives to traditional bio-assay methods. Due to their high stability, sensitivity and specificity, bio-mimetic sensors-based membranes are used for environmental, food, and clinical uses. This review deals with the development of molecularly imprinted polymers and their different preparation methods. Referring to the last decades, the application of these membranes as bio-mimetic sensor devices will be also reported.

  11. Combinatorial solid-phase synthesis of hapalosin mimetics

    DEFF Research Database (Denmark)

    Olsen, Jacob A.; Jensen, Knud J.; Nielsen, John

    2000-01-01

    The solid-phase synthesis of a small library of mimetics of the cyclic depsipeptide hapalosin is described. 3-Amino-4-hydroxy-5-nitrobenzoic acid was anchored through the anilino moiety to a backbone amide linker (BAL) handle support. Using chemoselective reactions and without the need for...

  12. Dark energy oscillations in mimetic F (R ) gravity

    Science.gov (United States)

    Odintsov, S. D.; Oikonomou, V. K.

    2016-08-01

    In this paper we address the problem of dark energy oscillations in the context of mimetic F (R ) gravity with potential. The issue of dark energy oscillations can be a problem in some models of ordinary F (R ) gravity, and a remedy that can make the oscillations milder is to introduce additional modifications in the functional form of the F (R ) gravity. As we demonstrate, the power-law modifications are not necessary in the mimetic F (R ) case, and by appropriately choosing the mimetic potential and the Lagrange multiplier, it is possible to make the oscillations almost vanish at the end of the matter domination era and during the late-time acceleration era. We examine the behavior of the dark energy equation of state parameter and of the total effective equation of state parameter as functions of the redshift, and we compare the resulting picture with the ordinary F (R ) gravity case. As we also show that the present day values of the dark energy equation of state parameter and of the total effective equation of state parameter are in better agreement with the observational data, in comparison to the ordinary F (R ) gravity case. Finally, we study the evolution of the growth factor as a function of the redshift for all the mimetic models we use.

  13. Elaborate Mimetic Vocal Displays by Female Superb Lyrebirds

    Directory of Open Access Journals (Sweden)

    Anastasia H Dalziell

    2016-04-01

    Full Text Available Some of the most striking vocalizations in birds are made by males that incorporate vocal mimicry in their sexual displays. Mimetic vocalization in females is largely undescribed, but it is unclear whether this is because of a lack of selection for vocal mimicry in females, or whether the phenomenon has simply been overlooked. These issues are thrown into sharp relief in the superb lyrebird, Menura novaehollandiae, a basal oscine passerine with a lek-like mating system and female uniparental care. The spectacular mimetic song display produced by courting male lyrebirds is a textbook example of a sexually selected trait, but the vocalizations of female lyrebirds are largely unknown. Here, we provide the first analysis of the structure and context of the vocalizations of female lyrebirds. Female lyrebirds were completely silent during courtship; however, females regularly produced sophisticated vocal displays incorporating both lyrebird-specific vocalizations and imitations of sounds within their environment. The structure of female vocalizations varied significantly with context. While foraging, females mostly produced a complex lyrebird-specific song, whereas they gave lyrebird-specific alarm calls most often during nest defense. Within their vocal displays females also included a variety of mimetic vocalizations, including imitations of the calls of dangerous predators, and of alarm calls and song of harmless heterospecifics. Females gave more mimetic vocalizations during nest defense than while foraging, and the types of sounds they imitated varied between these contexts, suggesting that mimetic vocalizations have more than one function. These results are inconsistent with previous portrayals of vocalizations by female lyrebirds as rare, functionless by-products of sexual selection on males. Instead, our results support the hypotheses that complex female vocalizations play a role in nest defense and mediate female-female competition for

  14. Metabolic effects of the incretin mimetic exenatide in the treatment of type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Catherine A Schnabel

    2006-03-01

    Full Text Available Catherine A Schnabel, Matthew Wintle, Orville KoltermanAmylin Pharmaceuticals, Inc, 9360 Towne Centre Drive, Suite 110, San Diego, CA 92121, USAAbstract: Interventional studies have demonstrated the impact of hyperglycemia on the development of vascular complications associated with type 2 diabetes, which underscores the importance of safely lowering glucose to as near-normal as possible. Among the current challenges to reducing the risk of vascular disease associated with diabetes is the management of body weight in a predominantly overweight patient population, and in which weight gain is likely with many current therapies. Exenatide is the first in a new class of agents termed incretin mimetics, which replicate several glucoregulatory effects of the endogenous incretin hormone, glucagon-like peptide-1 (GLP-1. Currently approved in the US as an injectable adjunct to metformin and/or sulfonylurea therapy, exenatide improves glycemic control through multiple mechanisms of action including: glucose-dependent enhancement of insulin secretion that potentially reduces the risk of hypoglycemia compared with insulin secretagogues; restoration of first-phase insulin secretion typically deficient in patients with type 2 diabetes; suppression of inappropriately elevated glucagon secretion to reduce postprandial hepatic output; and slowing the rate of gastric emptying to regulate glucose appearance into the circulation. Clinical trials in patients with type 2 diabetes treated with subcutaneous exenatide twice daily demonstrated sustained improvements in glycemic control, evidenced by reductions in postprandial and fasting glycemia and glycosylated hemoglobin (HbA1c levels. Notably, improvements in glycemic control with exenatide were coupled with progressive reductions in body weight, which represents a distinct therapeutic benefit for patients with type 2 diabetes. Acute effects of exenatide on beta-cell responsiveness along with significant reductions

  15. Bradykinin antagonists modified with dipeptide mimetic beta-turn inducers.

    Science.gov (United States)

    Alcaro, Maria C; Vinci, Valerio; D'Ursi, Anna M; Scrima, Mario; Chelli, Mario; Giuliani, Sandro; Meini, Stefania; Di Giacomo, Marcello; Colombo, Lino; Papini, Anna Maria

    2006-05-01

    Bradykinin (BK) is involved in a wide variety of pathophysiological processes. Potent BK peptide antagonists can be developed introducing constrained unnatural amino acids, necessary to force the secondary structure of the molecule. In this paper, we report a structure-activity relationship study of two peptide analogues of the potent B2 antagonist HOE 140 by replacing the D-Tic-Oic dipeptide with conformationally constrained dipeptide mimetic beta-turn inducers. PMID:16504505

  16. Dynamical behavior in mimetic F(R) gravity

    CERN Document Server

    Leon, Genly

    2015-01-01

    We investigate the cosmological behaviour of mimetic F(R) gravity. This scenario is the F(R) extension of usual mimetic gravity classes, which are based on re-parametrizations of the metric using new, but not extra, degrees of freedom, that can lead to a wider family of solutions. Performing a detailed dynamical analysis for exponential, power-law, and arbitrary F(R) forms, we extracted the corresponding critical points. Interestingly enough, we found that although the new features of mimetic F(R) gravity can affect the universe evolution at early and intermediate times, at late times they will not have any effect, and the universe will result at stable states that coincide with those of usual F(R) gravity. However, this feature holds for the late-time background evolution only. On the contrary, the behaviour of the perturbations is expected to be different since the new term contributes to the perturbations even if it does not contribute at the the background level.

  17. Dark Energy Oscillations in Mimetic $F(R)$ Gravity

    CERN Document Server

    Odintsov, S D

    2016-01-01

    In this paper we address the problem of dark energy oscillations in the context of mimetic $F(R)$ gravity with potential. The issue of dark energy oscillations can be a problem in some models of ordinary $F(R)$ gravity and a remedy that can make the oscillations milder is to introduce additional modifications in the functional form of the $F(R)$ gravity. As we demonstrate the power-law modifications are not necessary in the mimetic $F(R)$ case, and by appropriately choosing the mimetic potential and the Lagrange multiplier, it is possible to make the oscillations almost to vanish at the end of the matter domination era and during the late-time acceleration era. We examine the behavior of the dark energy equation of state parameter and of the total effective equation of state parameter as functions of the redshift and we compare the resulting picture with the ordinary $F(R)$ gravity case. As we also show, the present day values of the dark energy equation of state parameter and of the total effective equation ...

  18. Apolipoprotein A-I and A-I mimetic peptides: a role in atherosclerosis

    Directory of Open Access Journals (Sweden)

    Getz GS

    2011-06-01

    Full Text Available Godfrey S Getz, Catherine A ReardonThe University of Chicago, Department of Pathology, Chicago, IL, USAAbstract: Cardiovascular disease remains a major cause of morbidity and mortality in the westernized world. Atherosclerosis is the underlying cause of most cardiovascular diseases. Atherosclerosis is a slowly evolving chronic inflammatory disorder involving the intima of large and medium sized arteries that is initiated in response to high plasma lipid levels, especially LDL. Cells of both the innate and adaptive immunity are involved in this chronic inflammation. Although high plasma LDL levels are a major contributor to most stages of the evolution of atherosclerosis, HDL and its major protein apoA-I possess properties that attenuate and may even reverse atherosclerosis. Two major functions are the ability to induce the efflux of cholesterol from cells, particularly lipid-loaded macrophages, in the artery wall for transfer to the liver, a process referred to as reverse cholesterol transport, and the ability to attenuate the pro-inflammatory properties of LDL. The removal of cellular cholesterol from lipid-loaded macrophages may also be anti-inflammatory. One of the most promising therapies to enhance the anti-atherogenic, anti-inflammatory properties of HDL is apoA-I mimetic peptides. Several of these peptides have been shown to promote cellular cholesterol efflux, attenuate the production of pro-inflammatory cytokines by macrophages, and to attenuate the pro-inflammatory properties of LDL. This latter effect may be related to their high affinity for oxidized lipids present in LDL. This review discusses the functional properties of the peptides and their effect on experimental atherosclerosis and the results of initial clinical studies in humans.Keywords: apoA-I, mimetic peptides, HDL, anti-inflammatory, atherosclerosis

  19. Inhibition of PI3K/BMX Cell Survival Pathway Sensitizes to BH3 Mimetics in SCLC.

    Science.gov (United States)

    Potter, Danielle S; Galvin, Melanie; Brown, Stewart; Lallo, Alice; Hodgkinson, Cassandra L; Blackhall, Fiona; Morrow, Christopher J; Dive, Caroline

    2016-06-01

    Most small cell lung cancer (SCLC) patients are initially responsive to cytotoxic chemotherapy, but almost all undergo fatal relapse with progressive disease, highlighting an urgent need for improved therapies and better patient outcomes in this disease. The proapoptotic BH3 mimetic ABT-737 that targets BCL-2 family proteins demonstrated good single-agent efficacy in preclinical SCLC models. However, so far clinical trials of the BH3 mimetic Navitoclax have been disappointing. We previously demonstrated that inhibition of a PI3K/BMX cell survival signaling pathway sensitized colorectal cancer cells to ABT-737. Here, we show that SCLC cell lines, which express high levels of BMX, become sensitized to ABT-737 upon inhibition of PI3K in vitro, and this is dependent on inhibition of the PI3K-BMX-AKT/mTOR signaling pathway. Consistent with these cell line data, when combined with Navitoclax, PI3K inhibition suppressed tumor growth in both an established SCLC xenograft model and in a newly established circulating tumor cell-derived explant (CDX) model generated from a blood sample obtained at presentation from a chemorefractory SCLC patient. These data show for the first time that a PI3K/BMX signaling pathway plays a role in SCLC cell survival and that a BH3 mimetic plus PI3K inhibition causes prolonged tumor regression in a chemorefractory SCLC patient-derived model in vivo These data add to a body of evidence that this combination should move toward the clinic. Mol Cancer Ther; 15(6); 1248-60. ©2016 AACR. PMID:27197306

  20. FABRICATION AND BIOCOMPATIBILITY OF CELL OUTER MEMBRANE MIMETIC SURFACES

    Institute of Scientific and Technical Information of China (English)

    Ming-ming Zong; Yong-kuan Gong

    2011-01-01

    The surface design used for improving biocompatibility is one of the most important issues for the fabrication of medical devices. For mimicking the ideal surface structure of cell outer membrane, a large number of polymers bearing phosphorylcholine (PC) groups have been employed to modify the surfaces of biomaterials and medical devices. It has been demonstrated that the biocompatibility of the modified materials whose surface is required to interact with a living organism has been obviously improved by introducing PC groups. In this review, the fabrication strategies of cell outer membrane mimetic surfaces and their resulted biocompatibilities were summarized.

  1. Mimetic Finite Differences for Flow in Fractures from Microseismic Data

    KAUST Repository

    Al-Hinai, Omar

    2015-01-01

    We present a method for porous media flow in the presence of complex fracture networks. The approach uses the Mimetic Finite Difference method (MFD) and takes advantage of MFD\\'s ability to solve over a general set of polyhedral cells. This flexibility is used to mesh fracture intersections in two and three-dimensional settings without creating small cells at the intersection point. We also demonstrate how to use general polyhedra for embedding fracture boundaries in the reservoir domain. The target application is representing fracture networks inferred from microseismic analysis.

  2. Mimetic discretization of two-dimensional magnetic diffusion equations

    Science.gov (United States)

    Lipnikov, Konstantin; Reynolds, James; Nelson, Eric

    2013-08-01

    In case of non-constant resistivity, cylindrical coordinates, and highly distorted polygonal meshes, a consistent discretization of the magnetic diffusion equations requires new discretization tools based on a discrete vector and tensor calculus. We developed a new discretization method using the mimetic finite difference framework. It is second-order accurate on arbitrary polygonal meshes and a consistent calculation of the Joule heating is intrinsic within it. The second-order convergence rates in L2 and L1 norms were verified with numerical experiments.

  3. Activation of concurrent apoptosis and necroptosis by SMAC mimetics for the treatment of refractory and relapsed ALL.

    Science.gov (United States)

    McComb, Scott; Aguadé-Gorgorió, Júlia; Harder, Lena; Marovca, Blerim; Cario, Gunnar; Eckert, Cornelia; Schrappe, Martin; Stanulla, Martin; von Stackelberg, Arend; Bourquin, Jean-Pierre; Bornhauser, Beat C

    2016-05-18

    More precise treatment strategies are urgently needed to decrease toxicity and improve outcomes for treatment-refractory leukemia. We used ex vivo drug response profiling of high-risk, relapsed, or refractory acute lymphoblastic leukemia (ALL) cases and identified a subset with exquisite sensitivity to small-molecule mimetics of the second mitochondria-derived activator of caspases (SMAC) protein. Potent ex vivo activity of the SMAC mimetic (SM) birinapant correlated with marked in vivo antileukemic effects, as indicated by delayed engraftment, decreased leukemia burden, and prolonged survival of xenografted mice. Antileukemic activity was dependent on simultaneous execution of apoptosis and necroptosis, as demonstrated by functional genomic dissection with a multicolored lentiCRISPR approach to simultaneously disrupt multiple genes in patient-derived ALL. SM specifically targeted receptor-interacting protein kinase 1 (RIP1)-dependent death, and CRISPR-mediated disruption of RIP1 completely blocked SM-induced death yet had no impact on the response to standard antileukemic agents. Thus, SM compounds such as birinapant circumvent escape from apoptosis in leukemia by activating a potent dual RIP1-dependent apoptotic and necroptotic cell death, which is not exploited by current therapy. Ex vivo drug activity profiling could provide important functional diagnostic information to identify patients who may benefit from targeted treatment with birinapant in early clinical trials. PMID:27194728

  4. The mimetic repertoire of the spotted bowerbird Ptilonorhynchus maculatus

    Science.gov (United States)

    Kelley, Laura A.; Healy, Susan D.

    2011-06-01

    Although vocal mimicry in songbirds is well documented, little is known about the function of such mimicry. One possibility is that the mimic produces the vocalisations of predatory or aggressive species to deter potential predators or competitors. Alternatively, these sounds may be learned in error as a result of their acoustic properties such as structural simplicity. We determined the mimetic repertoires of a population of male spotted bowerbirds Ptilonorhynchus maculatus, a species that mimics predatory and aggressive species. Although male mimetic repertoires contained an overabundance of vocalisations produced by species that were generally aggressive, there was also a marked prevalence of mimicry of sounds that are associated with alarm such as predator calls, alarm calls and mobbing calls, irrespective of whether the species being mimicked was aggressive or not. We propose that it may be the alarming context in which these sounds are first heard that may lead both to their acquisition and to their later reproduction. We suggest that enhanced learning capability during acute stress may explain vocal mimicry in many species that mimic sounds associated with alarm.

  5. Activity of antimicrobial peptide mimetics in the oral cavity: I. Activity against biofilms of Candida albicans.

    Science.gov (United States)

    Hua, J; Yamarthy, R; Felsenstein, S; Scott, R W; Markowitz, K; Diamond, G

    2010-12-01

    Naturally occurring antimicrobial peptides hold promise as therapeutic agents against oral pathogens such as Candida albicans but numerous difficulties have slowed their development. Synthetic, non-peptidic analogs that mimic the properties of these peptides have many advantages and exhibit potent, selective antimicrobial activity. Several series of mimetics (with molecular weight oral Candida strains as a proof-of-principle for their antifungal properties. One phenylalkyne and several arylamide compounds with reduced mammalian cytotoxicities were found to be active against C. albicans. These compounds demonstrated rapid fungicidal activity in liquid culture even in the presence of saliva, and demonstrated synergy with standard antifungal agents. When assayed against biofilms grown on denture acrylic, the compounds exhibited potent fungicidal activity as measured by metabolic and fluorescent viability assays. Repeated passages in sub-minimum inhibitory concentration levels did not lead to resistant Candida, in contrast to fluconazole. Our results demonstrate the proof-of principle for the use of these compounds as anti-Candida agents, and their further testing is warranted as novel anti-Candida therapies.

  6. Self-assembly of fibronectin mimetic peptide-amphiphile nanofibers

    Science.gov (United States)

    Rexeisen, Emilie Lynn

    Many therapeutic strategies incorporate peptides into their designs to mimic the natural protein ligands found in vivo. A few examples are the short peptide sequences RGD and PHSRN that mimic the primary and synergy-binding domains of the extracellular matrix protein, fibronectin, which is recognized by the cell surface receptor, alpha5beta 1 integrin. Even though scaffold modification with biomimetic peptides remains one of the most promising approaches for tissue engineering, the use of these peptides in therapeutic tissue-engineered products and drug delivery systems available on the commercial market is limited because the peptides are not easily able to mimic the natural protein. The design of a peptide that can effectively target the alpha5beta1 integrin would greatly increase biomimetic scaffold therapeutic potential. A novel peptide containing both the RGD primary binding domain and PHSRN synergy-binding domain for fibronectin joined with the appropriate linker should bind alpha 5beta1 integrin more efficiently and lead to greater cell adhesion over RGD alone. Several fibronectin mimetic peptides were designed and coupled to dialkyl hydrocarbon tails to make peptide-amphiphiles. The peptides contained different linkers connecting the two binding domains and different spacers separating the hydrophobic tails from the hydrophilic headgroups. The peptide-amphiphiles were deposited on mica substrates using the Langmuir-Blodgett technique. Langmuir isotherms indicated that the peptide-amphiphiles that contained higher numbers of serine residues formed a more tightly packed monolayer, but the increased number of serines also made transferring the amphiphiles to the mica substrate more difficult. Atomic force microscopy (AFM) images of the bilayers showed that the headgroups might be bent, forming small divots in the surface. These divots may help expose the PHSRN synergy-binding domain. Parallel studies undertaken by fellow group members showed that human

  7. Fluorescence Spectra and Enzymatic Property of Hemoglobin as Mimetic Peroxidase

    Institute of Scientific and Technical Information of China (English)

    LiDe-jia; LiHai-cheng; ZouGuo-lin

    2003-01-01

    Intrinsic fluorescence emission maxima of hemo-lobin(Hb) was investigated in relation to peroxidase property of Hb. The peroxidase activity of Hb was based on its catalytic activity for oxidation of o-phenylenediamine by hydrogen peroxide. Hb was treated in the condition (temperature,ethanol and salt) that tetramer-dimer equilibrium of Hb is shifted to the dimer state and its fluorescence spectrum was measured. When Hb treated in temperature (60-70 ℃), ethanol concentration (60%-70%) and NaCl concentration (2. 5-3.0 mol/L), the fluorescence emission maxima of Hb shifted towards red wavelength and its activity decreased quickly.Experimental results revealed that the activity and stability of Hb as mimetic peroxidase was closely relative to the hydrophobic environment of active center of Hb, and when Hb (FeⅡ) converted into met Hb (FeⅢ ), its activity was 1. 6 times as much as that of Hb.

  8. Fluorescence Spectra and Enzymatic Property of Hemoglobin as Mimetic Peroxidase

    Institute of Scientific and Technical Information of China (English)

    Li De-jia; Li Hai-cheng; Zou Guo-lin

    2003-01-01

    Intrinsic fluorescence emission maxima of hemoglobin(Hb) was investigated in relation to peroxidase property of Hb. The peroxidase activity of Hb was based on its catalytic activity for oxidation of o-phenylenediamine by hydrogen peroxide. Hb was treated in the condition (temperature,ethanol and salt) that tetramer-dimer equilibrium of Hb is shifted to the dimer state and its fluorescence spectrum was measured. When Hb treated in temperature (60-70 ℃ ), ethanol concentration (60 %-70 % ) and NaCl concentration (2.5-3.0 mol/L), the fluorescence emission maxima of Hb shifted towards red wavelength and its activity decreased quickly.Experimental results revealed that the activity and stability of Hb as mimetic peroxidase was closely relative to the hydrophobic environment of active center of Hb, and when Hb (FeⅡ) converted into met Hb (FeⅢ ), its activity was 1. 6times as much as that of Hb.

  9. A Novel Bio-mimetic Wireless Micro Robot for Endoscope

    Institute of Scientific and Technical Information of China (English)

    YE Dong-dong; YAN Guo-zheng; WANG Kua-dong; MA Guan-ying

    2008-01-01

    A novel bio-mimetic wireless micro robot for endoscope is developed. Its autonomous manner is earthworm-like and driven by linear actuators based on DC motor. It is different from the conventional micro robot endoscope that wireless module is used for communicating and power transfer. The fabricated micro robot system is detailedly described, including structure, micro robot locomotion principle, communication control module and wireless power transfer module. The experimental results show that the driving force of the lineaar actuator can reach to 2.55 N and supplying power is up to 480 mW DC power for receiving coil in the proposed system, which all fulfill the need of the micro robot system. The micro robot can creep reliably in the large intestine of pig and other contact environments.

  10. Type I Collagen and Collagen Mimetics as Angiogenesis Promoting Superpolymers

    Energy Technology Data Exchange (ETDEWEB)

    Twardowski, T.; Fertala, A.; Orgel, J.P.R.O.; San Antonio, J.D. (TJU); (IIT); (Widener)

    2008-07-18

    Angiogenesis, the development of blood vessels from the pre-existing vasculature, is a key component of embryogenesis and tissue regeneration. Angiogenesis also drives pathologies such as tumor growth and metastasis, and hemangioma development in newborns. On the other hand, promotion of angiogenesis is needed in tissues with vascular insufficiencies, and in bioengineering, to endow tissue substitutes with appropriate microvasculatures. Therefore, much research has focused on defining mechanisms of angiogenesis, and identifying pro- and anti-angiogenic molecules. Type I collagen, the most abundant protein in humans, potently stimulates angiogenesis in vitro and in vivo. Crucial to its angiogenic activity appears to be ligation and possibly clustering of endothelial cell (EC) surface {alpha}1{beta}1/{alpha}2{beta}1 integrin receptors by the GFPGER502-507 sequence of the collagen fibril. However, additional aspects of collagen structure and function that may modulate its angiogenic properties are discussed. Moreover, type I collagen and fibrin, another angiogenic polymer, share several structural features. These observations suggest strategies for creating 'angiogenic superpolymers', including: modifying type I collagen to influence its biological half-life, immunogenicity, and integrin binding capacity; genetically engineering fibrillar collagens to include additional integrin binding sites or angiogenic determinants, and remove unnecessary or deleterious sequences without compromising fibril integrity; and exploring the suitability of poly(ortho ester), PEG-lysine copolymer, tubulin, and cholesteric cuticle as collagen mimetics, and suggesting means of modifying them to display ideal angiogenic properties. The collagenous and collagen mimetic angiogenic superpolymers described here may someday prove useful for many applications in tissue engineering and human medicine.

  11. A non-linear constrained optimization technique for the mimetic finite difference method

    Energy Technology Data Exchange (ETDEWEB)

    Manzini, Gianmarco [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Svyatskiy, Daniil [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Bertolazzi, Enrico [Univ. of Trento (Italy); Frego, Marco [Univ. of Trento (Italy)

    2014-09-30

    This is a strategy for the construction of monotone schemes in the framework of the mimetic finite difference method for the approximation of diffusion problems on unstructured polygonal and polyhedral meshes.

  12. Mimetic orthosis for lower limbs to be applied on rehabilitation for hemiplegic persons

    OpenAIRE

    P.S. Luna; E. Cardiel; R. Muñoz; Urrutia, R.; Villanueva, D.; P.R.Hernández

    2008-01-01

    A rehabilitation tool based on an innovative mimetic active orthosis for hemiplegics is presented. It follows concepts of neuronal learning from afferent information from movements, similar to those lost after brain damage. An artificial gait pattern is applied on knee and hip articulations of a functional modified limb by using an exoskeleton powered by pneumatic muscles. Key Words: Key Words: Key Words: Key Words: Key Words: Active orthosis, mimetic orthosis, gait rehabilitation.

  13. Nonconventional amide bond formation catalysis: programming enzyme specificity with substrate mimetics

    OpenAIRE

    F. Bordusa

    2000-01-01

    This article reports on the design and characteristics of substrate mimetics in protease-catalyzed reactions. Firstly, the basis of protease-catalyzed peptide synthesis and the general advantages of substrate mimetics over common acyl donor components are described. The binding behavior of these artificial substrates and the mechanism of catalysis are further discussed on the basis of hydrolysis, acyl transfer, protein-ligand docking, and molecular dynamics studies on the trypsin model. The g...

  14. Superoxide radical induces sclerotial differentiation in filamentous phytopathogenic fungi: a superoxide dismutase mimetics study.

    Science.gov (United States)

    Papapostolou, Ioannis; Georgiou, Christos D

    2010-03-01

    This study shows that the superoxide radical (O(2) *( -)), a direct indicator of oxidative stress, is involved in the differentiation of the phytopathogenic filamentous fungi Rhizoctonia solani, Sclerotinia sclerotiorum, Sclerotium rolfsii and Sclerotinia minor, shown by using superoxide dismutase (SOD) mimetics to decrease their sclerotial differentiation. The production rate of O(2) *(-) and SOD levels in these fungi, as expected, were significantly lowered by the SOD mimetics, with concomitant decrease of the indirect indicator of oxidative stress, lipid peroxidation. PMID:20007647

  15. A Novel Peptide Thrombopoietin Mimetic Designing and Optimization Using Computational Approach.

    Science.gov (United States)

    Singh, Vimal Kishor; Kumar, Neeraj; Kalsan, Manisha; Saini, Abhishek; Chandra, Ramesh

    2016-01-01

    Thrombopoietin receptor (TPOR) is a cytokine receptor protein present on the cell surface. The activation of TPOR by thrombopoietin (TPO) (a glycoprotein hormone) triggers an intracellular cascade of megakaryocytopoiesis for the formation of platelets. Recent studies on ex vivo megakaryocytopoiesis have evolved the possibilities of therapeutics uses. These findings have paved the way for the development of various TPO alternatives (recombinant TPO, peptide, and non-peptide TPO mimetics), which are useful in regenerative medicine. However, these alternatives possess various limitations such as induction of autoimmune effects, high production cost, low specificity, and hence activity. In the present study, a novel peptidic TPO mimetic was designed through computational studies by studying the binding sites of TPO and TMP to TPOR and analogs of known mimetics. Screening of combinatorial library was done through molecular docking using ClusPro. These studies indicated mimetic-9 as a significant molecule since it was found to have better binding score of -938.8 kcal/mol with seven hydrogen bonds and a high number of hydrophobic interactions, than known mimetic TMP with docking score of -798.4 kcal/mol and TMP dimer with docking score of -811.9 kcal/mol for TPOR. Mimetic9-TPOR complex was further assessed by the molecular dynamics simulation, and their complex was found to be stable with an RMSD value of 0.091 Å. While studying the parameters, mimetic-9 was found to have overall good physiochemical properties with positive grand average hydropathy (GRAVY) score and high instability index score and was found to be localized in the extracellular region. The designed mimetic-9 might prove to be a useful lead molecule for mimicking the role of TPO for in vitro platelet production with higher efficiency. PMID:27630985

  16. Reissner-Nordstr\\"om Black Holes in Mimetic $F(R)$ Gravity

    CERN Document Server

    Oikonomou, V K

    2015-01-01

    In this paper we study under which conditions the Reissner-Nordstr\\"om-anti de Sitter black hole can be a solution of the vacuum mimetic $F(R)$ gravity with Lagrange multiplier and mimetic scalar potential. As we demonstrate, the resulting picture in the mimetic $F(R)$ gravity case, is different in comparison to the ordinary $F(R)$ gravity case, with the two descriptions resulting to a different set of constraints that need to hold true. We also investigate the metric perturbations in the mimetic $F(R)$ gravity case, for the Reissner-Nordstr\\"om-anti de Sitter black hole metric, at first order of the perturbed variables. Interestingly enough, the resulting equations are identical to the ones corresponding to the ordinary $F(R)$ gravity Reissner-Nordstr\\"om-anti de Sitter black hole, at least at first order. We attribute this feature to the particular form of the Reissner-Nordstr\\"om-anti de Sitter metric, and we speculate for which cases there could be differences between the mimetic and non-mimetic case. Sin...

  17. Mixed mimetic spectral element method for Stokes flow: A pointwise divergence-free solution

    Science.gov (United States)

    Kreeft, Jasper; Gerritsma, Marc

    2013-05-01

    In this paper we apply the recently developed mimetic discretization method to the mixed formulation of the Stokes problem in terms of vorticity, velocity and pressure. The mimetic discretization presented in this paper and in Kreeft et al. [51] is a higher-order method for curvilinear quadrilaterals and hexahedrals. Fundamental is the underlying structure of oriented geometric objects, the relation between these objects through the boundary operator and how this defines the exterior derivative, representing the grad, curl and div, through the generalized Stokes theorem. The mimetic method presented here uses the language of differential k-forms with k-cochains as their discrete counterpart, and the relations between them in terms of the mimetic operators: reduction, reconstruction and projection. The reconstruction consists of the recently developed mimetic spectral interpolation functions. The most important result of the mimetic framework is the commutation between differentiation at the continuous level with that on the finite dimensional and discrete level. As a result operators like gradient, curl and divergence are discretized exactly. For Stokes flow, this implies a pointwise divergence-free solution. This is confirmed using a set of test cases on both Cartesian and curvilinear meshes. It will be shown that the method converges optimally for all admissible boundary conditions.

  18. Reissner–Nordström Anti-de Sitter Black Holes in Mimetic F(R Gravity

    Directory of Open Access Journals (Sweden)

    V. K. Oikonomou

    2016-05-01

    Full Text Available In this paper, we study under which conditions the Reissner–Nordström anti-de Sitter black hole can be a solution of the vacuum mimetic F ( R gravity with Lagrange multiplier and mimetic scalar potential. As the author demonstrates, the resulting picture in the mimetic F ( R gravity case is a trivial extension of the standard F ( R approach, and in effect, the metric perturbations in the mimetic F ( R gravity case, for the Reissner–Nordström anti-de Sitter black hole metric, at the first order of the perturbed variables are the same at the leading order.

  19. Glycosaminoglycan-Mimetic Signals Direct the Osteo/Chondrogenic Differentiation of Mesenchymal Stem Cells in a Three-Dimensional Peptide Nanofiber Extracellular Matrix Mimetic Environment.

    Science.gov (United States)

    Arslan, Elif; Guler, Mustafa O; Tekinay, Ayse B

    2016-04-11

    Recent efforts in bioactive scaffold development focus strongly on the elucidation of complex cellular responses through the use of synthetic systems. Designing synthetic extracellular matrix (ECM) materials must be based on understanding of cellular behaviors upon interaction with natural and artificial scaffolds. Hence, due to their ability to mimic both the biochemical and mechanical properties of the native tissue environment, supramolecular assemblies of bioactive peptide nanostructures are especially promising for development of bioactive ECM-mimetic scaffolds. In this study, we used glycosaminoglycan (GAG) mimetic peptide nanofiber gel as a three-dimensional (3D) platform to investigate how cell lineage commitment is altered by external factors. We observed that amount of fetal bovine serum (FBS) presented in the cell media had synergistic effects on the ability of GAG-mimetic nanofiber gel to mediate the differentiation of mesenchymal stem cells into osteogenic and chondrogenic lineages. In particular, lower FBS concentration in the culture medium was observed to enhance osteogenic differentiation while higher amount FBS promotes chondrogenic differentiation in tandem with the effects of the GAG-mimetic 3D peptide nanofiber network, even in the absence of externally administered growth factors. We therefore demonstrate that mesenchymal stem cell differentiation can be specifically controlled by the combined influence of growth medium components and a 3D peptide nanofiber environment.

  20. Basal Lamina Mimetic Nanofibrous Peptide Networks for Skeletal Myogenesis

    Science.gov (United States)

    Yasa, I. Ceren; Gunduz, Nuray; Kilinc, Murat; Guler, Mustafa O.; Tekinay, Ayse B.

    2015-11-01

    Extracellular matrix (ECM) is crucial for the coordination and regulation of cell adhesion, recruitment, differentiation and death. Therefore, equilibrium between cell-cell and cell-matrix interactions and matrix-associated signals are important for the normal functioning of cells, as well as for regeneration. In this work, we describe importance of adhesive signals for myoblast cells’ growth and differentiation by generating a novel ECM mimetic peptide nanofiber scaffold system. We show that not only structure but also composition of bioactive signals are important for cell adhesion, growth and differentiation by mimicking the compositional and structural properties of native skeletal muscle basal lamina. We conjugated laminin-derived integrin binding peptide sequence, “IKVAV”, and fibronectin-derived well known adhesive sequence, “RGD”, into peptide nanostructures to provide adhesive and myogenic cues on a nanofibrous morphology. The myogenic and adhesive signals exhibited a synergistic effect on model myoblasts, C2C12 cells. Our results showed that self-assembled peptide nanofibers presenting laminin derived epitopes support adhesion, growth and proliferation of the cells and significantly promote the expression of skeletal muscle-specific marker genes. The functional peptide nanofibers used in this study present a biocompatible and biodegradable microenvironment, which is capable of supporting the growth and differentiation of C2C12 myoblasts into myotubes.

  1. Light-Adaptive Supramolecular Nacre-Mimetic Nanocomposites.

    Science.gov (United States)

    Zhu, Baolei; Noack, Manuel; Merindol, Remi; Barner-Kowollik, Christopher; Walther, Andreas

    2016-08-10

    Nature provides design paradigms for adaptive, self-healing, and synergistic high-performance structural materials. Nacre's brick-and-mortar architecture is renowned for combining stiffness, toughness, strength, and lightweightness. Although elaborate approaches exist to mimic its static structure and performance, and to incorporate functionalities for the engineering world, there is a profound gap in addressing adaptable mechanical properties, particularly using remote, quick, and spatiotemporal triggers. Here, we demonstrate a generic approach to control the mechanical properties of nacre-inspired nanocomposites by designing a photothermal energy cascade using colloidal graphene as light-harvesting unit and coupling it to molecularly designed, thermoreversible, supramolecular bonds in the nanoconfined soft phase of polymer/nanoclay nacre-mimetics. The light intensity leads to adaptive steady-states balancing energy uptake and dissipation. It programs the mechanical properties and switches the materials from high stiffness/strength to higher toughness within seconds under spatiotemporal control. We envisage possibilities beyond mechanical materials, for example, light-controlled (re)shaping or actuation in highly reinforced nanocomposites. PMID:27455047

  2. An updated review on cancer risk associated with incretin mimetics and enhancers.

    Science.gov (United States)

    Tseng, Chin-Hsiao; Lee, Kuo-Yang; Tseng, Farn-Hsuan

    2015-01-01

    Incretin-based therapies, including the use of incretin mimetics of glucagon-like peptide-1 receptor (GLP-1R) agonists and incretin enhancers of dipeptidyl-peptidase 4 (DPP-4) inhibitors, are widely used by clinicians for glucose lowering in patients with type 2 diabetes mellitus. These agents have benefits of a lower risk of hypoglycemia, being neutral for body weight for DPP-4 inhibitors and having a potential for weight reduction with GLP-1R agonists. They may also have a neutral or beneficial cardiovascular effect. Despite these benefits, an increased risk of cancer (especially pancreatic cancer and thyroid cancer) associated with incretin-based therapies has been reported. In this article, we reviewed related literature of experimental animal and observational human studies, clinical trials, and meta-analyses published until December 15, 2014. Current studies suggested a probable role of GLP-1R activation on the development of pancreatic cancer and thyroid cancer in rodents, but such an effect in humans is not remarkable due to the lower or lack of expression of GLP-1R on human pancreatic ductal cells and thyroid tissues. Findings in human studies are controversial and inconclusive. In the analyses of the US Food and Drug Administration adverse events reporting system, a significantly higher risk of pancreatic cancer was observed for GLP-1R agonists and DPP-4 inhibitors, but a significantly higher risk of thyroid cancer was only observed for GLP-1R agonists. Such a higher risk of pancreatic cancer or thyroid cancer could not be similarly demonstrated in other human observational studies or analyses of data from clinical trials. With regards to cancers other than pancreatic cancer and thyroid cancer, available studies supported a neutral association in humans. Some preliminary studies even suggested a potentially beneficial effect on the development of other cancers with the use of incretins. Based on current evidence, continuous monitoring of the cancer issues

  3. Prey from the eyes of predators: Color discriminability of aposematic and mimetic butterflies from an avian visual perspective.

    Science.gov (United States)

    Su, Shiyu; Lim, Matthew; Kunte, Krushnamegh

    2015-11-01

    Predation exerts strong selection on mimetic butterfly wing color patterns, which also serve other functions such as sexual selection. Therefore, specific selection pressures may affect the sexes and signal components differentially. We tested three predictions about the evolution of mimetic resemblance by comparing wing coloration of aposematic butterflies and their Batesian mimics: (a) females gain greater mimetic advantage than males and therefore are better mimics, (b) due to intersexual genetic correlations, sexually monomorphic mimics are better mimics than female-limited mimics, and (c) mimetic resemblance is better on the dorsal wing surface that is visible to predators in flight. Using a physiological model of avian color vision, we quantified mimetic resemblance from predators' perspective, which showed that female butterflies were better mimics than males. Mimetic resemblance in female-limited mimics was comparable to that in sexually monomorphic mimics, suggesting that intersexual genetic correlations did not constrain adaptive response to selection for female-limited mimicry. Mimetic resemblance on the ventral wing surface was better than that on the dorsal wing surface, implying stronger natural and sexual selection on ventral and dorsal surfaces, respectively. These results suggest that mimetic resemblance in butterfly mimicry rings has evolved under various selective pressures acting in a sex- and wing surface-specific manner.

  4. Static spherically symmetric solutions in mimetic gravity: rotation curves and wormholes

    Science.gov (United States)

    Myrzakulov, Ratbay; Sebastiani, Lorenzo; Vagnozzi, Sunny; Zerbini, Sergio

    2016-06-01

    In this work, we analyse static spherically symmetric solutions in the framework of mimetic gravity, an extension of general relativity where the conformal degree of freedom of gravity is isolated in a covariant fashion. Here we extend previous works by considering, in addition, a potential for the mimetic field. An appropriate choice of such a potential allows for the reconstruction of a number of interesting cosmological and astrophysical scenarios. We explicitly show how to reconstruct such a potential for a general static spherically symmetric space-time. A number of applications and scenarios are then explored, among which are traversable wormholes. Finally, we analytically reconstruct potentials, which leads to solutions to the equations of motion featuring polynomial corrections to the Schwarzschild space-time. Accurate choices for such corrections could provide an explanation for the inferred flat rotation curves of spiral galaxies within the mimetic gravity framework, without the need for particle dark matter.

  5. The two faces of mimetic Horndeski gravity: disformal transformations and Lagrange multiplier

    CERN Document Server

    Arroja, Frederico; Karmakar, Purnendu; Matarrese, Sabino

    2015-01-01

    We show that very general scalar-tensor theories of gravity (including, e.g., Horndeski models) are generically invariant under disformal transformations. However there is a special subset, when the transformation is not invertible, that yields new equations of motion which are a generalization of the so-called "mimetic" dark matter theory recently introduced by Chamsedinne and Mukhanov. These new equations of motion can also be derived from an action containing an additional Lagrange multiplier field. The general mimetic scalar-tensor theory has the same number of derivatives in the equations of motion as the original scalar-tensor theory. As an application we show that the simplest mimetic scalar-tensor model is able to mimic the cosmological background of a flat FLRW model with an irrotational barotropic perfect fluid with any constant equation of state.

  6. An overview on antidiabetic medicinal plants having insulin mimetic property

    Directory of Open Access Journals (Sweden)

    DK Patel

    2012-04-01

    Full Text Available Diabetes mellitus is one of the common metabolic disorders acquiring around 2.8% of the world's population and is anticipated to cross 5.4% by the year 2025. Since long back herbal medicines have been the highly esteemed source of medicine therefore, they have become a growing part of modern, high-tech medicine. In view of the above aspects the present review provides profiles of plants (65 species with hypoglycaemic properties, available through literature source from various database with proper categorization according to the parts used, mode of reduction in blood glucose (insulinomimetic or insulin secretagogues activity and active phytoconstituents having insulin mimetics activity. From the review it was suggested that, plant showing hypoglycemic potential mainly belongs to the family Leguminoseae, Lamiaceae, Liliaceae, Cucurbitaceae, Asteraceae, Moraceae, Rosaceae and Araliaceae. The most active plants are Allium sativum, Gymnema sylvestre, Citrullus colocynthis, Trigonella foenum greacum, Momordica charantia and Ficus bengalensis. The review describes some new bioactive drugs and isolated compounds from plants such as roseoside, epigallocatechin gallate, beta-pyrazol-1-ylalanine, cinchonain Ib, leucocyandin 3-O-beta-d-galactosyl cellobioside, leucopelargonidin-3-O-alpha-L rhamnoside, glycyrrhetinic acid, dehydrotrametenolic acid, strictinin, isostrictinin, pedunculagin, epicatechin and christinin-A showing significant insulinomimetic and antidiabetic activity with more efficacy than conventional hypoglycaemic agents. Thus, from the review majorly, the antidiabetic activity of medicinal plants is attributed to the presence of polyphenols, flavonoids, terpenoids, coumarins and other constituents which show reduction in blood glucose levels. The review also discusses the management aspect of diabetes mellitus using these plants and their active principles.

  7. An overview on antidiabetic medicinal plants having insulin mimetic property

    Institute of Scientific and Technical Information of China (English)

    Patel DK; Prasad SK; Kumar R; Hemalatha S

    2012-01-01

    Diabetes mellitus is one of the common metabolic disorders acquiring around 2.8% of the world’s population and is anticipated to cross 5.4% by the year 2025. Since long back herbal medicines have been the highly esteemed source of medicine therefore, they have become a growing part of modern, high-tech medicine. In view of the above aspects the present review provides profiles of plants (65 species) with hypoglycaemic properties, available through literature source from various database with proper categorization according to the parts used, mode of reduction in blood glucose (insulinomimetic or insulin secretagogues activity) and active phytoconstituents having insulin mimetics activity. From the review it was suggested that, plant showing hypoglycemic potential mainly belongs to the family Leguminoseae, Lamiaceae, Liliaceae, Cucurbitaceae, Asteraceae, Moraceae, Rosaceae and Araliaceae. The most active plants are Allium sativum, Gymnema sylvestre, Citrullus colocynthis, Trigonella foenum greacum, Momordica charantia and Ficus bengalensis. The review describes some new bioactive drugs and isolated compounds from plants such as roseoside, epigallocatechin gallate, beta-pyrazol-1-ylalanine, cinchonain Ib, leucocyandin 3-O-beta-d-galactosyl cellobioside, leucopelargonidin-3- O-alpha-L rhamnoside, glycyrrhetinic acid, dehydrotrametenolic acid, strictinin, isostrictinin, pedunculagin, epicatechin and christinin-A showing significant insulinomimetic and antidiabetic activity with more efficacy than conventional hypoglycaemic agents. Thus, from the review majorly, the antidiabetic activity of medicinal plants is attributed to the presence of polyphenols, flavonoids, terpenoids, coumarins and other constituents which show reduction in blood glucose levels. The review also discusses the management aspect of diabetes mellitus using these plants and their active principles.

  8. An overview on antidiabetic medicinal plants having insulin mimetic property.

    Science.gov (United States)

    Patel, D K; Prasad, S K; Kumar, R; Hemalatha, S

    2012-04-01

    Diabetes mellitus is one of the common metabolic disorders acquiring around 2.8% of the world's population and is anticipated to cross 5.4% by the year 2025. Since long back herbal medicines have been the highly esteemed source of medicine therefore, they have become a growing part of modern, high-tech medicine. In view of the above aspects the present review provides profiles of plants (65 species) with hypoglycaemic properties, available through literature source from various database with proper categorization according to the parts used, mode of reduction in blood glucose (insulinomimetic or insulin secretagogues activity) and active phytoconstituents having insulin mimetics activity. From the review it was suggested that, plant showing hypoglycemic potential mainly belongs to the family Leguminoseae, Lamiaceae, Liliaceae, Cucurbitaceae, Asteraceae, Moraceae, Rosaceae and Araliaceae. The most active plants are Allium sativum, Gymnema sylvestre, Citrullus colocynthis, Trigonella foenum greacum, Momordica charantia and Ficus bengalensis. The review describes some new bioactive drugs and isolated compounds from plants such as roseoside, epigallocatechin gallate, beta-pyrazol-1-ylalanine, cinchonain Ib, leucocyandin 3-O-beta-d-galactosyl cellobioside, leucopelargonidin-3- O-alpha-L rhamnoside, glycyrrhetinic acid, dehydrotrametenolic acid, strictinin, isostrictinin, pedunculagin, epicatechin and christinin-A showing significant insulinomimetic and antidiabetic activity with more efficacy than conventional hypoglycaemic agents. Thus, from the review majorly, the antidiabetic activity of medicinal plants is attributed to the presence of polyphenols, flavonoids, terpenoids, coumarins and other constituents which show reduction in blood glucose levels. The review also discusses the management aspect of diabetes mellitus using these plants and their active principles.

  9. SIRT3 participates in glucose metabolism interruption and apoptosis induced by BH3 mimetic S1 in ovarian cancer cells.

    Science.gov (United States)

    Xiang, Xi-Yan; Kang, Jin-Song; Yang, Xiao-Chun; Su, Jing; Wu, Yao; Yan, Xiao-Yu; Xue, Ya-Nan; Xu, Ye; Liu, Yu-He; Yu, Chun-Yan; Zhang, Zhi-Chao; Sun, Lian-Kun

    2016-08-01

    The Bcl-2 antiapoptotic proteins are important cancer therapy targets; however, their role in cancer cell metabolism remains unclear. We found that the BH3-only protein mimetic S1, a novel pan Bcl-2 inhibitor, simultaneously interrupted glucose metabolism and induced apoptosis in human SKOV3 ovarian cancer cells, which was related to the activation of SIRT3, a stress-responsive deacetylase. S1 interrupted the cellular glucose metabolism mainly through causing damage to mitochondrial respiration and inhibiting glycolysis. Moreover, S1 upregulated the gene and protein expression of SIRT3, and induced the translocation of SIRT3 from the nucleus to mitochondria. SIRT3 silencing reversed the effects of S1 on glucose metabolism and apoptosis through increasing the level of HK-II localized to the mitochondria, while a combination of the glycolysis inhibitor 2-DG and S1 intensified the cytotoxicity through further upregulation of SIRT3 expression. This study underscores an essential role of SIRT3 in the antitumor effect of Bcl-2 inhibitors in human ovarian cancer through regulating both metabolism and apoptosis. The manipulation of Bcl-2 inhibitors combined with the use of classic glycolysis inhibitors may be rational strategies to improve ovarian cancer therapy. PMID:27277143

  10. Reproductive isolation related to mimetic divergence in the poison frog Ranitomeya imitator

    DEFF Research Database (Denmark)

    Twomey, Evan; Vestergaard, Jacob Schack; Summers, Kyle

    2014-01-01

    study the Peruvian poison frog Ranitomeya imitator, a species that has undergone a mimetic radiation into four distinct morphs. Using a combination of colour–pattern analysis, landscape genetics and mate-choice experiments, we show that a mimetic shift in R. imitator is associated with a narrow...... phenotypic transition zone, neutral genetic divergence and assortative mating, suggesting that divergent selection to resemble different model species has led to a breakdown in gene flow between these two populations. These results extend the effects of mimicry on speciation into a vertebrate system...

  11. A Note on Schwarzschild de Sitter Black Holes in Mimetic $F(R)$ Gravity

    CERN Document Server

    Oikonomou, V K

    2016-01-01

    In this brief note we investigate the conditions under which a Schwarzschild de Sitter black hole spacetime is a solution of the mimetic $F(R)$ gravity with Lagrange multiplier and potential. As we demonstrate, the resulting mimetic $F(R)$ gravity is a slight modification of the ordinary $F(R)$ gravity case, however the resulting perturbation equations are not in all cases identical to the ordinary $F(R)$ gravity case. In the latter case, the perturbation equations are identical to the ones corresponding to the Reissner-Nordstr\\"{o}m anti-de Sitter black hole.

  12. A note on Schwarzschild-de Sitter black holes in mimetic F(R) gravity

    Science.gov (United States)

    Oikonomou, V. K.

    2016-05-01

    In this paper, we investigate the conditions under which a Schwarzschild-de Sitter black hole spacetime is a solution of the mimetic F(R) gravity with Lagrange multiplier and potential. As we demonstrate, the resulting mimetic F(R) gravity is a slight modification of the ordinary F(R) gravity case, however the resulting perturbation equations are not in all cases identical to the ordinary F(R) gravity case. In the latter case, the perturbation equations are identical to the ones corresponding to the Reissner-Nordström anti-de Sitter black hole.

  13. A Note on Schwarzschild de Sitter Black Holes in Mimetic $F(R)$ Gravity

    OpenAIRE

    Oikonomou, V.K.

    2016-01-01

    In this brief note we investigate the conditions under which a Schwarzschild de Sitter black hole spacetime is a solution of the mimetic $F(R)$ gravity with Lagrange multiplier and potential. As we demonstrate, the resulting mimetic $F(R)$ gravity is a slight modification of the ordinary $F(R)$ gravity case, however the resulting perturbation equations are not in all cases identical to the ordinary $F(R)$ gravity case. In the latter case, the perturbation equations are identical to the ones c...

  14. Synthesis of new enantiopure poly(hydroxyaminooxepanes as building blocks for multivalent carbohydrate mimetics

    Directory of Open Access Journals (Sweden)

    Léa Bouché

    2014-01-01

    Full Text Available New compounds with carbohydrate-similar structure (carbohydrate mimetics are presented in this article. Starting from enantiopure nitrones and lithiated TMSE-allene we prepared three 1,2-oxazine derivatives which underwent a highly stereoselective Lewis acid-induced rearrangement to give bicyclic products in good yield. Subsequent reductive transformations delivered a library of new poly(hydroxyaminooxepane derivatives. The crucial final palladium-catalyzed hydrogenolysis of the 1,2-oxazine moiety was optimized resulting in a reasonably efficient approach to a series of new seven-membered carbohydrate mimetics.

  15. Reissner–Nordström Anti-de Sitter Black Holes in Mimetic F(R) Gravity

    Science.gov (United States)

    Oikonomou, V. K.

    2016-05-01

    In this paper we study under which conditions the Reissner-Nordstr\\"om-anti de Sitter black hole can be a solution of the vacuum mimetic $F(R)$ gravity with Lagrange multiplier and mimetic scalar potential. As we demonstrate, the resulting picture in the mimetic $F(R)$ gravity case, is different in comparison to the ordinary $F(R)$ gravity case, with the two descriptions resulting to a different set of constraints that need to hold true. We also investigate the metric perturbations in the mimetic $F(R)$ gravity case, for the Reissner-Nordstr\\"om-anti de Sitter black hole metric, at first order of the perturbed variables. Interestingly enough, the resulting equations are identical to the ones corresponding to the ordinary $F(R)$ gravity Reissner-Nordstr\\"om-anti de Sitter black hole, at least at first order. We attribute this feature to the particular form of the Reissner-Nordstr\\"om-anti de Sitter metric, and we speculate for which cases there could be differences between the mimetic and non-mimetic case. Since the perturbation equations are the same for the two cases, it is possible to have black hole instabilities in the mimetic $F(R)$ gravity case too, which can be interpreted as anti-evaporation of the black hole.

  16. Aspects of late-time evolution in mimetic F(R) gravity

    Science.gov (United States)

    Oikonomou, V. K.

    2016-09-01

    We demonstrate how to describe in an unified way early and late-time acceleration in the context of mimetic F(R) gravity. As we show, an exponential F(R) gravity model has appealing features, with regard to unification and we perform an analysis of the late-time evolution. The resulting picture is interesting since in the mimetic case, certain pathologies of some ordinary F(R) models are remedied in a consistent way, owing to the presence of the mimetic potential and the Lagrange multiplier. We quantify the late-time evolution analysis by studying the scaled dark energy density, the dark energy equation of state and the total effective equation of state, and as we show the late-time evolution is crucially affected by the functional form of the F(R) gravity. It is intriguing that the most appealing case corresponds to the exponential F(R) gravity which unifies late- and early-time acceleration. Finally, we study the behavior of the effective gravitational constant and the growth factor, and as we show, significant differences between the mimetic and ordinary F(R) exponential model are spotted in the growth factor.

  17. Incretin mimetics: a novel therapeutic option for patients with type 2 diabetes - a review

    DEFF Research Database (Denmark)

    Hansen, Katrine Bilberg; Vilsbøll, Tina; Knop, Filip K

    2010-01-01

    factors such as weight loss, decrease in blood pressure and changes in lipid profile. Current clinical data on the two available incretin mimetics, exenatide and liraglutide, are evaluated in this review, focusing on pharmacology, efficacy, safety and tolerability. The review is built on a systematic Pub...

  18. Gramicidin S derivatives containing cis- and trans-morpholine amino acids (MAAS) as turn mimetics

    NARCIS (Netherlands)

    Kapoerchan, V.V.; Spalburg, E.; Neeling, A.J. de; Mars-Groenendijk, R.H.; Noort, D.; Otero, J.M. de; Ferraces-Casais, P.; Llamas-Saiz, A.L.; Raaij, M.J. van; Doorn, J. van; Marel, G.A. van der; Overkleeft, H.S.; Overhand, M.

    2010-01-01

    The cyclic decapeptide gramicidin S (GS) was used as a model for the evaluation of four turn mimetics. For this purpose, one of the D-Phe-Pro two-residue turn motifs in the rigid cyclic β-hairp0in structure of GS was replaced with morpholine amino acids (MAA 2-5), differing in stereochemistry and le

  19. Application of Mn(Ⅱ) as a Mimetic Enzyme of Horseradish Peroxidase

    Institute of Scientific and Technical Information of China (English)

    Ai Xia HAN; Li Hong NIU; Rui CHANG; Fu Shi ZHANG

    2005-01-01

    In this study, Mn( Ⅱ ) as a mimetic enzyme of horseradish peroxidase (HRP) was applied to the determination of hydrogen peroxide (H2O2). The method introduced in this paper is based on Mn(Ⅱ)'s catalytic effect on the oxidation of 4-aminoantipyrine(4-AAP) with modified Trinder's reagent N-ethyl-N-(2-hydroxy-3-sulfopropyl)-3, 5-dimethoxyaniline(DAOS) by H2O2.By coupling this mimetic catalytic reaction with the catalytic reaction of glucose oxidase (GOD),glucose can be detected. Under optimum conditions, the calibration graphs for the determination of H2O2 and glucose are in the range of 1.0×10-3-1.0×10-1 mol/L and 1.0×10-3-14×10-3 mol/L respectively. The detection limit is 5.9×10-4 mol/L for H2O2 and is 9.2×10-4 mol/L for glucose.The feasibility of Mn ( Ⅱ ) as a HRP mimetic enzyme in practical clinical analysis has been proven in the determination of glucose in human serum. So far, Mn ( Ⅱ ) is the simplest and the most inexpensive mimetic enzyme.

  20. Reissner–Nordström Anti-de Sitter Black Holes in Mimetic F(R) Gravity

    OpenAIRE

    Oikonomou, V.K.

    2016-01-01

    In this paper we study under which conditions the Reissner-Nordstr\\"om-anti de Sitter black hole can be a solution of the vacuum mimetic $F(R)$ gravity with Lagrange multiplier and mimetic scalar potential. As we demonstrate, the resulting picture in the mimetic $F(R)$ gravity case, is different in comparison to the ordinary $F(R)$ gravity case, with the two descriptions resulting to a different set of constraints that need to hold true. We also investigate the metric perturbations in the mim...

  1. Social variables exert selective pressures in the evolution and form of primate mimetic musculature.

    Science.gov (United States)

    Burrows, Anne M; Li, Ly; Waller, Bridget M; Micheletta, Jerome

    2016-04-01

    Mammals use their faces in social interactions more so than any other vertebrates. Primates are an extreme among most mammals in their complex, direct, lifelong social interactions and their frequent use of facial displays is a means of proximate visual communication with conspecifics. The available repertoire of facial displays is primarily controlled by mimetic musculature, the muscles that move the face. The form of these muscles is, in turn, limited by and influenced by phylogenetic inertia but here we use examples, both morphological and physiological, to illustrate the influence that social variables may exert on the evolution and form of mimetic musculature among primates. Ecomorphology is concerned with the adaptive responses of morphology to various ecological variables such as diet, foliage density, predation pressures, and time of day activity. We present evidence that social variables also exert selective pressures on morphology, specifically using mimetic muscles among primates as an example. Social variables include group size, dominance 'style', and mating systems. We present two case studies to illustrate the potential influence of social behavior on adaptive morphology of mimetic musculature in primates: (1) gross morphology of the mimetic muscles around the external ear in closely related species of macaque (Macaca mulatta and Macaca nigra) characterized by varying dominance styles and (2) comparative physiology of the orbicularis oris muscle among select ape species. This muscle is used in both facial displays/expressions and in vocalizations/human speech. We present qualitative observations of myosin fiber-type distribution in this muscle of siamang (Symphalangus syndactylus), chimpanzee (Pan troglodytes), and human to demonstrate the potential influence of visual and auditory communication on muscle physiology. In sum, ecomorphologists should be aware of social selective pressures as well as ecological ones, and that observed morphology might

  2. BH3 mimetic ABT-737 sensitizes colorectal cancer cells to ixazomib through MCL-1 downregulation and autophagy inhibition.

    Science.gov (United States)

    Yang, Lifeng; Wan, Juefeng; Xiao, Sheng; Barkhouse, Darryll; Zhu, Ji; Li, Guichao; Lu, Bo; Zhang, Zhen

    2016-01-01

    The proteasome inhibitor MLN9708 is an orally administered drug that is hydrolyzed into its active form, MLN2238 (ixazomib). Compared with Bortezomib, MLN2238 has a shorter proteasome dissociation half-life and a lower incidence and severity of peripheral neuropathy, which makes it an attractive candidate for colorectal cancer treatment. In the present study, we observed that MLN2238 induced autophagy, as evidenced by conversion of the autophagosomal marker LC3 from LC3I to LC3II, in colorectal cancer cell lines. Mcl-1, an anti-apoptotic Bcl-2 family protein, was markedly elevated after treating a colorectal cancer cell line with MLN2238. We proved that inhibiting Mcl-1 expression enhances MLN2238 induced apoptosis and negatively regulates autophagy. Co-administration of BH3 mimetic ABT-737 with MLN2238 synergistically kills colorectal cancer cells through MCL-1 neutralization and autophagy inhibition. Furthermore, the synergistic killing effect of the combination therapy is correlated with P53 status in colorectal cancer. These data highlight that the combination of ABT-737 with MLN9708 is a promising therapeutic strategy for human colorectal cancer. PMID:27429848

  3. Combinational spinal GAD65 gene delivery and systemic GABA-mimetic treatment for modulation of spasticity.

    Directory of Open Access Journals (Sweden)

    Osamu Kakinohana

    Full Text Available BACKGROUND: Loss of GABA-mediated pre-synaptic inhibition after spinal injury plays a key role in the progressive increase in spinal reflexes and the appearance of spasticity. Clinical studies show that the use of baclofen (GABA(B receptor agonist, while effective in modulating spasticity is associated with major side effects such as general sedation and progressive tolerance development. The goal of the present study was to assess if a combined therapy composed of spinal segment-specific upregulation of GAD65 (glutamate decarboxylase gene once combined with systemic treatment with tiagabine (GABA uptake inhibitor will lead to an antispasticity effect and whether such an effect will only be present in GAD65 gene over-expressing spinal segments. METHODS/PRINCIPAL FINDINGS: Adult Sprague-Dawley (SD rats were exposed to transient spinal ischemia (10 min to induce muscle spasticity. Animals then received lumbar injection of HIV1-CMV-GAD65 lentivirus (LVs targeting ventral α-motoneuronal pools. At 2-3 weeks after lentivirus delivery animals were treated systemically with tiagabine (4, 10, 20 or 40 mg/kg or vehicle and the degree of spasticity response measured. In a separate experiment the expression of GAD65 gene after spinal parenchymal delivery of GAD65-lentivirus in naive minipigs was studied. Spastic SD rats receiving spinal injections of the GAD65 gene and treated with systemic tiagabine showed potent and tiagabine-dose-dependent alleviation of spasticity. Neither treatment alone (i.e., GAD65-LVs injection only or tiagabine treatment only had any significant antispasticity effect nor had any detectable side effect. Measured antispasticity effect correlated with increase in spinal parenchymal GABA synthesis and was restricted to spinal segments overexpressing GAD65 gene. CONCLUSIONS/SIGNIFICANCE: These data show that treatment with orally bioavailable GABA-mimetic drugs if combined with spinal-segment-specific GAD65 gene overexpression can

  4. Tunable elastin-mimetic multiblock hybrid copolymers for biomedical applications

    Science.gov (United States)

    Grieshaber, Sarah Elizabeth

    Elastin-mimetic hybrid polymers (EMHPs) have been developed to capture the multiblock molecular architecture of tropoelastin, allowing tunability in chemical, structural, biological, and mechanical properties. Multiblock EMHPs containing flexible synthetic segments were first synthesized via step growth polymerization of diazido-poly(ethylene glycol) (PEG) and alkyne-terminated AKA3KA (K = lysine, A = alanine) (AK2) peptide employing copper (I)-catalyzed alkyne-azide cycloaddition reaction (CuAAC, or orthogonal click chemistry). Covalent crosslinking of the EMHPs with hexamethylene diisocyanate (HMDI) through the lysine residues in the peptide domain afforded an elastomeric hydrogel (xEMHP) with a compressive modulus of 0.12 +/- 0.018 MPa when hydrated. xEMHPs exhibited minimal cytotoxicity to primary porcine vocal fold fibroblasts. The modular nature of the synthesis allowed facile adjustment of the peptide sequence to modulate the structural and the biological properties of EMHPs. Thus, EMHPs containing integrin-binding peptides were constructed using di-azido-PEG and an alkyne-terminated AK2 peptide with a terminal, integrin-binding GRGDSP domain via the step growth click coupling reaction. Hydrogels formed by covalent crosslinking of the RGD-containing EMHPs had a compressive modulus of 1.06 +/- 0.1MPa when hydrated. Neonatal human dermal fibroblasts (NHDFs) were able to adhere to the hydrogels within 1 h, and to spread and develop F-actin filaments 24 h post seeding. NHDF proliferation was only observed on hydrogels containing RGD domains, demonstrating the importance of integrin engagement for cell growth and the potential use of these EMHPs as tissue engineering scaffolds. The tunability of the EMHP system was further investigated by development of self-assembling, pH-responsive multiblock polymers composed of alternating domains of poly(acrylic acid) (PAA) and a peptide derived from the hydrophobic domains of elastin with the sequence (VPGVG)2 (VG2). The

  5. Triple-enzyme mimetic activity of nickel-palladium hollow nanoparticles and their application in colorimetric biosensing of glucose.

    Science.gov (United States)

    Wang, Qingqing; Zhang, Lingling; Shang, Changshuai; Zhang, Zhiquan; Dong, Shaojun

    2016-04-01

    We demonstrate that nickel-palladium hollow nanoparticles (NiPd hNPs) exhibit triple-enzyme mimetic activity: oxidase-like activity, peroxidase-like activity and catalase-like activity. As peroxidase mimetics, the catalytic activity of NiPd hNPs was investigated in detail. On this basis, a simple glucose biosensor with a wide linear range and low detection limit was developed. PMID:27009927

  6. Methylidynetrisphosphonates: Promising C1 building block for the design of phosphate mimetics

    Directory of Open Access Journals (Sweden)

    Vadim D. Romanenko

    2013-05-01

    Full Text Available Methylidynetrisphosphonates are representatives of geminal polyphosphonates bearing three phosphonate (PO3H2 groups at the bridged carbon atom. Like well-known methylenebisphosphonates (BPs, they are characterized by a P–C–P backbone structure and are chemically stable mimetics of the endogenous metabolites, i.e., inorganic pyrophosphates (PPi. Because of its analogy to PPi and an ability to chelate metal ions, the 1,1,1-trisphosphonate structure is of great potential as a C1 building block for the design of phosphate mimetics. The purpose of this review is to present a concise summary of the state of the art in trisphosphonate chemistry with particular emphasis on the synthesis, structure, reactions, and potential medicinal applications of these compounds.

  7. Mimetic Theory for Cell-Centered Lagrangian Finite Volume Formulation on General Unstructured Grids

    Energy Technology Data Exchange (ETDEWEB)

    Sambasivan, Shiv Kumar [Los Alamos National Laboratory; Shashkov, Mikhail J. [Los Alamos National Laboratory; Burton, Donald E. [Los Alamos National Laboratory; Christon, Mark A. [Los Alamos National Laboratory

    2012-07-19

    A finite volume cell-centered Lagrangian scheme for solving large deformation problems is constructed based on the hypo-elastic model and using the mimetic theory. Rigorous analysis in the context of gas and solid dynamics, and arbitrary polygonal meshes, is presented to demonstrate the ability of cell-centered schemes in mimicking the continuum properties and principles at the discrete level. A new mimetic formulation based gradient evaluation technique and physics-based, frame independent and symmetry preserving slope limiters are proposed. Furthermore, a physically consistent dissipation model is employed which is both robust and inexpensive to implement. The cell-centered scheme along with these additional new features are applied to solve solids undergoing elasto-plastic deformation.

  8. A new tool in peptide engineering: a photoswitchable stilbene-type beta-hairpin mimetic.

    Science.gov (United States)

    Erdélyi, Máté; Karlén, Anders; Gogoll, Adolf

    2005-12-23

    Peptide secondary structure mimetics are important tools in medicinal chemistry, as they provide analogues of endogenous peptides with new physicochemical and pharmacological properties. The development, synthesis, photochemical investigation, and conformational analysis of a stilbene-type beta-hairpin mimetic capable of light-triggered conformational changes have been achieved. In addition to standard spectroscopic techniques (nuclear Overhauser effects, amide temperature coefficients, circular dichroism spectroscopy), the applicability of self-diffusion measurements (longitudinal eddy current delay pulsed-field gradient spin echo (LED-PGSE) NMR technique) in conformational studies of oligopeptides is demonstrated. The title compound shows photoisomerization of the stilbene chromophore, resulting in a change in solution conformation between an unfolded structure and a folded beta-hairpin.

  9. Viable Mimetic Completion of Unified Inflation-Dark Energy Evolution in Modified Gravity

    CERN Document Server

    Nojiri, S; Oikonomou, V K

    2016-01-01

    In this paper, we demonstrate that a unified description of early and late-time acceleration is possible in the context of mimetic $F(R)$ gravity. We study the inflationary era in detail and demonstrate that it can be realized even in mimetic $F(R)$ gravity where traditional $F(R)$ gravity fails to describe the inflation. By using standard methods we calculated the spectral index of primordial curvature perturbations and the scalar-to-tensor ratio. We use two $F(R)$ gravity models and as it turns out, for both the models under study the observational indices are compatible with both the latest Planck and the BICEP2/Keck array data. Finally, the graceful exit from inflation is guaranteed by the existence of growing curvature perturbations when the slow-roll era ends.

  10. Incretin mimetics: a novel therapeutic option for patients with type 2 diabetes - a review

    DEFF Research Database (Denmark)

    Hansen, Katrine Bilberg; Vilsbøll, Tina; Knop, Filip K

    2010-01-01

    Type 2 diabetes mellitus is a metabolic disease associated with low quality of life and early death. The goal in diabetes treatment is to prevent these outcomes by tight glycemic control and minimizing vascular risk factors. So far, even intensified combination regimen with the traditional...... are initiated. Since the compounds have no insulinotropic activity at lower glucose concentrations the risk of hypoglycemia - a well-known shortcoming of existing antidiabetes treatments - is low. Additionally, incretin mimetics have been shown to be associated with beneficial effects on cardiovascular risk...... factors such as weight loss, decrease in blood pressure and changes in lipid profile. Current clinical data on the two available incretin mimetics, exenatide and liraglutide, are evaluated in this review, focusing on pharmacology, efficacy, safety and tolerability. The review is built on a systematic Pub...

  11. Camouflage mimetico e il problema della rappresentazione pittorica / Mimetic Camouflage and the Problem of Pictorial Representation

    OpenAIRE

    Méndez Baiges, Maite

    2015-01-01

    A hundred years ago , during the I World War, the first forms of military camouflage were devoloped. The earlier Unité de Camouflage was born in February 1915 in the french army. Mimetic camouflage design, called Disruptive Pattern Material (DPM), was the product of an intention of deceit based on concealment of equipment and facilities against the enemy. These primitive forms of invisibility searched the mimesis with the environment, and they developed both abstract and figurative solutions....

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

    Directory of Open Access Journals (Sweden)

    Xianglan eYao

    2012-03-01

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

  13. Endowing Single-Chain Polymer Nanoparticles with Enzyme-Mimetic Activity

    OpenAIRE

    Perez-Baena, Irma; Barroso-Bujans, Fabienne; Gasser, Urs; Arbe, Arantxa; Moreno Segurado, Ángel J.; Colmenero de León, Juan; Pomposo, José A.

    2013-01-01

    The development of simple, efficient, and robust strategies affording the facile construction of biomimetic organocatalytic nano-objects is currently a subject of great interest. Herein, a new pathway to artificial organocatalysts based on partially collapsed individual soft nano-objects displaying useful and diverse biomimetic catalytic functions is reported. Single-chain polymer nanoparticles endowed with enzyme-mimetic activity synthesized following this new route display (i) a relatively ...

  14. Female preferences drive the evolution of mimetic accuracy in male sexual displays

    OpenAIRE

    Coleman, Seth William; Patricelli, Gail Lisa; Coyle, Brian; Siani, Jennifer; Borgia, Gerald

    2007-01-01

    Males in many bird species mimic the vocalizations of other species during sexual displays, but the evolutionary and functional significance of interspecific vocal mimicry is unclear. Here we use spectrographic cross-correlation to compare mimetic calls produced by male satin bowerbirds (Ptilonorhynchus violaceus) in courtship with calls from several model species. We show that the accuracy of vocal mimicry and the number of model species mimicked are both independently related to male mating...

  15. Physics of cell adhesion: some lessons from cell-mimetic systems

    OpenAIRE

    Sackmann, Erich; Smith, Ana-Sunčana

    2014-01-01

    Cell adhesion is a paradigm of the ubiquitous interplay of cell signalling, modulation of material properties and biological functions of cells. It is controlled by competition of short range attractive forces, medium range repellant forces and the elastic stresses associated with local and global deformation of the composite cell envelopes. We review the basic physical rules governing the physics of cell adhesion learned by studying cell-mimetic systems and demonstrate the importance of thes...

  16. Mechanisms of heparanase inhibition by the heparan sulfate mimetic PG545 and three structural analogues ☆

    OpenAIRE

    Hammond, Edward; Handley, Paul; Dredge, Keith; Bytheway, Ian

    2013-01-01

    The tetrasaccharide heparan sulfate (HS) mimetic PG545, a clinical anti-cancer candidate, is an inhibitor of the HS-degrading enzyme heparanase. The kinetics of heparanase inhibition by PG545 and three structural analogues were investigated to understand their modes of inhibition. The cholestanol aglycon of PG545 significantly increased affinity for heparanase and also modified the inhibition mode. For the tetrasaccharides, competitive inhibition was modified to parabolic competition by the a...

  17. A mimetic spectral element solver for the Grad-Shafranov equation

    CERN Document Server

    Palha, Artur; Felici, Federico

    2015-01-01

    In this work we present a robust and accurate arbitrary order solver for the fixed-boundary plasma equilibria in toroidally axisymmetric geometries. To achieve this we apply the mimetic spectral element formulation presented in [56] to the solution of the Grad-Shafranov equation. This approach combines a finite volume discretization with the mixed finite element method. In this way the discrete differential operators ($\

  18. A unified approach to Mimetic Finite Difference, Hybrid Finite Volume and Mixed Finite Volume methods

    OpenAIRE

    Droniou, Jerome; Eymard,, Robert; Gallouët, Thierry; Herbin, Raphaele

    2008-01-01

    International audience We investigate the connections between several recent methods for the discretization of ani\\-so\\-tropic heterogeneous diffusion operators on general grids. We prove that the Mimetic Finite Difference scheme, the Hybrid Finite Volume scheme and the Mixed Finite Volume scheme are in fact identical up to some slight generalizations. As a consequence, some of the mathematical results obtained for each of the method (such as convergence properties or error estimates) may ...

  19. Supramolecular assembly of electrostatically stabilized, hydroxyproline-lacking collagen-mimetic peptides

    OpenAIRE

    Krishna, Ohm D.; Kiick, Kristi L.

    2009-01-01

    The mechanical and biological functions of the native collagens remain an inspiration in materials design, but widespread application of de novo collagens has been limited in part by the need for hydroxylated proline in the formation of stable triple helical structures. In order to address this continued need and to expand the potential for recombinant expression of functional, hydroxyproline-lacking collagen-mimetic peptides, we have designed a hydrophilic, non-repetitive, and thermally stab...

  20. Template-Tethered Collagen Mimetic Peptides for Studying Heterotrimeric Triple-Helical Interactions

    OpenAIRE

    Li, Yang; Mo, Xiao; Kim, Daniel; Yu, S. Michael

    2010-01-01

    Collagen mimetic peptides (CMPs) have been used to elucidate the structure and stability of the triple helical conformation of collagen molecules. Although CMP homotrimers have been widely studied, very little work has been reported regarding CMP heterotrimers because of synthetic difficulties. Here we present the synthesis and characterization of homotrimers and ABB type heterotrimers comprising natural and synthetic CMP sequences that are covalently tethered to a template, a tris(2-aminoeth...

  1. Aerodynamic Bio-Mimetics of Gliding Dragonflies for Ultra-Light Flying Robot

    OpenAIRE

    Akira Obata; Shotarou Shinohara; Kyohei Akimoto; Kakeru Suzuki; Miyuki Seki

    2014-01-01

    A detailed investigation including a low-speed flow study is presented on the development of ultra-light dragonfly mimetic flying robots with a focus on the dragonfly’s remarkable gliding capability. It is revealed that the dragonfly’s corrugated wing structure and cruciform configuration provide superior flying characteristics for fixed wing robots in low Reynolds number flight. It was also found that the dragonfly configuration has additional merit in its compatibility with propellers or hi...

  2. Modified Gauss-Bonnet gravity with Lagrange multiplier constraint as mimetic theory

    OpenAIRE

    Astashenok, Artyom V.; Odintsov, Sergei D.; Oikonomou, V.K.

    2015-01-01

    In this paper we propose and extensively study mimetic $f({\\cal G})$ modified gravity models, with various scenarios of cosmological evolution, with or without extra matter fluids. The easiest formulation is based on the use of Lagrange multiplier constraint. In certain versions of this theory, it is possible to realize accelerated expansion of the Universe or even unified evolution which includes inflation with dark energy, and at the same time in the same theoretical framework, dark matter ...

  3. A Smac-mimetic sensitizes prostate cancer cells to TRAIL-induced apoptosis via modulating both IAPs and NF-kappaB

    International Nuclear Information System (INIS)

    Although tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising agent for human cancer therapy, prostate cancer still remains resistant to TRAIL. Both X-linked inhibitor of apoptosis (XIAP) and nuclear factor-kappaB function as key negative regulators of TRAIL signaling. In this study, we evaluated the effect of SH122, a small molecule mimetic of the second mitochondria-derived activator of caspases (Smac), on TRAIL-induced apoptosis in prostate cancer cells. The potential of Smac-mimetics to bind XIAP or cIAP-1 was examined by pull-down assay. Cytotoxicity of TRAIL and/or Smac-mimetics was determined by a standard cell growth assay. Silencing of XIAP or cIAP-1 was achieved by transient transfection of short hairpin RNA. Apoptosis was detected by Annexin V-PI staining followed by flow cytometry and by Western Blot analysis of caspases, PARP and Bid. NF-kappaB activation was determined by subcellular fractionation, real time RT-PCR and reporter assay. SH122, but not its inactive analog, binds to XIAP and cIAP-1. SH122 significantly sensitized prostate cancer cells to TRAIL-mediated cell death. Moreover, SH122 enhanced TRAIL-induced apoptosis via both the death receptor and the mitochondrial pathway. Knockdown of both XIAP and cIAP-1 sensitized cellular response to TRAIL. XIAP-knockdown attenuated sensitivity of SH122 to TRAIL-induced cytotoxicity, confirming that XIAP is an important target for IAP-inhibitor-mediated TRAIL sensitization. SH122 also suppressed TRAIL-induced NF-kappaB activation by preventing cytosolic IkappaB-alpha degradation and RelA nuclear translocation, as well as by suppressing NF-kappaB target gene expression. These results demonstrate that SH122 sensitizes human prostate cancer cells to TRAIL-induced apoptosis by mimicking Smac and blocking both IAPs and NF-kappaB. Modulating IAPs may represent a promising approach to overcoming TRAIL-resistance in human prostate cancer with constitutively active NF-kappaB signaling

  4. Bio-mimetic mineralization potential of collagen hydrolysate obtained from chromium tanned leather waste.

    Science.gov (United States)

    Banerjee, Pradipta; Madhu, S; Chandra Babu, N K; Shanthi, C

    2015-04-01

    Hydroxyapatite (HA) ceramics serve as an alternative to autogenous-free bone grafting by virtue of their excellent biocompatibility. However, chemically synthesized HA lacks the strong load-bearing capacity as required by bone. The bio-mimetic growth of HA crystals on collagen surface provides a feasible solution for synthesizing bone substitutes with the desired properties. This study deals with the utilization of the collagen hydrolysate recovered from leather waste as a substrate for promoting HA crystal growth. Bio-mimetic growth of HA was induced by subjecting the hydrolysate to various mineralization conditions. Parameters that would have a direct effect on crystal growth were varied to determine the optimal conditions necessary. Maximum mineralization was achieved with a combination of 10mM of CaCl2, 5mM of Na2HPO4, 100mM of NaCl and 0.575% glutaraldehyde at a pH of 7.4. The metal-protein interactions leading to formation of HA were identified through Fourier-transform infrared (FTIR) spectroscopy and x-ray diffraction (XRD) studies. The crystal dimensions were determined to be in the nanoscale range by atomic force microscopy (AFM) and scanning electron microscopy (SEM). The size and crystallinity of bio-mimetically grown HA indicate that hydrolysate from leather waste can be used as an ideal alternative substrate for bone growth.

  5. Role of phosphate on stability and catalase mimetic activity of cerium oxide nanoparticles.

    Science.gov (United States)

    Singh, Ragini; Singh, Sanjay

    2015-08-01

    Cerium oxide nanoparticles (CeNPs) have been recently shown to scavenge reactive oxygen and nitrogen species (ROS and RNS) in different experimental model systems. CeNPs (3+) and CeNPs (4+) have been shown to exhibit superoxide dismutase (SOD) and catalase mimetic activity, respectively. Due to their nanoscale dimension, CeNPs are expected to interact with the components of biologically relevant buffers and medium, which could alter their catalytic properties. We have demonstrated earlier that CeNPs (3+) interact with phosphate and lose the SOD activity. However, very little is known about the interaction of CeNPs (4+) with the phosphate and other anions, predominantly present in biological buffers and their effects on the catalase mimetic-activity of these nanoparticles. In this study, we report that catalase mimetic-activity of CeNPs (4+) is resistant to the phosphate anions, pH changes and composition of cell culture media. Given the abundance of phosphate anions in the biological system, it is likely that internalized CeNPs would be influenced by cytoplasmic and nucleoplasmic concentration of phosphate.

  6. Interactions of Bio-Inspired Membranes with Peptides and Peptide-Mimetic Nanoparticles

    Directory of Open Access Journals (Sweden)

    Michael Sebastiano

    2015-08-01

    Full Text Available Via Dissipative Particle Dynamics (DPD and implicit solvent coarse-grained (CG Molecular Dynamics (MD we examine the interaction of an amphiphilic cell-penetrating peptide PMLKE and its synthetic counterpart with a bio-inspired membrane. We use the DPD technique to investigate the interaction of peptide-mimetic nanoparticles, or nanopins, with a three-component membrane. The CG MD approach is used to investigate the interaction of a cell-penetrating peptide PMLKE with single-component membrane. We observe the spontaneous binding and subsequent insertion of peptide and nanopin in the membrane by using CG MD and DPD approaches, respectively. In addition, we find that the insertion of peptide and nanopins is mainly driven by the favorable enthalpic interactions between the hydrophobic components of the peptide, or nanopin, and the membrane. Our study provides insights into the mechanism underlying the interactions of amphiphilic peptide and peptide-mimetic nanoparticles with a membrane. The result of this study can be used to guide the functional integration of peptide and peptide-mimetic nanoparticles with a cell membrane.

  7. Aspects of Late-time Evolution in Mimetic $F(R)$ Gravity

    CERN Document Server

    Oikonomou, V K

    2016-01-01

    We demonstrate how to describe in an unified way early and late-time acceleration in the context of mimetic $F(R)$ gravity. As we show, an exponential $F(R)$ gravity model has appealing features, with regard to unification, and we perform an analysis of the late-time evolution. The resulting picture is interesting since in the mimetic case, certain pathologies of some ordinary $F(R)$ models are remedied in a consistent way, owing to the presence of the mimetic potential and the Lagrange multiplier. We quantify the late-time evolution analysis by studying the scaled dark energy density, the dark energy equation of state and the total effective equation of state, and as we show the late-time evolution is crucially affected by the functional form of the $F(R)$ gravity. It is intriguing that the most appealing case corresponds to the exponential $F(R)$ gravity which unifies late and early-time acceleration. Finally, we study the behavior of the effective gravitational constant and the growth factor, and as we sho...

  8. Manipulation of health span and function by dietary caloric restriction mimetics.

    Science.gov (United States)

    Roth, George S; Ingram, Donald K

    2016-01-01

    After nearly a century of rigorous investigation and testing, dietary caloric restriction (CR) remains the most robust and reproducible method for slowing aging and maintaining health, function, and vitality. This intervention has been applied to species across the evolutionary spectrum, but for a number of reasons, practical applicability to humans has been questioned. To overcome these issues, we initiated the field of CR mimetics in 1998 and have observed its development into a full-fledged antiaging industry. Basically, strategies that enable individuals to obtain the biological benefits of CR without reducing actual food intake can be considered CR mimetics, whether functional, pharmaceutical, nutraceutical, or other. Some of the best known candidates include resveratrol and related agents, the antidiabetic drug metformin, and rapamycin and other mTOR regulators. While the mechanisms of action vary, these and essentially all CR mimetic candidates work through at least some of the same pathways as actual CR. While the entire field continues to evolve rapidly, the current status will be reviewed here, with particular focus on recent developments, the most practical relevance and applicability for potential consumers, and new strategies for the future. PMID:26214681

  9. Activity of potent and selective host defense peptide mimetics in mouse models of oral candidiasis.

    Science.gov (United States)

    Ryan, Lisa K; Freeman, Katie B; Masso-Silva, Jorge A; Falkovsky, Klaudia; Aloyouny, Ashwag; Markowitz, Kenneth; Hise, Amy G; Fatahzadeh, Mahnaz; Scott, Richard W; Diamond, Gill

    2014-07-01

    There is a strong need for new broadly active antifungal agents for the treatment of oral candidiasis that not only are active against many species of Candida, including drug-resistant strains, but also evade microbial countermeasures which may lead to resistance. Host defense peptides (HDPs) can provide a foundation for the development of such agents. Toward this end, we have developed fully synthetic, small-molecule, nonpeptide mimetics of the HDPs that improve safety and other pharmaceutical properties. Here we describe the identification of several HDP mimetics that are broadly active against C. albicans and other species of Candida, rapidly fungicidal, and active against yeast and hyphal cultures and that exhibit low cytotoxicity for mammalian cells. Importantly, specificity for Candida over commensal bacteria was also evident, thereby minimizing potential damage to the endogenous microbiome which otherwise could favor fungal overgrowth. Three compounds were tested as topical agents in two different mouse models of oral candidiasis and were found to be highly active. Following single-dose administrations, total Candida burdens in tongues of infected animals were reduced up to three logs. These studies highlight the potential of HDP mimetics as a new tool in the antifungal arsenal for the treatment of oral candidiasis.

  10. AGN 191976: a novel thromboxane A2-mimetic with ocular hypotensive properties.

    Science.gov (United States)

    Krauss, A H; Woodward, D F; Chen, J; Gibson, L L; Lai, R K; Protzman, C E; Shan, T; Williams, L S; Gac, T S; Burk, R M

    1995-01-01

    The possible subdivision of thromboxane A2-sensitive (TP) receptors is currently a controversial subject. We report herein on a novel thromboxane A2 mimetic, AGN 191976, which has almost identical pharmacological activity to the well-characterized prostaglandin H2/thromboxane A2 (PGH2/TxA2) mimetic U-46619, but its effects on intraocular pressure are quite distinct from U-46619. Prostanoid receptor activity was determined in vitro using different smooth muscle assays and platelets. Intraocular pressure was measured tonometrically in ocular normotensive Beagle dogs and Cynomolgus monkeys. Conjunctival microvascular permeability was determined in guinea pigs. Despite closely resembling U-46619 as a potent and selective TP receptor agonist, AGN 191976 was a potent ocular hypotensive in dogs and monkeys whereas U-46619 did not lower IOP in either species. The ocular hypotensive effect of AGN 191976 in dogs was attenuated by pretreatment with the TP receptor antagonist SQ 29548. Thus, the ocular hypotensive effects of AGN 191976 are consistent with TP receptor stimulation. Both TxA2-mimetics caused plasma leakage in the guinea pig conjunctiva. The disparate activities of U-46619 and AGN 191976 in our studies suggest the existence of heterogeneous populations of TP-receptors in the eye.

  11. Improved surface bioactivity of stainless steel substrates using osteocalcin mimetic peptide

    Energy Technology Data Exchange (ETDEWEB)

    Hosseini, Samaneh [Department of Nanobiotechnology, Faculty of Biological Sciences, Tarbiat Modares University, Tehran (Iran, Islamic Republic of); Tissue Engineering and Biomaterials Division, National Institute of Genetic Engineering and Biotechnology, Tehran 14965/161 (Iran, Islamic Republic of); Naderi-Manesh, Hossein, E-mail: naderman@modares.ac.ir [Department of Nanobiotechnology, Faculty of Biological Sciences, Tarbiat Modares University, Tehran (Iran, Islamic Republic of); Vali, Hojatollah [Department of Anatomy and Cell Biology, McGill University, 3640 University Street, Montréal, QC H3A 0C7 (Canada); Faghihi, Shahab, E-mail: sfaghihi@nigeb.ac.ir [Tissue Engineering and Biomaterials Division, National Institute of Genetic Engineering and Biotechnology, Tehran 14965/161 (Iran, Islamic Republic of)

    2014-02-14

    Although stainless steel has a good biocompatibility for most clinical cases, the higher tissue response (bone bonding property) is required in orthopedic field. In this study, to improve bone-bonding ability of stainless steel substrates, a specific sequence of osteocalcin mimetic peptide is used as bioactive coating material to biochemically modify the surface of metallic samples. This sequence consists of thirteen amino acids present in the first helix of osteocalcin is synthesized in amidic form and physically adsorbed on the surface of 316LS (316 low carbon surgical grade) stainless steel substrates. Atomic force microscopy (AFM) and scanning electron microscopy (SEM) are used to characterize the surface of peptide coated and uncoated substrates. The bioactivity and bone bonding ability of coated and uncoated substrates are assessed by level of hydroxyapatite formation, using transmission electron microscopy (TEM), energy-dispersive x-ray (EDS), and scanning electron microscopy (SEM). The pre-osteoblast cell attachment and proliferation are also evaluated by MTT assay. The results show that the surface of coated sample is homogenously covered by the peptide and display a rougher surface relative to uncoated sample. TEM images reveal the formation of plate-like hydroxyapatite crystals in the presence of the peptide and an amorphous calcium phosphate phase without the peptide. Pre-osteoblast cells proliferation is significantly higher on the surface of peptide coated substrate, while cell attachment remains unaffected by the peptide coatings. Pre-osteoblast cells also demonstrate a higher degree of spreading on the surface of coated sample. It is believed that osteocalcin mimetic peptide improve surface bioactivity and promote hydroxyapatite crystal formation may lead to increased mineralization and bone formation on the surface of metallic biomedical devices. - Graphical abstract: A peptide sequence located in the first helix of OC is selected based on its

  12. Antitumor effects of energy restriction-mimetic agents: thiazolidinediones.

    Science.gov (United States)

    Omar, Hany A; Salama, Samir A; Arafa, El-Shaimaa A; Weng, Jing-Ru

    2013-07-01

    Distinct metabolic strategies used by cancer cells to gain growth advantages, such as shifting from oxidative phosphorylation to glycolysis, constitute a basis for their selective targeting as a novel approach for cancer therapy. Thiazolidinediones (TZDs) are ligands for the nuclear transcription factor peroxisome proliferator-activated receptor gamma (PPARγ) and they are clinically used as oral hypoglycemic agents. Accumulating evidence suggests that the ability of TZDs to suppress cancer cell proliferation through the interplay between apoptosis and autophagy was, at least in part, mediated through PPARγ-independent mechanisms. This review highlights recent advances in the pharmacological exploitation of the PPARγ-independent anticancer effects of TZDs to develop novel agents targeting tumor metabolism, including glucose transporter inhibitors and adenosine monophosphate-activated protein kinase, which have translational potential as cancer therapeutic agents. PMID:23612598

  13. Incretin-based therapies for type 2 diabetes mellitus in Asian patients: Analysis of clinical trials

    OpenAIRE

    Melva Louisa; Madoka Takeuchi; Masahiro Takeuchi; Nafrialdi Nafrialdi; Rianto Setiabudy

    2010-01-01

    Aim To review the effi cacy and safety data on incretin-based therapies currently available (exenatide, liraglutide, sitagliptin, vildagliptin) for the treatment of type 2 diabetes mellitus in Asian population.Methods We conducted Medline search of all relevant randomized clinical trials of incretin-based therapies for type 2 diabetes mellitus in Asian populations. Data pertinent to the efficacy and safety of GLP-1 mimetics and DPP-4 inhibitors were extracted and used.Results We found 14 rand...

  14. [small beta]-Turn mimetic-based stabilizers of protein-protein interactions for the study of the non-canonical roles of leucyl-tRNA synthetase

    DEFF Research Database (Denmark)

    Kim, Chanwoo; Jung, Jinjoo; Thanh Tung, Truong;

    2016-01-01

    For the systematic perturbation of protein-protein interactions, we designed and synthesized tetra-substituted hexahydro-4H-pyrazino[2,1-c][1,2,4]triazine-4,7(6H)-diones as [small beta]-turn mimetics. We then devised a new synthetic route to obtain [small beta]-turn mimetic scaffolds via tandem N...

  15. Better Living through Chemistry: Caloric Restriction (CR) and CR Mimetics Alter Genome Function to Promote Increased Health and Lifespan.

    Science.gov (United States)

    Gillespie, Zoe E; Pickering, Joshua; Eskiw, Christopher H

    2016-01-01

    Caloric restriction (CR), defined as decreased nutrient intake without causing malnutrition, has been documented to increase both health and lifespan across numerous organisms, including humans. Many drugs and other compounds naturally occurring in our diet (nutraceuticals) have been postulated to act as mimetics of caloric restriction, leading to a wave of research investigating the efficacy of these compounds in preventing age-related diseases and promoting healthier, longer lifespans. Although well studied at the biochemical level, there are still many unanswered questions about how CR and CR mimetics impact genome function and structure. Here we discuss how genome function and structure are influenced by CR and potential CR mimetics, including changes in gene expression profiles and epigenetic modifications and their potential to identify the genetic fountain of youth. PMID:27588026

  16. Better Living through Chemistry: Caloric Restriction (CR) and CR Mimetics Alter Genome Function to Promote Increased Health and Lifespan

    Science.gov (United States)

    Gillespie, Zoe E.; Pickering, Joshua; Eskiw, Christopher H.

    2016-01-01

    Caloric restriction (CR), defined as decreased nutrient intake without causing malnutrition, has been documented to increase both health and lifespan across numerous organisms, including humans. Many drugs and other compounds naturally occurring in our diet (nutraceuticals) have been postulated to act as mimetics of caloric restriction, leading to a wave of research investigating the efficacy of these compounds in preventing age-related diseases and promoting healthier, longer lifespans. Although well studied at the biochemical level, there are still many unanswered questions about how CR and CR mimetics impact genome function and structure. Here we discuss how genome function and structure are influenced by CR and potential CR mimetics, including changes in gene expression profiles and epigenetic modifications and their potential to identify the genetic fountain of youth. PMID:27588026

  17. Bio-mimetic mineralization potential of collagen hydrolysate obtained from chromium tanned leather waste

    Energy Technology Data Exchange (ETDEWEB)

    Banerjee, Pradipta; Madhu, S. [School of Bio Science and Technology, Vellore Institute of Technology University, Vellore 632014, Tamil Nadu (India); Chandra Babu, N.K. [Tannery Division, CSIR-Central Leather Research Institute, Chennai 600 020, Tamil Nadu (India); Shanthi, C., E-mail: cshanthi@vit.ac.in [School of Bio Science and Technology, Vellore Institute of Technology University, Vellore 632014, Tamil Nadu (India)

    2015-04-01

    Hydroxyapatite (HA) ceramics serve as an alternative to autogenous-free bone grafting by virtue of their excellent biocompatibility. However, chemically synthesized HA lacks the strong load-bearing capacity as required by bone. The bio-mimetic growth of HA crystals on collagen surface provides a feasible solution for synthesizing bone substitutes with the desired properties. This study deals with the utilization of the collagen hydrolysate recovered from leather waste as a substrate for promoting HA crystal growth. Bio-mimetic growth of HA was induced by subjecting the hydrolysate to various mineralization conditions. Parameters that would have a direct effect on crystal growth were varied to determine the optimal conditions necessary. Maximum mineralization was achieved with a combination of 10 mM of CaCl{sub 2}, 5 mM of Na{sub 2}HPO{sub 4}, 100 mM of NaCl and 0.575% glutaraldehyde at a pH of 7.4. The metal–protein interactions leading to formation of HA were identified through Fourier-transform infrared (FTIR) spectroscopy and x-ray diffraction (XRD) studies. The crystal dimensions were determined to be in the nanoscale range by atomic force microscopy (AFM) and scanning electron microscopy (SEM). The size and crystallinity of bio-mimetically grown HA indicate that hydrolysate from leather waste can be used as an ideal alternative substrate for bone growth. - Highlights: • Collagen hydrolysate, extracted from leather industry waste is subjected to biomineralization. • Optimal conditions required for HA growth are identified. • FTIR studies reveal higher Ca−COO{sup −} and low C−N stretch with higher HA formation. • AFM and SEM studies reveal nanometer ranged HA crystals.

  18. Bio-mimetic mineralization potential of collagen hydrolysate obtained from chromium tanned leather waste

    International Nuclear Information System (INIS)

    Hydroxyapatite (HA) ceramics serve as an alternative to autogenous-free bone grafting by virtue of their excellent biocompatibility. However, chemically synthesized HA lacks the strong load-bearing capacity as required by bone. The bio-mimetic growth of HA crystals on collagen surface provides a feasible solution for synthesizing bone substitutes with the desired properties. This study deals with the utilization of the collagen hydrolysate recovered from leather waste as a substrate for promoting HA crystal growth. Bio-mimetic growth of HA was induced by subjecting the hydrolysate to various mineralization conditions. Parameters that would have a direct effect on crystal growth were varied to determine the optimal conditions necessary. Maximum mineralization was achieved with a combination of 10 mM of CaCl2, 5 mM of Na2HPO4, 100 mM of NaCl and 0.575% glutaraldehyde at a pH of 7.4. The metal–protein interactions leading to formation of HA were identified through Fourier-transform infrared (FTIR) spectroscopy and x-ray diffraction (XRD) studies. The crystal dimensions were determined to be in the nanoscale range by atomic force microscopy (AFM) and scanning electron microscopy (SEM). The size and crystallinity of bio-mimetically grown HA indicate that hydrolysate from leather waste can be used as an ideal alternative substrate for bone growth. - Highlights: • Collagen hydrolysate, extracted from leather industry waste is subjected to biomineralization. • Optimal conditions required for HA growth are identified. • FTIR studies reveal higher Ca−COO− and low C−N stretch with higher HA formation. • AFM and SEM studies reveal nanometer ranged HA crystals

  19. A phase II trial of the BCL-2 homolog domain 3 mimetic AT-101 in combination with docetaxel for recurrent, locally advanced, or metastatic head and neck cancer

    Science.gov (United States)

    Swiecicki, Paul L.; Bellile, Emily; Sacco, Assuntina G.; Pearson, Alexander T.; Taylor, Jeremy M. G.; Jackson, Trachette L.; Chepeha, Douglas B.; Spector, Matthew E.; Shuman, Andrew; Malloy, Kelly; Moyer, Jeffrey; McKean, Erin; McLean, Scott; Sukari, Ammar; Wolf, Gregory T.; Eisbruch, Avraham; Prince, Mark; Bradford, Carol; Carey, Thomas E.; Wang, Shaomeng; Nör, Jacques E.; Worden, Francis P.

    2016-01-01

    Background AT-101 is a BCL-2 Homolog domain 3 mimetic previously demonstrated to have tumoricidal effects in advanced solid organ malignancies. Given the evidence of activity in xenograft models, treatment with AT-101 in combination with docetaxel is a therapeutic doublet of interest in metastatic head and neck squamous cell carcinoma. Patients and Methods Patients included in this trial had unresectable, recurrent, or distantly metastatic head and neck squamous cell carcinoma (R/M HNSCC) not amenable to curative radiation or surgery. This was an open label randomized, phase II trial in which patients were administered AT-101 in addition to docetaxel. The three treatment arms were docetaxel, docetaxel plus pulse dose AT-101, and docetaxel plus metronomic dose AT-101. The primary endpoint of this trial was overall response rate. Results Thirty-five patients were registered and 32 were evaluable for treatment response. Doublet therapy with AT-101 and docetaxel was well tolerated with only 2 patients discontinuing therapy due to treatment related toxicities. The overall response rate was 11% (4 partial responses) with a clinical benefit rate of 74%. Median progression free survival was 4.3 months (range: 0.7–13.7) and overall survival was 5.5 months (range: 0.4–24). No significant differences were noted between dosing strategies. Conclusion Although met with a favorable toxicity profile, the addition of AT-101 to docetaxel in R/M HNSCC does not appear to demonstrate evidence of efficacy. PMID:27225873

  20. Arbitrary Order Mixed Mimetic Finite Differences Method with Nodal Degrees of Freedom

    Energy Technology Data Exchange (ETDEWEB)

    Iaroshenko, Oleksandr [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Gyrya, Vitaliy [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Manzini, Gianmarco [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-09-01

    In this work we consider a modification to an arbitrary order mixed mimetic finite difference method (MFD) for a diffusion equation on general polygonal meshes [1]. The modification is based on moving some degrees of freedom (DoF) for a flux variable from edges to vertices. We showed that for a non-degenerate element this transformation is locally equivalent, i.e. there is a one-to-one map between the new and the old DoF. Globally, on the other hand, this transformation leads to a reduction of the total number of degrees of freedom (by up to 40%) and additional continuity of the discrete flux.

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

    OpenAIRE

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

    2015-01-01

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

  2. Unified description of dark energy and dark matter in mimetic matter model

    CERN Document Server

    Matsumoto, Jiro

    2016-01-01

    The existence of dark matter and dark energy in cosmology is implied by various observations, however, they are still unclear because they have not been directly detected. In this Letter, an unified model of dark energy and dark matter that can explain the evolution history of the Universe later than inflationary era, the time evolution of the growth rate function of the matter density contrast, the flat rotation curves of the spiral galaxies, and the gravitational experiments in the solar system is proposed in mimetic matter model.

  3. From Complex Natural Products to Simple Synthetic Mimetics by Computational De Novo Design.

    Science.gov (United States)

    Friedrich, Lukas; Rodrigues, Tiago; Neuhaus, Claudia S; Schneider, Petra; Schneider, Gisbert

    2016-06-01

    We present the computational de novo design of synthetically accessible chemical entities that mimic the complex sesquiterpene natural product (-)-Englerin A. We synthesized lead-like probes from commercially available building blocks and profiled them for activity against a computationally predicted panel of macromolecular targets. Both the design template (-)-Englerin A and its low-molecular weight mimetics presented nanomolar binding affinities and antagonized the transient receptor potential calcium channel TRPM8 in a cell-based assay, without showing target promiscuity or frequent-hitter properties. This proof-of-concept study outlines an expeditious solution to obtaining natural-product-inspired chemical matter with desirable properties. PMID:27111835

  4. The Mimetic Finite Element Method and the Virtual Element Method for elliptic problems with arbitrary regularity.

    Energy Technology Data Exchange (ETDEWEB)

    Manzini, Gianmarco [Los Alamos National Laboratory

    2012-07-13

    We develop and analyze a new family of virtual element methods on unstructured polygonal meshes for the diffusion problem in primal form, that use arbitrarily regular discrete spaces V{sub h} {contained_in} C{sup {alpha}} {element_of} N. The degrees of freedom are (a) solution and derivative values of various degree at suitable nodes and (b) solution moments inside polygons. The convergence of the method is proven theoretically and an optimal error estimate is derived. The connection with the Mimetic Finite Difference method is also discussed. Numerical experiments confirm the convergence rate that is expected from the theory.

  5. Aerodynamic Bio-Mimetics of Gliding Dragonflies for Ultra-Light Flying Robot

    Directory of Open Access Journals (Sweden)

    Akira Obata

    2014-05-01

    Full Text Available A detailed investigation including a low-speed flow study is presented on the development of ultra-light dragonfly mimetic flying robots with a focus on the dragonfly’s remarkable gliding capability. It is revealed that the dragonfly’s corrugated wing structure and cruciform configuration provide superior flying characteristics for fixed wing robots in low Reynolds number flight. It was also found that the dragonfly configuration has additional merit in its compatibility with propellers or high lift devices. This combination with such classic aero-engineering makes possible robots with broader flight envelope than conventional fixed-wing flying robots.

  6. Connexin mimetic peptides fail to inhibit vascular conducted calcium responses in renal arterioles

    DEFF Research Database (Denmark)

    Sørensen, Charlotte Mehlin; Salomonsson, Max; Braunstein, Thomas Hartig;

    2008-01-01

    Vascular conducted responses are believed to play a central role in controlling the microcirculatory blood flow. The responses most likely spread through gap junctions in the vascular wall. At present, four different connexins (Cx) have been detected in the renal vasculature, but their role...... of mimetic peptides directed against one or more connexins. Preglomerular resistance vessels were microdissected from kidneys of Sprague-Dawley rats and loaded with fura 2. The vessels were stimulated locally by applying electrical current through a micropipette, and the conducted calcium response...

  7. Inflation in f(R,φ)-theories and mimetic gravity scenario

    Energy Technology Data Exchange (ETDEWEB)

    Myrzakulov, R.; Sebastiani, L. [Eurasian National University, Department of General and Theoretical Physics and Eurasian Center for Theoretical Physics, Astana (Kazakhstan); Vagnozzi, S. [University of Copenhagen, Niels Bohr International Academy and Discovery Center, Niels Bohr Institute, Copenhagen Oe (Denmark); Nordita, KTH Royal Institute of Technology and Stockholm University, Stockholm (Sweden); Stockholm University, AlbaNova, Department of Physics, The Oskar Klein Centre for Cosmoparticle Physics, Stockholm (Sweden); University of Melbourne, ARC Centre of Excellence for Particle Physics at the Terascale, School of Physics, Melbourne, VIC (Australia)

    2015-09-15

    We investigate inflation within f(R,φ)-theories, where a dynamical scalar field is coupled to gravity. A class of models which can support early-time acceleration with the emerging of an effective cosmological constant at high curvature is studied. The dynamics of the field allow for exit from inflation leading to the correct amount of inflation in agreement with cosmological data. Furthermore, the spectral index and tensor-to-scalar ratio of the models are carefully analyzed. A generalization of the theory to incorporate dark matter in the context of mimetic gravity, and further extensions of the latter, are also discussed. (orig.)

  8. Cluster Based Hybrid Niche Mimetic and Genetic Algorithm for Text Document Categorization

    Directory of Open Access Journals (Sweden)

    A. K. Santra

    2011-09-01

    Full Text Available An efficient cluster based hybrid niche mimetic and genetic algorithm for text document categorization to improve the retrieval rate of relevant document fetching is addressed. The proposal minimizes the processing of structuring the document with better feature selection using hybrid algorithm. In addition restructuring of feature words to associated documents gets reduced, in turn increases document clustering rate. The performance of the proposed work is measured in terms of cluster objects accuracy, term weight, term frequency and inverse document frequency. Experimental results demonstrate that it achieves very good performance on both feature selection and text document categorization, compared to other classifier methods.

  9. RNAi delivery by exosome-mimetic nanovesicles - Implications for targeting c-Myc in cancer.

    Science.gov (United States)

    Lunavat, Taral R; Jang, Su Chul; Nilsson, Lisa; Park, Hyun Taek; Repiska, Gabriela; Lässer, Cecilia; Nilsson, Jonas A; Gho, Yong Song; Lötvall, Jan

    2016-09-01

    To develop RNA-based therapeutics, it is crucial to create delivery vectors that transport the RNA molecule into the cell cytoplasm. Naturally released exosomes vesicles (also called "Extracellular Vesicles") have been proposed as possible RNAi carriers, but their yield is relatively small in any cell culture system. We have previously generated exosome-mimetic nanovesicles (NV) by serial extrusions of cells through nano-sized filters, which results in 100-times higher yield of extracellular vesicles. We here test 1) whether NV can be loaded with siRNA exogenously and endogenously, 2) whether the siRNA-loaded NV are taken up by recipient cells, and 3) whether the siRNA can induce functional knock-down responses in recipient cells. A siRNA against GFP was first loaded into NV by electroporation, or a c-Myc shRNA was expressed inside of the cells. The NV were efficiently loaded with siRNA with both techniques, were taken up by recipient cells, which resulted in attenuation of target gene expression. In conclusion, our study suggests that exosome-mimetic nanovesicles can be a platform for RNAi delivery to cell cytoplasm. PMID:27344366

  10. The action of mimetic peptides on connexins protects fibroblasts from the negative effects of ischemia reperfusion

    Science.gov (United States)

    Glass, Beverley J.; Hu, Rebecca G.; Phillips, Anthony R. J.; Becker, David L.

    2015-01-01

    ABSTRACT Connexins have been proposed as a target for therapeutic treatment of a variety of conditions. The main approaches have been by antisense or small peptides specific against connexins. Some of these peptides enhance communication while others interfere with connexin binding partners or bind to the intracellular and extracellular loops of connexins. Here, we explored the mechanism of action of a connexin mimetic peptide by evaluating its effect on gap junction channels, connexin protein levels and hemichannel activity in fibroblast cells under normal conditions and following ischemia reperfusion injury which elevates Cx43 levels, increases hemichannel activity and causes cell death. Our results showed that the effects of the mimetic peptide were concentration-dependent. High concentrations (100-300 μM) significantly reduced Cx43 protein levels and GJIC within 2 h, while these effects did not appear until 6 h when using lower concentrations (10-30 μM). Cell death can be reduced when hemichannel opening and GJIC were minimised. PMID:26471768

  11. The action of mimetic peptides on connexins protects fibroblasts from the negative effects of ischemia reperfusion

    Directory of Open Access Journals (Sweden)

    Beverley J. Glass

    2015-11-01

    Full Text Available Connexins have been proposed as a target for therapeutic treatment of a variety of conditions. The main approaches have been by antisense or small peptides specific against connexins. Some of these peptides enhance communication while others interfere with connexin binding partners or bind to the intracellular and extracellular loops of connexins. Here, we explored the mechanism of action of a connexin mimetic peptide by evaluating its effect on gap junction channels, connexin protein levels and hemichannel activity in fibroblast cells under normal conditions and following ischemia reperfusion injury which elevates Cx43 levels, increases hemichannel activity and causes cell death. Our results showed that the effects of the mimetic peptide were concentration-dependent. High concentrations (100-300 μM significantly reduced Cx43 protein levels and GJIC within 2 h, while these effects did not appear until 6 h when using lower concentrations (10-30 μM. Cell death can be reduced when hemichannel opening and GJIC were minimised.

  12. BH3 Mimetics Reactivate Autophagic Cell Death in Anoxia-Resistant Malignant Glioma Cells

    Directory of Open Access Journals (Sweden)

    Holger Hetschko

    2008-08-01

    Full Text Available Here, we investigated the specific roles of Bcl-2 family members in anoxia tolerance of malignant glioma. Flow cytometry analysis of cell death in 17 glioma cell lines revealed drastic differences in their sensitivity to oxygen withdrawal (<0.1% O2. Cell death correlated with mitochondrial depolarization, cytochrome C release, and translocation of green fluorescent protein (GFP-tagged light chain 3 to autophagosomes but occurred in the absence of caspase activation or phosphatidylserine exposure. In both sensitive and tolerant glioma cell lines, anoxia caused a significant up-regulation of BH3-only genes previously implicated in mediating anoxic cell death in other cell types (BNIP3, NIX, PUMA, and Noxa. In contrast, we detected a strong correlation between anoxia resistance and high expression levels of antiapoptotic Bcl-2 family proteins Bcl-xL, Bcl-2, and Mcl-1 that function to neutralize the proapoptotic activity of BH3-only proteins. Importantly, inhibition of both Bcl-2 and Bcl-xL with the small-molecule BH3 mimetics HA14-1 and BH3I-2′ and by RNA interference reactivated anoxia-induced autophagic cell death in previously resistant glioma cells. Our data suggest that endogenous BH3-only protein induction may not be able to compensate for the high expression of antiapoptotic Bcl-2 family proteins in anoxia-resistant astrocytomas. They also support the conjecture that BH3 mimetics may represent an exciting new approach for the treatment of malignant glioma.

  13. Catalytic mechanism of Cu(p-OTs)2/ethanolamine as mimetic enzyme

    Institute of Scientific and Technical Information of China (English)

    宋继国; 沈培康

    2004-01-01

    The electrochemical behaviors of various copper salts complexes coordinated with equal molar ethanolamine were studied, and those of Cu(p-OTs)2 and Cu(p-OTs)2/ethanolamine(1:1) complex in CH3OH or DMF were characterized. The results show that the reduction of Cu( Ⅱ ) in Cu(p-OTs)2 is via one two-electron step mechanism both in CH3 OH and DMF. The reduction mechanism transforms to two one-electron steps in the case of Cu (p-OTs)2/ethanolamine(1:1) in DMF. However, it does not change in CH3 OH. All the Cu( Ⅱ )/ethanolamine(1:1) with the electrochemical reactions are through two one-electron steps, and can act as mimetic enzyme to oxidize 1, 1'-bi-2-naphthol. The Cu( Ⅱ )/ethanolamine(1:1) with electrochemical reactions through one two-electron step could not act as mimetic enzyme. It is concluded that the transformation between centre Cu( Ⅱ ) and Cu( Ⅰ ) is the crucial condition for the catalytic activity of copper-amine complex.

  14. Inhibition of Antiapoptotic BCL-XL, BCL-2, and MCL-1 Proteins by Small Molecule Mimetics

    Directory of Open Access Journals (Sweden)

    D.S. Dalafave

    2010-08-01

    Full Text Available Informatics and computational design methods were used to create new molecules that could potentially bind antiapoptotic proteins, thus promoting death of cancer cells. Apoptosis is a cellular process that leads to the death of damaged cells. Its malfunction can cause cancer and poor response to conventional chemotherapy. After being activated by cellular stress signals, proapoptotic proteins bind antiapoptotic proteins, thus allowing apoptosis to go forward. An excess of antiapoptotic proteins can prevent apoptosis. Designed molecules that mimic the roles of proapoptotic proteins can promote the death of cancer cells. The goal of our study was to create new putative mimetics that could simultaneously bind several antiapoptotic proteins. Five new small molecules were designed that formed stable complexes with BCL-2, BCL-XL, and MCL-1 antiapoptotic proteins. These results are novel because, to our knowledge, there are not many, if any, small molecules known to bind all three proteins. Drug-likeness studies performed on the designed molecules, as well as previous experimental and preclinical studies on similar agents, strongly suggest that the designed molecules may indeed be promising drug candidates. All five molecules showed “drug-like” properties and had overall drug-likeness scores between 81% and 96%. A single drug based on these mimetics should cost less and cause fewer side effects than a combination of drugs each aimed at a single protein. Computer-based molecular design promises to accelerate drug research by predicting potential effectiveness of designed molecules prior to laborious experiments and costly preclinical trials.

  15. Modeling anisotropic flow and heat transport by using mimetic finite differences

    Science.gov (United States)

    Chen, Tao; Clauser, Christoph; Marquart, Gabriele; Willbrand, Karen; Büsing, Henrik

    2016-08-01

    Modeling anisotropic flow in porous or fractured rock often assumes that the permeability tensor is diagonal, which means that its principle directions are always aligned with the coordinate axes. However, the permeability of a heterogeneous anisotropic medium usually is a full tensor. For overcoming this shortcoming, we use the mimetic finite difference method (mFD) for discretizing the flow equation in a hydrothermal reservoir simulation code, SHEMAT-Suite, which couples this equation with the heat transport equation. We verify SHEMAT-Suite-mFD against analytical solutions of pumping tests, using both diagonal and full permeability tensors. We compare results from three benchmarks for testing the capability of SHEMAT-Suite-mFD to handle anisotropic flow in porous and fractured media. The benchmarks include coupled flow and heat transport problems, three-dimensional problems and flow through a fractured porous medium with full equivalent permeability tensor. It shows firstly that the mimetic finite difference method can model anisotropic flow both in porous and in fractured media accurately and its results are better than those obtained by the multi-point flux approximation method in highly anisotropic models, secondly that the asymmetric permeability tensor can be included and leads to improved results compared the symmetric permeability tensor in the equivalent fracture models, and thirdly that the method can be easily implemented in existing finite volume or finite difference codes, which has been demonstrated successfully for SHEMAT-Suite.

  16. Synthesis of cellulose nanocrystals carrying tyrosine sulfate mimetic ligands and inhibition of alphavirus infection.

    Science.gov (United States)

    Zoppe, Justin O; Ruottinen, Ville; Ruotsalainen, Janne; Rönkkö, Seppo; Johansson, Leena-Sisko; Hinkkanen, Ari; Järvinen, Kristiina; Seppälä, Jukka

    2014-04-14

    We present two facile approaches for introducing multivalent displays of tyrosine sulfate mimetic ligands on the surface of cellulose nanocrystals (CNCs) for application as viral inhibitors. We tested the efficacy of cellulose nanocrystals, prepared either from cotton fibers or Whatman filter paper, to inhibit alphavirus infectivity in Vero (B) cells. Cellulose nanocrystals were produced by sulfuric acid hydrolysis leading to nanocrystal surfaces decorated with anionic sulfate groups. When the fluorescent marker expressing Semliki Forest virus vector, VA7-EGFP, was incubated with CNCs, strong inhibition of virus infectivity was achieved, up to 100 and 88% for cotton and Whatman CNCs, respectively. When surface sulfate groups of CNCs were exchanged for tyrosine sulfate mimetic groups (i.e. phenyl sulfonates), improved viral inhibition was attained. Our observations suggest that the conjugation of target-specific functionalities to CNC surfaces provides a means to control their antiviral activity. Multivalent CNCs did not cause observable in vitro cytotoxicity to Vero (B) cells or human corneal epithelial (HCE-T) cells, even within the 100% virus-inhibitory concentrations. Based on the similar chemistry of known polyanionic inhibitors, our results suggest the potential application of CNCs as inhibitors of other viruses, such as human immunodeficiency virus (HIV) and herpes simplex viruses. PMID:24628489

  17. A mimetic finite difference method for the Stokes problem with elected edge bubbles

    Energy Technology Data Exchange (ETDEWEB)

    Lipnikov, K [Los Alamos National Laboratory; Berirao, L [DIPARTMENTO DI MATERMATICA

    2009-01-01

    A new mimetic finite difference method for the Stokes problem is proposed and analyzed. The unstable P{sub 1}-P{sub 0} discretization is stabilized by adding a small number of bubble functions to selected mesh edges. A simple strategy for selecting such edges is proposed and verified with numerical experiments. The discretizations schemes for Stokes and Navier-Stokes equations must satisfy the celebrated inf-sup (or the LBB) stability condition. The stability condition implies a balance between discrete spaces for velocity and pressure. In finite elements, this balance is frequently achieved by adding bubble functions to the velocity space. The goal of this article is to show that the stabilizing edge bubble functions can be added only to a small set of mesh edges. This results in a smaller algebraic system and potentially in a faster calculations. We employ the mimetic finite difference (MFD) discretization technique that works for general polyhedral meshes and can accomodate non-uniform distribution of stabilizing bubbles.

  18. Copper Complexes of Nicotinic-Aromatic Carboxylic Acids as Superoxide Dismutase Mimetics

    Directory of Open Access Journals (Sweden)

    Virapong Prachayasittikul

    2008-12-01

    Full Text Available Nicotinic acid (also known as vitamin B3 is a dietary element essential for physiological and antihyperlipidemic functions. This study reports the synthesis of novel mixed ligand complexes of copper with nicotinic and other select carboxylic acids (phthalic, salicylic and anthranilic acids. The tested copper complexes exhibited superoxide dismutase (SOD mimetic activity and antimicrobial activity against Bacillus subtilis ATCC 6633, with a minimum inhibition concentration of 256 μg/mL. Copper complex of nicotinic-phthalic acids (CuNA/Ph was the most potent with a SOD mimetic activity of IC50 34.42 μM. The SOD activities were observed to correlate well with the theoretical parameters as calculated using density functional theory (DFT at the B3LYP/LANL2DZ level of theory. Interestingly, the SOD activity of the copper complex CuNA/Ph was positively correlated with the electron affinity (EA value. The two quantum chemical parameters, highest occupied molecular orbital (HOMO and lowest unoccupied molecular orbital (LUMO, were shown to be appropriate for understanding the mechanism of the metal complexes as their calculated energies show good correlation with the SOD activity. Moreover, copper complex with the highest SOD activity were shown to possess the lowest HOMO energy. These findings demonstrate a great potential for the development of value-added metallovitamin-based therapeutics.

  19. Theoretical studies on the interactions of XIAP-BIR3 domain with bicyclic and tricyclic core monovalent Smac mimetics.

    Science.gov (United States)

    Ling, Baoping; Dong, Lihua; Zhang, Rui; Wang, Zhiguo; Liu, Yongjun; Liu, Chengbu

    2010-11-01

    X-linked IAP can bind caspase-9 and inhibit its activity. Mitochondrial protein Smac/DIABLO can also interact with XIAP and relieve the inhibition on caspase-9 to induce apoptosis. A series of artificial Smac mimetics have been used to mimic the Smac N-terminal tetrapeptide AVPI to bind to XIAP-BIR3, but these structural diverse mimetics exhibited distinct binding affinities. To get an insight into the binding nature and optimize the structures, molecular docking and dynamics simulations were used to study the binding of XIAP-BIR3 with three groups of Smac mimetics. The docking results reveal that these Smac mimetics anchored on the surface groove of XIAP-BIR3 and superimposed well with AVPI. The modifications on the seven-membered ring of bicyclic core segment do not strengthen the binding affinity, while a benzyl introduced to the five-membered ring is favorable to the binding. Molecular dynamics simulations on three typical systems show that these complexes are very stable. Hydrogen bonds between the bicyclic core segment and Thr308 play critical roles in maintaining the stability of complex. The binding free energies calculated by MM_PBSA method are consistent with the experimental results. PMID:20980180

  20. Design and modular parallel synthesis of a MCR derived α-helix mimetic protein-protein interaction inhibitor scaffold

    NARCIS (Netherlands)

    Antuch, Walfrido; Menon, Sanjay; Chen, Quin-Zene; Lu, Yingchun; Sakamuri, Sukumar; Beck, Barbara; Schauer-Vukašinović, Vesna; Agarwal, Seema; Hess, Sibylle; Dömling, Alexander

    2006-01-01

    A terphenyl α-helix mimetic scaffold recognized to be capable of disrupting protein-protein interactions was structurally morphed into an easily amenable and versatile multicomponent reaction (MCR) backbone. The design, modular in-parallel library synthesis, initial cell based biological data, and p

  1. Fibronectin- and collagen-mimetic ligands regulate bone marrow stromal cell chondrogenesis in three-dimensional hydrogels

    Directory of Open Access Journals (Sweden)

    JT Connelly

    2011-09-01

    Full Text Available Modification of tissue engineering scaffolds with bioactive molecules is a potential strategy for modulating cell behavior and guiding tissue regeneration. While adhesion to RGD peptides has been shown to inhibit in vitro chondrogenesis, the effects of extracellular matrix (ECM-mimetic ligands with complex secondary and tertiary structures are unknown. This study aimed to determine whether collagen- and fibronectin-mimetic ligands would retain biologic functionality in three-dimensional (3D hydrogels, whether different ECM-mimetic ligands differentially influence in vitro chondrogenesis, and if effects of ligands on differentiation depend on soluble biochemical stimuli. A linear RGD peptide, a recombinant fibronectin fragment containing the seven to ten Type III repeats (FnIII7-10 and a triple helical, collagen mimetic peptide with the GFOGER motif were covalently coupled to agarose gels using the sulfo-SANPAH crosslinker, and bone marrow stromal cells (BMSCs were cultured within the 3D hydrogels. The ligands retained biologic functionality within the agarose gels and promoted density-dependent BMSC spreading. Interactions with all adhesive ligands inhibited stimulation by chondrogenic factors of collagen Type II and aggrecan mRNA levels and deposition of sulfated glycosaminoglycans. In medium containing fetal bovine serum, interactions with the GFOGER peptide enhanced mRNA expression of the osteogenic gene osteocalcin whereas FnIII7-10 inhibited osteocalcin expression. In conclusion, modification of agarose hydrogels with ECM-mimetic ligands can influence the differentiation of BMSCs in a manner that depends strongly on the presence and nature of soluble biochemical stimuli.

  2. EGFR-targeted TRAIL and a Smac mimetic synergize to overcome apoptosis resistance in KRAS mutant colorectal cancer cells.

    Directory of Open Access Journals (Sweden)

    Yvonne Möller

    Full Text Available TRAIL is a death receptor ligand that induces cell death preferentially in tumor cells. Recombinant soluble TRAIL, however, performs poorly as an anti-cancer therapeutic because oligomerization is required for potent biological activity. We previously generated a diabody format of tumor-targeted TRAIL termed Db(αEGFR-scTRAIL, comprising single-stranded TRAIL molecules (scTRAIL and the variable domains of a humanized variant of the EGFR blocking antibody Cetuximab. Here we define the bioactivity of Db(αEGFR-scTRAIL with regard to both EGFR inhibition and TRAIL receptor activation in 3D cultures of Caco-2 colorectal cancer cells, which express wild-type K-Ras. Compared with conventional 2D cultures, Caco-2 cells displayed strongly enhanced sensitivity toward Db(αEGFR-scTRAIL in these 3D cultures. We show that the antibody moiety of Db(αEGFR-scTRAIL not only efficiently competed with ligand-induced EGFR function, but also determined the apoptotic response by specifically directing Db(αEGFR-scTRAIL to EGFR-positive cells. To address how aberrantly activated K-Ras, which leads to Cetuximab resistance, affects Db(αEGFR-scTRAIL sensitivity, we generated stable Caco-2tet cells inducibly expressing oncogenic K-Ras(G12V. In the presence of doxycycline, these cells showed increased resistance to Db(αEGFR-scTRAIL, associated with the elevated expression of the anti-apoptotic proteins cIAP2, Bcl-xL and FlipS. Co-treatment of cells with the Smac mimetic SM83 restored the Db(αEGFR-scTRAIL-induced apoptotic response. Importantly, this synergy between Db(αEGFR-scTRAIL and SM83 also translated to 3D cultures of oncogenic K-Ras expressing HCT-116 and LoVo colorectal cancer cells. Our findings thus support the notion that Db(αEGFR-scTRAIL therapy in combination with apoptosis-sensitizing agents may be promising for the treatment of EGFR-positive colorectal cancers, independently of their KRAS status.

  3. A BDNF loop-domain mimetic acutely reverses spontaneous apneas and respiratory abnormalities during behavioral arousal in a mouse model of Rett syndrome

    Directory of Open Access Journals (Sweden)

    Miriam Kron

    2014-09-01

    Full Text Available Reduced levels of brain-derived neurotrophic factor (BDNF are thought to contribute to the pathophysiology of Rett syndrome (RTT, a severe neurodevelopmental disorder caused by loss-of-function mutations in the gene encoding methyl-CpG-binding protein 2 (MeCP2. In Mecp2 mutant mice, BDNF deficits have been associated with breathing abnormalities, a core feature of RTT, as well as with synaptic hyperexcitability within the brainstem respiratory network. Application of BDNF can reverse hyperexcitability in acute brainstem slices from Mecp2-null mice, suggesting that therapies targeting BDNF or its receptor, TrkB, could be effective at acute reversal of respiratory abnormalities in RTT. Therefore, we examined the ability of LM22A-4, a small-molecule BDNF loop-domain mimetic and TrkB partial agonist, to modulate synaptic excitability within respiratory cell groups in the brainstem nucleus tractus solitarius (nTS and to acutely reverse abnormalities in breathing at rest and during behavioral arousal in Mecp2 mutants. Patch-clamp recordings in Mecp2-null brainstem slices demonstrated that LM22A-4 decreases excitability at primary afferent synapses in the nTS by reducing the amplitude of evoked excitatory postsynaptic currents and the frequency of spontaneous and miniature excitatory postsynaptic currents. In vivo, acute treatment of Mecp2-null and -heterozygous mutants with LM22A-4 completely eliminated spontaneous apneas in resting animals, without sedation. Moreover, we demonstrate that respiratory dysregulation during behavioral arousal, a feature of human RTT, is also reversed in Mecp2 mutants by acute treatment with LM22A-4. Together, these data support the hypothesis that reduced BDNF signaling and respiratory dysfunction in RTT are linked, and establish the proof-of-concept that treatment with a small-molecule structural mimetic of a BDNF loop domain and a TrkB partial agonist can acutely reverse abnormal breathing at rest and in response to

  4. A novel anti-inflammatory role of NCAM-derived mimetic peptide, FGL

    DEFF Research Database (Denmark)

    Downer, Eric J; Cowley, Thelma R; Lyons, Anthony;

    2010-01-01

    novel anti-inflammatory agent. Administration of FGL to aged rats attenuated the increased expression of markers of activated microglia, the increase in pro-inflammatory interleukin-1beta (IL-1beta) and the impairment in long-term potentiation (LTP). We report that the age-related increase in microglial......Age-related cognitive deficits in hippocampus are correlated with neuroinflammatory changes, typified by increased pro-inflammatory cytokine production and microglial activation. We provide evidence that the neural cell adhesion molecule (NCAM)-derived mimetic peptide, FG loop (FGL), acts as a...... CD200 in vitro. We provide evidence that the increase in CD200 is reliant on IL-4-induced extracellular signal-regulated kinase (ERK) signal transduction. These findings provide the first evidence of a role for FGL as an anti-inflammatory agent and identify a mechanism by which FGL controls...

  5. Targeting p38 or MK2 Enhances the Anti-Leukemic Activity of Smac-Mimetics.

    Science.gov (United States)

    Lalaoui, Najoua; Hänggi, Kay; Brumatti, Gabriela; Chau, Diep; Nguyen, Nhu-Y N; Vasilikos, Lazaros; Spilgies, Lisanne M; Heckmann, Denise A; Ma, Chunyan; Ghisi, Margherita; Salmon, Jessica M; Matthews, Geoffrey M; de Valle, Elisha; Moujalled, Donia M; Menon, Manoj B; Spall, Sukhdeep Kaur; Glaser, Stefan P; Richmond, Jennifer; Lock, Richard B; Condon, Stephen M; Gugasyan, Raffi; Gaestel, Matthias; Guthridge, Mark; Johnstone, Ricky W; Munoz, Lenka; Wei, Andrew; Ekert, Paul G; Vaux, David L; Wong, W Wei-Lynn; Silke, John

    2016-02-01

    Birinapant is a smac-mimetic (SM) in clinical trials for treating cancer. SM antagonize inhibitor of apoptosis (IAP) proteins and simultaneously induce tumor necrosis factor (TNF) secretion to render cancers sensitive to TNF-induced killing. To enhance SM efficacy, we screened kinase inhibitors for their ability to increase TNF production of SM-treated cells. We showed that p38 inhibitors increased TNF induced by SM. Unexpectedly, even though p38 is required for Toll-like receptors to induce TNF, loss of p38 or its downstream kinase MK2 increased induction of TNF by SM. Hence, we show that the p38/MK2 axis can inhibit or promote TNF production, depending on the stimulus. Importantly, clinical p38 inhibitors overcame resistance of primary acute myeloid leukemia to birinapant.

  6. Myoglobin as Mimetic Enzyme and Its Analytical Application in Determination of H2O2

    Institute of Scientific and Technical Information of China (English)

    ZHENG Qi; CAO Qihua; LIU Zhihong; CAI Ruxiu

    2006-01-01

    The characteristic of Myoglobin as mimetic enzyme was studied and applied in the determination of H2 O2with o-phenylenediamine as substrate. The absorbance obtained at 40 ℃ was found to be proportional to the concentration of H2O2 in the range oF2.0×10-5-2.0×10-7 mol/L,with a correlation coefficient of 0. 999 1. The proposed method is simple and highly sensitive to a detection limit oF2.7 ×10-8 mol/L. The relative standard deviations were within 5% for the determination of different concentrations of H2O2.Satisfied results were obtained in the determination of H2O2 in rainwater by this method, and the recoveries were at the range of 97.2%-105.4%.

  7. Triple Effect of Mimetic Peptides Interfering with Neural Cell Adhesion Molecule Homophilic Cis Interactions

    DEFF Research Database (Denmark)

    Li, S. Z.; Kolkova, Kateryna; Rudenko, Olga;

    2005-01-01

    The neural cell adhesion molecule (NCAM) is pivotal in neural development, regeneration, and learning. Here we characterize two peptides, termed P1-B and P2, derived from the homophilic binding sites in the first two N-terminal immunoglobulin (Ig) modules of NCAM, with regard to their effects...... on neurite extension and adhesion. To evaluate how interference of these mimetic peptides with NCAM homophilic interactions in cis influences NCAM binding in trans, we employed a coculture system in which PC12-E2 cells were grown on monolayers of fibroblasts with or without NCAM expression and the rate...... of neurite outgrowth subsequently was analyzed. P2, but not P1-B, induced neurite outgrowth in the absence of NCAM binding in trans. When PC12-E2 cells were grown on monolayers of NCAM-expressing fibroblasts, the effect of both P1-B and P2 on neurite outgrowth was dependent on peptide concentrations. P1-B...

  8. The characterization of decellularized human skeletal muscle as a blueprint for mimetic scaffolds.

    Science.gov (United States)

    Wilson, Klaire; Terlouw, Abby; Roberts, Kevin; Wolchok, Jeffrey C

    2016-08-01

    The use of decellularized skeletal muscle (DSM) as a cell substrate and scaffold for the repair of volumetric muscle loss injuries has shown therapeutic promise. The performance of DSM materials motivated our interest in exploring the chemical and physical properties of this promising material. We suggest that these properties could serve as a blueprint for the development of next generation engineered materials with DSM mimetic properties. In this study, whole human lower limb rectus femoris (n = 10) and upper limb supraspinatus muscle samples (n = 10) were collected from both male and female tissue donors. Skeletal muscle samples were decellularized and nine property values, capturing key compositional, architectural, and mechanical properties, were measured and statistically analyzed. Mean values for each property were determined across muscle types and sexes. Additionally, the influence of muscle type (upper vs lower limb) and donor sex (male vs female) on each of the DSM material properties was examined. The data suggests that DSM materials prepared from lower limb rectus femoris samples have an increased modulus and contain a higher collagen content then upper limb supraspinatus muscles. Specifically, lower limb rectus femoris DSM material modulus and collagen content was approximately twice that of lower limb supraspinatus DSM samples. While muscle type did show some influence on material properties, we did not find significant trends related to sex. The material properties reported herein may be used as a blueprint for the data-driven design of next generation engineered scaffolds with muscle mimetic properties, as well as inputs for computational and physical models of skeletal muscle. PMID:27324779

  9. Covariant Hořava-like and mimetic Horndeski gravity: cosmological solutions and perturbations

    Science.gov (United States)

    Cognola, Guido; Myrzakulov, Ratbay; Sebastiani, Lorenzo; Vagnozzi, Sunny; Zerbini, Sergio

    2016-11-01

    We consider a variant of the Nojiri–Odintsov covariant Hořava-like gravitational model, where diffeomorphism invariance is broken dynamically via a non-standard coupling to a perfect fluid. The theory allows one to address some of the potential instability problems present in Hořava–Lifshitz gravity due to explicit diffeomorphism invariance breaking. The fluid is instead constructed from a scalar field constrained by a Lagrange multiplier. In fact, the Lagrange multiplier construction allows for an extension of the Hořava-like model to include the scalar field of mimetic gravity, an extension which we thoroughly explore. By adding a potential for the scalar field, we show how one can reproduce a number of interesting cosmological scenarios. We then turn to the study of perturbations around a flat FLRW background, showing that the fluid in question behaves as an irrotational fluid, with zero sound speed. To address this problem, we consider a modified version of the theory, adding higher derivative terms in a way which brings us beyond the Horndeski framework. We compute the sound speed in this modified higher order mimetic Hořava-like model and show that it is non-zero, which means that perturbations therein can be sensibly defined. Caveats to our analysis, as well as comparisons to projectable Hořava–Lifshitz gravity, are also discussed. In conclusion, we present a theory of gravity which preserves diffeomorphism invariance at the level of the action but breaks it dynamically in the UV, reduces to General Relativity (GR) in the IR, allows the realization of a number of interesting cosmological scenarios, is well defined when considering perturbations around a flat FLRW background, and features cosmological dark matter emerging as an integration constant.

  10. Inhibition of Salmonella enterica biofilm formation using small-molecule adenosine mimetics.

    Science.gov (United States)

    Koopman, Jacob A; Marshall, Joanna M; Bhatiya, Aditi; Eguale, Tadesse; Kwiek, Jesse J; Gunn, John S

    2015-01-01

    Biofilms have been widely implicated in chronic infections and environmental persistence of Salmonella enterica, facilitating enhanced colonization of surfaces and increasing the ability of the bacteria to be transmitted to new hosts. Salmonella enterica serovar Typhi biofilm formation on gallstones from humans and mice enhances gallbladder colonization and bacterial shedding, while Salmonella enterica serovar Typhimurium biofilms facilitate long-term persistence in a number of environments important to food, medical, and farming industries. Salmonella regulates expression of many virulence- and biofilm-related processes using kinase-driven pathways. Kinases play pivotal roles in phosphorylation and energy transfer in cellular processes and possess an ATP-binding pocket required for their functions. Many other cellular proteins also require ATP for their activity. Here we test the hypothesis that pharmacological interference with ATP-requiring enzymes utilizing adenosine mimetic compounds would decrease or inhibit bacterial biofilm formation. Through the screening of a 3,000-member ATP mimetic library, we identified a single compound (compound 7955004) capable of significantly reducing biofilm formation by S. Typhimurium and S. Typhi. The compound was not bactericidal or bacteriostatic toward S. Typhimurium or cytotoxic to mammalian cells. An ATP-Sepharose affinity matrix technique was used to discover potential protein-binding targets of the compound and identified GroEL and DeoD. Compound 7955004 was screened against other known biofilm-forming bacterial species and was found to potently inhibit biofilms of Acinetobacter baumannii as well. The identification of a lead compound with biofilm-inhibiting capabilities toward Salmonella provides a potential new avenue of therapeutic intervention against Salmonella biofilm formation, with applicability to biofilms of other bacterial pathogens.

  11. The BH3 Mimetic Obatoclax Accumulates in Lysosomes and Causes Their Alkalinization.

    Directory of Open Access Journals (Sweden)

    Vasileios A Stamelos

    Full Text Available Obatoclax belongs to a class of compounds known as BH3 mimetics which function as antagonists of Bcl-2 family apoptosis regulators. It has undergone extensive preclinical and clinical evaluation as a cancer therapeutic. Despite this, it is clear that obatoclax has additional pharmacological effects that contribute to its cytotoxic activity. It has been claimed that obatoclax, either alone or in combination with other molecularly targeted therapeutics, induces an autophagic form of cell death. In addition, obatoclax has been shown to inhibit lysosomal function, but the mechanism of this has not been elucidated. We have evaluated the mechanism of action of obatoclax in eight ovarian cancer cell lines. Consistent with its function as a BH3 mimetic, obatoclax induced apoptosis in three cell lines. However, in the remaining cell lines another form of cell death was evident because caspase activation and PARP cleavage were not observed. Obatoclax also failed to show synergy with carboplatin and paclitaxel, chemotherapeutic agents which we have previously shown to be synergistic with authentic Bcl-2 family antagonists. Obatoclax induced a profound accumulation of LC-3 but knockdown of Atg-5 or beclin had only minor effects on the activity of obatoclax in cell growth assays suggesting that the inhibition of lysosomal function rather than stimulation of autophagy may play a more prominent role in these cells. To evaluate how obatoclax inhibits lysosomal function, confocal microscopy studies were conducted which demonstrated that obatoclax, which contains two basic pyrrole groups, accumulates in lysosomes. Studies using pH sensitive dyes demonstrated that obatoclax induced lysosomal alkalinization. Furthermore, obatoclax was synergistic in cell growth/survival assays with bafilomycin and chloroquine, two other drugs which cause lysosomal alkalinization. These studies explain, for the first time, how obatoclax inhibits lysosomal function and suggest that

  12. Smac mimetic and oleanolic acid synergize to induce cell death in human hepatocellular carcinoma cells.

    Science.gov (United States)

    Liese, Juliane; Abhari, Behnaz Ahangarian; Fulda, Simone

    2015-08-28

    Chemotherapy resistance of hepatocellular carcinoma (HCC) is still a major unsolved problem highlighting the need to develop novel therapeutic strategies. Here, we identify a novel synergistic induction of cell death by the combination of the Smac mimetic BV6, which antagonizes Inhibitor of apoptosis (IAP) proteins, and the triterpenoid oleanolic acid (OA) in human HCC cells. Importantly, BV6 and OA also cooperate to suppress long-term clonogenic survival as well as tumor growth in a preclinical in vivo model of HCC underscoring the clinical relevance of our findings. In contrast, BV6/OA cotreatment does not exert cytotoxic effects against normal primary hepatocytes, pointing to some tumor selectivity. Mechanistic studies show that BV6/OA cotreatment leads to DNA fragmentation and caspase-3 cleavage, while supply of the pan-caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (zVAD.fmk) revealed a cell type-dependent requirement of caspases for BV6/OA-induced cell death. The receptor interacting protein (RIP)1 kinase Inhibitor Necrostatin-1 (Nec-1) or genetic knockdown of RIP1 fails to rescue BV6/OA-mediated cell death, indicating that BV6/OA cotreatment does not primarily engage necroptotic cell death. Notably, the addition of several reactive oxygen species (ROS) scavengers significantly decreases BV6/OA-triggered cell death, indicating that ROS production contributes to BV6/OA-induced cell death. In conclusion, cotreatment of Smac mimetic and OA represents a novel approach for the induction of cell death in HCC and implicates further studies.

  13. Programming of enzyme specificity by substrate mimetics: investigations on the Glu-specific V8 protease reveals a novel general principle of biocatalysis.

    Science.gov (United States)

    Wehofsky, N; Bordusa, F

    1999-01-25

    In this paper the universal validity of the substrate mimetic concept in enzymatic C-N ligations was expanded to anionic leaving groups based on the specificity determinants of Glu-specific endopeptidase from Staphylococcus aureus (V8 protease). In an empirical way a specific mimetic moiety was designed from simple structure-function relationship studies. The general function of the newly developed substrate mimetics to serve as an artificial recognition site for V8 protease have been examined by hydrolysis kinetic studies. Enzymatic peptide syntheses qualify the strategy of substrate mimetics as a powerful concept for programming the enzyme specificity in the direction of a more universal application of enzymes in the general area of biocatalysis. PMID:9989609

  14. Bioinspired Hydroxyapatite/Poly(methyl methacrylate) Composite with a Nacre-Mimetic Architecture by a Bidirectional Freezing Method.

    Science.gov (United States)

    Bai, Hao; Walsh, Flynn; Gludovatz, Bernd; Delattre, Benjamin; Huang, Caili; Chen, Yuan; Tomsia, Antoni P; Ritchie, Robert O

    2016-01-01

    Using a bidirectional freezing technique, combined with uniaxial pressing and in situ polymerization, "nacre-mimetic" hydroxyapatite/poly(methyl methacrylate) (PMMA) composites are developed by processing large-scale aligned lamellar ceramic scaffolds. Structural and mechanical characterization shows "brick-and-mortar" structures, akin to nacre, with interesting combinations of strength, stiffness, and work of fracture, which provide a pathway to making strong and tough lightweight materials. PMID:26554760

  15. 表情肌强化训练对特发性面神经麻痹的疗效%Effects of Intensive Training for Mimetic Muscle on Idiopathic Facial Paralysis

    Institute of Scientific and Technical Information of China (English)

    徐文玉; 刘新; 李阔

    2014-01-01

    目的:探讨表情肌强化训练对面神经麻痹的疗效。方法105例面神经麻痹患者分为对照组(n=53)和治疗组(n=52),两组均接受药物治疗、物理治疗、针刺治疗和心理支持治疗,治疗组在此基础上给予表情肌强化训练,治疗1个月后进行疗效评定。结果治疗后,治疗组肌力明显优于对照组(P<0.01)。治疗组痊愈率65.38%,明显优于对照组39.62%(P<0.01);总有效率96.15%,优于对照组83.02%(P<0.05)。结论强化训练表情肌能进一步提高面神经麻痹的康复疗效。%Objective To investigate the effects of intensive training for mimetic muscle on idiopathic facial paralysis. Methods 105 pa-tients with idiopathic facial paralysis were divided into control group (n=53) and treatment group (n=52). All the patients received the rou-tine treatment, including drugs, physical therapy, acupuncture and psychological support, while the treatment group was treated with inten-sive training for mimetic muscle in addition. Results 1 month after treatment, the muscle strength improved more in the treatment group than in the control group (P<0.01). The incidence of cure was 65.38%in the treatment group, more than 39.62%in the control group (P<0.01), as well the the total improvement of 96.15%and 83.02%respectively (P<0.05). Conclusion The intensive training for mimetic mus-cle can improve recovery of facial paralysis.

  16. The SMAC mimetic, LCL-161, reduces survival in aggressive MYC-driven lymphoma while promoting susceptibility to endotoxic shock.

    Science.gov (United States)

    West, A C; Martin, B P; Andrews, D A; Hogg, S J; Banerjee, A; Grigoriadis, G; Johnstone, R W; Shortt, J

    2016-01-01

    Inhibitor of apoptosis proteins (IAPs) antagonize caspase activation and regulate death receptor signaling cascades. LCL-161 is a small molecule second mitochondrial activator of caspase (SMAC) mimetic, which both disengages IAPs from caspases and induces proteasomal degradation of cIAP-1 and -2, resulting in altered signaling through the NFκB pathway, enhanced TNF production and sensitization to apoptosis mediated by the extrinsic pathway. SMAC mimetics are undergoing clinical evaluation in a range of hematological malignancies. Burkitt-like lymphomas are hallmarked by a low apoptotic threshold, conveying sensitivity to a range of apoptosis-inducing stimuli. While evaluating LCL-161 in the Eμ-Myc model of aggressive Burkitt-like lymphoma, we noted unexpected resistance to apoptosis induction despite 'on-target' IAP degradation and NFκB activation. Moreover, LCL-161 treatment of lymphoma-bearing mice resulted in apparent disease acceleration concurrent to augmented inflammatory cytokine-release in the same animals. Indiscriminate exposure of lymphoma patients to SMAC mimetics may therefore be detrimental due to both unanticipated prolymphoma effects and increased susceptibility to endotoxic shock. PMID:27043662

  17. Highly stable and self-repairing membrane-mimetic 2D nanomaterials assembled from lipid-like peptoids

    Science.gov (United States)

    Jin, Haibao; Jiao, Fang; Daily, Michael D.; Chen, Yulin; Yan, Feng; Ding, Yan-Huai; Zhang, Xin; Robertson, Ellen J.; Baer, Marcel D.; Chen, Chun-Long

    2016-07-01

    An ability to develop sequence-defined synthetic polymers that both mimic lipid amphiphilicity for self-assembly of highly stable membrane-mimetic 2D nanomaterials and exhibit protein-like functionality would revolutionize the development of biomimetic membranes. Here we report the assembly of lipid-like peptoids into highly stable, crystalline, free-standing and self-repairing membrane-mimetic 2D nanomaterials through a facile crystallization process. Both experimental and molecular dynamics simulation results show that peptoids assemble into membranes through an anisotropic formation process. We further demonstrated the use of peptoid membranes as a robust platform to incorporate and pattern functional objects through large side-chain diversity and/or co-crystallization approaches. Similar to lipid membranes, peptoid membranes exhibit changes in thickness upon exposure to external stimuli; they can coat surfaces in single layers and self-repair. We anticipate that this new class of membrane-mimetic 2D nanomaterials will provide a robust matrix for development of biomimetic membranes tailored to specific applications.

  18. Deleterious Effects of High Dose Connexin 43 Mimetic Peptide Infusion After Cerebral Ischaemia in Near-Term Fetal Sheep

    Directory of Open Access Journals (Sweden)

    Alistair J. Gunn

    2012-05-01

    Full Text Available Hypoxic-ischaemic brain injury at birth is associated with 1–3/1000 cases of moderate to severe encephalopathy. Previously, we have shown that connexin 43 hemichannel blockade, with a specific mimetic peptide, reduced the occurrence of seizures, improved recovery of EEG power and sleep state cycling, and improved cell survival following global cerebral ischaemia. In the present study, we examined the dose response for intracerebroventricular mimetic peptide infusion (50 µmol/kg/h for 1 h, followed by 50 µmol/kg/24 h (low dose or 50 µmol/kg/h for 25 h (high dose or vehicle only (control group, starting 90 min after the end of ischaemia, following global cerebral ischaemia, induced by 30 min bilateral carotid artery occlusion, in near-term fetal sheep (128 ± 1 days gestation. Both peptide infusion groups were associated with a transient significant increase in EEG power between 2–12 h after ischaemia. The ischaemia-low dose group showed a significant recovery of EEG power from day five compared to the ischaemia-vehicle and -high dose groups. In contrast, the high dose infusion was associated with greater secondary increase in impedance (brain cell swelling, as well as a trend towards a greater increase in lactate concentration and mortality. These data suggest that higher doses of connexin mimetic peptide are not beneficial and may be associated with adverse outcomes, most likely attributable to uncoupling of connexin 43 gap junctions leading to dysfunction of the astrocytic syncytium.

  19. Interfacial Cavity Filling To Optimize CD4-Mimetic Miniprotein Interactions with HIV-1 Surface Glycoprotein

    Energy Technology Data Exchange (ETDEWEB)

    Morellato-Castillo, Laurence; Acharya, Priyamvada; Combes, Olivier; Michiels, Johan; Descours, Anne; Ramos, Oscar H.P.; Yang, Yongping; Vanham, Guido; Ariën, Kevin K.; Kwong, Peter D.; Martin, Loïc; Kessler, Pascal [ITM-Antwerp; (CEA-CNRS); (NIH)

    2013-08-05

    Ligand affinities can be optimized by interfacial cavity filling. A hollow (Phe43 cavity) between HIV-1 surface glycoprotein (gp120) and cluster of differentiation 4 (CD4) receptor extends beyond residue phenylalanine 43 of CD4 and cannot be fully accessed by natural amino acids. To increase HIV-1 gp120 affinity for a family of CD4-mimetic miniproteins (miniCD4s), we targeted the gp120 Phe43 cavity with 11 non-natural phenylalanine derivatives, introduced into a miniCD4 named M48 (1). The best derivative, named M48U12 (13), bound HIV-1 YU2 gp120 with 8 pM affinity and showed potent HIV-1 neutralization. It contained a methylcyclohexyl derivative of 4-aminophenylalanine, and its cocrystal structure with gp120 revealed the cyclohexane ring buried within the gp120 hydrophobic core but able to assume multiple orientations in the binding pocket, and the aniline nitrogen potentially providing a focus for further improvement. Altogether, the results provide a framework for filling the interfacial Phe43 cavity to enhance miniCD4 affinity.

  20. Impact of peptide clustering on unbinding forces in the context of fusion mimetics

    International Nuclear Information System (INIS)

    Highlights: ► Coiled-coil peptides as SNARE mimetics for membrane fusion. ► Interaction forces assessed by colloidal probe microscopy. ► Lateral organization of lipopeptides visualized by atomic force microscopy. -- Abstract: Coiled-coil zipping and unzipping is a pivotal process in SNARE-regulated membrane fusion. In this study we examine this process mediated by a minimal model for coiled-coil formation employing force spectroscopy in the context of membrane-coated surfaces and probes. The interaction forces of several hundred pN are surprisingly low considering the proposed amount of molecular bonds in the contact zone. However, by means of high-resolution imaging employing atomic force microscopy and studying the lateral mobility of lipids and peptides as a function of coiled-coil formation, we are able to supply a detailed view on processes occurring on the membrane surfaces during force measurements. The interaction forces determined here are not only dependent on the peptide concentration on the surface, but also on the regional organization of lateral peptide clusters found prior to coiled-coil formation

  1. Magnetic field-induced ordering of a polymer-grafted biomembrane-mimetic hydrogel

    Energy Technology Data Exchange (ETDEWEB)

    Firestone, M.A.; Tiede, D.M.; Seifert, S.

    2000-03-23

    A biomembrane-mimetic complex fluid that spontaneously orients in the presence of a magnetic field to yield a highly ordered lamellar structure is described. Macroscopically oriented lamellae were produced by exploiting the inverted thermoreversible phase transition of the material, that is, by aligning the sample below the phase transition temperature (<16 C)(i.e., in the fluid, hexagonal micellar phase) and warming to produce the lamellar gel phase in a 7.05 T magnetic field. The in situ field-induced alignment was studied by deuterium NMR. The lamellar domains were found to preferentially orient perpendicular to the applied field (negative order). Characterization of the magnetic field-induced anisotropy by polarized optical microscopy and small-angle X-ray scattering/diffraction (SAXS) indicates that it persists even upon field termination. The directional alignment was flipped by 90{degree}, with the lamellar domains oriented parallel to the field (positive order), simply by modifying the composition through the addition of a lanthanide ion (EU{sup 3+}). The system offers the opportunity to spatially organize both membrane and aqueous soluble proteins in an anisotropic matrix, thereby facilitating structure and dynamic studies using a range of techniques, including magnetic resonance (both NMR as well as EPR), optical spectroscopy, and small-angle neutron and X-ray scattering.

  2. New mimetic peptides inhibitors of Αβ aggregation. Molecular guidance for rational drug design.

    Science.gov (United States)

    Barrera Guisasola, Exequiel E; Andujar, Sebastián A; Hubin, Ellen; Broersen, Kerensa; Kraan, Ivonne M; Méndez, Luciana; Delpiccolo, Carina M L; Masman, Marcelo F; Rodríguez, Ana M; Enriz, Ricardo D

    2015-05-01

    A new series of mimetic peptides possessing a significant Aβ aggregation modulating effect was reported here. These compounds were obtained based on a molecular modelling study which allowed us to perform a structural-based virtual selection. Monitoring Aβ aggregation by thioflavin T fluorescence and transmission electron microscopy revealed that fibril formation was significantly decreased upon prolonged incubation in presence of the active compounds. Dot blot analysis suggested a decrease of soluble oligomers strongly associated with cognitive decline in Alzheimer's disease. For the molecular dynamics simulations, we used an Aβ42 pentameric model where the compounds were docked using a blind docking technique. To analyze the dynamic behaviour of the complexes, extensive molecular dynamics simulations were carried out in explicit water. We also measured parameters or descriptors that allowed us to quantify the effect of these compounds as potential inhibitors of Aβ aggregation. Thus, significant alterations in the structure of our Aβ42 protofibril model were identified. Among others we observed the destruction of the regular helical twist, the loss of a stabilizing salt bridge and the loss of a stabilizing hydrophobic interaction in the β1 region. Our results may be helpful in the structural identification and understanding of the minimum structural requirements for these molecules and might provide a guide in the design of new aggregation modulating ligands.

  3. Mimetic finite difference method for the stokes problem on polygonal meshes

    Energy Technology Data Exchange (ETDEWEB)

    Lipnikov, K [Los Alamos National Laboratory; Beirao Da Veiga, L [DIPARTIMENTO DI MATE; Gyrya, V [PENNSYLVANIA STATE UNIV; Manzini, G [ISTIUTO DI MATEMATICA

    2009-01-01

    Various approaches to extend the finite element methods to non-traditional elements (pyramids, polyhedra, etc.) have been developed over the last decade. Building of basis functions for such elements is a challenging task and may require extensive geometry analysis. The mimetic finite difference (MFD) method has many similarities with low-order finite element methods. Both methods try to preserve fundamental properties of physical and mathematical models. The essential difference is that the MFD method uses only the surface representation of discrete unknowns to build stiffness and mass matrices. Since no extension inside the mesh element is required, practical implementation of the MFD method is simple for polygonal meshes that may include degenerate and non-convex elements. In this article, we develop a MFD method for the Stokes problem on arbitrary polygonal meshes. The method is constructed for tensor coefficients, which will allow to apply it to the linear elasticity problem. The numerical experiments show the second-order convergence for the velocity variable and the first-order for the pressure.

  4. Carbohydrate Mimetic Peptides Augment Carbohydrate-Reactive Immune Responses in the Absence of Immune Pathology

    Energy Technology Data Exchange (ETDEWEB)

    Hennings, Leah; Artaud, Cecile; Jousheghany, Fariba; Monzavi-Karbassi, Behjatolah; Pashov, Anastas; Kieber-Emmons, Thomas, E-mail: tke@uams.edu [Winthrop P. Rockefeller Cancer Institute and Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR 72205 (United States)

    2011-11-11

    Among the most challenging of clinical targets for cancer immunotherapy are Tumor Associated Carbohydrate Antigens (TACAs). To augment immune responses to TACA we are developing carbohydrate mimetic peptides (CMPs) that are sufficiently potent to activate broad-spectrum anti-tumor reactivity. However, the activation of immune responses against terminal mono- and disaccharide constituents of TACA raises concerns regarding the balance between “tumor destruction” and “tissue damage”, as mono- and disaccharides are also expressed on normal tissue. To support the development of CMPs for clinical trial testing, we demonstrate in preclinical safety assessment studies in mice that vaccination with CMPs can enhance responses to TACAs without mediating tissue damage to normal cells expressing TACA. BALB/c mice were immunized with CMPs that mimic TACAs reactive with Griffonia simplicifolia lectin 1 (GS-I), and tissue reactivity of serum antibodies were compared with the tissue staining profile of GS-I. Tissues from CMP immunized mice were analyzed using hematoxylin and eosin stain, and Luxol-fast blue staining for myelination. Western blots of membranes from murine mammary 4T1 cells, syngeneic with BALB/c mice, were also compared using GS-I, immunized serum antibodies, and naive serum antibodies. CMP immunization enhanced glycan reactivities with no evidence of pathological autoimmunity in any immunized mice demonstrating that tissue damage is not an inevitable consequence of TACA reactive responses.

  5. Synthesis and characterization of an elastin-mimetic amphiphilic block copolymer protein

    Science.gov (United States)

    Lee, Terrence Anita-Talley

    2000-10-01

    The overall goal in material science is to be able to control the molecular architecture of a material and thus its end properties. There is no method that offers greater control than the biological synthesis of proteins. From the DNA sequence to the final synthesized protein, the entire process is finitely controlled. This present work describes methods developed and used to synthesize protein polymers by manipulating this process. From the initial DNA sequence chosen, the end properties that the protein polymer will have are dictated. An amphiphilic diblock copolymer was designed based on environmentally responsive elastin-mimetic peptide sequences [(Val/Ile)-Pro-Gly-Xaa-Gly] (Xaa = Ala or Glu for the hydrophilic block, Val or Phe for the hydrophobic block) and synthesized using a genetic engineering approach. Differential scanning calorimetry measurements in aqueous solution revealed that reversible hydrophobic folding and assembly of the copolymer occurs above the inverse temperature transition, Tt, of the hydrophobic block. This process results in the formation of 50 nm protein-based micellar aggregates, which were characterized by electron microscopy and temperature-dependent dynamic light scattering techniques. The distribution of micellar aggregates can be altered reproducibly through variation of environmental conditions including pH and temperature. The uniform and defined macromolecular architecture of this protein copolymer permits greater control over the physical properties of the micelles, which therefore may facilitate applications in controlled release of small molecules.

  6. Species limits in polymorphic mimetic Eniclases net-winged beetles from New Guinean mountains (Coleoptera, Lycidae).

    Science.gov (United States)

    Bocek, Matej; Bocak, Ladislav

    2016-01-01

    Species delimitation was compared in a group of closely related lineages of aposematically colored Eniclases (Coleoptera, Lycidae) using morphology, genetic distances, and Bayesian implementation of the Poisson Tree Processes model. A high diversity of net-winged beetles was found in previously unsampled regions of New Guinea and ten new species are described: Eniclases bicolor sp. n., Eniclases bokondinensis sp. n., Eniclases brancuccii sp. n., Eniclases elelimensis sp. n., Eniclases infuscatus sp. n., Eniclases niger sp. n., Eniclases pseudoapertus sp. n., Eniclases pseudoluteolus sp. n., Eniclases tikapurensis sp. n., and Eniclases variabilis sp. n. Different levels of genetic and morphological diversification were identified in various sister-species pairs. As a result, both morphological and molecular analyses are used to delimit species. Sister-species with uncorrected pairwise genetic divergence as low as 0.45% were morphologically distinct not only in color pattern, but also in the relative size of eyes. Conversely, differences in color pattern regardless of their magnitude did not necessarily indicate genetic distance and intraspecific mimicry polymorphism was common. Additionally, genetic divergence without morphological differentiation was detected in one sister-species pair. Low dispersal propensity, diverse mimicry patterns, and mimetic polymorphism resulted in complex diversification of Eniclases and uncertain species delimitation in recently diversified lineages.

  7. Bacterial mimetics of endocrine secretory granules as immobilized in vivo depots for functional protein drugs

    Science.gov (United States)

    Céspedes, María Virtudes; Fernández, Yolanda; Unzueta, Ugutz; Mendoza, Rosa; Seras-Franzoso, Joaquin; Sánchez-Chardi, Alejando; Álamo, Patricia; Toledo-Rubio, Verónica; Ferrer-Miralles, Neus; Vázquez, Esther; Schwartz, Simó; Abasolo, Ibane; Corchero, José Luis; Mangues, Ramon; Villaverde, Antonio

    2016-01-01

    In the human endocrine system many protein hormones including urotensin, glucagon, obestatin, bombesin and secretin, among others, are supplied from amyloidal secretory granules. These granules form part of the so called functional amyloids, which within the whole aggregome appear to be more abundant than formerly believed. Bacterial inclusion bodies (IBs) are non-toxic, nanostructured functional amyloids whose biological fabrication can be tailored to render materials with defined biophysical properties. Since under physiological conditions they steadily release their building block protein in a soluble and functional form, IBs are considered as mimetics of endocrine secretory granules. We have explored here if the in vivo implantation of functional IBs in a given tissue would represent a stable local source of functional protein. Upon intratumoral injection of bacterial IBs formed by a potent protein ligand of CXCR4 we have observed high stability and prevalence of the material in absence of toxicity, accompanied by apoptosis of CXCR4+ cells and tumor ablation. Then, the local immobilization of bacterial amyloids formed by therapeutic proteins in tumors or other tissues might represent a promising strategy for a sustained local delivery of protein drugs by mimicking the functional amyloidal architecture of the mammals’ endocrine system. PMID:27775083

  8. Smac mimetics and innate immune stimuli synergize to promote tumor death

    Science.gov (United States)

    Beug, Shawn T.; Tang, Vera A.; LaCasse, Eric C.; Cheung, Herman H.; Beauregard, Caroline E.; Brun, Jan; Nuyens, Jeffrey P.; Earl, Nathalie; St-Jean, Martine; Holbrook, Janelle; Dastidar, Himika; Mahoney, Douglas J.; Ilkow, Carolina; Le Boeuf, Fabrice; Bell, John C.; Korneluk, Robert G.

    2016-01-01

    Smac mimetic compounds (SMC), a class of drugs that sensitize cells to apoptosis by counteracting the activity of inhibitor of apoptosis (IAP) proteins, have proven safe in Phase I clinical trials in cancer patients. However, because SMCs act by enabling transduction of pro-apoptotic signals, SMC monotherapy may only be efficacious in the subset of patients whose tumors produce large quantities of death-inducing proteins such as inflammatory cytokines. As such, we reasoned that SMCs would synergize with agents that stimulate a potent yet safe “cytokine storm”. Here we show that oncolytic viruses and adjuvants such as poly(I:C) and CpG induce bystander death of cancer cells treated with SMCs that is mediated by interferon beta (IFNβ), tumor necrosis factor alpha (TNFα) and/or TNF-related apoptosis-inducing ligand (TRAIL). This combinatorial treatment resulted in tumor regression and extended survival in two mouse models of cancer. As these and other adjuvants have been proven safe in clinical trials, it may be worthwhile to explore their clinical efficacy in combination with SMCs. PMID:24463573

  9. Characterization of the insertase BamA in three different membrane mimetics by solution NMR spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Morgado, Leonor; Zeth, Kornelius; Burmann, Björn M.; Maier, Timm; Hiller, Sebastian, E-mail: sebastian.hiller@unibas.ch [University of Basel, Biozentrum (Switzerland)

    2015-04-15

    The insertase BamA is the central protein of the Bam complex responsible for outer membrane protein biogenesis in Gram-negative bacteria. BamA features a 16-stranded transmembrane β-barrel and five periplasmic POTRA domains, with a total molecular weight of 88 kDa. Whereas the structure of BamA has recently been determined by X-ray crystallography, its functional mechanism is not well understood. This mechanism comprises the insertion of substrates from a dynamic, chaperone-bound state into the bacterial outer membrane, and NMR spectroscopy is thus a method of choice for its elucidation. Here, we report solution NMR studies of different BamA constructs in three different membrane mimetic systems: LDAO micelles, DMPC:DiC{sub 7}PC bicelles and MSP1D1:DMPC nanodiscs. The impact of biochemical parameters on the spectral quality was investigated, including the total protein concentration and the detergent:protein ratio. The barrel of BamA is folded in micelles, bicelles and nanodiscs, but the N-terminal POTRA5 domain is flexibly unfolded in the absence of POTRA4. Measurements of backbone dynamics show that the variable insertion region of BamA, located in the extracellular lid loop L6, features high local flexibility. Our work establishes biochemical preparation schemes for BamA, which will serve as a platform for structural and functional studies of BamA and its role within the Bam complex by solution NMR spectroscopy.

  10. An NCAM mimetic, FGL, alters hippocampal cellular morphometry in young adult (4 month-old) rats.

    Science.gov (United States)

    Ojo, Bunmi; Gabbott, Paul L; Rezaie, Payam; Corbett, Nicola; Medvedev, Nikolay I; Cowley, Thelma R; Lynch, Marina A; Stewart, Michael G

    2013-06-01

    The neural cell adhesion molecule, NCAM, is ubiquitously expressed within the CNS and has roles in development, cognition, neural plasticity and regulation of the immune system. NCAM is thus potentially an important pharmacological target for treatment of brain diseases. A cell adhesion mimetic FGL, a 15 amino-acid peptide derived from the second fibronectin type-III module of NCAM, has been shown to act as a neuroprotective agent in experimental disease and ageing models, restoring hippocampal/cognitive function and markedly alleviating deleterious changes in the CNS. However, the effects of FGL on the hippocampus of young healthy rats are unknown. The present study has examined the cellular neurobiological consequences of subcutaneous injections of FGL, on hippocampal cell morphometry in young (4 month-old) rats. We determined the effects of FGL on hippocampal volume, pyramidal neuron number/density (using unbiased quantitative stereology), and examined aspects of neurogenesis (using 2D morphometric analyses). FGL treatment reduced total volume of the dorsal hippocampus (associated with a decrease in total pyramidal neuron numbers in CA1 and CA3), and elevated the number of doublecortin immunolabeled neurons in the dentate gyrus, indicating a likely influence on neurogenesis in young healthy rats. These data indicate that FGL has a specific age dependent effect on the hippocampus, differing according to the development and maturity of the CNS.

  11. A mimetic spectral element solver for the Grad-Shafranov equation

    Science.gov (United States)

    Palha, A.; Koren, B.; Felici, F.

    2016-07-01

    In this work we present a robust and accurate arbitrary order solver for the fixed-boundary plasma equilibria in toroidally axisymmetric geometries. To achieve this we apply the mimetic spectral element formulation presented in [56] to the solution of the Grad-Shafranov equation. This approach combines a finite volume discretization with the mixed finite element method. In this way the discrete differential operators (∇, ∇×, ∇ṡ) can be represented exactly and metric and all approximation errors are present in the constitutive relations. The result of this formulation is an arbitrary order method even on highly curved meshes. Additionally, the integral of the toroidal current Jϕ is exactly equal to the boundary integral of the poloidal field over the plasma boundary. This property can play an important role in the coupling between equilibrium and transport solvers. The proposed solver is tested on a varied set of plasma cross sections (smooth and with an X-point) and also for a wide range of pressure and toroidal magnetic flux profiles. Equilibria accurate up to machine precision are obtained. Optimal algebraic convergence rates of order p + 1 and geometric convergence rates are shown for Soloviev solutions (including high Shafranov shifts), field-reversed configuration (FRC) solutions and spheromak analytical solutions. The robustness of the method is demonstrated for non-linear test cases, in particular on an equilibrium solution with a pressure pedestal.

  12. Gene Transcriptional and Metabolic Profile Changes in Mimetic Aging Mice Induced by D-Galactose.

    Directory of Open Access Journals (Sweden)

    Yue-Yue Zhou

    Full Text Available D-galactose injection has been shown to induce many changes in mice that represent accelerated aging. This mouse model has been widely used for pharmacological studies of anti-aging agents. The underlying mechanism of D-galactose induced aging remains unclear, however, it appears to relate to glucose and 1ipid metabolic disorders. Currently, there has yet to be a study that focuses on investigating gene expression changes in D-galactose aging mice. In this study, integrated analysis of gas chromatography/mass spectrometry-based metabonomics and gene expression profiles was used to investigate the changes in transcriptional and metabolic profiles in mimetic aging mice injected with D-galactose. Our findings demonstrated that 48 mRNAs were differentially expressed between control and D-galactose mice, and 51 potential biomarkers were identified at the metabolic level. The effects of D-galactose on aging could be attributed to glucose and 1ipid metabolic disorders, oxidative damage, accumulation of advanced glycation end products (AGEs, reduction in abnormal substance elimination, cell apoptosis, and insulin resistance.

  13. The Thrombospondin-1 Mimetic ABT-510 Increases the Uptake and Effectiveness of Cisplatin and Paclitaxel in a Mouse Model of Epithelial Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Nicole E. Campbell

    2010-03-01

    Full Text Available Epithelial ovarian cancer (EOC comprises approximately 90% of ovarian cancers and arises from the surface epithelium. Typical treatment of EOC involves cytoreductive surgery combined with chemotherapy. More recent therapies have targeted the tumor vasculature using antiangiogenic compounds such as thrombospondin-1 (TSP-1. TSP-1 mimetic peptides such as ABT-510 have been created and have been in various clinical trials. We have previously shown that ABT-510 reduces abnormal vasculature associated with tumor tissue and increases the presence of mature blood vessels. It has been hypothesized that treatment with antiangiogenic compounds would allow increased delivery of cytotoxic agents and enhance treatment. In this study, we evaluated the potential role of ABT-510 and various chemotherapeutics (cisplatin and paclitaxel on tumor progression, angiogenesis, and the benefits of combinational treatments on tissue uptake and perfusion using an orthotopic syngeneic mouse model of EOC. Animals were treated with ABT-510 (100 mg/kg per day alone or in combination with cisplatin (2 mg/kg per 3 days or paclitaxel (10 mg/kg per 2 days at 60 days after tumor induction. Radiolabeled and fluorescently labeled paclitaxel demonstrated a significant increase in tumor uptake after ABT-510 treatment. Combined treatment with ABT-510 and cisplatin or paclitaxel resulted in a significant increase in tumor cell and tumor endothelial cell apoptosis and a resultant decrease in ovarian tumor size. Combined treatment also regressed secondary lesions and eliminated the presence of abdominal ascites. The results from this study show that through vessel normalization, ABT-510 increases uptake of chemotherapy drugs and can induce regression of advanced ovarian cancer.

  14. An investigation of the mimetic enzyme activity of two-dimensional Pd-based nanostructures

    Science.gov (United States)

    Wei, Jingping; Chen, Xiaolan; Shi, Saige; Mo, Shiguang; Zheng, Nanfeng

    2015-11-01

    In this work, we investigated the mimetic enzyme activity of two-dimensional (2D) Pd-based nanostructures (e.g. Pd nanosheets, Pd@Au and Pd@Pt nanoplates) and found that they possess intrinsic peroxidase-, oxidase- and catalase-like activities. These nanostructures were able to activate hydrogen peroxide or dissolved oxygen for catalyzing the oxidation of organic substrates, and decompose hydrogen peroxide to generate oxygen. More systematic investigations revealed that the peroxidase-like activities of these Pd-based nanomaterials were highly structure- and composition-dependent. Among them, Pd@Pt nanoplates displayed the highest peroxidase-like activity. Based on these findings, Pd-based nanostructures were applied for the colorimetric detection of H2O2 and glucose, and also the electro-catalytic reduction of H2O2. This work offers a promising prospect for the application of 2D noble metal nanostructures in biocatalysis.In this work, we investigated the mimetic enzyme activity of two-dimensional (2D) Pd-based nanostructures (e.g. Pd nanosheets, Pd@Au and Pd@Pt nanoplates) and found that they possess intrinsic peroxidase-, oxidase- and catalase-like activities. These nanostructures were able to activate hydrogen peroxide or dissolved oxygen for catalyzing the oxidation of organic substrates, and decompose hydrogen peroxide to generate oxygen. More systematic investigations revealed that the peroxidase-like activities of these Pd-based nanomaterials were highly structure- and composition-dependent. Among them, Pd@Pt nanoplates displayed the highest peroxidase-like activity. Based on these findings, Pd-based nanostructures were applied for the colorimetric detection of H2O2 and glucose, and also the electro-catalytic reduction of H2O2. This work offers a promising prospect for the application of 2D noble metal nanostructures in biocatalysis. Electronic supplementary information (ESI) available: TEM images, EDX and dispersion stability of Pd-based nanomaterials

  15. Mimetic Muscles in a Despotic Macaque (Macaca mulatta) Differ from Those in a Closely Related Tolerant Macaque (M. nigra).

    Science.gov (United States)

    Burrows, Anne M; Waller, Bridget M; Micheletta, Jérôme

    2016-10-01

    Facial displays (or expressions) are a primary means of visual communication among conspecifics in many mammalian orders. Macaques are an ideal model among primates for investigating the co-evolution of facial musculature, facial displays, and social group size/behavior under the umbrella of "ecomorphology". While all macaque species share some social behaviors, dietary, and ecological parameters, they display a range of social dominance styles from despotic to tolerant. A previous study found a larger repertoire of facial displays in tolerant macaque species relative to despotic species. The present study was designed to further explore this finding by comparing the gross morphological features of mimetic muscles between the Sulawesi macaque (Macaca nigra), a tolerant species, and the rhesus macaque (M. mulatta), a despotic species. Five adult M. nigra heads were dissected and mimetic musculature was compared to those from M. mulatta. Results showed that there was general similarity in muscle presence/absence between the species as well as muscle form except for musculature around the external ear. M. mulatta had more musculature around the external ear than M. nigra. In addition, M. nigra lacked a zygomaticus minor while M. mulatta is reported to have one. These morphological differences match behavioral observations documenting a limited range of ear movements used by M. nigra during facial displays. Future studies focusing on a wider phylogenetic range of macaques with varying dominance styles may further elucidate the roles of phylogeny, ecology, and social variables in the evolution of mimetic muscles within Macaca Anat Rec, 299:1317-1324, 2016. © 2016 Wiley Periodicals, Inc. PMID:27343148

  16. Chronic delivery of a thrombospondin-1 mimetic decreases skeletal muscle capillarity in mice.

    Science.gov (United States)

    Audet, Gerald N; Fulks, Daniel; Stricker, Janelle C; Olfert, I Mark

    2013-01-01

    Angiogenesis is an essential process for normal skeletal muscle function. There is a growing body of evidence suggesting that thrombospondin-1 (TSP-1), a potent antiangiogenic protein in tumorigenesis, is an important regulator of both physiological and pathological skeletal muscle angiogenesis. We tested the hypothesis that chronic exposure to a TSP-1 mimetic (ABT-510), which targets the CD36 TSP-1 receptor, would decrease skeletal muscle capillarity as well as alter the balance between positive and negative angiogenic proteins under basal conditions. Osmotic minipumps with either ABT-510 or vehicle (5% dextrose) were implanted subcutaneously in the subscapular region of C57/BL6 mice for 14 days. When compared to the vehicle treated mice, the ABT-510 group had a 20% decrease in capillarity in the superficial region of the gastrocnemius (GA), 11% decrease in the plantaris (PLT), and a 35% decrease in the soleus (SOL). ABT-510 also decreased muscle protein expression of vascular endothelial growth factor (VEGF) in both the GA (-140%) and SOL (-62%); however there was no change in VEGF in the PLT. Serum VEGF was not altered in ABT-510 treated animals. Endogenous TSP-1 protein expression in all muscles remained unaltered. Tunnel staining revealed no difference in muscle apoptosis between ABT-510 and vehicle treated groups. These data provide evidence that the anti-angiogenic effects of TSP-1 are mediated, at least in part, via the CD36 receptor. It also suggests that under physiologic conditions the TSP-1/CD36 axis plays a role in regulating basal skeletal muscle microvessel density.

  17. Chronic delivery of a thrombospondin-1 mimetic decreases skeletal muscle capillarity in mice.

    Directory of Open Access Journals (Sweden)

    Gerald N Audet

    Full Text Available Angiogenesis is an essential process for normal skeletal muscle function. There is a growing body of evidence suggesting that thrombospondin-1 (TSP-1, a potent antiangiogenic protein in tumorigenesis, is an important regulator of both physiological and pathological skeletal muscle angiogenesis. We tested the hypothesis that chronic exposure to a TSP-1 mimetic (ABT-510, which targets the CD36 TSP-1 receptor, would decrease skeletal muscle capillarity as well as alter the balance between positive and negative angiogenic proteins under basal conditions. Osmotic minipumps with either ABT-510 or vehicle (5% dextrose were implanted subcutaneously in the subscapular region of C57/BL6 mice for 14 days. When compared to the vehicle treated mice, the ABT-510 group had a 20% decrease in capillarity in the superficial region of the gastrocnemius (GA, 11% decrease in the plantaris (PLT, and a 35% decrease in the soleus (SOL. ABT-510 also decreased muscle protein expression of vascular endothelial growth factor (VEGF in both the GA (-140% and SOL (-62%; however there was no change in VEGF in the PLT. Serum VEGF was not altered in ABT-510 treated animals. Endogenous TSP-1 protein expression in all muscles remained unaltered. Tunnel staining revealed no difference in muscle apoptosis between ABT-510 and vehicle treated groups. These data provide evidence that the anti-angiogenic effects of TSP-1 are mediated, at least in part, via the CD36 receptor. It also suggests that under physiologic conditions the TSP-1/CD36 axis plays a role in regulating basal skeletal muscle microvessel density.

  18. Dramatic nano-fluidic properties of carbon nanotube membranes as a platform for protein channel mimetics

    Science.gov (United States)

    Hinds, Bruce

    2013-03-01

    Carbon nanotubes have three key attributes that make them of great interest for novel membrane applications: 1) atomically flat graphite surface allows for ideal fluid slip boundary conditions and extremely fast flow rates 2) the cutting process to open CNTs inherently places functional chemistry at CNT core entrance for chemical selectivity and 3) CNT are electrically conductive allowing for electrochemical reactions and application of electric fields gradients at CNT tips. Pressure driven flux of a variety of solvents (H2O, hexane, decane ethanol, methanol) are 4-5 orders of magnitude higher than conventional Newtonian flow [Nature 2005, 438, 44] due to atomically flat graphite planes inducing nearly ideal slip conditions. However this is eliminated with selective chemical functionalization [ACS Nano 2011 5(5) 3867-3877] needed to give chemical selectivity. These unique properties allow us to explore the hypothesis of producing ``Gatekeeper'' membranes that mimic natural protein channels to actively pump through rapid nm-scale channels. With anionic tip functionality strong electroosmotic flow is induced by unimpeded cation flow with similar 10,000 fold enhancements [Nature Nano 2012 7(2) 133-39]. With enhanced power efficiency, carbon nanotube membranes were employed as the active element of a switchable transdermal drug delivery device that can facilitate more effective treatments of drug abuse and addiction. Recently methods to deposit Pt monolayers on CNT surface have been developed making for highly efficient catalytic platforms. Discussed are other applications of CNT protein channel mimetics, for large area robust engineering platforms, including water purification, flow battery energy storage, and biochemical/biomass separations. DOE EPSCoR (DE-FG02-07ER46375) and DARPA, W911NF-09-1-0267

  19. Self-Assembled, Iridescent, Crustacean-Mimetic Nanocomposites with Tailored Periodicity and Layered Cuticular Structure.

    Science.gov (United States)

    Wang, Baochun; Walther, Andreas

    2015-11-24

    Natural high-performance materials inspire the pursuit of ordered hard/soft nanocomposite structures at high fractions of reinforcements and with balanced molecular interactions. Herein, we develop a facile, waterborne self-assembly pathway to mimic the multiscale cuticle structure of the crustacean armor by combining hard reinforcing cellulose nanocrystals (CNCs) with soft poly(vinyl alcohol) (PVA). We show iridescent CNC nanocomposites with cholesteric liquid-crystal structure, in which different helical pitches and photonic band gaps can be realized by varying the CNC/PVA ratio. We further show that multilayered crustacean-mimetic materials with tailored periodicity and layered cuticular structure can be obtained by sequential preparation pathways. The transition from a cholesteric to a disordered structure occurs for a critical polymer concentration. Correspondingly, we find a transition from stiff and strong mechanical behavior to materials with increasing ductility. Crack propagation studies using scanning electron microscopy visualize the different crack growth and toughening mechanisms inside cholesteric nanocomposites as a function of the interstitial polymer content for the first time. Different extents of crack deflection, layered delamination, ligament bridging, and constrained microcracking can be observed. Drawing of highly plasticized films sheds light on the mechanistic details of the transition from a cholesteric/chiral nematic to a nematic structure. The study demonstrates how self-assembly of biobased CNCs in combination with suitable polymers can be used to replicate a hierarchical biological structure and how future design of these ordered multifunctional nanocomposites can be optimized by understanding mechanistic details of deformation and fracture. PMID:26372330

  20. Structure of the nociceptin/orphanin FQ receptor in complex with a peptide mimetic

    Energy Technology Data Exchange (ETDEWEB)

    Thompson, Aaron A.; Liu, Wei; Chun, Eugene; Katritch, Vsevolod; Wu, Huixian; Vardy, Eyal; Huang, Xi-Ping; Trapella, Claudio; Guerrini, Remo; Calo, Girolamo; Roth, Bryan L.; Cherezov, Vadim; Stevens, Raymond C. (Ferrara); (Scripps); (UNC)

    2012-07-11

    Members of the opioid receptor family of G-protein-coupled receptors (GPCRs) are found throughout the peripheral and central nervous system, where they have key roles in nociception and analgesia. Unlike the 'classical' opioid receptors, {delta}, {kappa} and {mu} ({delta}-OR, {kappa}-OR and {mu}-OR), which were delineated by pharmacological criteria in the 1970s and 1980s, the nociceptin/orphanin FQ (N/OFQ) peptide receptor (NOP, also known as ORL-1) was discovered relatively recently by molecular cloning and characterization of an orphan GPCR. Although it shares high sequence similarity with classical opioid GPCR subtypes ({approx}60%), NOP has a markedly distinct pharmacology, featuring activation by the endogenous peptide N/OFQ, and unique selectivity for exogenous ligands. Here we report the crystal structure of human NOP, solved in complex with the peptide mimetic antagonist compound-24 (C-24) (ref. 4), revealing atomic details of ligand-receptor recognition and selectivity. Compound-24 mimics the first four amino-terminal residues of the NOP-selective peptide antagonist UFP-101, a close derivative of N/OFQ, and provides important clues to the binding of these peptides. The X-ray structure also shows substantial conformational differences in the pocket regions between NOP and the classical opioid receptors {kappa} (ref. 5) and {mu} (ref. 6), and these are probably due to a small number of residues that vary between these receptors. The NOP-compound-24 structure explains the divergent selectivity profile of NOP and provides a new structural template for the design of NOP ligands.

  1. Stable Incretin Mimetics Counter Rapid Deterioration of Bone Quality in Type 1 Diabetes Mellitus.

    Science.gov (United States)

    Mansur, Sity Aishah; Mieczkowska, Aleksandra; Bouvard, Béatrice; Flatt, Peter R; Chappard, Daniel; Irwin, Nigel; Mabilleau, Guillaume

    2015-12-01

    Type 1 diabetes mellitus is associated with a high risk for bone fractures. Although bone mass is reduced, bone quality is also dramatically altered in this disorder. However, recent evidences suggest a beneficial effect of the glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) pathways on bone quality. The aims of the present study were to conduct a comprehensive investigation of bone strength at the organ and tissue level; and to ascertain whether enzyme resistant GIP or GLP-1 mimetic could be beneficial in preventing bone fragility in type 1 diabetes mellitus. Streptozotocin-treated mice were used as a model of type 1 diabetes mellitus. Control and streptozotocin-diabetic animals were treated for 21 days with an enzymatic-resistant GIP peptide ([D-Ala(2) ]GIP) or with liraglutide (each at 25 nmol/kg bw, ip). Bone quality was assessed at the organ and tissue level by microCT, qXRI, 3-point bending, qBEI, nanoindentation, and Fourier-transform infrared microspectroscopy. [D-Ala2]GIP and liraglutide treatment did prevent loss of whole bone strength and cortical microstructure in the STZ-injected mice. However, tissue material properties were significantly improved in STZ-injected animals following treatment with [D-Ala2]GIP or liraglutide. Treatment of STZ-diabetic mice with [D-Ala(2) ]GIP or liraglutide was capable of significantly preventing deterioration of the quality of the bone matrix. Further studies are required to further elucidate the molecular mechanisms involved and to validate whether these findings can be translated to human patients.

  2. Bio-Mimetics of Disaster Anticipation-Learning Experience and Key-Challenges.

    Science.gov (United States)

    Tributsch, Helmut

    2013-01-01

    Anomalies in animal behavior and meteorological phenomena before major earthquakes have been reported throughout history. Bio-mimetics or bionics aims at learning disaster anticipation from animals. Since modern science is reluctant to address this problem an effort has been made to track down the knowledge available to ancient natural philosophers. Starting with an archaeologically documented human sacrifice around 1700 B.C. during the Minoan civilization immediately before a large earthquake, which killed the participants, earthquake prediction knowledge throughout antiquity is evaluated. Major practical experience with this phenomenon has been gained from a Chinese earthquake prediction initiative nearly half a century ago. Some quakes, like that of Haicheng, were recognized in advance. However, the destructive Tangshan earthquake was not predicted, which was interpreted as an inherent failure of prediction based on animal phenomena. This is contradicted on the basis of reliable Chinese documentation provided by the responsible earthquake study commission. The Tangshan earthquake was preceded by more than 2,000 reported animal anomalies, some of which were of very dramatic nature. They are discussed here. Any physical phenomenon, which may cause animal unrest, must involve energy turnover before the main earthquake event. The final product, however, of any energy turnover is heat. Satellite based infrared measurements have indeed identified significant thermal anomalies before major earthquakes. One of these cases, occurring during the 2001 Bhuj earthquake in Gujarat, India, is analyzed together with parallel animal anomalies observed in the Gir national park. It is suggested that the time window is identical and that both phenomena have the same geophysical origin. It therefore remains to be demonstrated that energy can be released locally before major earthquake events. It is shown that by considering appropriate geophysical feedback processes, this is

  3. Allosteric inhibition of factor XIa. Sulfated non-saccharide glycosaminoglycan mimetics as promising anticoagulants.

    Science.gov (United States)

    Al-Horani, Rami A; Gailani, David; Desai, Umesh R

    2015-08-01

    Recent development of sulfated non-saccharide glycosaminoglycan mimetics, especially sulfated pentagalloyl glucopyranoside (SPGG), as potent inhibitors of factor XIa (FXIa) (J. Med. Chem. 2013; 56:867-878 and J. Med. Chem. 2014; 57:4805-4818) has led to a strong possibility of developing a new line of factor XIa-based anticoagulants. In fact, SPGG represents the first synthetic, small molecule inhibitor that appears to bind in site remote from the active site. Considering that allosteric inhibition of FXIa is a new mechanism for developing a distinct line of anticoagulants, we have studied SPGG's interaction with FXIa with a goal of evaluating its pre-clinical relevance. Comparative inhibition studies with several glycosaminoglycans revealed the importance of SPGG's non-saccharide backbone. SPGG did not affect the activity of plasma kallikrein, activated protein C and factor XIIIa suggesting that SPGG-based anticoagulation is unlikely to affect other pathways connected with coagulation factors. SPGG's effect on APTT of citrated human plasma was also not dependent on antithrombin or heparin cofactor II. Interestingly, SPGG's anticoagulant potential was diminished by serum albumin as well as factor XI, while it could be reversed by protamine or polybrene, which implies possible avenues for developing antidote strategy. Studies with FXIa mutants indicated that SPGG engages Lys529, Arg530 and Arg532, but not Arg250, Lys252, Lys253 and Lys255. Finally, SPGG competes with unfractionated heparin, but not with polyphosphates and/or glycoprotein Ibα, for binding to FXIa. These studies enhance understanding on the first allosteric inhibitor of FXIa and highlight its value as a promising anticoagulant. PMID:25935648

  4. Preferred conformation of endomorphin-1 in aqueous and membrane-mimetic environments.

    Science.gov (United States)

    Fiori, S; Renner, C; Cramer, J; Pegoraro, S; Moroder, L

    1999-08-01

    The newly discovered endomorphin-1 (Tyr-Pro-Trp-Phe-NH2) and endomorphin-2 (Tyr-Pro-Phe-Phe-NH2) are potent opioid peptides with the highest affinity and selectivity for the mu receptor among all known endogenous ligands. To investigate a possible correlation between these biological properties and the conformational preferences of the small peptides, a comparative structural analysis was performed of endomorphin-1 in aqueous buffer and in membrane-mimicking SDS and AOT normal and reverse micelles by the use of CD, FT-IR, fluorescence and(1)H-NMR spectroscopy. It is well established for opioid peptides that, independently of the receptor selectivity, the Tyr1 residue plays the role of the primary pharmacophore and that the orientation of the second aromatic pharmacophore relative to the tyrosine side-chain dictates the mu or delta-receptor selectivity. By varying the environment of endomorphin-1 from water to the amphipathic SDS micelles and even more efficiently to the AOT reverse micelles, the display of the aromatic side-chains changes from an interaction of the Tyr1 and Phe4 residues to a switch of the Trp3 indole group into close contact with the phenolic moiety to prevent this type of interaction and to force an orientation of the Phe4 side-chain into the opposite direction. This conformational switch is accompanied by a stabilization of the cis -Pro2 isomer and the resulting spatial array of the pharmacophoric groups correlate well with the structural model of mu receptor-bound opioid peptides. The results indicate that AOT reverse micelles with a woof 10, where almost exclusively ordered water is secluded in the cavity, constitute with their electrostatic and hydrophobic potential an excellent mimetic of amphipathic surfaces as present on lipid bilayers and on ligand-recognition and ligand-binding sites of proteins. PMID:10438613

  5. The effect of superoxide dismutase mimetic and catalase on the quality of postthawed goat semen.

    Science.gov (United States)

    Shafiei, Mojtaba; Forouzanfar, Mohsen; Hosseini, Sayyed Morteza; Esfahani, Mohammad Hossein Nasr

    2015-05-01

    Manganese(III) meso-tetrakis(N-ethylpyridinium-2-yl)porphyrin chloride (MnTE) is a cell-permeable superoxide dismutase mimetic agent which can convert superoxide to hydrogen peroxide (H2O2). Supplementation of MnTE to a commercial semen extender can protect sperm from superoxide but not H2O2. Therefore, we proposed that addition of catalase (0.0, 200, or 400 IU/mL) in combination with MnTE (0.1 μM) may further improve the cryopreservation efficiency of goat semen in commercially optimized freezing media such as Andromed. Therefore, ejaculates were obtained from three adult bucks twice a week during the breeding season and diluted with Andromed supplemented with or without MnTE and catalase and were frozen in liquid nitrogen. Sperm parameters and reactive oxygen species contents were evaluated 2 hours after dilution (before freezing) and after freezing/thawing. The results revealed that all the treatments significantly (P ≤ 0.05) improved sperm motility, viability, and membrane integrity after freezing and reduced reactive oxygen species content compared with the control group, but maximum improvement was obtained in MnTE + 400 IU/mL catalase. In addition, supplementation with these antioxidants significantly (P ≤ 0.05) increases the cleavage rate after IVF. In conclusion, the results of present study suggest that addition of antioxidant MnTE or catalase to commercial optimized media, such as Andromed, improves total motility, membrane integrity, and viability of goat semen samples after thawing. But the degree of improvement for these parameters significantly (P ≤ 0.05) higher when MnTE and catalase were simultaneously added to the cryopreservation media.

  6. Temporally degradable collagen-mimetic hydrogels tuned to chondrogenesis of human mesenchymal stem cells.

    Science.gov (United States)

    Parmar, Paresh A; Skaalure, Stacey C; Chow, Lesley W; St-Pierre, Jean-Philippe; Stoichevska, Violet; Peng, Yong Y; Werkmeister, Jerome A; Ramshaw, John A M; Stevens, Molly M

    2016-08-01

    collagen-mimetic protein, cross-linked via multiple enzymatically degradable peptides, provides a highly adaptable and well defined platform to recapitulate a high degree of biological complexity, which could be applicable to numerous tissue engineering and regenerative medicine applications. PMID:27214650

  7. Leukocyte mimetic polysaccharide microparticles tracked in vivo on activated endothelium and in abdominal aortic aneurysm.

    Science.gov (United States)

    Bonnard, Thomas; Serfaty, Jean-Michel; Journé, Clément; Ho Tin Noe, Benoît; Arnaud, Denis; Louedec, Liliane; Derkaoui, Sidi Mohammed; Letourneur, Didier; Chauvierre, Cédric; Le Visage, Catherine

    2014-08-01

    We have developed injectable microparticles functionalized with fucoidan, in which sulfated groups mimic the anchor sites of P-selectin glycoprotein ligand-1 (PSGL-1), one of the principal receptors supporting leukocyte adhesion. These targeted microparticles were combined with a fluorescent dye and a T2(∗) magnetic resonance imaging (MRI) contrast agent, and then tracked in vivo with small animal imaging methods. Microparticles of 2.5μm were obtained by a water-in-oil emulsification combined with a cross-linking process of polysaccharide dextran, fluorescein isothiocyanate dextran, pullulan and fucoidan mixed with ultrasmall superparamagnetic particles of iron oxide. Fluorescent intravital microscopy observation revealed dynamic adsorption and a leukocyte-like behaviour of fucoidan-functionalized microparticles on a calcium ionophore induced an activated endothelial layer of a mouse mesentery vessel. We observed 20times more adherent microparticles on the activated endothelium area after the injection of functionalized microparticles compared to non-functionalized microparticles (197±11 vs. 10±2). This imaging tool was then applied to rats presenting an elastase perfusion model of abdominal aortic aneurysm (AAA) and 7.4T in vivo MRI was performed. Visual analysis of T2(∗)-weighted MR images showed a significant contrast enhancement on the inner wall of the aneurysm from 30min to 2h after the injection. Histological analysis of AAA cryosections revealed microparticles localized inside the aneurysm wall, in the same areas in which immunostaining shows P-selectin expression. The developed leukocyte mimetic imaging tool could therefore be relevant for molecular imaging of vascular diseases and for monitoring biologically active areas prone to rupture in AAA. PMID:24769117

  8. An apoA-I mimetic peptide increases LCAT activity in mice through increasing HDL concentration

    Directory of Open Access Journals (Sweden)

    Xun Chen, Charlotte Burton, Xuelei Song, Lesley Mcnamara, Annunziata Langella, Simona Cianetti, Ching H. Chang, Jun Wang

    2009-01-01

    Full Text Available Lecithin cholesterol acyltransferase (LCAT plays a key role in the reverse cholesterol transport (RCT process by converting cholesterol to cholesteryl ester to form mature HDL particles, which in turn deliver cholesterol back to the liver for excretion and catabolism. HDL levels in human plasma are negatively correlated with cardiovascular risk and HDL functions are believed to be more important in atheroprotection. This study investigates whether and how D-4F, an apolipoprotein A-I (apoA-I mimetic peptide, influences LCAT activity in the completion of the RCT process. We demonstrated that the apparent rate constant value of the LCAT enzyme reaction gives a measure of LCAT activity and determined the effects of free metals and a reducing agent on LCAT activity, showing an inhibition hierarchy of Zn2+>Mg2+>Ca2+ and no inhibition with β-mercaptoethanol up to 10 mM. We reconstituted nano-disc particles using apoA-I or D-4F with phospholipids. These particles elicited good activity in vitro in the stimulation of cholesterol efflux from macrophages through the ATP-binding cassette transporter A1 (ABCA1. With these particles we studied the LCAT activity and demonstrated that D-4F did not activate LCAT in vitro. Furthermore, we have done in vivo experiments with apoE-null mice and demonstrated that D-4F (20 mg/kg body weight, once daily subcutaneously increased LCAT activity and HDL level as well as apoA-I concentration at 72 hours post initial dosing. Finally, we have established a correlation between HDL concentration and LCAT activity in the D-4F treated mice.

  9. Smac mimetic SM-164 potentiates APO2L/TRAIL- and doxorubicin-mediated anticancer activity in human hepatocellular carcinoma cells.

    Directory of Open Access Journals (Sweden)

    Shuijun Zhang

    Full Text Available BACKGROUND: The members of inhibitor of apoptosis proteins (IAPs family are key negative regulators of apoptosis. Overexpression of IAPs are found in hepatocellular carcinoma (HCC, and can contribute to chemotherapy resistance and recurrence of HCC. Small-molecule Second mitochondria-derived activator of caspases (Smac mimetics have recently emerged as novel anticancer drugs through targeting IAPs. The specific aims of this study were to 1 examine the anticancer activity of Smac mimetics as a single agent and in combination with chemotherapy in HCC cells, and 2 investigate the mechanism of anticancer action of Smac mimetics. METHODS: Four HCC cell lines, including SMMC-7721, BEL-7402, HepG2 and Hep3B, and 12 primary HCC cells were used in this study. Smac mimetic SM-164 was used to treat HCC cells. Cell viability, cell death induction and clonal formation assays were used to evaluate the anticancer activity. Western blotting analysis and a pancaspase inhibitor were used to investigate the mechanisms. RESULTS: Although SM-164 induced complete cIAP-1 degradation, it displayed weak inhibitory effects on the viability of HCC cells. Nevertheless, SM-164 considerably potentiated Apo2 ligand or TNF-related apoptosis-inducing ligand (APO2L/TRAIL- and Doxorubicin-mediated anticancer activity in HCC cells. Mechanistic studies demonstrated that SM-164 in combination with chemotherapeutic agents resulted in enhanced activation of caspases-9, -3 and cleavage of poly ADP-ribose polymerase (PARP, and also led to decreased AKT activation. CONCLUSIONS: Smac mimetics can enhance chemotherapeutic-mediated anticancer activity by enhancing apoptosis signaling and suppressing survival signaling in HCC cells. This study suggests Smac mimetics are potential therapeutic agents for HCC.

  10. A mimetic finite difference method for two-phase flow models with dynamic capillary pressure and hysteresis

    CERN Document Server

    Zhang, Hong

    2016-01-01

    Saturation overshoot and pressure overshoot are studied by incorporating dynamic capillary pressure, capillary pressure hysteresis and hysteretic dynamic coefficient with a traditional fractional flow equation. Using the method of lines, the discretizations are constructed by applying Castillo-Grone's mimetic operators in the space direction and explicit trapezoidal integrator in the time direction. Convergence tests and conservation property of the schemes are presented. Computed profiles capture both the saturation overshoot and pressure overshoot phenomena. Comparisons between numerical results and experiments illustrate the effectiveness and different features of the models.

  11. Intracellular Ca2+ Modulation during Short Exposure to Ischemia-Mimetic Factors in Isolated Rat Ventricular Myocytes

    OpenAIRE

    Danijel, Pravdic; Nikolina, Vladic; Zeljko, Bosnjak J

    2009-01-01

    We investigated the effects of different ischemia-mimetic factors on intracellular Ca2+ concentration ([Ca2+]i). Ventricular myocytes were isolated from adult Wistar rats, and [Ca2+]i was measured using fluorescent indicator fluo-4 AM by confocal microscopy. Intracellular pH was measured using c5-(and-6)-carboxy SNARF-1 AM, a dual emission pH-sensitive ionophore. Myocytes were exposed to hypoxia, extracellular acidosis (pHo 6.8), Na-lactate (10 mM), or to combination of those factors for 25 m...

  12. Synthesis and conformational analysis of constrained beta-turn mimetics using a bicyclic turn inducer and the Petasis three-component reaction on solid-phase

    OpenAIRE

    Danieli, E; Trabocchi, A.; G. MENCHI; Guarna, A

    2007-01-01

    A new set of β-turn mimetics incorporating a bicyclic turn inducer was achieved by use of the solid-phase Petasis reaction in a stereoselective fashion. The stereoselectivity of the reaction turned out to be dependent on the side chain of the amino acid preceding the reverse turn inducer. The β-turn mimetics were stabilized by strong intramolecular 10-membered ring hydrogen bonds, detected by conformational analysis by NMR and molecular modelling, whilst the turn type was controlled by the fi...

  13. SMAC mimetic Debio 1143 synergizes with taxanes, topoisomerase inhibitors and bromodomain inhibitors to impede growth of lung adenocarcinoma cells.

    Science.gov (United States)

    Langdon, Casey G; Wiedemann, Norbert; Held, Matthew A; Mamillapalli, Ramanaiah; Iyidogan, Pinar; Theodosakis, Nicholas; Platt, James T; Levy, Frederic; Vuagniaux, Gregoire; Wang, Shaomeng; Bosenberg, Marcus W; Stern, David F

    2015-11-10

    Targeting anti-apoptotic proteins can sensitize tumor cells to conventional chemotherapies or other targeted agents. Antagonizing the Inhibitor of Apoptosis Proteins (IAPs) with mimetics of the pro-apoptotic protein SMAC is one such approach. We used sensitization compound screening to uncover possible agents with the potential to further sensitize lung adenocarcinoma cells to the SMAC mimetic Debio 1143. Several compounds in combination with Debio 1143, including taxanes, topoisomerase inhibitors, and bromodomain inhibitors, super-additively inhibited growth and clonogenicity of lung adenocarcinoma cells. Co-treatment with Debio 1143 and the bromodomain inhibitor JQ1 suppresses the expression of c-IAP1, c-IAP2, and XIAP. Non-canonical NF-κB signaling is also activated following Debio 1143 treatment, and Debio 1143 induces the formation of the ripoptosome in Debio 1143-sensitive cell lines. Sensitivity to Debio 1143 and JQ1 co-treatment was associated with baseline caspase-8 expression. In vivo treatment of lung adenocarcinoma xenografts with Debio 1143 in combination with JQ1 or docetaxel reduced tumor volume more than either single agent alone. As Debio 1143-containing combinations effectively inhibited both in vitro and in vivo growth of lung adenocarcinoma cells, these data provide a rationale for Debio 1143 combinations currently being evaluated in ongoing clinical trials and suggest potential utility of other combinations identified here.

  14. Comparison of CR36, a new heparan mimetic, and pentosan polysulfate in the treatment of prion diseases.

    Science.gov (United States)

    Larramendy-Gozalo, Claire; Barret, Agnès; Daudigeos, Estelle; Mathieu, Emilie; Antonangeli, Lucie; Riffet, Cécile; Petit, Emmanuel; Papy-Garcia, Dulce; Barritault, Denis; Brown, Paul; Deslys, Jean-Philippe

    2007-03-01

    Sulfated polyanions, including pentosan polysulfate (PPS) and heparan mimetics, number among the most effective drugs that have been used in experimental models of prion disease and are presumed to act in competition with endogenous heparan sulfate proteoglycans as co-receptors for prion protein (PrP) on the cell surface. PPS has been shown to prolong the survival of animals after intracerebral perfusion and is in limited use for the experimental treatment of human transmissible spongiform encephalopathies (TSEs). Here, PPS is compared with CR36, a new heparan mimetic. Ex vivo, CR36 was more efficient than PPS in reducing PrPres in scrapie-infected cell cultures and showed long-lasting activity. In vivo, CR36 showed none of the acute toxicity observed with PPS and reduced PrPres accumulation in spleens, but had only a marginal effect on the survival time of mice infected with bovine spongiform encephalopathy. In contrast, mice treated with PPS that survived the initial toxic mortality had no detectable PrPres in the spleens and lived 185 days longer than controls (+55%). These results show, once again, that anti-TSE drugs cannot be encouraged for human therapeutic trials solely on the basis of in vitro or ex vivo observations, but must first be subjected to in vivo animal studies.

  15. Influence of Block Copolymerization on the Antifreeze Protein Mimetic Ice Recrystallization Inhibition Activity of Poly(vinyl alcohol).

    Science.gov (United States)

    Congdon, Thomas R; Notman, Rebecca; Gibson, Matthew I

    2016-09-12

    Antifreeze (glyco) proteins are produced by many cold-acclimatized species to enable them to survive subzero temperatures. These proteins have multiple macroscopic effects on ice crystal growth which makes them appealing for low-temperature applications-from cellular cryopreservation to food storage. Poly(vinyl alcohol) has remarkable ice recrystallization inhibition activity, but its mode of action is uncertain as is the extent at which it can be incorporated into other high-order structures. Here the synthesis and characterization of well-defined block copolymers containing poly(vinyl alcohol) and poly(vinylpyrrolidone) by RAFT/MADIX polymerization is reported, as new antifreeze protein mimetics. The effect of adding a large second hydrophilic block is studied across a range of compositions, and it is found to be a passive component in ice recrystallization inhibition assays, enabling retention of all activity. In the extreme case, a block copolymer with only 10% poly(vinyl alcohol) was found to retain all activity, where statistical copolymers of PVA lose all activity with very minor changes to composition. These findings present a new method to increase the complexity of antifreeze protein mimetic materials, while retaining activity, and also to help understand the underlying mechanisms of action.

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

    Directory of Open Access Journals (Sweden)

    Svetlana Sarantseva

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

  17. A small molecule glycosaminoglycan mimetic blocks Plasmodium invasion of the mosquito midgut.

    Directory of Open Access Journals (Sweden)

    Derrick K Mathias

    Full Text Available Malaria transmission-blocking (T-B interventions are essential for malaria elimination. Small molecules that inhibit the Plasmodium ookinete-to-oocyst transition in the midgut of Anopheles mosquitoes, thereby blocking sporogony, represent one approach to achieving this goal. Chondroitin sulfate glycosaminoglycans (CS-GAGs on the Anopheles gambiae midgut surface are putative ligands for Plasmodium falciparum ookinetes. We hypothesized that our synthetic polysulfonated polymer, VS1, acting as a decoy molecular mimetic of midgut CS-GAGs confers malaria T-B activity. In our study, VS1 repeatedly reduced midgut oocyst development by as much as 99% (P<0.0001 in mosquitoes fed with P. falciparum and Plasmodium berghei. Through direct-binding assays, we observed that VS1 bound to two critical ookinete micronemal proteins, each containing at least one von Willebrand factor A (vWA domain: (i circumsporozoite protein and thrombospondin-related anonymous protein-related protein (CTRP and (ii vWA domain-related protein (WARP. By immunofluorescence microscopy, we observed that VS1 stains permeabilized P. falciparum and P. berghei ookinetes but does not stain P. berghei CTRP knockouts or transgenic parasites lacking the vWA domains of CTRP while retaining the thrombospondin repeat region. We produced structural homology models of the first vWA domain of CTRP and identified, as expected, putative GAG-binding sites on CTRP that align closely with those predicted for the human vWA A1 domain and the Toxoplasma gondii MIC2 adhesin. Importantly, the models also identified patches of electropositive residues that may extend CTRP's GAG-binding motif and thus potentiate VS1 binding. Our molecule binds to a critical, conserved ookinete protein, CTRP, and exhibits potent malaria T-B activity. This study lays the framework for a high-throughput screen of existing libraries of safe compounds to identify those with potent T-B activity. We envision that such compounds when

  18. Bio-Mimetics of Disaster Anticipation—Learning Experience and Key-Challenges

    Directory of Open Access Journals (Sweden)

    Helmut Tributsch

    2013-03-01

    Full Text Available Anomalies in animal behavior and meteorological phenomena before major earthquakes have been reported throughout history. Bio-mimetics or bionics aims at learning disaster anticipation from animals. Since modern science is reluctant to address this problem an effort has been made to track down the knowledge available to ancient natural philosophers. Starting with an archaeologically documented human sacrifice around 1700 B.C. during the Minoan civilization immediately before a large earthquake, which killed the participants, earthquake prediction knowledge throughout antiquity is evaluated. Major practical experience with this phenomenon has been gained from a Chinese earthquake prediction initiative nearly half a century ago. Some quakes, like that of Haicheng, were recognized in advance. However, the destructive Tangshan earthquake was not predicted, which was interpreted as an inherent failure of prediction based on animal phenomena. This is contradicted on the basis of reliable Chinese documentation provided by the responsible earthquake study commission. The Tangshan earthquake was preceded by more than 2,000 reported animal anomalies, some of which were of very dramatic nature. They are discussed here. Any physical phenomenon, which may cause animal unrest, must involve energy turnover before the main earthquake event. The final product, however, of any energy turnover is heat. Satellite based infrared measurements have indeed identified significant thermal anomalies before major earthquakes. One of these cases, occurring during the 2001 Bhuj earthquake in Gujarat, India, is analyzed together with parallel animal anomalies observed in the Gir national park. It is suggested that the time window is identical and that both phenomena have the same geophysical origin. It therefore remains to be demonstrated that energy can be released locally before major earthquake events. It is shown that by considering appropriate geophysical feedback

  19. Development of electrospun bone-mimetic matrices for bone regenerative applications

    Science.gov (United States)

    Phipps, Matthew Christopher

    Although bone has a dramatic capacity for regeneration, certain injuries and procedures present defects that are unable to heal properly, requiring surgical intervention to induce and support osteoregeneration. Our research group has hypothesized that the development of a biodegradable material that mimics the natural composition and architecture of bone extracellular matrix has the potential to provide therapeutic benefit to these patients. Utilizing a process known as electrospinning, our lab has developed a bone-mimetic matrix (BMM) consisting of composite nanofibers of the mechanically sta-ble polymer polycaprolactone (PCL), and the natural bone matrix molecules type-I colla-gen and hydroxyapatite nanocrystals (HA). We herein show that BMMs supported great-er adhesion, proliferation, and integrin activation of mesenchymal stem cells (MSCs), the multipotent bone-progenitor cells within bone marrow and the periosteum, in comparison to electrospun PCL alone. These cellular responses, which are essential early steps in the process of bone regeneration, highlight the benefits of presenting cells with natural bone molecules. Subsequently, evaluation of new bone formation in a rat cortical tibia defect showed that BMMs are highly osteoconductive. However, these studies also revealed the inability of endogenous cells to migrate within electrospun matrices due to the inherently small pore sizes. To address this limitation, which will negatively impact the rate of scaf-fold-to-bone turnover and inhibit vascularization, sacrificial fibers were added to the ma-trix. The removal of these fibers after fabrication resulted in BMMs with larger pores, leading to increased infiltration of MSCs and endogenous bone cells. Lastly, we evaluat-ed the potential of our matrices to stimulate the recruitment of MSCs, a vital step in bone healing, through the sustained delivery of platelet derived growth factor-BB (PDGF-BB). BMMs were found to adsorb and subsequently release greater

  20. A multilevel multiscale mimetic (M 3) method for two-phase flows in porous media

    Science.gov (United States)

    Lipnikov, K.; Moulton, J. D.; Svyatskiy, D.

    2008-07-01

    We describe a multilevel multiscale mimetic (M 3) method for solving two-phase flow (water and oil) in a heterogeneous reservoir. The governing equations are the elliptic equation for the reservoir pressure and the hyperbolic equation for the water saturation. On each time step, we first solve the pressure equation and then use the computed flux in an explicit upwind finite volume method to update the saturation. To reduce the computational cost, the pressure equation is solved on a much coarser grid than the saturation equation. The coarse-grid pressure discretization captures the influence of multiple scales via the subgrid modeling technique for single-phase flow recently proposed in [Yu. A. Kuznetsov. Mixed finite element method for diffusion equations on polygonal meshes with mixed cells. J. Numer. Math., 14 (4) (2006) 305-315; V. Gvozdev. discretization of the diffusion and Maxwell equations on polyhedral meshes. Technical Report Ph.D. Thesis, University of Houston, 2007; Yu. Kuznetsov. Mixed finite element methods on polyhedral meshes for diffusion equations, in: Computational Modeling with PDEs in Science and Engineering, Springer-Verlag, Berlin, in press]. We extend significantly the applicability of this technique by developing a new robust and efficient method for estimating the flux coarsening parameters. Specifically, with this advance the M 3 method can handle full permeability tensors and general coarsening strategies, which may generate polygonal meshes on the coarse grid. These problem dependent coarsening parameters also play a critical role in the interpolation of the flux, and hence, in the advection of saturation for two-phase flow. Numerical experiments for two-phase flow in highly heterogeneous permeability fields, including layer 68 of the SPE Tenth Comparative Solution Project, demonstrate that the M 3 method retains good accuracy for high coarsening factors in both directions, up to 64 for the considered models. Moreover, we demonstrate

  1. GM-3 Lactone Mimetic Interacts with CD4 and HIV-1 Env Proteins, Hampering HIV-1 Infection without Inducing a Histopathological Alteration.

    Science.gov (United States)

    Richichi, Barbara; Pastori, Claudia; Gherardi, Stefano; Venuti, Assunta; Cerreto, Antonella; Sanvito, Francesca; Toma, Lucio; Lopalco, Lucia; Nativi, Cristina

    2016-08-12

    Glycosphingolipids (GSLs) are involved in HIV-1 entry. GM-3 ganglioside, a widespread GSL, affects HIV entry and infection in different ways, depending on the concentration, through its anchoring activity in lipid rafts. This explains why the induction of an altered GSLs metabolism was a tempting approach to reducing HIV-1 cell infection. This study assayed the biological properties of a synthetic GM-3 lactone mimetic, 1, aimed at blocking HIV-1 infection without inducing the adverse events expected by an altered metabolism of GLSs in vivo. The mimetic, conjugated to immunogenic protein ovalbumin and multivalently presented, was able to bind the CD4 molecule with high affinity and block its engagement with gp120, thus inhibiting virus entry. Elicited antimimetic antibodies were also able to block HIV-1 infection in vitro, with activity complementary to that observed for 1. These preliminary results show that the use of GSLs mimetics can be a novel promising mode to block HIV-1 infection and that 1 and other GSL mimetics deserve further attention. PMID:27626296

  2. [Conservative therapy of female urinary incontinence--potential and effect].

    Science.gov (United States)

    Horcicka, L; Chmel, R; Novácková, M

    2005-01-01

    Non-surgical treatment of female stress urinary incontinence is not as effective as surgical methods but it is very successful in indicated cases. Rehabilitation of the pelvic floor muscles (Kegel exercises, vaginal cones, and electrostimulation of the pelvic floor muscles), drug treatment (alfa-mimetics, tricyclic antidepressives, estrogens, duloxetin), pessarotherapy and uretral obturator devices represent possibilities of conservative therapy of the stress incontinence. Conservative therapy is the method of choice in the treatment of urge incontinence. The most successful are anticholinergic drugs but they have very frequent serious side effects (dryness of the mucous membranes, accommodation disorders, constipation). Spasmolytics, estrogens and tricyclic antidepressives are the other popular used drugs. Life style modification, bladder training and electrostimulation represent very important parts of the conservative treatment. Effectiveness of the non-surgical treatment of both urge and stress urinary incontinence can not reach 100 percent but it helps very much in the quality of life improvement of incontinent women. PMID:15887395

  3. [Conservative therapy of female urinary incontinence--potential and effect].

    Science.gov (United States)

    Horcicka, L; Chmel, R; Novácková, M

    2005-01-01

    Non-surgical treatment of female stress urinary incontinence is not as effective as surgical methods but it is very successful in indicated cases. Rehabilitation of the pelvic floor muscles (Kegel exercises, vaginal cones, and electrostimulation of the pelvic floor muscles), drug treatment (alfa-mimetics, tricyclic antidepressives, estrogens, duloxetin), pessarotherapy and uretral obturator devices represent possibilities of conservative therapy of the stress incontinence. Conservative therapy is the method of choice in the treatment of urge incontinence. The most successful are anticholinergic drugs but they have very frequent serious side effects (dryness of the mucous membranes, accommodation disorders, constipation). Spasmolytics, estrogens and tricyclic antidepressives are the other popular used drugs. Life style modification, bladder training and electrostimulation represent very important parts of the conservative treatment. Effectiveness of the non-surgical treatment of both urge and stress urinary incontinence can not reach 100 percent but it helps very much in the quality of life improvement of incontinent women.

  4. Proton Therapy

    Science.gov (United States)

    ... News Physician Resources Professions Site Index A-Z Proton Therapy Proton therapy delivers radiation to tumor tissue ... feel during and after the procedure? What is proton therapy and how is it used? Protons are ...

  5. Oxygen Therapy

    Science.gov (United States)

    Oxygen therapy is a treatment that provides you with extra oxygen. Oxygen is a gas that your body ... machine in your home. A different kind of oxygen therapy is called hyperbaric oxygen therapy. It uses oxygen ...

  6. Detection of Hg2+ based on the selective inhibition of peroxidase mimetic activity of BSA-Au clusters.

    Science.gov (United States)

    Zhu, Rui; Zhou, Yan; Wang, Xi-Liang; Liang, Li-Ping; Long, Yi-Juan; Wang, Qin-Long; Zhang, Hai-Jie; Huang, Xiao-Xiao; Zheng, Hu-Zhi

    2013-12-15

    It was found that Hg(2+) can inhibit the peroxidase mimetic activity of bovine serum albumin (BSA) protected Au clusters (BSA-Au) due to the specific interaction between Hg(2+) and Au(+) existed onto the surface of BSA-Au clusters. By coupling with 3, 3', 5, 5'-tetramethylbenzidine (TMB)-H2O2 chromogenic reaction, a novel method for Hg(2+) detection was developed based on the inhibiting effect of Hg(2+) on BSA-Au clusters peroxidase-like activity. This method exhibited high selectivity and sensitivity. As low as 3 nM (0.6 ppb, 3σ) Hg(2+) could be detected with a linear range from 10 nM (2 ppb) to 10 µM (2 ppm) and this method was successfully applied for the determination of total mercury content in skin lightening products.

  7. Synthesis of multivalent carbohydrate mimetics with aminopolyol end groups and their evaluation as L-selectin inhibitors

    Directory of Open Access Journals (Sweden)

    Joana Salta

    2015-05-01

    Full Text Available In this article a series of divalent and trivalent carbohydrate mimetics on the basis of an enantiopure aminopyran and of serinol is described. These aminopolyols are connected by amide bonds to carboxylic acid derived spacer units either by Schotten–Baumann acylation or by coupling employing HATU as reagent. The O-sulfation employing the SO3·DMF complex was optimized. It was crucial to follow this process by 700 MHz 1H NMR spectroscopy to ensure full conversion and to use a refined neutralization and purification protocol. Many of the compounds could not be tested as L-selectin inhibitor by SPR due to their insolubility in water, nevertheless, a divalent and a trivalent amide showed surprisingly good activities with IC50 values in the low micromolar range.

  8. The CNTF-derived peptide mimetic Cintrofin attenuates spatial-learning deficits in a rat post-status epilepticus model

    DEFF Research Database (Denmark)

    Russmann, Vera; Seeger, Natalie; Zellinger, Christina;

    2013-01-01

    Ciliary neurotrophic growth factor is considered a potential therapeutic agent for central nervous system diseases. We report first in vivo data of the ciliary neurotrophic growth factor peptide mimetic Cintrofin in a rat post-status epilepticus model. Cintrofin prevented long-term alterations...... in the number of doublecortin-positive neuronal progenitor cells and attenuated the persistence of basal dendrites. In contrast, Cintrofin did neither affect acute status epilepticus-associated alterations in hippocampal cell proliferation and neurogenesis nor reveal any relevant effect on seizure activity....... Whereas status epilepticus caused a significant disturbance in spatial learning in reversed peptide-treated rats, the performance of Cintrofin-treated rats did not differ from controls. The study confirms that Cintrofin comprises an active sequence mimicking effects of its parent molecule. While the data...

  9. Sulfated levan from Halomonas smyrnensis as a bioactive, heparin-mimetic glycan for cardiac tissue engineering applications.

    Science.gov (United States)

    Erginer, Merve; Akcay, Ayca; Coskunkan, Binnaz; Morova, Tunc; Rende, Deniz; Bucak, Seyda; Baysal, Nihat; Ozisik, Rahmi; Eroglu, Mehmet S; Agirbasli, Mehmet; Toksoy Oner, Ebru

    2016-09-20

    Chemical derivatives of levan from Halomonas smyrnensis AAD6(T) with low, medium and high levels of sulfation were synthesized and characterized by FTIR and 2D-NMR. Sulfated levan samples were found to exhibit anticoagulation activity via the intrinsic pathway like heparin in a dose-dependent manner. Exceptionally high heparin equivalent activity of levan sulfate was shown to proceed via thrombin inhibition where decreased Factor Xa activity with increasing concentration was observed in antithrombin tests and above a certain concentration, levan sulfate showed a better inhibitor activity than heparin. In vitro experimental results were then verified in silico by docking studies using equilibrium structures obtained by molecular dynamic simulations and results suggested a sulfation dependent binding mechanism. With its high biocompatibility and heparin mimetic activity, levan sulfate can be considered as a suitable functional biomaterial to design biologically active, functionalized, thin films and engineered smart scaffolds for cardiac tissue engineering applications. PMID:27261753

  10. Mesenchymal stem cell responses to bone-mimetic electrospun matrices composed of polycaprolactone, collagen I and nanoparticulate hydroxyapatite.

    Directory of Open Access Journals (Sweden)

    Matthew C Phipps

    Full Text Available The performance of biomaterials designed for bone repair depends, in part, on the ability of the material to support the adhesion and survival of mesenchymal stem cells (MSCs. In this study, a nanofibrous bone-mimicking scaffold was electrospun from a mixture of polycaprolactone (PCL, collagen I, and hydroxyapatite (HA nanoparticles with a dry weight ratio of 50/30/20 respectively (PCL/col/HA. The cytocompatibility of this tri-component scaffold was compared with three other scaffold formulations: 100% PCL (PCL, 100% collagen I (col, and a bi-component scaffold containing 80% PCL/20% HA (PCL/HA. Scanning electron microscopy, fluorescent live cell imaging, and MTS assays showed that MSCs adhered to the PCL, PCL/HA and PCL/col/HA scaffolds, however more rapid cell spreading and significantly greater cell proliferation was observed for MSCs on the tri-component bone-mimetic scaffolds. In contrast, the col scaffolds did not support cell spreading or survival, possibly due to the low tensile modulus of this material. PCL/col/HA scaffolds adsorbed a substantially greater quantity of the adhesive proteins, fibronectin and vitronectin, than PCL or PCL/HA following in vitro exposure to serum, or placement into rat tibiae, which may have contributed to the favorable cell responses to the tri-component substrates. In addition, cells seeded onto PCL/col/HA scaffolds showed markedly increased levels of phosphorylated FAK, a marker of integrin activation and a signaling molecule known to be important for directing cell survival and osteoblastic differentiation. Collectively these results suggest that electrospun bone-mimetic matrices serve as promising degradable substrates for bone regenerative applications.

  11. The effect of a diiodothyronine mimetic on insulin sensitivity in male cardiometabolic patients: a double-blind randomized controlled trial.

    Directory of Open Access Journals (Sweden)

    Fleur van der Valk

    Full Text Available BACKGROUND AND AIMS: Obesity and its associated cardiometabolic co-morbidities are increasing worldwide. Since thyroid hormone mimetics are capable of uncoupling the beneficial metabolic effects of thyroid hormones from their deleterious effects on heart, bone and muscle, this class of drug is considered as adjacent therapeutics to weight-lowering strategies. This study investigated the safety and efficacy of TRC150094, a thyroid hormone mimetic. MATERIALS AND METHODS: This 4-week, randomized, placebo-controlled, double-blind trial was conducted in India and The Netherlands. Forty subjects were randomized at a 1:1 ratio to receive either TRC150094 dosed at 50 mg or placebo once daily for 4 weeks. Hyperinsulinemic euglycemic clamp and (1H-Magnetic Resonance Spectroscopy (MRS were performed before and after treatment. RESULTS: At baseline, subjects were characterized by markedly impaired hepatic and peripheral insulin sensitivity. TRC150094 dosed 50 mg once daily was safe and well tolerated. Hepatic nor peripheral insulin sensitivity improved after TRC150094 treatment, expressed as the suppression of Endogenous Glucose Production from 59.5 to 62.1%; p = 0.477, and the rate of glucose disappearance from 28.8 to 26.4 µmol kg(-1min(-1, p = 0.185. TRC150094 administration did not result in differences in fasting plasma free fatty acids from 0.51 to 0.51 mmol/L, p = 0.887 or in insulin-mediated suppression of lipolysis from 57 to 54%, p = 0.102. Also, intrahepatic triglyceride content was unaltered. CONCLUSION: Collectively, these data show that, in contrast to the potent metabolic effects in experimental models, TRC150094 at a dose of 50 mg daily does not improve the metabolic homeostasis in subjects at an increased cardiometabolic risk. Further studies are needed to evaluate whether TRC150094 has beneficial effects in patients with more severe metabolic derangement, such as overt diabetes mellitus and hypertriglyceridemia. TRIAL REGISTRATION

  12. NiCoBP-doped carbon nanotube hybrid: A novel oxidase mimetic system for highly efficient electrochemical immunoassay

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Bing; He, Yu; Liu, Bingqian; Tang, Dianping, E-mail: dianping.tang@fzu.edu.cn

    2014-12-03

    Highlights: • We report a new oxidase mimetic system for highly efficient electrochemical immunoassay. • NiCoBP-doped carbon nanotube hybrids were used as the nanocatalysts. • NiCoBP-doped carbon nanotube hybrids were used as the mimic oxidase. - Abstract: NiCoBP-doped multi-walled carbon nanotube (NiCoBP–MWCNT) was first synthesized by using induced electroless-plating method and functionalized with the biomolecules for highly efficient electrochemical immunoassay of prostate-specific antigen (PSA, used as a model analyte). We discovered that the as-synthesized NiCoBP–MWCNT had the ability to catalyze the glucose oxidization with a stable and well-defined redox peak. The catalytic current increased with the increment of the immobilized NiCoBP–MWCNT on the electrode. Transmission electron microscope (TEM) and energy dispersive X-ray spectrometry (EDX) were employed to characterize the as-prepared NiCoBP–MWCNT. Using the NiCoBP–MWCNT-conjugated anti-PSA antibody as the signal-transduction tag, a new enzyme-free electrochemical immunoassay protocol could be designed for the detection of target PSA on the capture antibody-functionalized immunosensing interface. Experimental results revealed that the designed immunoassay system could exhibit good electrochemical responses toward target PSA, and allowed the detection of PSA at a concentration as low as 0.035 ng mL{sup −1}. More importantly, the NiCoBP-MWCNT-based oxidase mimetic system could be further extended for the monitoring of other low-abundance proteins or disease-related biomarkers by tuning the target antibody.

  13. Structure-Activity Studies of Brassinosteroids and the Search for Novel Analogues and Mimetics with Improved Bioactivity.

    Science.gov (United States)

    Back, Thomas G.; Pharis, Richard P.

    2003-12-01

    A number of novel brassinosteroid analogues were synthesized and subjected to the rice leaf lamina inclination bioassay. Modified B-ring analogues included lactam, thiolactone, cyclic ether, ketone, hydroxyl, and exocyclic methylene derivatives of brassinolide. Those derivatives containing polar functional groups retained considerable bioactivity, whereas the exocyclic methylene compounds were devoid of activity. Analogues containing normal alkyl and cycloalkyl substituents at C-24 (in place of the isopropyl group of brassinolide) showed an inverse relationship between activity and chain length or ring size, respectively. The corresponding cyclopropyl and cyclobutyl derivatives were significantly more active than brassinolide and appear to be the most potent brassinosteroids reported to date. When synergized with the auxin indole-3-acetic acid (IAA), their bioactivity can be further enhanced by 1-2 orders of magnitude. The cyclopropyl derivative, when coapplied with the auxin naphthaleneacetic acid, gave a significant increase in yield of wheat in a field trial. Certain 25- and 26-hydroxy derivatives are known metabolites of brassinosteroids. All of the C-25 stereoisomers of 25-hydroxy, 26-hydroxy, and 25,26-dihydroxy derivatives of brassinolide were prepared and shown to be much less active than brassinolide. This indicates that they are likely metabolic deactivation products of the parent phytohormone. A series of methyl ethers of brassinolide was synthesized to block deactivation by glucosylation of the free hydroxyl groups. The most significant finding was that the compound where three of the four hydroxyl groups (at C-3, C-22, and C-23) had been converted to methyl ethers retained substantial bioactivity. This type of modification could, in theory, allow brassinolide or 24-epibrassinolide to resist deactivation and thus offer greater persistence in field applications. A series of nonsteroidal mimetics of brassinolide was designed and synthesized. Two of the

  14. A recombinant mimetics of the HIV-1 gp41 prehairpin fusion intermediate fused with human IgG Fc fragment elicits neutralizing antibody response in the vaccinated mice

    Energy Technology Data Exchange (ETDEWEB)

    Qi, Zhi; Pan, Chungen; Lu, Hong; Shui, Yuan [Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY 10065 (United States); Li, Lin [Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY 10065 (United States); School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong 510515 (China); Li, Xiaojuan; Xu, Xueqing; Liu, Shuwen [School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong 510515 (China); Jiang, Shibo, E-mail: sjiang@nybloodcenter.org [Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY 10065 (United States); School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong 510515 (China)

    2010-07-30

    Research highlights: {yields} One recombinant mimetics of gp41 prehairpin fusion intermediate (PFI) consisting of gp41 N46 sequence, foldon and IgG Fc, designated N46FdFc, was expressed. {yields} N46FdFc-induced antibodies in mice that neutralized HIV-1 infection, inhibited PIE7 binding to PFI, blocked gp41 six-helix bundle formation, and suppressed HIV-1 mediated cell-cell fusion. {yields} These findings provide an important clue for developing recombinant gp41 PFI mimetics-based HIV vaccines. -- Abstract: HIV-1 gp41 prehairpin fusion intermediate (PFI) composed of three N-terminal heptad repeats (NHR) plays a crucial role in viral fusion and entry and represents an attractive target for anti-HIV therapeutics (e.g., enfuvirtide) and vaccines. In present study, we constructed and expressed two recombinant gp41 PFI mimetics, designated N46Fd and N46FdFc. N46Fd consists of N46 (residues 536-581) in gp41 NHR and foldon (Fd), a trimerization motif. N46FdFc is composed of N46Fd fused with human IgG Fc fragment as an immunoenhancer. We immunized mice with N46 peptide, N46Fd and N46FdFc, respectively, and found that only N46FdFc elicited neutralizing antibody response in mice against infection by HIV-1 strains IIIB (clade B, X4), 92US657 (clade B, R5), and 94UG103 (clade A, X4R5). Anti-N46FdFc antibodies inhibited PIE7 binding to PFI, blocked gp41 six-helix bundle formation, and suppressed HIV-1 mediated cell-cell fusion. These findings provide an important clue for developing recombinant gp41 PFI mimetics-based HIV vaccines.

  15. Organization of Hyaluronan and Versican in the Extracellular Matrix of Human Fibroblasts Treated With the Viral Mimetic Poly I:C

    OpenAIRE

    Evanko, Stephen P.; Potter-Perigo, Susan; Johnson, Pamela Y.; Wight, Thomas N.

    2009-01-01

    We have examined structural details of hyaluronan- and versican-rich pericellular matrices in human lung fibroblasts, as well as fixation effects after treatment with the viral mimetic, poly I:C. Lateral aggregation of hyaluronan chains was promoted by acid-ethanol-formalin fixation compared with a network appearance with formalin alone. However, hyaluronidase-sensitive cable structures were seen in live cells, suggesting that they are not a fixation artifact. With all fixatives, versican and...

  16. On the Translation of Onomatopoeia and Mimetic Words from Japanese to Chinese%小议日语拟声拟态词的汉译

    Institute of Scientific and Technical Information of China (English)

    张新

    2011-01-01

    日语具有丰富的拟声拟态词。拟声拟态词用于生动地描摹事物的声音和形态,弥补了日语形容词数量较少的缺陷,在日语中出现的频率很高,数量上也远远高于汉语的拟声词。由于这个特点,在对它们进行汉译时,就会产生无法与汉语一一对应的问题。本文以高慧勤和叶渭渠的《伊豆的舞女》的中译本为例,探讨拟声拟态词汉译的方法。%Japanese has a large number of onomatopoeia and mimetic words.These words are used to vividly describe the sounds and shapes of various things,and they makes up the defect of small amount of Japanese adjectives.The occurrence frequency of onomatopoeia and mimetic words in Japanese is very high,and the number of them is far bigger than the ones in Chinese.Therefore,it is difficult to exactly translate Japanese onomatopoeia and mimetic words to Chinese.Taking the Chinese versions of The Izu Dancer translated by Gao Huiqin and Ye Weiqu for example,this article discusses the methods of translating Japanese onomatopoeia and mimetic words into Chinese.

  17. 鞋靴仿生设计思维与方法的研究%Research on the Idea and Method of Footwear Bio-mimetic Design

    Institute of Scientific and Technical Information of China (English)

    赵坚; 赵强; 周海燕

    2013-01-01

    On the basis of research on the thought and method for footwear bio-mimetic design was carried out,the bionic footwear design process was divided into four steps which were observation,analysis,refactoring and design.Taking butterfly as prototype,the specific methods for footwear bio-mimetic design was explored from shape,pattern,texture and color,so as the application space ofbio-mimetic design thinking and method were presented.%通过对鞋靴仿生设计思维方法的研究,将鞋靴仿生设计过程分为观察、分析、重构、设计四个步骤.以蝴蝶为仿生原型,从色彩、形态、图案、肌理四方面,探讨了鞋靴仿生设计的具体方法,以期拓展鞋靴仿生设计思维和方法的应用空间.

  18. A novel BH3 mimetic efficiently induces apoptosis in melanoma cells through direct binding to anti-apoptotic Bcl-2 family proteins, including phosphorylated Mcl-1.

    Science.gov (United States)

    Liu, Yubo; Xie, Mingzhou; Song, Ting; Sheng, Hongkun; Yu, Xiaoyan; Zhang, Zhichao

    2015-03-01

    The Bcl-2 family modulates sensitivity to chemotherapy in many cancers, including melanoma, in which the RAS/BRAF/MEK/ERK pathway is constitutively activated. Mcl-1, a major anti-apoptotic protein in the Bcl-2 family, is extensively expressed in melanoma and contributes to melanoma's well-documented chemoresistance. Here, we provide the first evidence that Mcl-1 phosphorylation at T163 by ERK1/2 and JNK is associated with the resistance of melanoma cell lines to the existing BH3 mimetics gossypol, S1 and ABT-737, and a novel anti-apoptotic mechanism of phosphorylated Mcl-1 (pMcl-1) is revealed. pMcl-1 antagonized the known BH3 mimetics by sequestering pro-apoptotic proteins that were released from Bcl-2/Mcl-1. Furthermore, an anthraquinone BH3 mimetic, compound 6, was identified to be the first small molecule to that induces endogenous apoptosis in melanoma cells by directly binding Bcl-2, Mcl-1, and pMcl-1 and disrupting the heterodimers of these proteins. Although compound 6 induced upregulation of the pro-apoptotic protein Noxa, its apoptotic induction was independent of Noxa. These data reveal the promising therapeutic potential of targeting pMcl-1 to treat melanoma. Compound 6 is therefore a potent drug that targets pMcl-1 in melanoma.

  19. EPOR-Based Purification and Analysis of Erythropoietin Mimetic Peptides from Human Urine by Cys-Specific Cleavage and LC/MS/MS

    Science.gov (United States)

    Vogel, Matthias; Thomas, Andreas; Schänzer, Wilhelm; Thevis, Mario

    2015-09-01

    The development of a new class of erythropoietin mimetic agents (EMA) for treating anemic conditions has been initiated with the discovery of oligopeptides capable of dimerizing the erythropoietin (EPO) receptor and thus stimulating erythropoiesis. The most promising amino acid sequences have been mounted on various different polymeric structures or carrier molecules to obtain highly active EPO-like drugs exhibiting beneficial and desirable pharmacokinetic profiles. Concomitant with creating new therapeutic options, erythropoietin mimetic peptide (EMP)-based drug candidates represent means to artificially enhance endurance performance and necessitate coverage by sports drug testing methods. Therefore, the aim of the present study was to develop a strategy for the comprehensive detection of EMPs in doping controls, which can be used complementary to existing protocols. Three model EMPs were used to provide proof-of-concept data. Following EPO receptor-facilitated purification of target analytes from human urine, the common presence of the cysteine-flanked core structure of EMPs was exploited to generate diagnostic peptides with the aid of a nonenzymatic cleavage procedure. Sensitive detection was accomplished by targeted-SIM/data-dependent MS2 analysis. Method characterization was conducted for the EMP-based drug peginesatide concerning specificity, linearity, precision, recovery, stability, ion suppression/enhancement, and limit of detection (LOD, 0.25 ng/mL). Additionally, first data for the identification of the erythropoietin mimetic peptides EMP1 and BB68 were generated, demonstrating the multi-analyte testing capability of the presented approach.

  20. Targeted delivery of a model immunomodulator to the lymphatic system: comparison of alkyl ester versus triglyceride mimetic lipid prodrug strategies.

    Science.gov (United States)

    Han, Sifei; Quach, Tim; Hu, Luojuan; Wahab, Anisa; Charman, William N; Stella, Valentino J; Trevaskis, Natalie L; Simpson, Jamie S; Porter, Christopher J H

    2014-03-10

    A lipophilic prodrug approach has been used to promote the delivery of a model immunomodulator, mycophenolic acid (MPA), to the lymphatic system after oral administration. Lymphatic transport was employed to facilitate enhanced drug uptake into lymphocytes, as recent studies demonstrate that targeted drug delivery to lymph resident lymphocytes may enhance immunomodulatory effects. Two classes of lymph-directing prodrugs were synthesised. Alkyl chain derivatives (octyl mycophenolate, MPA-C8E; octadecyl mycophenolate, MPA-C18E; and octadecyl mycophenolamide, MPA-C18AM), to promote passive partitioning into lipids in lymphatic transport pathways, and a triglyceride mimetic prodrug (1,3-dipalmitoyl-2-mycophenoloyl glycerol, 2-MPA-TG) to facilitate metabolic integration into triglyceride deacylation-reacylation pathways. Lymphatic transport, lymphocyte uptake and plasma pharmacokinetics were assessed in mesenteric lymph and carotid artery cannulated rats following intraduodenal infusion of lipid-based formulations containing MPA or MPA prodrugs. Patterns of prodrug hydrolysis in rat digestive fluid, and cellular re-esterification in vivo, were evaluated to examine the mechanisms responsible for lymphatic transport. Poor enzyme stability and low absorption appeared to limit lymphatic transport of the alkyl derivatives, although two of the three alkyl chain prodrugs - MPA-C18AM (6-fold) and MPA-C18E (13-fold) still increased lymphatic drug transport when compared to MPA. In contrast, 2-MPA-TG markedly increased lymphatic drug transport (80-fold) and drug concentrations in lymphocytes (103-fold), and this was achieved via biochemical incorporation into triglyceride deacylation-reacylation pathways. The prodrug was hydrolysed rapidly to 2-mycophenoloyl glycerol (2-MPA-MG) in the presence of rat digestive fluid, and 2-MPA-MG was subsequently re-esterified in the enterocyte with oleic acid (most likely originating from the co-administered formulation) prior to accessing the

  1. Targeted delivery of a model immunomodulator to the lymphatic system: comparison of alkyl ester versus triglyceride mimetic lipid prodrug strategies.

    Science.gov (United States)

    Han, Sifei; Quach, Tim; Hu, Luojuan; Wahab, Anisa; Charman, William N; Stella, Valentino J; Trevaskis, Natalie L; Simpson, Jamie S; Porter, Christopher J H

    2014-03-10

    A lipophilic prodrug approach has been used to promote the delivery of a model immunomodulator, mycophenolic acid (MPA), to the lymphatic system after oral administration. Lymphatic transport was employed to facilitate enhanced drug uptake into lymphocytes, as recent studies demonstrate that targeted drug delivery to lymph resident lymphocytes may enhance immunomodulatory effects. Two classes of lymph-directing prodrugs were synthesised. Alkyl chain derivatives (octyl mycophenolate, MPA-C8E; octadecyl mycophenolate, MPA-C18E; and octadecyl mycophenolamide, MPA-C18AM), to promote passive partitioning into lipids in lymphatic transport pathways, and a triglyceride mimetic prodrug (1,3-dipalmitoyl-2-mycophenoloyl glycerol, 2-MPA-TG) to facilitate metabolic integration into triglyceride deacylation-reacylation pathways. Lymphatic transport, lymphocyte uptake and plasma pharmacokinetics were assessed in mesenteric lymph and carotid artery cannulated rats following intraduodenal infusion of lipid-based formulations containing MPA or MPA prodrugs. Patterns of prodrug hydrolysis in rat digestive fluid, and cellular re-esterification in vivo, were evaluated to examine the mechanisms responsible for lymphatic transport. Poor enzyme stability and low absorption appeared to limit lymphatic transport of the alkyl derivatives, although two of the three alkyl chain prodrugs - MPA-C18AM (6-fold) and MPA-C18E (13-fold) still increased lymphatic drug transport when compared to MPA. In contrast, 2-MPA-TG markedly increased lymphatic drug transport (80-fold) and drug concentrations in lymphocytes (103-fold), and this was achieved via biochemical incorporation into triglyceride deacylation-reacylation pathways. The prodrug was hydrolysed rapidly to 2-mycophenoloyl glycerol (2-MPA-MG) in the presence of rat digestive fluid, and 2-MPA-MG was subsequently re-esterified in the enterocyte with oleic acid (most likely originating from the co-administered formulation) prior to accessing the

  2. Radiation Therapy

    Science.gov (United States)

    ... therapy. At this time, you will have a physical exam , talk about your medical history , and maybe have imaging tests . Your doctor or nurse will discuss external beam radiation therapy, its benefits and side effects, and ways you can care ...

  3. Therapy Services.

    Science.gov (United States)

    Austin Independent School District, TX.

    Reviewed are the goals and activities of the therapy services in the Austin Early Childhood Special Education Program. Specific sections detail activities for speech therapy (such as diagnostic assessment, habilitation, consultation, and reporting procedures), occupational therapy (including identification and assessment, and services to children,…

  4. Furoxans (1,2,5-Oxadiazole-N-Oxides) as Novel NO Mimetic Neuroprotective and Procognitive Agents

    Energy Technology Data Exchange (ETDEWEB)

    Schiefer, Isaac T.; VandeVrede, Lawren; Fa; , Mauro; Arancio, Ottavio; Thatcher, Gregory R.J. (Columbia); (UIC)

    2012-08-31

    Furoxans (1,2,5-oxadiazole-N-oxides) are thiol-bioactivated NO-mimetics that have not hitherto been studied in the CNS. Incorporation of varied substituents adjacent to the furoxan ring system led to modulation of reactivity toward bioactivation, studied by HPLC-MS/MS analysis of reaction products. Attenuated reactivity unmasked the cytoprotective actions of NO in contrast to the cytotoxic actions of higher NO fluxes reported previously for furoxans. Neuroprotection was observed in primary neuronal cell cultures following oxygen glucose deprivation (OGD). Neuroprotective activity was observed to correlate with thiol-dependent bioactivation to produce NO{sub 2}{sup -}, but not with depletion of free thiol itself. Neuroprotection was abrogated upon cotreatment with a sGC inhibitor, ODQ, thus supporting activation of the NO/sGC/CREB signaling cascade by furoxans. Long-term potentiation (LTP), essential for learning and memory, has been shown to be potentiated by NO signaling, therefore, a peptidomimetic furoxan was tested in hippocampal slices treated with oligomeric amyloid-{beta} peptide (A{beta}) and was shown to restore synaptic function. The novel observation of furoxan activity of potential therapeutic use in the CNS warrants further studies.

  5. Effect of Resveratrol as Caloric Restriction Mimetic and Environmental Enrichment on Neurobehavioural Responses in Young Healthy Mice

    Directory of Open Access Journals (Sweden)

    Mustapha Shehu Muhammad

    2014-01-01

    Full Text Available Caloric restriction and environmental enrichment have been separately reported to possess health benefits such as improvement in motor and cognitive functions. Resveratrol, a natural polyphenolic compound, has been reported to be caloric restriction mimetic. This study therefore aims to investigate the potential benefit of the combination of resveratrol as CR and EE on learning and memory, motor coordination, and motor endurance in young healthy mice. Fifty mice of both sexes were randomly divided into five groups of 10 animals each: group I animals received carboxymethylcellulose (CMC orally per kg/day (control, group II animals were maintained on every other day feeding, group III animals received resveratrol 50 mg/kg, suspended in 10 g/L of (CMC orally per kg/day, group IV animals received CMC and were kept in an enriched environment, and group V animals received resveratrol 50 mg/kg and were kept in EE. The treatment lasted for four weeks. On days 26, 27, and 28 of the study period, the animals were subjected to neurobehavioural evaluation. The results obtained showed that there was no significant change (P>0.05 in neurobehavioural responses in all the groups when compared to the control which indicates that 50 mg/kg of resveratrol administration and EE have no significant effects on neurobehavioural responses in young healthy mice over a period of four weeks.

  6. Ochre Bathing of the Bearded Vulture: A Bio-Mimetic Model for Early Humans towards Smell Prevention and Health

    Directory of Open Access Journals (Sweden)

    Helmut Tributsch

    2016-01-01

    Full Text Available Since primordial times, vultures have been competing with man for animal carcasses. One of these vultures, the once widespread bearded vulture ( Gypaetus barbatus , has the habit of bathing its polluted feathers and skin in red iron oxide - ochre - tainted water puddles. Why? Primitive man may have tried to find out and may have discovered its advantages. Red ochre, which has accompanied human rituals and everyday life for more than 100,000 years, is not just a simple red paint for decoration or a symbol for blood. As modern experiments demonstrate, it is active in sunlight producing aggressive chemical species. They can kill viruses and bacteria and convert smelly organic substances into volatile neutral carbon dioxide gas. In this way, ochre can in sunlight sterilize and clean the skin to provide health and comfort and make it scentless, a definitive advantage for nomadic meat hunters. This research thus also demonstrates a sanitary reason for the vulture’s habit of bathing in red ochre mud. Prehistoric people have therefore included ochre use into their rituals, especially into those in relation to birth and death. Significant ritual impulses during evolution of man may thus have developed bio-mimetically, inspired from the habits of a vulture. It is discussed how this health strategy could be developed to a modern standard helping to fight antibiotics-resistant bacteria in hospitals.

  7. Sera from children with autism induce autistic features which can be rescued with a CNTF small peptide mimetic in rats.

    Directory of Open Access Journals (Sweden)

    Syed Faraz Kazim

    Full Text Available Autism is a neurodevelopmental disorder characterized clinically by impairments in social interaction and verbal and non-verbal communication skills as well as restricted interests and repetitive behavior. It has been hypothesized that altered brain environment including an imbalance in neurotrophic support during early development contributes to the pathophysiology of autism. Here we report that sera from children with autism which exhibited abnormal levels of various neurotrophic factors induced cell death and oxidative stress in mouse primary cultured cortical neurons. The effects of sera from autistic children were rescued by pre-treatment with a ciliary neurotrophic factor (CNTF small peptide mimetic, Peptide 6 (P6, which was previously shown to exert its neuroprotective effect by modulating CNTF/JAK/STAT pathway and LIF signaling and by enhancing brain derived neurotrophic factor (BDNF expression. Similar neurotoxic effects and neuroinflammation were observed in young Wistar rats injected intracerebroventricularly with autism sera within hours after birth. The autism sera injected rats demonstrated developmental delay and deficits in social communication, interaction, and novelty. Both the neurobiological changes and the behavioral autistic phenotype were ameliorated by P6 treatment. These findings implicate the involvement of neurotrophic imbalance during early brain development in the pathophysiology of autism and a proof of principle of P6 as a potential therapeutic strategy for autism.

  8. Nanoscopic substructures of raft-mimetic liquid-ordered membrane domains revealed by high-speed single-particle tracking.

    Science.gov (United States)

    Wu, Hsiao-Mei; Lin, Ying-Hsiu; Yen, Tzu-Chi; Hsieh, Chia-Lung

    2016-01-01

    Lipid rafts are membrane nanodomains that facilitate important cell functions. Despite recent advances in identifying the biological significance of rafts, nature and regulation mechanism of rafts are largely unknown due to the difficulty of resolving dynamic molecular interaction of rafts at the nanoscale. Here, we investigate organization and single-molecule dynamics of rafts by monitoring lateral diffusion of single molecules in raft-containing reconstituted membranes supported on mica substrates. Using high-speed interferometric scattering (iSCAT) optical microscopy and small gold nanoparticles as labels, motion of single lipids is recorded via single-particle tracking (SPT) with nanometer spatial precision and microsecond temporal resolution. Processes of single molecules partitioning into and escaping from the raft-mimetic liquid-ordered (Lo) domains are directly visualized in a continuous manner with unprecedented clarity. Importantly, we observe subdiffusion of saturated lipids in the Lo domain in microsecond timescale, indicating the nanoscopic heterogeneous molecular arrangement of the Lo domain. Further analysis of the diffusion trajectory shows the presence of nano-subdomains of the Lo phase, as small as 10 nm, which transiently trap the lipids. Our results provide the first experimental evidence of non-uniform molecular organization of the Lo phase, giving a new view of how rafts recruit and confine molecules in cell membranes. PMID:26861908

  9. Nanoscopic substructures of raft-mimetic liquid-ordered membrane domains revealed by high-speed single-particle tracking

    Science.gov (United States)

    Wu, Hsiao-Mei; Lin, Ying-Hsiu; Yen, Tzu-Chi; Hsieh, Chia-Lung

    2016-02-01

    Lipid rafts are membrane nanodomains that facilitate important cell functions. Despite recent advances in identifying the biological significance of rafts, nature and regulation mechanism of rafts are largely unknown due to the difficulty of resolving dynamic molecular interaction of rafts at the nanoscale. Here, we investigate organization and single-molecule dynamics of rafts by monitoring lateral diffusion of single molecules in raft-containing reconstituted membranes supported on mica substrates. Using high-speed interferometric scattering (iSCAT) optical microscopy and small gold nanoparticles as labels, motion of single lipids is recorded via single-particle tracking (SPT) with nanometer spatial precision and microsecond temporal resolution. Processes of single molecules partitioning into and escaping from the raft-mimetic liquid-ordered (Lo) domains are directly visualized in a continuous manner with unprecedented clarity. Importantly, we observe subdiffusion of saturated lipids in the Lo domain in microsecond timescale, indicating the nanoscopic heterogeneous molecular arrangement of the Lo domain. Further analysis of the diffusion trajectory shows the presence of nano-subdomains of the Lo phase, as small as 10 nm, which transiently trap the lipids. Our results provide the first experimental evidence of non-uniform molecular organization of the Lo phase, giving a new view of how rafts recruit and confine molecules in cell membranes.

  10. Functional characterization of solute carrier (SLC) 26/sulfate permease (SulP) proteins in membrane mimetic systems.

    Science.gov (United States)

    Srinivasan, Lakshmi; Baars, Tonie Luise; Fendler, Klaus; Michel, Hartmut

    2016-04-01

    Solute carrier (SLC) 26 or sulfate permease (SulP) anion transporters, belong to a phylogenetically ancient family of secondary active transporters. Members of the family are involved in several human genetic diseases and cell physiological processes. Despite their importance, the substrates for transport by this family of proteins have been poorly characterized. In this study, recombinant StmYchM/DauA, a SulP from Salmonella typhimurium was purified to homogeneity and functionally characterized. StmYchM/DauA was found to be a dimer in solution as determined by size exclusion chromatography coupled to multiple angle light scattering. We report a functional characterization of the SulP proteins in two membrane mimetic systems and reveal a dual nature of anionic substrates for SulP. StmYchM/DauA functionally incorporated into nanodiscs could bind fumarate with millimolar affinities (KD = 4.6 ± 0.29 mM) as detected by intrinsic tryptophan fluorescence quench studies. In contrast, electrophysiological experiments performed in reconstituted liposomes indicate a strong bicarbonate transport in the presence of chloride but no detectable electrogenic fumarate transport. We hence suggest that while SulP acts as an electrogenic bicarbonate transporter, fumarate may serve as substrate under different conditions indicating multiple functions of SulP. PMID:26774215

  11. Structural basis of activation-dependent binding of ligand-mimetic antibody AL-57 to integrin LFA-1

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Hongmin; Liu, Jin-huan; Yang, Wei; Springer, Timothy; Shimaoka, Motomu; Wang, Jia-huai; (CH-Boston); (DFCI)

    2010-09-21

    The activity of integrin LFA-1 ({alpha}{sub L}{beta}{sub 2}) to its ligand ICAM-1 is regulated through the conformational changes of its ligand-binding domain, the I domain of {alpha}{sub L} chain, from an inactive, low-affinity closed form (LA), to an intermediate-affinity form (IA), and then finally, to a high-affinity open form (HA). A ligand-mimetic human monoclonal antibody AL-57 (activated LFA-1 clone 57) was identified by phage display to specifically recognize the affinity-upregulated I domain. Here, we describe the crystal structures of the Fab fragment of AL-57 in complex with IA, as well as in its unligated form. We discuss the structural features conferring AL-57's strong selectivity for the high affinity, open conformation of the I domain. The AL-57-binding site overlaps the ICAM-1 binding site on the I domain. Furthermore, an antibody Asp mimics an ICAM Glu by forming a coordination to the metal-ion dependent adhesion site (MIDAS). The structure also reveals better shape complementarity and a more hydrophobic interacting interface in AL-57 binding than in ICAM-1 binding. The results explain AL-57's antagonistic mimicry of LFA-1's natural ligands, the ICAM molecules.

  12. Nanoscopic substructures of raft-mimetic liquid-ordered membrane domains revealed by high-speed single-particle tracking.

    Science.gov (United States)

    Wu, Hsiao-Mei; Lin, Ying-Hsiu; Yen, Tzu-Chi; Hsieh, Chia-Lung

    2016-01-01

    Lipid rafts are membrane nanodomains that facilitate important cell functions. Despite recent advances in identifying the biological significance of rafts, nature and regulation mechanism of rafts are largely unknown due to the difficulty of resolving dynamic molecular interaction of rafts at the nanoscale. Here, we investigate organization and single-molecule dynamics of rafts by monitoring lateral diffusion of single molecules in raft-containing reconstituted membranes supported on mica substrates. Using high-speed interferometric scattering (iSCAT) optical microscopy and small gold nanoparticles as labels, motion of single lipids is recorded via single-particle tracking (SPT) with nanometer spatial precision and microsecond temporal resolution. Processes of single molecules partitioning into and escaping from the raft-mimetic liquid-ordered (Lo) domains are directly visualized in a continuous manner with unprecedented clarity. Importantly, we observe subdiffusion of saturated lipids in the Lo domain in microsecond timescale, indicating the nanoscopic heterogeneous molecular arrangement of the Lo domain. Further analysis of the diffusion trajectory shows the presence of nano-subdomains of the Lo phase, as small as 10 nm, which transiently trap the lipids. Our results provide the first experimental evidence of non-uniform molecular organization of the Lo phase, giving a new view of how rafts recruit and confine molecules in cell membranes.

  13. Ochre Bathing of the Bearded Vulture: A Bio-Mimetic Model for Early Humans towards Smell Prevention and Health.

    Science.gov (United States)

    Tributsch, Helmut

    2016-01-01

    Since primordial times, vultures have been competing with man for animal carcasses. One of these vultures, the once widespread bearded vulture ( Gypaetus barbatus ), has the habit of bathing its polluted feathers and skin in red iron oxide - ochre - tainted water puddles. Why? Primitive man may have tried to find out and may have discovered its advantages. Red ochre, which has accompanied human rituals and everyday life for more than 100,000 years, is not just a simple red paint for decoration or a symbol for blood. As modern experiments demonstrate, it is active in sunlight producing aggressive chemical species. They can kill viruses and bacteria and convert smelly organic substances into volatile neutral carbon dioxide gas. In this way, ochre can in sunlight sterilize and clean the skin to provide health and comfort and make it scentless, a definitive advantage for nomadic meat hunters. This research thus also demonstrates a sanitary reason for the vulture's habit of bathing in red ochre mud. Prehistoric people have therefore included ochre use into their rituals, especially into those in relation to birth and death. Significant ritual impulses during evolution of man may thus have developed bio-mimetically, inspired from the habits of a vulture. It is discussed how this health strategy could be developed to a modern standard helping to fight antibiotics-resistant bacteria in hospitals. PMID:26784238

  14. Biologically and mechanically driven design of an RGD-mimetic macroporous foam for adipose tissue engineering applications.

    Science.gov (United States)

    Rossi, Eleonora; Gerges, Irini; Tocchio, Alessandro; Tamplenizza, Margherita; Aprile, Paola; Recordati, Camilla; Martello, Federico; Martin, Ivan; Milani, Paolo; Lenardi, Cristina

    2016-10-01

    Despite clinical treatments for adipose tissue defects, in particular breast tissue reconstruction, have certain grades of efficacy, many drawbacks are still affecting the long-term survival of new formed fat tissue. To overcome this problem, in the last decades, several scaffolding materials have been investigated in the field of adipose tissue engineering. However, a strategy able to recapitulate a suitable environment for adipose tissue reconstruction and maintenance is still missing. To address this need, we adopted a biologically and mechanically driven design to fabricate an RGD-mimetic poly(amidoamine) oligomer macroporous foam (OPAAF) for adipose tissue reconstruction. The scaffold was designed to fulfil three fundamental criteria: capability to induce cell adhesion and proliferation, support of in vivo vascularization and match of native tissue mechanical properties. Poly(amidoamine) oligomers were formed into soft scaffolds with hierarchical porosity through a combined free radical polymerization and foaming reaction. OPAAF is characterized by a high water uptake capacity, progressive degradation kinetics and ideal mechanical properties for adipose tissue reconstruction. OPAAF's ability to support cell adhesion, proliferation and adipogenesis was assessed in vitro using epithelial, fibroblast and endothelial cells (MDCK, 3T3L1 and HUVEC respectively). In addition, in vivo subcutaneous implantation in murine model highlighted OPAAF potential to support both adipogenesis and vessels infiltration. Overall, the reported results support the use of OPAAF as a scaffold for engineered adipose tissue construct. PMID:27428768

  15. Rational Structure-Based Rescaffolding Approach to De Novo Design of Interleukin 10 (IL-10) Receptor-1 Mimetics.

    Science.gov (United States)

    Ruiz-Gómez, Gloria; Hawkins, John C; Philipp, Jenny; Künze, Georg; Wodtke, Robert; Löser, Reik; Fahmy, Karim; Pisabarro, M Teresa

    2016-01-01

    Tackling protein interfaces with small molecules capable of modulating protein-protein interactions remains a challenge in structure-based ligand design. Particularly arduous are cases in which the epitopes involved in molecular recognition have a non-structured and discontinuous nature. Here, the basic strategy of translating continuous binding epitopes into mimetic scaffolds cannot be applied, and other innovative approaches are therefore required. We present a structure-based rational approach involving the use of a regular expression syntax inspired in the well established PROSITE to define minimal descriptors of geometric and functional constraints signifying relevant functionalities for recognition in protein interfaces of non-continuous and unstructured nature. These descriptors feed a search engine that explores the currently available three-dimensional chemical space of the Protein Data Bank (PDB) in order to identify in a straightforward manner regular architectures containing the desired functionalities, which could be used as templates to guide the rational design of small natural-like scaffolds mimicking the targeted recognition site. The application of this rescaffolding strategy to the discovery of natural scaffolds incorporating a selection of functionalities of interleukin-10 receptor-1 (IL-10R1), which are relevant for its interaction with interleukin-10 (IL-10) has resulted in the de novo design of a new class of potent IL-10 peptidomimetic ligands. PMID:27123592

  16. Rational Structure-Based Rescaffolding Approach to De Novo Design of Interleukin 10 (IL-10 Receptor-1 Mimetics.

    Directory of Open Access Journals (Sweden)

    Gloria Ruiz-Gómez

    Full Text Available Tackling protein interfaces with small molecules capable of modulating protein-protein interactions remains a challenge in structure-based ligand design. Particularly arduous are cases in which the epitopes involved in molecular recognition have a non-structured and discontinuous nature. Here, the basic strategy of translating continuous binding epitopes into mimetic scaffolds cannot be applied, and other innovative approaches are therefore required. We present a structure-based rational approach involving the use of a regular expression syntax inspired in the well established PROSITE to define minimal descriptors of geometric and functional constraints signifying relevant functionalities for recognition in protein interfaces of non-continuous and unstructured nature. These descriptors feed a search engine that explores the currently available three-dimensional chemical space of the Protein Data Bank (PDB in order to identify in a straightforward manner regular architectures containing the desired functionalities, which could be used as templates to guide the rational design of small natural-like scaffolds mimicking the targeted recognition site. The application of this rescaffolding strategy to the discovery of natural scaffolds incorporating a selection of functionalities of interleukin-10 receptor-1 (IL-10R1, which are relevant for its interaction with interleukin-10 (IL-10 has resulted in the de novo design of a new class of potent IL-10 peptidomimetic ligands.

  17. Spontaneous Packaging and Hypothermic Storage of Mammalian Cells with a Cell-Membrane-Mimetic Polymer Hydrogel in a Microchip.

    Science.gov (United States)

    Xu, Yan; Mawatari, Kazuma; Konno, Tomohiro; Kitamori, Takehiko; Ishihara, Kazuhiko

    2015-10-21

    Currently, continuous culture/passage and cryopreservation are two major, well-established methods to provide cultivated mammalian cells for experiments in laboratories. Due to the lack of flexibility, however, both laboratory-oriented methods are unable to meet the need for rapidly growing cell-based applications, which require cell supply in a variety of occasions outside of laboratories. Herein, we report spontaneous packaging and hypothermic storage of mammalian cells under refrigerated (4 °C) and ambient conditions (25 °C) using a cell-membrane-mimetic methacryloyloxyethyl phosphorylcholine (MPC) polymer hydrogel incorporated within a glass microchip. Its capability for hypothermic storage of cells was comparatively evaluated over 16 days. The results reveal that the cytocompatible MPC polymer hydrogel, in combination with the microchip structure, enabled hypothermic storage of cells with quite high viability, high intracellular esterase activity, maintained cell membrane integrity, and small morphological change for more than 1 week at 4 °C and at least 4 days at 25 °C. Furthermore, the stored cells could be released from the hydrogel and exhibited the ability to adhere to a surface and achieve confluence under standard cell culture conditions. Both hypothermic storage conditions are ordinary flexible conditions which can be easily established in places outside of laboratories. Therefore, cell packaging and storage using the hydrogel incorporated within the microchip would be a promising miniature and portable solution for flexible supply and delivery of small amounts of cells from bench to bedside.

  18. Light-switched inhibitors of protein tyrosine phosphatase PTP1B based on phosphonocarbonyl phenylalanine as photoactive phosphotyrosine mimetic.

    Science.gov (United States)

    Wagner, Stefan; Schütz, Anja; Rademann, Jörg

    2015-06-15

    Phosphopeptide mimetics containing the 4-phosphonocarbonyl phenylalanine (pcF) as a photo-active phosphotyrosine isoster are developed as potent, light-switchable inhibitors of the protein tyrosine phosphatase PTP1B. The photo-active inhibitors 6-10 are derived from phosphopeptide substrates and are prepared from the suitably protected pcF building block 12 by Fmoc-based solid phase peptide synthesis. All pcF-containing peptides are moderate inhibitors of PTP1B with KI values between 10 and 50μM. Irradiation of the inhibitors at 365nm in the presence of the protein PTP1B amplify the inhibitory activity of pcF-peptides up to 120-fold, switching the KI values of the best inhibitors to the sub-micromolar range. Photo-activation of the inhibitors results in the formation of triplet intermediates of the benzoylphosphonate moiety, which deactivate PTP1B following an oxidative radical mechanism. Deactivation of PTP1B proceeds without covalent crosslinking of the protein target with the photo-switched inhibitors and can be reverted by subsequent addition of reducing agent dithiothreitol (DTT).

  19. [Insulin therapy for type 1 diabetes mellitus: past and present].

    Science.gov (United States)

    Pires, Antonio Carlos; Chacra, Antonio Roberto

    2008-03-01

    The discovery of insulin can be considered the milestone of diabetes mellitus history and a great achievement for its treatment. The first insulin available was the regular. Afterwards, Hagedorn added the protamine to the insulin, thus, creating the NPH insulin. In the 1950s an insulin free of protamine was synthesized: the lente insulin. With the advent of molecular biology, synthetic human insulin was synthesized using recombinant DNA technology. Most recently several types of insulin analogues were available, providing the patients with better metabolic control. Type 1 diabetes mellitus treatment includes plain substitution and individualization for short-acting plus long-acting insulin according to the physician's assistance, besides regular practice of physical activities and diet orientations. In type 1 diabetes mellitus the insulin of low variability is the best choice since basal/bolus insulin therapy or continuous subcutaneous insulin infusion pump can mimetize the physiological release of insulin by beta cells. PMID:18438537

  20. Proton therapy

    International Nuclear Information System (INIS)

    Proton therapy has become a subject of considerable interest in the radiation oncology community and it is expected that there will be a substantial growth in proton treatment facilities during the next decade. I was asked to write a historical review of proton therapy based on my personal experiences, which have all occurred in the United States, so therefore I have a somewhat parochial point of view. Space requirements did not permit me to mention all of the existing proton therapy facilities or the names of all of those who have contributed to proton therapy. (review)

  1. Ionic supramolecular bonds preserve mechanical properties and enable synergetic performance at high humidity in water-borne, self-assembled nacre-mimetics

    Science.gov (United States)

    Das, Paramita; Walther, Andreas

    2013-09-01

    Although tremendous effort has been focused on enhancing the mechanical properties of nacre-mimetic materials, conservation of high stiffness and strength against hydration-induced decay of mechanical properties at high humidity remains a fundamental challenge in such water-borne high-performance materials. Herein, we demonstrate that ionic supramolecular bonds, introduced by infiltration of divalent Cu2+ ions, allow efficient stabilization of the mechanical properties of self-assembled water-borne nacre-mimetics based on sustainable sodium carboxymethylcellulose (Na+CMC) and natural sodium montmorillonite nanoclay (Na+MTM) against high humidity (95% RH). The mechanical properties in the highly hydrated state (Young's modulus up to 13.5 GPa and tensile strength up to 125 MPa) are in fact comparable to a range of non-crosslinked nacre-mimetic materials in the dry state. Moreover, the Cu2+-treated nacre-inspired materials display synergetic mechanical properties as found in a simultaneous improvement of stiffness, strength and toughness, as compared to the pristine material. Significant inelastic deformation takes place considering the highly reinforced state. This contrasts the typical behaviour of tight, covalent crosslinks and is suggested to originate from a sacrificial, dynamic breakage and rebinding of transient supramolecular ionic bonds. Considering easy access to a large range of ionic interactions and alteration of counter-ion charge via external stimuli, we foresee responsive and adaptive mechanical properties in highly reinforced and stiff bio-inspired bulk nanocomposites and in other bio-inspired materials, e.g. nanocellulose papers and peptide-based materials.Although tremendous effort has been focused on enhancing the mechanical properties of nacre-mimetic materials, conservation of high stiffness and strength against hydration-induced decay of mechanical properties at high humidity remains a fundamental challenge in such water-borne high

  2. Endurance training prevents negative effects of the hypoxia mimetic dimethyloxalylglycine on cardiac and skeletal muscle function.

    Science.gov (United States)

    Favier, Francois B; Britto, Florian A; Ponçon, Benjamin; Begue, Gwenaelle; Chabi, Beatrice; Reboul, Cyril; Meyer, Gregory; Py, Guillaume

    2016-02-15

    Hypoxic preconditioning is a promising strategy to prevent hypoxia-induced damages to several tissues. This effect is related to prior stabilization of the hypoxia-inducible factor-1α via inhibition of the prolyl-hydroxylases (PHDs), which are responsible for its degradation under normoxia. Although PHD inhibition has been shown to increase endurance performance in rodents, potential side effects of such a therapy have not been explored. Here, we investigated the effects of 1 wk of dimethyloxalylglycine (DMOG) treatment (150 mg/kg) on exercise capacity, as well as on cardiac and skeletal muscle function in sedentary and endurance-trained rats. DMOG improved maximal aerobic velocity and endurance in both sedentary and trained rats. This effect was associated with an increase in red blood cells without significant alteration of skeletal muscle contractile properties. In sedentary rats, DMOG treatment resulted in enhanced left ventricle (LV) weight together with impairment in diastolic function, LV relaxation, and pulse pressure. Moreover, DMOG decreased maximal oxygen uptake (state 3) of isolated mitochondria from skeletal muscle. Importantly, endurance training reversed the negative effects of DMOG treatment on cardiac function and restored maximal mitochondrial oxygen uptake to the level of sedentary placebo-treated rats. In conclusion, we provide here evidence that the PHD inhibitor DMOG has detrimental influence on myocardial and mitochondrial function in healthy rats. However, one may suppose that the deleterious influence of PHD inhibition would be potentiated in patients with already poor physical condition. Therefore, the present results prompt us to take into consideration the potential side effects of PHD inhibitors when administrated to patients. PMID:26679609

  3. The apolipoprotein-AI mimetic peptide L4F at a modest dose does not attenuate weight gain, inflammation, or atherosclerosis in LDLR-null mice.

    Directory of Open Access Journals (Sweden)

    Michelle M Averill

    Full Text Available High density lipoprotein (HDL cholesterol levels are inversely related to cardiovascular disease risk and associated with a reduced risk of type 2 diabetes. Apolipoprotein A-I (apoA-I; major HDL protein mimetics have been reported to reduce atherosclerosis and decrease adiposity. This study investigated the effect of L4F mimetic peptide and apoA-I overexpression on weight gain, insulin resistance, and atherosclerosis in an LDL receptor deficient (Ldlr-/- model fed a high fat high sucrose with cholesterol (HFHSC diet.Studies in differentiated 3T3-L1 adipocytes tested whether L4F could inhibit palmitate-induced adipocyte inflammation. In vivo studies used male Ldlr-/- mice fed a HFHSC diet for 12 weeks and were injected daily with L4F (100 µg/mouse subcutaneously during the last 8 weeks. Wild-type and apoA-I overexpressing Ldlr-/- mice were fed HFHSC diet for 16 weeks.Neither L4F administration nor apoA-I overexpression affected weight gain, total plasma cholesterol or triglycerides in our studies. While pre-treatment of 3T3-L1 adipocytes with either L4F or HDL abolished palmitate-induced cytokine expression in vitro, L4F treatment did not affect circulating or adipose tissue inflammatory markers in vivo. Neither L4F administration nor apoA-I overexpression affected glucose tolerance. ApoA-I overexpression significantly reduced atherosclerotic lesion size, yet L4F treatment did not affect atherosclerosis.Our results suggest that neither L4F (100 µg/day/mouse nor apoA-I overexpression affects adiposity or insulin resistance in this model. We also were unable to confirm a reduction in atherosclerosis with L4F in our particular model. Further studies on the effect of apoA-I mimetics on atherosclerosis and insulin resistance in a variety of dietary contexts are warranted.

  4. Tempol, a superoxide dismutase mimetic agent, ameliorates cisplatin-induced nephrotoxicity through alleviation of mitochondrial dysfunction in mice.

    Directory of Open Access Journals (Sweden)

    Lamiaa A Ahmed

    Full Text Available Mitochondrial dysfunction is a crucial mechanism by which cisplatin, a potent chemotherapeutic agent, causes nephrotoxicity where mitochondrial electron transport complexes are shifted mostly toward imbalanced reactive oxygen species versus energy production. In the present study, the protective role of tempol, a membrane-permeable superoxide dismutase mimetic agent, was evaluated on mitochondrial dysfunction and the subsequent damage induced by cisplatin nephrotoxicity in mice.Nephrotoxicity was assessed 72 h after a single i.p. injection of cisplatin (25 mg/kg with or without oral administration of tempol (100 mg/kg/day. Serum creatinine and urea as well as glucosuria and proteinuria were evaluated. Both kidneys were isolated for estimation of oxidative stress markers, adenosine triphosphate (ATP content and caspase-3 activity. Moreover, mitochondrial oxidative phosphorylation capacity, complexes I-IV activities and mitochondrial nitric oxide synthase (mNOS protein expression were measured along with histological examinations of renal tubular damage and mitochondrial ultrastructural changes. Tempol was effective against cisplatin-induced elevation of serum creatinine and urea as well as glucosuria and proteinuria. Moreover, pretreatment with tempol notably inhibited cisplatin-induced oxidative stress and disruption of mitochondrial function by restoring mitochondrial oxidative phosphorylation, complexes I and III activities, mNOS protein expression and ATP content. Tempol also provided significant protection against apoptosis, tubular damage and mitochondrial ultrastructural changes. Interestingly, tempol did not interfere with the cytotoxic effect of cisplatin against the growth of solid Ehrlich carcinoma.This study highlights the potential role of tempol in inhibiting cisplatin-induced nephrotoxicity without affecting its antitumor activity via amelioration of oxidative stress and mitochondrial dysfunction.

  5. Allosteric Inhibition of Factor XIIIa. Non-Saccharide Glycosaminoglycan Mimetics, but Not Glycosaminoglycans, Exhibit Promising Inhibition Profile.

    Science.gov (United States)

    Al-Horani, Rami A; Karuturi, Rajesh; Lee, Michael; Afosah, Daniel K; Desai, Umesh R

    2016-01-01

    Factor XIIIa (FXIIIa) is a transglutaminase that catalyzes the last step in the coagulation process. Orthostery is the only approach that has been exploited to design FXIIIa inhibitors. Yet, allosteric inhibition of FXIIIa is a paradigm that may offer a key advantage of controlled inhibition over orthosteric inhibition. Such an approach is likely to lead to novel FXIIIa inhibitors that do not carry bleeding risks. We reasoned that targeting a collection of basic amino acid residues distant from FXIIIa's active site by using sulfated glycosaminoglycans (GAGs) or non-saccharide GAG mimetics (NSGMs) would lead to the discovery of the first allosteric FXIIIa inhibitors. We tested a library of 22 variably sulfated GAGs and NSGMs against human FXIIIa to discover promising hits. Interestingly, although some GAGs bound to FXIIIa better than NSGMs, no GAG displayed any inhibition. An undecasulfated quercetin analog was found to inhibit FXIIIa with reasonable potency (efficacy of 98%). Michaelis-Menten kinetic studies revealed an allosteric mechanism of inhibition. Fluorescence studies confirmed close correspondence between binding affinity and inhibition potency, as expected for an allosteric process. The inhibitor was reversible and at least 9-fold- and 26-fold selective over two GAG-binding proteins factor Xa (efficacy of 71%) and thrombin, respectively, and at least 27-fold selective over a cysteine protease papain. The inhibitor also inhibited the FXIIIa-mediated polymerization of fibrin in vitro. Overall, our work presents the proof-of-principle that FXIIIa can be allosterically modulated by sulfated non-saccharide agents much smaller than GAGs, which should enable the design of selective and safe anticoagulants. PMID:27467511

  6. Chemical ultraviolet absorbers topically applied in a skin barrier mimetic formulation remain in the outer stratum corneum of porcine skin.

    Science.gov (United States)

    Haque, T; Crowther, J M; Lane, M E; Moore, D J

    2016-08-20

    The objective of the present study was to evaluate the fate of three chemical sunscreens, isoamyl p-methoxycinnamate (IPMC), diethylamino hydroxybenzoyl hexyl benzoate (DHHB), and bis-ethylhexylphenol methoxyphenyl triazine (BEMT), topically applied to mammalian skin from a skin barrier mimetic oil-in-water formulation. High Performance Liquid Chromatography (HPLC) methods were developed for the analysis of each molecule and validated. Franz cell permeation studies were conducted following application of finite doses of the formulations to excised porcine skin. A vehicle formulation containing no sunscreens was evaluated as a control. Permeation studies were conducted for 12h after which full mass balance studies were carried out. Analysis of individual UV sunscreens was achieved with HPLC following application of the formulation to the skin with no interference from the vehicle components. No skin permeation of any of the chemical sunscreens was evident after 12h. While sunscreens were detected in up to 12 tape strips taken from the SC, 87% or more of the applied doses recovered in the first 5 tape strips. When corrected for the amount of protein removed per tape strip this corresponded to a penetration depth in porcine stratum corneum of ∼1.7μm. Mass balance studies indicated total recovery values were within accepted guidelines for cosmetic formulations. Overall, only superficial penetration into the SC was observed for each compound. These findings are consistent with the physicochemical properties of the selected UV absorbing molecules and their formulation into an ordered biomimetic barrier formulation thus support their intended use in topical consumer formulations designed to protect from UV exposure. To our knowledge this is the first report of depth profiling of chemical sunscreens in the SC that combines tape stripping and protein determination following in vitro Franz cell studies. PMID:27321112

  7. Effects of transmembrane potential and pH gradient on the cytochrome c-promoted fusion of mitochondrial mimetic membranes.

    Science.gov (United States)

    Kawai, Cintia; Pessoto, Felipe S; Graves, Catharine V; Carmona-Ribeiro, Ana Maria; Nantes, Iseli L

    2013-08-01

    The present study investigated the effects of ΔΨ and ΔpH (pH gradient) on the interaction of cytochrome c with a mitochondrial mimetic membrane composed of phosphatidylcholine (PC), phosphatidylethanolamine (PE), and cardiolipin (CL) leading to vesicle fusion. ΔpH generated by lowered bulk pH (pH(out)) of PCPECL liposomes, with an internal pH (pH(in)) of 8.0, favored vesicle fusion with a titration sigmoidal profile (pK(a) ~ 6.9). Conversely, ΔpH generated by enhanced pH(in) of PCPECL at a pH(out) of 6.0 favored the fusion of vesicles with a linear profile. We did not observe a significant amount of liposome fusion when ΔpH was generated by lowered pH(in) at a pH(out) of 8.0. At bulk acidic pH, ΔΨ generated by Na⁺ gradient also favored cyt c-promoted vesicle fusion. At acidic and alkaline pH(out), the presence of ΔpH and ΔΨ did not affect cytochrome c binding affinity measured by pyrene quenching. Therefore, cytochrome c-mediated PC/PE/CL vesicle fusion is dependent of ionization of the protein site L (acidic pH) and the presence of transmembrane potential. The effect of transmembrane potential is probably related to the generation of defects on the lipid bilayer. These results are consistent with previous reports showing that cytochrome c release prior to the dissipation of the ΔΨ(M) blocks inner mitochondrial membrane fusion during apoptosis.

  8. A peptide mimetic targeting trans-homophilic NCAM binding sites promotes spatial learning and neural plasticity in the hippocampus.

    Directory of Open Access Journals (Sweden)

    Igor Kraev

    Full Text Available The key roles played by the neural cell adhesion molecule (NCAM in plasticity and cognition underscore this membrane protein as a relevant target to develop cognitive-enhancing drugs. However, NCAM is a structurally and functionally complex molecule with multiple domains engaged in a variety of actions, which raise the question as to which NCAM fragment should be targeted. Synthetic NCAM mimetic peptides that mimic NCAM sequences relevant to specific interactions allow identification of the most promising targets within NCAM. Recently, a decapeptide ligand of NCAM--plannexin, which mimics a homophilic trans-binding site in Ig2 and binds to Ig3--was developed as a tool for studying NCAM's trans-interactions. In this study, we investigated plannexin's ability to affect neural plasticity and memory formation. We found that plannexin facilitates neurite outgrowth in primary hippocampal neuronal cultures and improves spatial learning in rats, both under basal conditions and under conditions involving a deficit in a key plasticity-promoting posttranslational modification of NCAM, its polysialylation. We also found that plannexin enhances excitatory synaptic transmission in hippocampal area CA1, where it also increases the number of mushroom spines and the synaptic expression of the AMPAR subunits GluA1 and GluA2. Altogether, these findings provide compelling evidence that plannexin is an important facilitator of synaptic functional, structural and molecular plasticity in the hippocampal CA1 region, highlighting the fragment in NCAM's Ig3 module where plannexin binds as a novel target for the development of cognition-enhancing drugs.

  9. Rediscovering Chemical Gardens: Self-Assembling Cytocompatible Protein-Intercalated Silicate-Phosphate Sponge-Mimetic Tubules.

    Science.gov (United States)

    Punia, Kamia; Bucaro, Michael; Mancuso, Andrew; Cuttitta, Christina; Marsillo, Alexandra; Bykov, Alexey; L'Amoreaux, William; Raja, Krishnaswami S

    2016-08-30

    The classic chemical garden experiment is reconstructed to produce protein-intercalated silicate-phosphate tubules that resemble tubular sponges. The constructs were synthesized by seeding calcium chloride into a solution of sodium silicate-potassium phosphate and gelatin. Sponge-mimetic tubules were fabricated with varying percentages of gelatin (0-15% w/v), in diameters ranging from 200 μm to 2 mm, characterized morphologically and compositionally, functionalized with biomolecules for cell adhesion, and evaluated for cytocompatibility. Scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy analysis (EDS) experiments showed that the external surface of the tubules was relatively more amorphous in texture and carbon/protein-rich in comparison to the interior surface. Transmission electron microscopy (TEM) images indicate a network composed of gelatin incorporated into the inorganic scaffold. The presence of gelatin in the constructs was confirmed by infrared spectroscopy. Powder X-ray diffraction (XRD) was used to identify inorganic crystalline phases in the scaffolds that are mainly composed of Ca(OH)2, NaCl, and Ca2SiO4 along with a band corresponding to amorphous gelatin. Bioconjugation and coating protocols were developed to program the scaffolds with cues for cell adhesion, and the resulting constructs were employed for 3D cell culture of marine (Pyrocystis lunula) and mammalian (HeLa and H9C2) cell lines. The cytocompatibility of the constructs was demonstrated by live cell assays. We have successfully shown that these biomimetic materials can indeed support life; they serve as scaffolds that facilitate the attachment and assembly of individual cells to form multicellular entities, thereby revisiting the 350-year-old effort to link chemical gardens with the origins of life. Hybrid chemical garden biomaterials are programmable, readily fabricated and could be employed in tissue engineering, biomolecular materials development, 3D mammalian

  10. Substrate-Independent Robust and Heparin-Mimetic Hydrogel Thin Film Coating via Combined LbL Self-Assembly and Mussel-Inspired Post-Cross-linking.

    Science.gov (United States)

    Ma, Lang; Cheng, Chong; He, Chao; Nie, Chuanxiong; Deng, Jie; Sun, Shudong; Zhao, Changsheng

    2015-12-01

    In this work, we designed a robust and heparin-mimetic hydrogel thin film coating via combined layer-by-layer (LbL) self-assembly and mussel-inspired post-cross-linking. Dopamine-grafted heparin-like/-mimetic polymers (DA-g-HepLP) with abundant carboxylic and sulfonic groups were synthesized by the conjugation of adhesive molecule, DA, which exhibited substrate-independent adhesive affinity to various solid surfaces because of the formation of irreversible covalent bonds. The hydrogel thin film coated substrates were prepared by a three-step reaction: First, the substrates were coated with DA-g-HepLP to generate negatively charged surfaces. Then, multilayers were obtained via LbL coating of chitosan and the DA-g-HepLP. Finally, the noncovalent multilayers were oxidatively cross-linked by NaIO4. Surface ATR-FTIR and XPS spectra confirmed the successful fabrication of the hydrogel thin film coatings onto membrane substrates; SEM images revealed that the substrate-independent coatings owned 3D porous morphology. The soaking tests in highly alkaline, acid, and concentrated salt solutions indicated that the cross-linked hydrogel thin film coatings owned high chemical resistance. In comparison, the soaking tests in physiological solution indicated that the cross-linked hydrogel coatings owned excellent long-term stability. The live/dead cell staining and morphology observations of the adhered cells revealed that the heparin-mimetic hydrogel thin film coated substrates had low cell toxicity and high promotion ability for cell proliferation. Furthermore, systematic in vitro investigations of protein adsorption, platelet adhesion, blood clotting, and blood-related complement activation confirmed that the hydrogel film coated substrates showed excellent hemocompatibility. Both the results of inhibition zone and bactericidal activity indicated that the gentamycin sulfate loaded hydrogel thin films had significant inhibition capability toward both Escherichia coli and

  11. Reaction kinetics and targeting to cellular glutathione S-transferase of the glutathione peroxidase mimetic PhSeZnCl and its D,L-polylactide microparticle formulation.

    Science.gov (United States)

    Bartolini, D; Piroddi, M; Tidei, C; Giovagnoli, S; Pietrella, D; Manevich, Y; Tew, K D; Giustarini, D; Rossi, R; Townsend, D M; Santi, C; Galli, F

    2015-01-01

    Catalytic properties and cellular effects of the glutathione peroxidase (GPx)-mimetic compound PhSeZnCl or its d,l-lactide polymer microencapsulation form (M-PhSeZnCl) were investigated and compared with the prototypical Se-organic compounds ebselen and diselenide (PhSe)2. PhSeZnCl was confirmed to catalyze the ping-pong reaction of GPx with higher Vmax than ebselen and (PhSe)2, but the catalytic efficiency calculated for the cosubstrates glutathione (GSH) and H2O2, and particularly the high reactivity against thiols (lowest KM for GSH in the series of test molecules), suggested poor biological applicability of PhSeZnCl as a GPx mimetic. Cytotoxicity of PhSeZnCl was demonstrated in various cancer cell lines via increased reactive oxygen species (ROS) generation, depletion of intracellular thiols, and induction of apoptosis. Experiments carried out in GSH S-transferase P (GSTP)-overexpressing K562 human erythroleukemia cells and in GSTP1-1-knockout murine embryonic fibroblasts (MEFs) demonstrated that this cytosolic enzyme represents a preferential target of the redox disturbances produced by this Se-compound with a key role in controlling H2O2 generation and the perturbation of stress/survival kinase signaling. Microencapsulation was adopted as a strategy to control the thiol reactivity and oxidative stress effects of PhSeZnCl, then assessing applications alternative to anticancer. The uptake of this "depowered" GPx-mimetic formulation, which occurred through an endocytosis-like mechanism, resulted in a marked reduction of cytotoxicity. In MCF-7 cells transfected with different allelic variants of GSTP, M-PhSeZnCl lowered the burst of cellular ROS induced by the exposure to extracellular H2O2, and the extent of this effect changed between the GSTP variants. Microencapsulation is a straightforward strategy to mitigate the toxicity of thiol-reactive Se-organic drugs that enhanced the antioxidant and cellular protective effects of PhSeZnCl. A mechanistic linkage of

  12. Deceit, desire, and The Dunciad: mimetic theory and Alexander Pope – and – Birthing the canon: Eliot, Hegel, Marx and literary labour

    OpenAIRE

    Doolittle, Allan Laurence

    2008-01-01

    Essay 1: This paper analyses Alexander Pope’s depiction of apocalypse in his seminal satiric masterpiece, The Dunciad. Rene Girard’s mimetic theory explains Pope’s relationship to his literary rivals and his motivation in writing, expanding and obsessing over this work throughout the entire course of his life. This paper reads Pope’s literary and critical efforts to control the literary scene of early eighteenth-century England in a Girardian framework. Essay 2: This two-part study examines t...

  13. A mass, energy, enstrophy and vorticity conserving (MEEVC) mimetic spectral element discretization for the 2D incompressible Navier-Stokes equations

    CERN Document Server

    Palha, Artur

    2016-01-01

    In this work we present a mimetic spectral element discretization for the 2D incompressible Navier-Stokes equations that in the limit of vanishing dissipation exactly preserves mass, kinetic energy, enstrophy and total vorticity on unstructured grids. The essential ingredients to achieve this are: (i) a velocity-vorticity formulation in rotational form, (ii) a sequence of function spaces capable of exactly satisfying the divergence free nature of the velocity field, and (iii) a conserving time integrator. Proofs for the exact discrete conservation properties are presented together with numerical test cases on highly irregular grids.

  14. Hypoxia and Hypoxia Mimetics Decrease Aquaporin 5 (AQP5) Expression through Both Hypoxia Inducible Factor-1α and Proteasome-Mediated Pathways

    OpenAIRE

    Kawedia, Jitesh D.; Fan Yang; Sartor, Maureen A.; David Gozal; Maria Czyzyk-Krzeska; Menon, Anil G.

    2013-01-01

    The alveolar epithelium plays a central role in gas exchange and fluid transport, and is therefore critical for normal lung function. Since the bulk of water flux across this epithelium depends on the membrane water channel Aquaporin 5 (AQP5), we asked whether hypoxia had any effect on AQP5 expression. We show that hypoxia causes a significant (70%) decrease in AQP5 expression in the lungs of mice exposed to hypoxia. Hypoxia and the hypoxia mimetic, cobalt, also caused similar decreases in AQ...

  15. Sweat Therapy.

    Science.gov (United States)

    Colmant, Stephen A.; Merta, Rod J.

    2000-01-01

    A study combined group sweating and group counseling. Four adolescent boys with disruptive behavior disorders participated in 12 sweat therapy sessions. They reported the sessions useful for sharing personal concerns and receiving assistance with problem solving. Three boys showed improvement in self-esteem. Advantages of sweat therapy over other…

  16. Gene therapy.

    OpenAIRE

    Mota Biosca, Anna

    1992-01-01

    Applications of gene therapy have been evaluated in virtually every oral tissue, and many of these have proved successful at least in animal models. While gene therapy will not be used routinely in the next decade, practitioners of oral medicine should be aware of the potential of this novel type of treatment that doubtless will benefit many patients with oral diseases.

  17. Significant in vivo anti-inflammatory activity of Pytren4Q-Mn a superoxide dismutase 2 (SOD2 mimetic scorpiand-like Mn (II complex.

    Directory of Open Access Journals (Sweden)

    Carolina Serena

    Full Text Available The clinical use of purified SOD enzymes has strong limitations due to their large molecular size, high production cost and immunogenicity. These limitations could be compensated by using instead synthetic SOD mimetic compounds of low molecular weight.We have recently reported that two SOD mimetic compounds, the Mn(II complexes of the polyamines Pytren2Q and Pytren4Q, displayed high antioxidant activity in bacteria and yeast. Since frequently molecules with antioxidant properties or free-radical scavengers also have anti-inflammatory properties we have assessed the anti-inflammatory potential of Pytren2Q and Pytren4Q Mn(II complexes, in cultured macrophages and in a murine model of inflammation, by measuring the degree of protection they could provide against the cellular injury produced by lipopolisacharide, a bacterial endotoxin.In this report we show that the Mn(II complex of Pytren4Q but not that of Pytren2Q effectively protected human cultured THP-1 macrophages and whole mice from the inflammatory effects produced by LPS. These results obtained with two molecules that are isomers highlight the importance of gathering experimental data from animal models of disease in assessing the potential of candidate molecules.The effective anti-inflammatory activity of the Mn(II complex of Pytren4Q in addition to its low toxicity, water solubility and ease of production would suggest it is worth taking into consideration for future pharmacological studies.

  18. Morphometric comparisons of plant-mimetic juvenile fish associated with plant debris observed in the coastal subtropical waters around Kuchierabu-jima Island, southern Japan

    Science.gov (United States)

    2016-01-01

    The general morphological shape of plant-resembling fish and plant parts were compared using a geometric morphometrics approach. Three plant-mimetic fish species, Lobotes surinamensis (Lobotidae), Platax orbicularis (Ephippidae) and Canthidermis maculata (Balistidae), were compared during their early developmental stages with accompanying plant debris (i.e., leaves of several taxa) in the coastal subtropical waters around Kuchierabu-jima Island, closely facing the Kuroshio Current. The degree of similarity shared between the plant parts and co-occurring fish species was quantified, however fish remained morphologically distinct from their plant models. Such similarities were corroborated by analysis of covariance and linear discriminant analysis, in which relative body areas of fish were strongly related to plant models. Our results strengthen the paradigm that morphological clues can lead to ecological evidence to allow predictions of behavioural and habitat choice by mimetic fish, according to the degree of similarity shared with their respective models. The resemblance to plant parts detected in the three fish species may provide fitness advantages via convergent evolutionary effects. PMID:27547571

  19. A mimetic, semi-implicit, forward-in-time, finite volume shallow water model: comparison of hexagonal–icosahedral and cubed-sphere grids

    Directory of Open Access Journals (Sweden)

    J. Thuburn

    2014-05-01

    Full Text Available A new algorithm is presented for the solution of the shallow water equations on quasi-uniform spherical grids. It combines a mimetic finite volume spatial discretization with a Crank–Nicolson time discretization of fast waves and an accurate and conservative forward-in-time advection scheme for mass and potential vorticity (PV. The algorithm is implemented and tested on two families of grids: hexagonal–icosahedral Voronoi grids, and modified equiangular cubed-sphere grids. Results of a variety of tests are presented, including convergence of the discrete scalar Laplacian and Coriolis operators, advection, solid body rotation, flow over an isolated mountain, and a barotropically unstable jet. The results confirm a number of desirable properties for which the scheme was designed: exact mass conservation, very good available energy and potential enstrophy conservation, consistent mass, PV and tracer transport, and good preservation of balance including vanishing ∇ × ∇, steady geostrophic modes, and accurate PV advection. The scheme is stable for large wave Courant numbers and advective Courant numbers up to about 1. In the most idealized tests the overall accuracy of the scheme appears to be limited by the accuracy of the Coriolis and other mimetic spatial operators, particularly on the cubed-sphere grid. On the hexagonal grid there is no evidence for damaging effects of computational Rossby modes, despite attempts to force them explicitly.

  20. Identification of antiviral mimetic peptides with interferon α-2b-like activity from a random peptide library using a novel functional biopanning method

    Institute of Scientific and Technical Information of China (English)

    Qi ZHANG; Gang BAI; Jia-qi CHEN; Wang TIAN; Yu CAO; Peng-wei PAN; Chao WANG

    2008-01-01

    Aim: To screen for interferon (IFN) α-2b mimetic peptides with antiviral activity. Methods: Selecting IFN receptor-binding peptides from a phage-display heptapeptide library using a novel functional biopanning method. This method was developed to identify peptides with activity against vesicular stomatitis virus (VSV) inducing cytopathic effects on WISH cells. Results: Sixteen positive clones were obtained after 3 rounds of functional selection. Ten clones were picked from these positive clones according to the results of phage ELISA and were sequenced. The amino acid sequences homologous to IFNα-2b were defined by residues AB loop 31-37, BC loop 68-74, C helix 93-99, CD loop 106-112, D helix 115-121, DE loop 132-138, and E helix 143-161. Two of the peptides, designated clones T3 and T9, aligned with the IFNAR2-binding domains (AB loop and E helix), were synthe-sized and designated as IR-7 and KP-7, respectively. Both KP-7 and IR-7 were found to compete with GFP/IFNtα-2b for receptor binding and mimicked the antivi-ral activity of IFNα-2b cooperatively. Conclusion: Two IFNα-2b mimetic peptides with antiviral activity were derived from a phage-display heptapeptide library using a novel functional selection method.

  1. Methanol extract ofDesmodium gangeticumDC root mimetic post-conditioning effect in isolated perfused rat heart by stimulating muscarinic receptors

    Institute of Scientific and Technical Information of China (English)

    Gino A Kurian; Jose Paddikkala

    2012-01-01

    Objective:To evaluate pharmacological mimetic action of herbal extractDesmodium gangeticum (DG) roots on ischemia reperfusion injury.Methods:With the help of Langendroff perfusion technique, ischemic post condition (POC) mimetic action of DG methanol root extract was evaluated and compared by using standard drugs that acts as muscarinic receptor agonist and antagonist, namely acetylcholine (Ach) and atropine (Atr) respectively in an isolated rat heart. Results:The physiological parameters like left ventricular developed pressure, end diastolic pressure and working index of isolated rat heart showed significant recovery in DG root extract administrated rat heart, similar to the recovery by POC. Kymogram results showed muscarinic receptor agonist like action for DG methanol root extract, confirmed in rat heart by muscarnic receptor agonist (acetylcholine) and anatoginst (atropine). Administration of DG root extract prior to reperfusion showed better antioxidant status in myocardial tissue homogenate and mitochondrial, complemented by the levels of cardiac specific marker proteins in myocardial tissue and perfusate. Even though DG methanol root extract mimics its action similar to that of Ach, the myocardial protection mediated by the extract was superior to Ach, due to the presence of antioxidants in the crude extract.Conclusions: DG methanol root extract provides myocardial protection towards IRI by stimulating muscarinic receptors.

  2. Highly stable hexacoordinated nonoxidovanadium(IV) complexes of sterically constrained ligands: syntheses, structure, and study of antiproliferative and insulin mimetic activity.

    Science.gov (United States)

    Dash, Subhashree P; Pasayat, Sagarika; Bhakat, Saswati; Roy, Satabdi; Dinda, Rupam; Tiekink, Edward R T; Mukhopadhyay, Subhadip; Bhutia, Sujit K; Hardikar, Manasi R; Joshi, Bimba N; Patil, Yogesh P; Nethaji, M

    2013-12-16

    Three highly stable, hexacoordinated nonoxidovanadium(IV), V(IV)(L)2, complexes (1-3) have been isolated and structurally characterized with tridentate aroylhydrazonates containing ONO donor atoms. All the complexes are stable in the open air in the solid state as well as in solution, a phenomenon rarely observed in nonoxidovanadium(IV) complexes. The complexes have good solubility in organic solvents, permitting electrochemical and various spectroscopic investigations. The existence of nonoxidovanadium(IV) complexes was confirmed by elemental analysis, ESI mass spectroscopy, cyclic voltammetry, EPR, and magnetic susceptibility measurements. X-ray crystallography showed the N3O3 donor set to define a trigonal prismatic geometry in each case. All the complexes show in vitro insulin mimetic activity against insulin responsive L6 myoblast cells, with complex 3 being the most potent, which is comparable to insulin at the complex concentration of 4 μM, while the others have moderate insulin mimetic activity. In addition, the in vitro antiproliferative activity of complexes 1-3 against the HeLa cell line was assayed. The cytotoxicity of the complexes is affected by the various functional groups attached to the bezoylhydrazone derivative and 2 showed considerable antiproliferative activity compared to the most commonly used chemotherapeutic drugs.

  3. Physical Therapy and Occupational Therapy in Progeria

    Science.gov (United States)

    Physical Therapy and Occupational Therapy in Progeria Information for Families and Caretakers from The Progeria Research Foundation Written ... accelerated aging in children. Children with Progeria need Physical Therapy (PT) and Occupational Therapy (OT) as often as ...

  4. Oxygen Therapy

    Science.gov (United States)

    Oxygen therapy is a treatment that provides you with extra oxygen. Oxygen is a gas that your body needs to function. Normally, your lungs absorb oxygen from the air you breathe. But some conditions ...

  5. Oxygen Therapy

    Science.gov (United States)

    ... therapy works, it helps to understand how your respiratory system works. This system is a group of organs and tissues that help you breathe. The respiratory system includes the airways and lungs. The airways carry ...

  6. An easily accessible sulfated saccharide mimetic inhibits in vitro human tumor cell adhesion and angiogenesis of vascular endothelial cells

    Directory of Open Access Journals (Sweden)

    Grazia Marano

    2012-05-01

    Full Text Available Oligosaccharides aberrantly expressed on tumor cells influence processes such as cell adhesion and modulation of the cell’s microenvironment resulting in an increased malignancy. Schmidt’s imidate strategy offers an effective method to synthesize libraries of various oligosaccharide mimetics. With the aim to perturb interactions of tumor cells with extracellular matrix proteins and host cells, molecules with 3,4-bis(hydroxymethylfuran as core structure were synthesized and screened in biological assays for their abilities to interfere in cell adhesion and other steps of the metastatic cascade, such as tumor-induced angiogenesis.The most active compound, (4-{[(β-D-galactopyranosyloxy]methyl}furan-3-ylmethyl hydrogen sulfate (GSF, inhibited the activation of matrix-metalloproteinase-2 (MMP-2 as well as migration of the human melanoma cells of the lines WM-115 and WM-266-4 in a two-dimensional migration assay. GSF inhibited completely the adhesion of WM-115 cells to the extracellular matrix (ECM proteins, fibrinogen and fibronectin.In an in vitro angiogenesis assay with human endothelial cells, GSF very effectively inhibited endothelial tubule formation and sprouting of blood vessels, as well as the adhesion of endothelial cells to ECM proteins. GSF was not cytotoxic at biologically active concentrations; neither were 3,4-bis{[(β-D-galactopyranosyloxy]methyl}furan (BGF nor methyl β-D-galactopyranoside nor 3,4-bis(hydroxymethylfuran, which were used as controls, eliciting comparable biological activity. In silico modeling experiments, in which binding of GSF to the extracellular domain of the integrin αvβ3 was determined, revealed specific docking of GSF to the same binding site as the natural peptidic ligands of this integrin. The sulfate in the molecule coordinated with one manganese ion in the binding site.These studies show that this chemically easily accessible molecule GSF, synthesized in three steps from 3,4-bis

  7. An easily accessible sulfated saccharide mimetic inhibits in vitro human tumor cell adhesion and angiogenesis of vascular endothelial cells

    Science.gov (United States)

    Marano, Grazia; Gronewold, Claas; Frank, Martin; Merling, Anette; Kliem, Christian; Sauer, Sandra; Wiessler, Manfred; Frei, Eva

    2012-01-01

    Summary Oligosaccharides aberrantly expressed on tumor cells influence processes such as cell adhesion and modulation of the cell’s microenvironment resulting in an increased malignancy. Schmidt’s imidate strategy offers an effective method to synthesize libraries of various oligosaccharide mimetics. With the aim to perturb interactions of tumor cells with extracellular matrix proteins and host cells, molecules with 3,4-bis(hydroxymethyl)furan as core structure were synthesized and screened in biological assays for their abilities to interfere in cell adhesion and other steps of the metastatic cascade, such as tumor-induced angiogenesis. The most active compound, (4-{[(β-D-galactopyranosyl)oxy]methyl}furan-3-yl)methyl hydrogen sulfate (GSF), inhibited the activation of matrix-metalloproteinase-2 (MMP-2) as well as migration of the human melanoma cells of the lines WM-115 and WM-266-4 in a two-dimensional migration assay. GSF inhibited completely the adhesion of WM-115 cells to the extracellular matrix (ECM) proteins, fibrinogen and fibronectin. In an in vitro angiogenesis assay with human endothelial cells, GSF very effectively inhibited endothelial tubule formation and sprouting of blood vessels, as well as the adhesion of endothelial cells to ECM proteins. GSF was not cytotoxic at biologically active concentrations; neither were 3,4-bis{[(β-D-galactopyranosyl)oxy]methyl}furan (BGF) nor methyl β-D-galactopyranoside nor 3,4-bis(hydroxymethyl)furan, which were used as controls, eliciting comparable biological activity. In silico modeling experiments, in which binding of GSF to the extracellular domain of the integrin αvβ3 was determined, revealed specific docking of GSF to the same binding site as the natural peptidic ligands of this integrin. The sulfate in the molecule coordinated with one manganese ion in the binding site. These studies show that this chemically easily accessible molecule GSF, synthesized in three steps from 3,4-bis

  8. Maintenance Therapy in IBD

    Science.gov (United States)

    ... Help Center Home > Resources > Maintenance Therapy Go Back Maintenance Therapy Email Print + Share The term "maintenance therapy" ... are referred to as "maintenance therapies." Why is Maintenance Therapy Needed in IBD? Both Crohn's disease and ...

  9. The Role of Bcl-2 Family Proteins in Therapy Responses of Malignant Astrocytic Gliomas: Bcl2L12 and Beyond

    Directory of Open Access Journals (Sweden)

    Fotini M. Kouri

    2012-01-01

    Full Text Available Glioblastoma (GBM is a highly aggressive and lethal brain cancer with a median survival of less than two years after diagnosis. Hallmarks of GBM tumors include soaring proliferative indices, high levels of angiogenesis, diffuse invasion into normal brain parenchyma, resistance toward therapy-induced apoptosis, and pseudopallisading necrosis. Despite the recent advances in neurosurgery, radiation therapy, and the development of targeted chemotherapeutic regimes, GBM remains one of the deadliest types of cancer. Particularly, the alkylating agent temozolomide (TMZ in combination with radiation therapy prolonged patient survival only marginally, and clinical studies assessing efficacies of targeted therapies, foremost ATP mimetics inhibiting the activity of receptor tyrosine kinases (RTKs, revealed only few initial responders; tumor recurrence is nearly universal, and salvage therapies to combat such progression remain ineffective. Consequently, myriad preclinical and clinical studies began to define the molecular mechanisms underlying therapy resistance of GBM tumors, and pointed to the Bcl-2 protein family, in particular the atypical member Bcl2-Like 12 (Bcl2L12, as important regulators of therapy-induced cell death. This review will discuss the multi-faceted modi operandi of Bcl-2 family proteins, describe their roles in therapy resistance of malignant glioma, and outline current and future drug development efforts to therapeutically target Bcl-2 proteins.

  10. Family therapy

    Directory of Open Access Journals (Sweden)

    Shaikh Altamash

    2013-01-01

    Full Text Available Another major force not letting us succeed in the treatment of diabetes remains right inside the patients home, their family members. Hence, it is important to know the perception of the close family members about this simple and strong tool in diabetes, ′insulin′. The drug is nearing its century, it has not fully being accepted gracefully even in todays electronic savvy society. So, we need to strongly discover the reason for its non-acceptance, while trials are out inventing new drugs. One vital thing that can change this attitude is increasing the understanding of this drug, insulin in depth to close people around the patient, the ′family′. Underestimating family′s perception about disease and treatment for diabetes is detrimental to both diseased and the doctor. This consists of a biopsychosocial model; biological, psychological and social factors. Family forms the most important part of it. The strategies in family therapy include psychodynamic, structural, strategic, and cognitive-behavioral component. Diabetes has and will continue to rise, so will be the treatment options. From the clinicians side its to fix fasting first but from patients its fix family first. Family therapy demonstrates the importance of insulin initiation and maintenance in insulin naive patients, and continuation for others. The specific needs of such patients and their impact on family life are met with family therapy. Who needs family therapy? Benefits of family therapy and a case based approach is covered.

  11. Art Therapy

    DEFF Research Database (Denmark)

    Skov, Vibeke; Pedersen, Inge Nygaard

    2014-01-01

    Abstract Based on a Jungian approach, this article will introduce an integrative model to therapeutic change using art therapy methods as practical tools, with the aim of improving quality of life and in the prevention of depression. In a research study involving six participants, painting, clay...... work and drumming were used together with imagination and personal dialogues linked to the artwork. These art therapy processes attempted to combine the participant’s experience of inner and outer reality. The effect of gaining more knowledge about their inner reality using dreams and symbols......, was that participants gained a new understanding about their personal life. In addition, some participants were able to continue to use art therapy experiences as selfdevelopmental tools after the research study terminated. Jung’s description of the interactive relationship between the two living parts of the psyche...

  12. Delivery of platelet-derived growth factor as a chemotactic factor for mesenchymal stem cells by bone-mimetic electrospun scaffolds.

    Directory of Open Access Journals (Sweden)

    Matthew C Phipps

    Full Text Available The recruitment of mesenchymal stem cells (MSCs is a vital step in the bone healing process, and hence the functionalization of osteogenic biomaterials with chemotactic factors constitutes an important effort in the tissue engineering field. Previously we determined that bone-mimetic electrospun scaffolds composed of polycaprolactone, collagen I and nanohydroxyapatite (PCL/col/HA supported greater MSC adhesion, proliferation and activation of integrin-related signaling cascades than scaffolds composed of PCL or collagen I alone. In the current study we investigated the capacity of bone-mimetic scaffolds to serve as carriers for delivery of an MSC chemotactic factor. In initial studies, we compared MSC chemotaxis toward a variety of molecules including PDGF-AB, PDGF-BB, BMP2, and a mixture of the chemokines SDF-1α, CXCL16, MIP-1α, MIP-1β, and RANTES. Transwell migration assays indicated that, of these factors, PDGF-BB was the most effective in stimulating MSC migration. We next evaluated the capacity of PCL/col/HA scaffolds, compared with PCL scaffolds, to adsorb and release PDGF-BB. We found that significantly more PDGF- BB was adsorbed to, and subsequently released from, PCL/col/HA scaffolds, with sustained release extending over an 8-week interval. The PDGF-BB released was chemotactically active in transwell migration assays, indicating that bioactivity was not diminished by adsorption to the biomaterial. Complementing these studies, we developed a new type of migration assay in which the PDGF-BB-coated bone-mimetic substrates were placed 1.5 cm away from the cell migration front. These experiments confirmed the ability of PDGF-BB-coated PCL/col/HA scaffolds to induce significant MSC chemotaxis under more stringent conditions than standard types of migration assays. Our collective results substantiate the efficacy of PDGF-BB in stimulating MSC recruitment, and further show that the incorporation of native bone molecules, collagen I and nano

  13. Truth therapy/lie therapy.

    Science.gov (United States)

    Langs, R

    In this paper an attempt is made to conceptualize a basic dimension of various psychotherapeutic treatment modalities, especially psychoanalysis and psychoanalytically oriented psychotherapy. The central variable under consideration is the extent to which each endeavors to approach the truth within both patient and therapist as it exists dynamically in terms of their spiraling unconscious communicative interaction. That treatment modality which takes into account every possible dimension of such truths is termed truth therapy. Treatment modalities that make no attempt to arrive at these truths or that deliberately or inadvertently falsify their nature are termed lie or barrier therapies. Extensive consideration is given to truth therapy and the truth system on which it is based. The basis for the need for lie therapies is explored, and lie systems, which may arise from either patient or therapist, or both, are identified. A classification of common types of lie patients and lie therapists (and their main techniques) is offered. The implications of this delineation for our understanding of the dynamic therapies are discussed, and a number of new clinical issues arising from this perspective are addressed.

  14. What Is Music Therapy?

    Science.gov (United States)

    American Music Therapy Association Home Contact News Help/FAQ Members Only Login About Music Therapy & AMTA What is Music Therapy? Definition and Quotes ... is Music Therapy? Print Email Share What is Music Therapy What is Music Therapy? Music Therapy is the ...

  15. Pet Therapy.

    Science.gov (United States)

    Kavanagh, Kim

    1994-01-01

    This resource guide presents information on a variety of ways that animals can be used as a therapeutic modality with people having disabilities. Aspects addressed include: pet ownership and selection criteria; dogs (including service dogs, hearing/signal dogs, seeing leader dogs, and social/specialty dogs); horseriding for both therapy and fun;…

  16. Synthesis of rigid tryptophan mimetics by the diastereoselective Pictet-Spengler reaction of β³-homo-tryptophan derivatives with chiral α-amino aldehydes.

    Science.gov (United States)

    Slupska, Marta; Pulka-Ziach, Karolina; Deluga, Edyta; Sosnowski, Piotr; Wilenska, Beata; Kozminski, Wiktor; Misicka, Aleksandra

    2015-12-01

    The Pictet-Spengler (PS) cyclizations of β(3)-hTrp derivatives as arylethylamine substrates were performed with L-α-amino and D-α-amino aldehydes as carbonyl components. During the PS reaction, a new stereogenic center was created, and the mixture of cis/trans 1,3-disubstituted 1,2,3,4-tetrahydro-β-carbolines was obtained. The ratio of cis/trans diastereomers depends on the stereogenic centre of used amino aldehyde and the size of substituents. It was confirmed by 1H and 2D NMR (ROESY) spectra. The conformations of cyclic products were studied by 2D NMR ROESY spectra. Products of the PS condensation after removal of protecting group(s) can be incorporated into a peptide chain as tryptophan mimetics with the possibility of the β-turn induction. PMID:26767743

  17. A cell adhesion molecule mimetic, FGL peptide, induces alterations in synapse and dendritic spine structure in the dentate gyrus of aged rats: a three-dimensional ultrastructural study

    DEFF Research Database (Denmark)

    Popov, Victor I; Medvedev, Nikolay I; Kraev, Igor V;

    2008-01-01

    through enhancement of synaptic function. We examined the effect of FGL on synaptic and dendritic structure in the brains of aged (22-month-old) rats that were injected subcutaneously (8 mg/kg) at 2-day intervals until 19 days after the start of the experiment. Animals were perfused with fixative, brains...... structure of synapses and dendritic spines in hippocampus of aged rats, complementing data showing its effect on cognitive processes.......The FGL peptide is a neural cell adhesion molecule (NCAM) mimetic comprising a 15-amino-acid-long sequence of the FG loop region of the second fibronectin type III module of NCAM. It corresponds to the binding site of NCAM for the fibroblast growth factor receptor 1. FGL improves cognitive function...

  18. Study on the Intermediate in the o-Phenylenediamine Oxidative Reaction Using Hemoglobin as A Mimetic Peroxidase in Aqueous-Organic Two Phase

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Hemoglobin was used as a mimetic enzyme for peroxidase to catalyze the oxidative reaction ofo-phenylenediamine with H2O2 which functioned as an oxidant. The relationship between physicochemicalproperties of the intermediate and enzymatic activity of hemoglobin was studied. Since the solubility of theintermediate in the reaction is higher in butanol phase than in water phase, the intermediate itself diffusedfrom the aqueous phase to the butanol phase. The experimental results showed that the rate of product andthe stability of intermediate were associated with the temperature and the pH value of the buffer. The for-mation rate of intermediate and half-life period reveal the maximal in pH7, nevertheless, the whole rate ofthe catalytic reaction is the greatest in pH5, which the ratio of the initial rate in final product formationcompared to that intermediate formation is the greatest.

  19. Development of phosphonate modified Fe 1-x MnxFe2O4 mixed ferrite nanoparticles: novel peroxidase mimetics in enzyme linked immunosorbent assay.

    Science.gov (United States)

    Bhattacharya, Dipsikha; Baksi, Ananya; Banerjee, Indranil; Ananthakrishnan, Rajakumar; Maiti, Tapas K; Pramanik, Panchanan

    2011-10-30

    A highly facile and feasible strategy on the fabrication of advanced intrinsic peroxidase mimetics based on Mn(2+) doped mixed ferrite (Mn(II)(x)Fe(II)(1-x)Fe(III)(2)O(4)) nanoparticles was demonstrated for the quantitative and sensitive detection of mouse IgG (as a model analyte). Mn(2+) doped Fe(1-x)Mn(x)Fe(2)O(4) nanoparticles were synthesized using varying ratios of Mn(2+):Fe(2+) ions and characterized by the well known complementary techniques. The increase of Mn(2+) proportion had remarkably enhanced the peroxidase activity and magnetism. The catalytic activity of mixed ferrites was found to follow Michaelis-Menten kinetics and was noticeably higher than native Fe(3)O(4). The calculated K(m) and K(cat) exhibited strong affinity with substrates which were remarkably higher than similar sized native magnetite nanoparticles and horseradish peroxidase (HRP). These findings stimulated us to develop carboxyl modified Fe(1-x)Mn(x)Fe(2)O(4) nanoparticles using phosphonomethyl immunodiacetic acid (PMIDA) to engineer PMIDA-Fe(1-x)Mn(x)Fe(2)O(4) fabricated enzyme linked immunosorbent assay (ELISA). Results of both PMIDA-Fe(1-x)Mn(x)Fe(2)O(4) linked ELISA revealed that the enhancements in absorbance during the catalysis of enzyme substrate were linearly proportional to the concentration of mouse IgG within the range between 0.1 μg/ml and 2.5 μg/ml. Further, this detection was ten times lower than previous reports and the detection limit of mouse IgG was 0.1 μg/ml. The advantages of our fabricated artificial peroxidase mimetics are combined of low cost, easy to prepare, better stability and tunable catalytic activity. Moreover, this method provides a new horizon for the development of promising analytical tools in the application of biocatalysis, bioassays, and bioseparation.

  20. Clinical profiling of BCL-2 family members in the setting of BRAF inhibition offers a rationale for targeting de novo resistance using BH3 mimetics.

    Directory of Open Access Journals (Sweden)

    Dennie T Frederick

    Full Text Available While response rates to BRAF inhibitiors (BRAFi are high, disease progression emerges quickly. One strategy to delay the onset of resistance is to target anti-apoptotic proteins such as BCL-2, known to be associated with a poor prognosis. We analyzed BCL-2 family member expression levels of 34 samples from 17 patients collected before and 10 to 14 days after treatment initiation with either vemurafenib or dabrafenib/trametinib combination. The observed changes in mRNA and protein levels with BRAFi treatment led us to hypothesize that combining BRAFi with a BCL-2 inhibitor (the BH3-mimetic navitoclax would improve outcome. We tested this hypothesis in cell lines and in mice. Pretreatment mRNA levels of BCL-2 negatively correlated with maximal tumor regression. Early increases in mRNA levels were seen in BIM, BCL-XL, BID and BCL2-W, as were decreases in MCL-1 and BCL2A. No significant changes were observed with BCL-2. Using reverse phase protein array (RPPA, significant increases in protein levels were found in BIM and BID. No changes in mRNA or protein correlated with response. Concurrent BRAF (PLX4720 and BCL2 (navitoclax inhibition synergistically reduced viability in BRAF mutant cell lines and correlated with down-modulation of MCL-1 and BIM induction after PLX4720 treatment. In xenograft models, navitoclax enhanced the efficacy of PLX4720. The combination of a selective BRAF inhibitor with a BH3-mimetic promises to be an important therapeutic strategy capable of enhancing the clinical efficacy of BRAF inhibition in many patients that might otherwise succumb quickly to de novo resistance. Trial registrations: ClinicalTrials.gov NCT01006980; ClinicalTrials.gov NCT01107418; ClinicalTrials.gov NCT01264380; ClinicalTrials.gov NCT01248936; ClinicalTrials.gov NCT00949702; ClinicalTrials.gov NCT01072175.

  1. Fabrication highly dispersed Fe3O4 nanoparticles on carbon nanotubes and its application as a mimetic enzyme to degrade Orange II.

    Science.gov (United States)

    Deng, Jingheng; Wen, Xianghua; Li, Jiaxi

    2016-09-01

    Fe3O4 nanoparticles were grown in situ on carbon nanotubes (CNTs) by a solvothermal method. The Fe3O4/CNTs composites were characterised by the Brunauer-Emmett-Teller method and transmission electron microscopy. The results indicated that the Fe3O4 nanoparticles were uniformly deposited on CNTs, and the average diameter was approximately 7.0 nm. The Fe3O4/CNTs were applied as an enzyme mimetic to decompose Orange II, and the decomposing conditions were optimised. At 500 mg L(-1) of Fe3O4/CNTs in the presence of 15.0 mmol L(-1) of H2O2, at 30°C, it degraded 94.0% of Orange II (0.25 mmol L(-1), pH = 3.5), showing higher catalytic activity than pure Fe3O4 nanoparticles. The high activity was attributed to the uniform Fe3O4 nanoparticles growing on the side walls of the CNTs and the synergetic effect between Fe3O4 and CNTs. The Fe3O4/CNTs maintained their activity at temperatures as high as 65°C. The Fe3O4/CNTs presented high reusability and stability even after eight uses. These data proved that the Fe3O4/CNTs-catalysed degradation is a promising technique for wastewater treatment. Fe3O4 nanoparticles were grown in situ on carbon nanotubes (CNTs) by a solvothermal method. The Fe3O4/CNTs was applied as a mimetic enzyme to decompose Orange II. The Fe3O4/CNTs were collected after the reaction by applying an external magnetic field and can use repeatedly. PMID:26828855

  2. Hydrophobic amino acids in the hinge region of the 5A apolipoprotein mimetic peptide are essential for promoting cholesterol efflux by the ABCA1 transporter.

    Science.gov (United States)

    Sviridov, Denis O; Andrianov, Alexander M; Anishchenko, Ivan V; Stonik, John A; Amar, Marcelo J A; Turner, Scott; Remaley, Alan T

    2013-01-01

    The bihelical apolipoprotein mimetic peptide 5A effluxes cholesterol from cells and reduces inflammation and atherosclerosis in animal models. We investigated how hydrophobic residues in the hinge region between the two helices are important in the structure and function of this peptide. By simulated annealing analysis and molecular dynamics modeling, two hydrophobic amino acids, F-18 and W-21, in the hinge region were predicted to be relatively surface-exposed and to interact with the aqueous solvent. Using a series of 5A peptide analogs in which F-18 or W-21 was changed to either F, W, A, or E, only peptides with hydrophobic amino acids in these two positions were able to readily bind and solubilize phospholipid vesicles. Compared with active peptides containing F or W, peptides containing E in either of these two positions were more than 10-fold less effective in effluxing cholesterol by the ABCA1 transporter. Intravenous injection of 5A in C57BL/6 mice increased plasma-free cholesterol (5A: 89.9 ± 13.6 mg/dl; control: 38.7 ± 4.3 mg/dl (mean ± S.D.); P < 0.05) and triglycerides (5A: 887.0 ± 172.0 mg/dl; control: 108.9 ± 9.9 mg/dl; P < 0.05), whereas the EE peptide containing E in both positions had no effect. Finally, 5A increased cholesterol efflux approximately 2.5-fold in vivo from radiolabeled macrophages, whereas the EE peptide was inactive. These results provide a rationale for future design of therapeutic apolipoprotein mimetic peptides and provide new insights into the interaction of hydrophobic residues on apolipoproteins with phospholipids in the lipid microdomain created by the ABCA1 transporter during the cholesterol efflux process.

  3. Anecdotal therapies.

    Science.gov (United States)

    Millikan, L E

    1999-01-01

    Traditionally, many advances in medicine have been serendipitous. Are serendipitous and anecdotal synonymous? Many of our materia medica today relate to initial probes and anecdotal reports that matured to full investigation and therapeutic indications. The recent situation regarding Skin Cap is one that highlights the downside of this scenario. Several drugs in the US continue usage largely related to anecdotal indications, and anecdotal extension of legend indications is a standard for American Dermatology. The situation with systemic drugs, such as Trental, zinc preparations, imidazoles for extended indications, lysine and melatonin, all will be discussed. Topical preparations such as skin cap, cantharone, Vioform, all also are included in this category. It is important to place this topic in perspective in regards to geographic variation and therapeutic need. Many diseases lacking specific therapy are important targets for anecdotal therapy, and this will foster continued approaches in this area. The growing standardization of medicine and pharmaceutical regulation, threatens the anecdotal approach, but it provides still an important link to the future for some forms of therapy in diseases that are difficult to treat. Traditionally, the anecdote has been the first step in the therapeutic chain. Withering discovery of the benefits of the common fox glove in dropsy, was followed by many other anecdotes arriving via folk-medicine in the New World. This approach of utilizing folk medicine has now reached new heights, with very active searches by major pharmaceutical companies throughout the third world for remedies that may have potential. Couched with this is the history of anecdotal "snake-oil" remedies, that clearly had no benefit to anyone except the huckster marketing same. The excesses in this area of unproven and false therapies, led to the gradual organization of therapeutic trials and the Food and Drug Administration in the US as we know it today. The

  4. Hadron therapy

    International Nuclear Information System (INIS)

    Full text: Historically discoveries and technological advances in radiation and accelerator physics have been rapidly applied in the healing arts. X rays, discovered by Roentgen in 1895, and radioisotopes, discovered by Becquerel in 1896, were both applied to the treatment of cancer by the first year of the twentieth century. By the time that Chadwick discovered the neutron in 1932 radiotherapy was a well-established modality for the treatment of cancer. The potential use of neutrons in radiotherapy was immediately recognized by L.H. Gray (a recent Ph.D. graduate from the Cavendish laboratories in Cambridge). He built a neutron generator for radiobiology research at Mount Vernon Hospital in London, it's design was based on a similar device built at Cambridge by Mark Oliphant. In parallel with these developments Earnest Lawrence, in collaboration with his brother John Lawrence, a physician, were also studying the radiobiology of neutrons. They obtained some funding from the US National Cancer Institute to construct a 60'' cyclotron for neutron radiation therapy. These clinical trials, started in 1938, were the first application of heavy particles for cancer therapy. Immediately after the second World War advances in accelerator technology lead to the building of the first synchrocyclotrons, which produced proton beams with ranges approaching 30 cm in water. At the Harvard synchrocyclotron Robert R. Wilson realized that proton beams might have considerable advantages over other radiation beams in the treatment of deep-seated tumors. This advantage derives from the increase in stopping power at the end of the proton range, first observed by W.H.Bragg at the University of Adelaide; a phenomenon now known as the Bragg peak. Conventional X-ray beams are exponentially attenuated by matter and, hence, delivering large radiation doses to tumors at depth while not causing excessive damage to the overlying normal tissues can be problematical. The Bragg peak and the well

  5. Particle therapy

    Energy Technology Data Exchange (ETDEWEB)

    Raju, M.R.

    1993-09-01

    Particle therapy has a long history. The experimentation with particles for their therapeutic application got started soon after they were produced in the laboratory. Physicists played a major role in proposing the potential applications in radiotherapy as well as in the development of particle therapy. A brief review of the current status of particle radiotherapy with some historical perspective is presented and specific contributions made by physicists will be pointed out wherever appropriate. The rationale of using particles in cancer treatment is to reduce the treatment volume to the target volume by using precise dose distributions in three dimensions by using particles such as protons and to improve the differential effects on tumors compared to normal tissues by using high-LET radiations such as neutrons. Pions and heavy ions combine the above two characteristics.

  6. Radioiodine therapy

    International Nuclear Information System (INIS)

    For over 40 years now, radioiodine (131I) has remained one of the most useful radionuclide for diagnosis and therapy in Nuclear Medicine. The wide application of radioiodine in the study of the thyroid gland and in the management of its disorders has been most rewarding. The medical literature is replete with reports of its efficacy, failures, and complications, but most of these studies have been conducted among Caucasian persons and in relatively affluent societies. Very few reports are available from the less developed and economically depressed areas of the world where thyroid disorders abound or and are even endemic. This chapter is an attempt to highlight the use of radioactive iodine therapy in the developing countries, particularly those in the Asian region

  7. Music Therapy

    DEFF Research Database (Denmark)

    Trondalen, Gro; Bonde, Lars Ole

    2012-01-01

    Music therapy (MT) is most commonly defined as an intervention where “the therapist helps the client to promote health, using music experiences and the relationships developing through them” (Bruscia 1998). Also other definitions of MT agree that a therapeutic relationship is important for a music...... intervention to be considered MT. Other interventions that “use music for health-related goals, but in ways that do not qualify as music therapy” (Gold 2009), may be described as music medicine, or simply as music listening. In this text we elaborate on an overview chapter covering some of the different major...... music therapy orientations/models (Guided Imagery and Music, Nordoff-Robbins, Psychoanalytic, Cognitive-behavioral etc), their theoretical foundations and their practical approaches to health and wellbeing or ‘health musicking’. The relational context – the interplay of (expressive as well as receptive...

  8. Music Therapy

    DEFF Research Database (Denmark)

    Sanfi, Ilan

    2012-01-01

    may cause detrimental long-term effects. Three studies have examined the effect of music therapy procedural support (MTPS) under needle procedures. Consequently, this study aims at examining the effects of MTPS in an RCT. Moreover, the study addresses clinical aspects of the applied MT intervention...... and provides research-based clinical tools. Methods 41 children (1 to 10 years) were enrolled and underwent a single PIVA procedure. The children were randomly assigned to either an MT or a comparable control group receiving PIVA. In addition, the music therapy (MT) group received individualised MTPS (i.......e. music alternate engagement) before, during, and after PIVA. The intervention was performed by a trained music therapist and comprised preferred songs, improvised songs/music, and instrument playing. The study was carried out in accordance with the rules in force regarding research ethics and clinical MT...

  9. Proton Therapy

    Science.gov (United States)

    Oelfke, Uwe

    Proton therapy is one of the most rapidly developing new treatment technologies in radiation oncology. This treatment approach has — after roughly 40 years of technical developments — reached a mature state that allows a widespread clinical application. We therefore review the basic physical and radio-biological properties of proton beams. The main physical aspect is the elemental dose distribution arising from an infinitely narrow proton pencil beam. This includes the physics of proton stopping powers and the concept of CSDA range. Furthermore, the process of multiple Coulomb scattering is discussed for the lateral dose distribution. Next, the basic terms for the description of radio-biological properties of proton beams like LET and RBE are briefly introduced. Finally, the main concepts of modern proton dose delivery concepts are introduced before the standard method of inverse treatment planning for hadron therapy is presented.

  10. Music therapy

    DEFF Research Database (Denmark)

    Ridder, Hanne Mette Ochsner

    alternate with clear and lucid mental states. These states are important as it is here that it is possible to meet the person’s psychosocial needs. Ketil Normann’s conceps of periods of lucidity are presented and connected to clinical music therapy practice and how it is possible to use music in order...... as a consequence of person-centred care. Umeå University Medical Dissertations. New Series. Ridder, H.M. (2005). Music therapy as a way to enhance lucidity in persons with dementia in advanced stages. In: Esch, A.; Frohne-Hagemann, I.; Laqua, M.; Schirmer, H.; Seitz, E. (Eds.) Jahrbuch Musicktherapie. Forschung......Neurodegenerative diseases and dementia might be followed by symptoms of confusion. In this paper a view on dementia is presented where the person is not described as “demented” and in a permanent state of non-lucidity and confusion, but is described as a person where periods of confusion might...

  11. Antiproton therapy

    CERN Document Server

    Knudsen, Helge V; Bassler, Niels; Alsner, Jan; Beyer, Gerd-Jürgen; DeMarco, John J; Doser, Michael; Hajdukovic, Dragan; Hartley, Oliver; Iwamoto, Keisuke S; Jäkel, Oliver; Kovacevic, Sandra; Møller, Søren Pape; Overgaard, Jens; Petersen, Jørgen B; Ratib, Osman; Solberg, Timothy D; Vranjes, Sanja; Wouters, Bradly G

    2008-01-01

    Radiotherapy is one of the most important means we have for the treatment of localised tumours. It is therefore essential to optimize the technique, and a lot of effort goes into this endeavour. Since the proposal by Wilson in 1946 [R.R. Wilson, Radiology use of fast protons, Radiology 47 (1946) 487.] that proton beams might be better than photon beams at inactivating cancer cells, hadron therapy has been developed in parallel with photon therapy and a substantial knowledge has been gained on the effects of pions, protons and heavy ions (mostly carbon ions). Here we discuss the recent measurements by the CERN ACE collaboration of the biological effects of antiprotons, and argue that these particles very likely are the optimal agents for radiotherapy.

  12. Gene therapy

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    2005147 CNHK200-hA-a gene-viral therapeutic system and its antitumor effect on lung cancer. WANG Wei-guo(王伟国),et al. Viral & Gene Ther Center, Eastern Hepatobilli Surg Instit 2nd Milit Univ, Shanghai 200438. Chin J Oncol,2005:27(2):69-72. Objective: To develop a novel vector system, which combines the advantages of the gene therapy,

  13. Music Therapy: A Career in Music Therapy

    Science.gov (United States)

    About Music Therapy & Music Therapy Training M usic therapy is a healthcare profession that uses music to help individuals of all ages improve physical, ... grateful I chose a career as rewarding as music therapy. I love what I do each day!” Where ...

  14. A Placebo-Controlled Study on the Effects of the Glucagon-Like Peptide-1 Mimetic, Exenatide, on Insulin Secretion, Body Composition and Adipokines in Obese, Client-Owned Cats

    DEFF Research Database (Denmark)

    Hoelmkjaer, Kirsten M.; Albrechtsen, Nicolai J. Wewer; Holst, Jens J.;

    2016-01-01

    Glucagon-like Peptide-1 mimetics increase insulin secretion and reduces body weight in humans. In lean, healthy cats, short-term treatment has produced similar results, whereas the effect in obese cats or with extended duration of treatment is unknown. Here, prolonged (12 weeks) treatment...... with the Glucagon-like Peptide-1 mimetic, exenatide, was evaluated in 12 obese, but otherwise healthy, client-owned cats. Cats were randomized to exenatide (1.0 μg/kg) or placebo treatment twice daily for 12 weeks. The primary endpoint was changes in insulin concentration; the secondary endpoints were glucose...... by exenatide (P>0.05). Twelve weeks of exenatide was well-tolerated, with only two cases of mild, self-limiting gastrointestinal signs and a single case of mild hypoglycemia. The long-term insulinotropic effect of exenatide appeared less pronounced in obese cats compared to previous short-term studies in lean...

  15. Synergy between a collagen IV mimetic peptide and a somatotropin-domain derived peptide as angiogenesis and lymphangiogenesis inhibitors

    OpenAIRE

    Koskimaki, Jacob E.; Lee, Esak; Chen, William; Rivera, Corban G.; Rosca, Elena V.; Pandey, Niranjan B.; Popel, Aleksander S.

    2012-01-01

    Angiogenesis is central to many physiological and pathological processes. Here we show two potent bioinformatically-identified peptides, one derived from collagen IV and translationally optimized, and one from a somatotropin domain-containing protein, synergize in angiogenesis and lymphangiogenesis assays including cell adhesion, migration and in vivo Matrigel plugs. Peptide-peptide combination therapies have recently been applied to diseases such as human immunodeficiency virus (HIV), but re...

  16. Current guidelines for high-density lipoprotein cholesterol in therapy and future directions

    Science.gov (United States)

    Subedi, Bishnu H; Joshi, Parag H; Jones, Steven R; Martin, Seth S; Blaha, Michael J; Michos, Erin D

    2014-01-01

    Many studies have suggested that a significant risk factor for atherosclerotic cardiovascular disease (ASCVD) is low high-density lipoprotein cholesterol (HDL-C). Therefore, increasing HDL-C with therapeutic agents has been considered an attractive strategy. In the prestatin era, fibrates and niacin monotherapy, which cause modest increases in HDL-C, reduced ASCVD events. Since their introduction, statins have become the cornerstone of lipoprotein therapy, the benefits of which are primarily attributed to decrease in low-density lipoprotein cholesterol. Findings from several randomized trials involving niacin or cholesteryl ester transfer protein inhibitors have challenged the concept that a quantitative elevation of plasma HDL-C will uniformly translate into ASCVD benefits. Consequently, the HDL, or more correctly, HDL-C hypothesis has become more controversial. There are no clear guidelines thus far for targeting HDL-C or HDL due to lack of solid outcomes data for HDL specific therapies. HDL-C levels are only one marker of HDL out of its several structural or functional properties. Novel approaches are ongoing in developing and assessing agents that closely mimic the structure of natural HDL or replicate its various functions, for example, reverse cholesterol transport, vasodilation, anti-inflammation, or inhibition of platelet aggregation. Potential new approaches like HDL infusions, delipidated HDL, liver X receptor agonists, Apo A-I upregulators, Apo A mimetics, and gene therapy are in early phase trials. This review will outline current therapies and describe future directions for HDL therapeutics. PMID:24748800

  17. Complexes of neutralizing and non-neutralizing affinity matured Fabs with a mimetic of the internal trimeric coiled-coil of HIV-1 gp41.

    Directory of Open Access Journals (Sweden)

    Elena Gustchina

    Full Text Available A series of mini-antibodies (monovalent and bivalent Fabs targeting the conserved internal trimeric coiled-coil of the N-heptad repeat (N-HR of HIV-1 gp41 has been previously constructed and reported. Crystal structures of two closely related monovalent Fabs, one (Fab 8066 broadly neutralizing across a wide panel of HIV-1 subtype B and C viruses, and the other (Fab 8062 non-neutralizing, representing the extremes of this series, were previously solved as complexes with 5-Helix, a gp41 pre-hairpin intermediate mimetic. Binding of these Fabs to covalently stabilized chimeric trimers of N-peptides of HIV-1 gp41 (named (CCIZN363 or 3-H has now been investigated using X-ray crystallography, cryo-electron microscopy, and a variety of biophysical methods. Crystal structures of the complexes between 3-H and Fab 8066 and Fab 8062 were determined at 2.8 and 3.0 Å resolution, respectively. Although the structures of the complexes with the neutralizing Fab 8066 and its non-neutralizing counterpart Fab 8062 were generally similar, small differences between them could be correlated with the biological properties of these antibodies. The conformations of the corresponding CDRs of each antibody in the complexes with 3-H and 5-Helix are very similar. The adaptation to a different target upon complex formation is predominantly achieved by changes in the structure of the trimer of N-HR helices, as well as by adjustment of the orientation of the Fab molecule relative to the N-HR in the complex, via rigid-body movement. The structural data presented here indicate that binding of three Fabs 8062 with high affinity requires more significant changes in the structure of the N-HR trimer compared to binding of Fab 8066. A comparative analysis of the structures of Fabs complexed to different gp41 intermediate mimetics allows further evaluation of biological relevance for generation of neutralizing antibodies, as well as provides novel structural insights into immunogen

  18. The SMAC mimetic BV6 sensitizes colorectal cancer cells to ionizing radiation by interfering with DNA repair processes and enhancing apoptosis

    International Nuclear Information System (INIS)

    In the present study, we aimed to investigate the effect of counteracting inhibitor of apoptosis (IAP) proteins using the small molecule Second Mitochondria-derived Activator of Caspase (SMAC) mimetic BV6 in combination with ionizing radiation on apoptosis, cell cycle regulation, DNA double-strand break (DSB) repair, three-dimensional (3D) clonogenic survival and expression of IAPs in colorectal carcinoma cells. Colorectal cancer cell lines (HCT-15, HT-29, SW480) were subjected to BV6 treatment (0–4 μM) with or without irradiation (2–8 Gy, single dose) followed by MTT, Caspase 3/7 activity, γH2AX/53BP1 foci assays, AnnexinV staining, cell cycle analysis, 3D colony forming assays and Western blotting (cellular IAP1 (cIAP1) and cIAP2, Survivin, X-linked IAP (XIAP)). BV6 treatment decreased cell viability and significantly increased irradiation-induced apoptosis as analyzed by Caspase 3/7 activity, AnnexinV-positive and subG1 phase cells. While basal 3D clonogenic survival was decreased in a cell line-dependent manner, BV6 significantly enhanced cellular radiosensitivity of all cell lines in a concentration-dependent manner and increased the number of radiation-induced γH2AX/53BP1-positive foci. Western blot analysis revealed a markedly reduced cIAP1 expression at 4 h after BV6 treatment in all cell lines, a substantial reduction of XIAP expression in SW480 and HT-29 cells at 24 h and a slightly decreased cIAP2 expression in HCT-15 cells at 48 h after treatment. Moreover, single or double knockdown of cIAP1 and XIAP resulted in significantly increased residual γH2AX/53BP1-positive foci 24 h after 2 Gy and radiosensitization relative to control small interfering RNA (siRNA)-treated cells. The SMAC mimetic BV6 induced apoptosis and hampered DNA damage repair to radiosensitize 3D grown colorectal cancer cells. Our results demonstrate IAP targeting as a promising strategy to counteract radiation resistance of colorectal cancer cells. The online version of this

  19. Structure-based design, synthesis and validation of CD4-mimetic small molecule inhibitors of HIV-1 entry: conversion of a viral entry agonist to an antagonist.

    Science.gov (United States)

    Courter, Joel R; Madani, Navid; Sodroski, Joseph; Schön, Arne; Freire, Ernesto; Kwong, Peter D; Hendrickson, Wayne A; Chaiken, Irwin M; LaLonde, Judith M; Smith, Amos B

    2014-04-15

    This Account provides an overview of a multidisciplinary consortium focused on structure-based strategies to devise small molecule antagonists of HIV-1 entry into human T-cells, which if successful would hold considerable promise for the development of prophylactic modalities to prevent HIV transmission and thereby alter the course of the AIDS pandemic. Entry of the human immunodeficiency virus (HIV) into target T-cells entails an interaction between CD4 on the host T-cell and gp120, a component of the trimeric envelope glycoprotein spike on the virion surface. The resultant interaction initiates a series of conformational changes within the envelope spike that permits binding to a chemokine receptor, formation of the gp41 fusion complex, and cell entry. A hydrophobic cavity at the CD4-gp120 interface, defined by X-ray crystallography, provided an initial site for small molecule antagonist design. This site however has evolved to facilitate viral entry. As such, the binding of prospective small molecule inhibitors within this gp120 cavity can inadvertently trigger an allosteric entry signal. Structural characterization of the CD4-gp120 interface, which provided the foundation for small molecule structure-based inhibitor design, will be presented first. An integrated approach combining biochemical, virological, structural, computational, and synthetic studies, along with a detailed analysis of ligand binding energetics, revealed that modestly active small molecule inhibitors of HIV entry can also promote viral entry into cells lacking the CD4 receptor protein; these competitive inhibitors were termed small molecule CD4 mimetics. Related congeners were subsequently identified with both improved binding affinity and more potent viral entry inhibition. Further assessment of the affinity-enhanced small molecule CD4 mimetics demonstrated that premature initiation of conformational change within the viral envelope spike, prior to cell encounter, can lead to irreversible

  20. Radioactive Iodine (Radioiodine) Therapy

    Science.gov (United States)

    ... lymph nodes and other parts of the body. Radioactive iodine therapy improves the survival rate of patients with papillary ... and benefits of RAI therapy with your doctor. Radioactive iodine therapy cannot be used to treat anaplastic (undifferentiated) and ...

  1. External Beam Therapy (EBT)

    Science.gov (United States)

    ... Physician Resources Professions Site Index A-Z External Beam Therapy (EBT) External beam therapy (EBT) is a ... follow-up should I expect? What is external beam therapy and how is it used? External beam ...

  2. Laser therapy for cancer

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000905.htm Laser therapy for cancer To use the sharing features ... Lasers are also used on the skin. How Laser Therapy is Used Laser therapy can be used ...

  3. Occupational Therapy (For Parents)

    Science.gov (United States)

    ... Story" 5 Things to Know About Zika & Pregnancy Occupational Therapy KidsHealth > For Parents > Occupational Therapy Print A A ... for some kids. continue Kids Who Might Need Occupational Therapy According to the AOTA, kids with these medical ...

  4. American Music Therapy Association

    Science.gov (United States)

    American Music Therapy Association Home Contact News Help/FAQ Members Only Login Quick Links Facts About Music Therapy Qualifications ... with AMTA Sponsor AMTA Events Social Networking Support Music Therapy When you shop at AmazonSmile, Amazon will ...

  5. Apo A1 Mimetic Rescues the Diabetic Phenotype of HO-2 Knockout Mice via an Increase in HO-1 Adiponectin and LKBI Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Jian Cao

    2012-01-01

    Full Text Available Insulin resistance, with adipose tissue dysfunction, is one of the hallmarks of metabolic syndrome. We have reported a metabolic syndrome-like phenotype in heme oxygenase (HO-2 knockout mice, which presented with concurrent HO-1 deficiency and were amenable to rescue by an EET analog. Apo A-I mimetic peptides, such as L-4F, have been shown to induce HO-1 expression and decrease oxidative stress and adiposity. In this study we aimed to characterize alleviatory effects of HO-1 induction (if any on metabolic imbalance observed in HO-2 KO mice. In this regard, HO-2(−/− mice were injected with 2 mg/kg/day L-4F, or vehicle, i.p., for 6 weeks. As before, compared to WT animals, the HO-2 null mice were obese, displayed insulin resistance, and had elevated blood pressure. These changes were accompanied by enhanced tissue (hepatic oxidative stress along with attenuation of HO-1 expression and activity and reduced adiponectin, pAMPK, and LKB1 expression. Treatment with L-4F restored HO-1 expression and activity and increased adiponectin, LKB1, and pAMPK in the HO-2(−/− mice. These alterations resulted in a decrease in blood pressure, insulin resistance, blood glucose, and adiposity. Taken together, our results show that a deficient HO-1 response, in a state with reduced HO-2 basal levels, is accompanied by disruption of metabolic homeostasis which is successfully restored by an HO-1 inducer.

  6. Age-dependent modulation of synaptic plasticity and insulin mimetic effect of lipoic acid on a mouse model of Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Harsh Sancheti

    Full Text Available Alzheimer's disease is a progressive neurodegenerative disease that entails impairments of memory, thinking and behavior and culminates into brain atrophy. Impaired glucose uptake (accumulating into energy deficits and synaptic plasticity have been shown to be affected in the early stages of Alzheimer's disease. This study examines the ability of lipoic acid to increase brain glucose uptake and lead to improvements in synaptic plasticity on a triple transgenic mouse model of Alzheimer's disease (3xTg-AD that shows progression of pathology as a function of age; two age groups: 6 months (young and 12 months (old were used in this study. 3xTg-AD mice fed 0.23% w/v lipoic acid in drinking water for 4 weeks showed an insulin mimetic effect that consisted of increased brain glucose uptake, activation of the insulin receptor substrate and of the PI3K/Akt signaling pathway. Lipoic acid supplementation led to important changes in synaptic function as shown by increased input/output (I/O and long term potentiation (LTP (measured by electrophysiology. Lipoic acid was more effective in stimulating an insulin-like effect and reversing the impaired synaptic plasticity in the old mice, wherein the impairment of insulin signaling and synaptic plasticity was more pronounced than those in young mice.

  7. Superoxide Dismutase (SOD)-mimetic M40403 Is Protective in Cell and Fly Models of Paraquat Toxicity: IMPLICATIONS FOR PARKINSON DISEASE.

    Science.gov (United States)

    Filograna, Roberta; Godena, Vinay K; Sanchez-Martinez, Alvaro; Ferrari, Emanuele; Casella, Luigi; Beltramini, Mariano; Bubacco, Luigi; Whitworth, Alexander J; Bisaglia, Marco

    2016-04-22

    Parkinson disease is a debilitating and incurable neurodegenerative disorder affecting ∼1-2% of people over 65 years of age. Oxidative damage is considered to play a central role in the progression of Parkinson disease and strong evidence links chronic exposure to the pesticide paraquat with the incidence of the disease, most probably through the generation of oxidative damage. In this work, we demonstrated in human SH-SY5Y neuroblastoma cells the beneficial role of superoxide dismutase (SOD) enzymes against paraquat-induced toxicity, as well as the therapeutic potential of the SOD-mimetic compound M40403. Having verified the beneficial effects of superoxide dismutation in cells, we then evaluated the effects using Drosophila melanogaster as an in vivo model. Besides protecting against the oxidative damage induced by paraquat treatment, our data demonstrated that in Drosophila M40403 was able to compensate for the loss of endogenous SOD enzymes, acting both at a cytosolic and mitochondrial level. Because previous clinical trials have indicated that the M40403 molecule is well tolerated in humans, this study may have important implication for the treatment of Parkinson disease.

  8. Peptide mimetic of the S100A4 protein modulates peripheral nerve regeneration and attenuates the progression of neuropathy in myelin protein P0 null mice

    DEFF Research Database (Denmark)

    Moldovan, Mihai; Pinchenko, Volodymyr; Dmytriyeva, Oksana;

    2013-01-01

    We recently found that S100A4, a member of the multifunctional S100 protein family, protects neurons in the injured brain and identified two sequence motifs in S100A4 mediating its neurotrophic effect. Synthetic peptides encompassing these motifs stimulated neuritogenesis and survival in vitro an......, such as Charcot-Marie-Tooth type 1 disease. Moreover, our data suggest that S100A4 is a neuroprotectant in PNS and that other S100 proteins, sharing high homology in the H3 motif, may have important functions in PNS pathologies......., these effects were attributed to the modulatory effect of H3 on initial axonal sprouting. In contrast to the modest effect of H3 on the time course of regeneration, H3 had a long-term neuroprotective effect in the myelin protein P0 null mice, a model of dysmyelinating neuropathy (Charcot-Marie-Tooth type 1...... disease), where the peptide attenuated the deterioration of nerve conduction, demyelination and axonal loss. From these results, S100A4 mimetics emerge as a possible means to enhance axonal sprouting and survival, especially in the context of demyelinating neuropathies with secondary axonal loss...

  9. Three-layer microfibrous peripheral nerve guide conduit composed of elastin-laminin mimetic artificial protein and poly(L-lactic acid

    Directory of Open Access Journals (Sweden)

    Sachiro eKakinoki

    2014-07-01

    Full Text Available We developed a microfibrous poly(L-lactic acid (PLLA nerve conduit with a three-layered structure to simultaneously enhance nerve regeneration and prevent adhesion of surrounding tissue. The inner layer was composed of PLLA microfiber containing 25% elastin-laminin mimetic protein (AG73-(VPGIG30 that promotes neurite outgrowth. The thickest middle layer was constructed of pure PLLA microfibers that impart the large mechanical stremgth to the conduit. A 10% poly(ethylene glycol was added to the outer layer to prevent the adhesion with the surrounding tissue. The AG73-(VPGIG30 composisting of an elastin-like repetitive sequence (VPGIG30 and a laminin-derived sequence (RKRLQVQLSIRT: AG73 was biosynthesized using Escherichia coli. The PLLA microfibrous conduits were fabricated using an electrospinning procedure. AG73-(VPGIG30 was successfully mixed in the PLLA microfibers, and the PLLA/AG73-(VPGIG30 microfibers were stable under physiological conditions. The PLLA/AG73-(VPGIG30 microfibers enhanced adhesion and neurite outgrowth of PC12 cells. The electrospun microfibrous conduit with a three-layered structure was implanted for bridging a 2.0-cm gap in the tibial nerve of a rabbit. Two months after implantation, no adhesion of surrounding tissue was observed, and the action potential was slightly improved in the nerve conduit with the PLLA/AG73-(VPGIG30 inner layer.

  10. Hypoxia and hypoxia mimetics decrease aquaporin 5 (AQP5 expression through both hypoxia inducible factor-1α and proteasome-mediated pathways.

    Directory of Open Access Journals (Sweden)

    Jitesh D Kawedia

    Full Text Available The alveolar epithelium plays a central role in gas exchange and fluid transport, and is therefore critical for normal lung function. Since the bulk of water flux across this epithelium depends on the membrane water channel Aquaporin 5 (AQP5, we asked whether hypoxia had any effect on AQP5 expression. We show that hypoxia causes a significant (70% decrease in AQP5 expression in the lungs of mice exposed to hypoxia. Hypoxia and the hypoxia mimetic, cobalt, also caused similar decreases in AQP5 mRNA and protein expression in the mouse lung epithelial cell line MLE-12. The action of hypoxia and cobalt on AQP5 transcription was demonstrated by directly quantifying heternonuclear RNA by real-time PCR. Dominant negative mutants of Hypoxia Inducible Factor (HIF-1α and HIF-1α siRNA blocked the action of cobalt, showing that HIF-1α is a key component in this mechanism. The proteasome inhibitors, lactacystin or proteasome inhibitor-III completely abolished the effect of hypoxia and cobalt both at the protein and mRNA level indicating that the proteasome pathway is probably involved not only for the stability of HIF-1α protein, but for the stability of unidentified transcription factors that regulate AQP5 transcription. These studies reveal a potentially important physiological mechanism linking hypoxic stress and membrane water channels.

  11. Lixisenatide as add-on therapy to basal insulin

    Directory of Open Access Journals (Sweden)

    Brown DX

    2013-12-01

    Full Text Available Dominique Xavier Brown, Emma Louise Butler, Marc Evans Diabetes Department, University Hospital Llandough, Cardiff, UK Abstract: Many patients with type 2 diabetes mellitus do not achieve target glycosylated hemoglobin A1c levels despite optimally titrated basal insulin and satisfactory fasting plasma glucose levels. Current evidence suggests that HbA1c levels are dictated by both basal glucose and postprandial glucose levels. This has led to a consensus that postprandial glucose excursions contribute to poor glycemic control in these patients. Lixisenatide is a once-daily, prandial glucagon-like peptide 1 (GLP-1 receptor agonist with a four-fold affinity for the GLP-1 receptor compared with native GLP-1. Importantly, lixisenatide causes a significant delay in gastric emptying time, an important determinant of the once-daily dosing regimen. An exendin-4 mimetic with six lysine residues removed at the C-terminal, lixisenatide has pronounced postprandial glucose-lowering effects, making it a novel incretin agent for use in combination with optimally titrated basal insulin. Lixisenatide exerts profound effects on postprandial glucose through established mechanisms of glucose-dependent insulin secretion and glucagon suppression in combination with delayed gastric emptying. This review discusses the likely place that lixisenatide will occupy in clinical practice, given its profound effects on postprandial glucose and potential to reduce glycemic variability. Keywords: lixisenatide, add-on therapy, insulin, GLP-1 receptor agonist, postprandial glucose, pharmacodynamics

  12. Substrate and Substrate-Mimetic Chaperone Binding Sites in Human α-Galactosidase A Revealed by Affinity-Mass Spectrometry

    Science.gov (United States)

    Moise, Adrian; Maeser, Stefan; Rawer, Stephan; Eggers, Frederike; Murphy, Mary; Bornheim, Jeff; Przybylski, Michael

    2016-06-01

    Fabry disease (FD) is a rare metabolic disorder of a group of lysosomal storage diseases, caused by deficiency or reduced activity of the enzyme α-galactosidase. Human α-galactosidase A (hαGAL) hydrolyses the terminal α-galactosyl moiety from glycosphingolipids, predominantly globotriaosylceramide (Gb3). Enzyme deficiency leads to incomplete or blocked breakdown and progressive accumulation of Gb3, with detrimental effects on normal organ functions. FD is successfully treated by enzyme replacement therapy (ERT) with purified recombinant hαGAL. An emerging treatment strategy, pharmacologic chaperone therapy (PCT), employs small molecules that can increase and/or reconstitute the activity of lysosomal enzyme trafficking by stabilizing misfolded isoforms. One such chaperone, 1-deoxygalactonojirimycin (DGJ), is a structural galactose analogue currently validated in clinical trials. DGJ is an active-site-chaperone that binds at the same or similar location as galactose; however, the molecular determination of chaperone binding sites in lysosomal enzymes represents a considerable challenge. Here we report the identification of the galactose and DGJ binding sites in recombinant α-galactosidase through a new affinity-mass spectrometry-based approach that employs selective proteolytic digestion of the enzyme-galactose or -inhibitor complex. Binding site peptides identified by mass spectrometry, [39-49], [83-100], and [141-168], contain the essential ligand-contacting amino acids, in agreement with the known X-ray crystal structures. The inhibitory effect of DGJ on galactose recognition was directly characterized through competitive binding experiments and mass spectrometry. The methods successfully employed in this study should have high potential for the characterization of (mutated) enzyme-substrate and -chaperone interactions, and for identifying chaperones without inhibitory effects.

  13. Physical Therapy (For Parents)

    Science.gov (United States)

    ... Story" 5 Things to Know About Zika & Pregnancy Physical Therapy KidsHealth > For Parents > Physical Therapy Print A A ... Finding a Physical Therapist en español Terapia física Physical Therapy Basics Doctors often recommend physical therapy (PT) for ...

  14. Family Play Therapy.

    Science.gov (United States)

    Ariel, Shlomo

    This paper examines a case study of family play therapy in Israel. The unique contributions of play therapy are evaluated including the therapy's accessibility to young children, its richness and flexibility, its exposure of covert patterns, its wealth of therapeutic means, and its therapeutic economy. The systematization of the therapy attempts…

  15. Marriage or Family Therapy.

    Science.gov (United States)

    Haley, Jay

    1984-01-01

    Reviews the differences between family therapy and marriage counseling in terms of professional organization, theory, and practice. Suggests that training in marriage therapy does not appear adequate for family therapy. The goal of the therapy field should be more consensus in theory and a single profession of therapists. (JAC)

  16. Interaction of GABA-mimetics with the taurine transporter (TauT, Slc6a6) in hyperosmotic treated Caco-2, LLC-PK1 and rat renal SKPT cells.

    Science.gov (United States)

    Rasmussen, Rune Nørgaard; Lagunas, Candela; Plum, Jakob; Holm, René; Nielsen, Carsten Uhd

    2016-01-20

    The aim of the present study was to investigate if basic GABA-mimetics interact with the taurine transporter (TauT, Slc6a6), and to find a suitable cell based model that is robust towards extracellular changes in osmolality during uptake studies. Taurine uptake was measured in human Caco-2 cells, porcine LLC-PK1 cells, and rat SKPT cells using radiolabelled taurine. Hyperosmotic conditions were obtained by incubation with raffinose (final osmolality of 500mOsm) for 24h prior to the uptake experiments. Expression of the taurine transporter, TauT, was investigated at the mRNA level by real-time PCR. Uptake of the GABA-mimetics gaboxadol and vigabatrin was investigated in SKPT cells, and quantified by liquid scintillation or HPLC-MS/MS analysis, respectively. The uptake rate of [(3)H]-taurine was Na(+) and Cl(-) and concentration dependent with taurine with an apparent Vmax of 6.3±1.6pmolcm(-2)min(-1) and a Km of 24.9±15.0μM. β-alanine, nipecotic acid, gaboxadol, GABA, vigabatrin, δ-ALA and guvacine inhibited the taurine uptake rate in a concentration dependent manner. The order of affinity for TauT was β-alanine>GABA>nipecotic acid>guvacine>δ-ALA>vigabatrin>gaboxadol with IC50-values of 0.04, 1.07, 2.02, 4.19, 4.94, 31.4 and 39.9mM, respectively. In conclusion, GABA mimetics inhibited taurine uptake in hyperosmotic rat renal SKPT cells. SKPT cells, which seem to be a useful model for investigating taurine transport in the short-term presence of high concentrations of osmolytes. Furthermore, analogues of β-alanine appear to have higher affinities for TauT than GABA-analogues.

  17. Effect of THIP and SL 76002, two clinically experimented GABA-mimetic compounds, on anterior pituitary GABA receptors and prolactin secretion in the rat

    Energy Technology Data Exchange (ETDEWEB)

    Apud, J.A.; Masotto, C.; Racagni, G.

    1987-03-02

    In the present study, the ability of three direct GABA agonists, muscimol, THIP and SL 76002 to displace /sup 3/H-GABA binding from anterior pituitary and medio-basal hypothalamus membranes was evaluated. Further, the effect of both THIP and SL 76002 on baseline prolactin levels or after stimulation of hormone release with haloperidol has been also studied. Either muscimol, THIP or SL 76002 have shown to posses 7-, 7- and 3-fold higher affinity, respectively, for the central nervous system than for the anterior pituitary /sup 3/H-GABA binding sites. Moreover, THIP and SL 76002 have demonstrated to be respectively, 25- and 1000- fold less potent than muscimol in inhibiting /sup 3/H- GABA binding at the level of the anterior pituitary and about 25- and 2700-fold less potent at the level of the medio-basal hypothalamus. Under basal conditions, either THIP or SL 76002 were ineffective to reduce prolactin release. However, after stimulation of prolactin secretion through blockade of the dopaminergic neurotransmission with haloperidol (0.1 mg/kg), both THIP (10 mg/kg) and SL 76002 (200 mg/kg) significantly counteracted the neuroleptic-induced prolactin rise with a potency which is in line with their ability to inhibit /sup 3/H-GABA binding in the anterior pituitary. The present results indicate that both compounds inhibit prolactin release under specific experimental situations probably through a GABAergic mechanism. In view of the endocrine effects of these GABA-mimetic compounds, the possibility arises for an application of these type of drugs in clinical neuroendocrinology. 35 references, 3 figures, 2 tables.

  18. The combination of BH3-mimetic ABT-737 with the alkylating agent temozolomide induces strong synergistic killing of melanoma cells independent of p53.

    Directory of Open Access Journals (Sweden)

    Steven N Reuland

    Full Text Available Metastatic melanoma has poor prognosis and is refractory to most conventional chemotherapies. The alkylating agent temozolomide (TMZ is commonly used in treating melanoma but has a disappointing response rate. Agents that can act cooperatively with TMZ and improve its efficacy are thus highly sought after. The BH3 mimetic ABT-737, which can induce apoptosis by targeting pro-survival Bcl-2 family members, has been found to enhance the efficacy of many conventional chemotherapeutic agents in multiple cancers. We found that combining TMZ and ABT-737 induced strong synergistic apoptosis in multiple human melanoma cell lines. When the drugs were used in combination in a mouse xenograft model, they drastically reduced tumor growth at concentrations where each individual drug had no significant effect. We found that TMZ treatment elevated p53 levels, and that the pro-apoptotic protein Noxa was elevated in TMZ/ABT-737 treated cells. Experiments with shRNA demonstrated that the synergistic effect of TMZ and ABT-737 was largely dependent on Noxa. Experiments with nutlin-3, a p53 inducer, demonstrated that p53 induction was sufficient for synergistic cell death with ABT-737 in a Noxa-dependent fashion. However, p53 was not necessary for TMZ/ABT-737 synergy as demonstrated by a p53-null line, indicating that TMZ and ABT-737 together induce Noxa in a p53-independent fashion. These results demonstrate that targeting anti-apoptotic Bcl-2 members is a promising method for treating metastatic melanoma, and that clinical trials with TMZ and Bcl-2 inhibitors are warranted.

  19. Enhancing sensitivity and selectivity in a label-free colorimetric sensor for detection of iron(II) ions with luminescent molybdenum disulfide nanosheet-based peroxidase mimetics.

    Science.gov (United States)

    Wang, Yong; Hu, Jie; Zhuang, Qianfen; Ni, Yongnian

    2016-06-15

    In the present study, we demonstrated that the luminescent molybdenum disulfide (MoS2) nanosheets, which were prepared hydrothermally by using sodium molybdate and thiourea as precursors, possessed peroxidase-like activity, and could catalyze the oxidation of peroxidase substrate o-phenylenediamine (OPD) in the presence of hydrogen peroxide (H2O2) to produce a yellow color reaction. Further addition of Fe(2+) into the nanosheets led to peroxidase mimetics with greatly enhanced catalytic activity. The observation was exploited to develop a label-free colorimetric nanozyme sensor for detection of Fe(2+). The fabricated MoS2/OPD/H2O2 sensor showed a wide linear range of 0.01-0.8 µM with a detection limit of 7 nM. Moreover, it was found that the MoS2/OPD/H2O2 sensor displayed enhanced sensitivity and selectivity toward Fe(2+) compared with the OPD/H2O2 sensor, suggesting that the MoS2 nanosheets could improve the performance of the Fe(2+) sensor. An advanced chemometrics algorithm, multivariate curve resolution by alternating least squares (MCR-ALS), was further applied to interpret the origin of enhancing sensitivity and selectivity in the Fe(2+) sensor with the MoS2 nanosheets. The time-dependent UV-vis spectral data of the studied systems were collected, and submitted to the MCR-ALS. The results showed that the increased sensitivity and selectivity of the MoS2/OPD/H2O2 sensor for Fe(2+) detection likely arose from its large reaction rate constant. Finally, the proposed MoS2/OPD/H2O2 sensor was successfully applied for detection of Fe(2+) in water samples.

  20. Identification and Testing of Novel CARP-1 Functional Mimetic Compounds as Inhibitors of Non-Small Cell Lung and Triple Negative Breast Cancers

    Science.gov (United States)

    Muthu, Magesh; Somagoni, Jaganmohan; Cheriyan, Vino T.; Munie, Sara; Levi, Edi; Ashour, Abdelkader E.; Yassin, Alaa Eldeen B.; Alafeefy, Ahmed M.; Sochacki, Paula; Polin, Lisa A.; Reddy, Kaladhar B.; Larsen, Scott D.; Singh, Mandip; Rishi, Arun K.

    2016-01-01

    The triple negative breast cancer (TNBCs) and non-small cell lung cancers (NSCLCs) often acquire mutations that contribute to failure of drugs in clinic and poor prognosis, thus presenting an urgent need to develop new and improved therapeutic modalities. Here we report that CARP-1 functional mimetic (CFMs) compounds 4 and 5, and 4.6, a structurally related analog of CFM-4, are potent inhibitors of TNBC and NSCLC cells in vitro. Cell growth suppression by CFM-4 and -4.6 involved interaction and elevated expression of CARP-1/CCAR1 and Death Effector Domain (DED) containing DNA binding (DEDD)2 proteins. Apoptosis by these compounds also involved activation of pro-apoptotic stress-activated kinases p38 and JNK1/2, cleavage of PARP and loss of mitotic cyclin B1. Both the CFMs inhibited abilities of NSCLC and TNBC cells to migrate, invade, and form colonies in suspension, while disrupting tubule formation by the human umbilical vein endothelial cells (HUVECs). Nano-lipid formulation of CFM-4 (CFM-4 NLF) enhanced its serum bioavailability when compared with the free CFM-4. Oral administration of CFM-4 NLF reduced weights and volume of the xenografted tumors derived from A549 NSCLC and MDA-MB-231 TNBC cells. Although no gross tissue or histological toxicities were noticed, the immuno-histochemical analysis revealed increased CARP-1 and DNA fragmentation in tumors of the CFM-4 NLF-treated animals. In conclusion, while stimulation of pro-apoptotic CARP-1 and DEDD2 expression and their binding underscore a novel mechanism of apoptosis transduction by CFM compounds, our proof-of-concept xenograft studies demonstrate therapeutic potential of CFM-4 for TNBC and NSCLC. PMID:26485930

  1. Synergetic catalysis based on the proline tailed metalloporphyrin with graphene sheet as efficient mimetic enzyme for ultrasensitive electrochemical detection of dopamine.

    Science.gov (United States)

    Yan, Xiaoyi; Gu, Yue; Li, Cong; Tang, Liu; Zheng, Bo; Li, Yaru; Zhang, Zhiquan; Yang, Ming

    2016-03-15

    In this paper, linking with the butoxycarbonyl (BOC) protection of proline, a new tailed metalloporphyrin with many useful active functions, nickel (II) 5-[4-N-(tert-Butoxycarbonyl)-l-prolinecoxylpropyloxy]phenyl-10,15,20-triphenylporphyrin (NiTBLPyP), was designed and synthesized. And the NiTBLPyP polymer (poly(NiTBLPyP)) was successfully obtained via a low-cost electrochemical method and exploited as an efficient mimic enzyme. Subsequently, a noncovalent nanohybrid of poly(NiTBLPyP) with graphene (rGO) sheet (rGO-poly(NiTBLPyP)) was prepared through π-π stacking interaction for the ultrasensitive and selective detection of DA. The nanohybrid was characterized by UV-vis spectroscopy, Fourier transform infrared spectra, Raman spectroscopy, scanning electron microscopy and electrochemical impedance spectroscopy. Due to the excellent electrocatalytic ability of poly(NiTBLPyP) film and aromatic π-π stacking interaction between poly(NiTBLPyP and rGO sheet, the obtained rGO-poly(NiTBLPyP) film exhibited a great synergistic amplification effect toward dopamine oxidation. Under optimum experimental conditions, the logarithm of catalytic currents showed a good linear relationship with that of the dopamine concentration in the range of 0.01-200 μM with a low detection limit of 1.40 nM. With good sensitivity and selectivity, the present method was applied to the determination of DA in real sample and the results was satisfactory. Thus, the rGO-poly(NiTBLPyP) film is one of the promising mimetic enzyme for electrocatalysis and relevant fields. PMID:26556183

  2. Selective anti-platelet aggregation synergism between a prostacyclin-mimetic, RS93427 and the nitrodilators sodium nitroprusside and glyceryl trinitrate.

    Science.gov (United States)

    Willis, A L; Smith, D L; Loveday, M; Fulks, J; Lee, C H; Hedley, L; VanAntwerp, D

    1989-12-01

    1. Citrated platelet-rich plasma from human donors was used to examine turbidometrically the platelet aggregation response to collagen (2.5 micrograms ml-1) and ADP (1.6 microgram ml-1). 2. With collagen as an aggregating agent, the limited (35% maximal inhibition) inhibitory effects of glyceryl trinitrate (GTN, 0.78-50 micrograms ml-1) were markedly potentiated by threshold (3.3-10 ng ml-1) concentrations of RS93427, an orally active prostacyclin-mimetic. Almost complete inhibition of aggregation could then be produced. 3. A threshold concentration of RS93427 (3.3 ng ml-1) similarly potentiated the ability of sodium nitroprusside (NaNp, 0.78-10 micrograms ml-1) to inhibit collagen-induced platelet aggregation. There was an 8 fold reduction in the IC25 concentration of NaNp. 4. Threshold concentrations of the nitrodilators were also able to potentiate the anti-aggregatory effects of RS93427 (0.03-30 ng ml-1) on collagen-induced platelet aggregation. With threshold concentrations of either GTN (6.3-25 micrograms ml-1) or NaNp (0.3-1.3 microgram ml-1), the mean IC50 concentration of RS93427 was reduced 4 or 6 fold, respectively, while the IC25 concentration was reduced 6 or 10 fold, respectively. 5. No similar synergistic interactions were seen between RS93427 and the nitrodilators when ADP was used as an aggregating agent. 6. In spontaneously hypertensive rats, the dose-response for the hypotensive response to bolus doses of RS93427 was not altered by concomitant steady state infusion of a threshold dose (1 micrograms kg-1 min-1) of GTN. 7. Possible therapeutic implications of these findings are discussed.

  3. PG545, a heparan sulfate mimetic, reduces heparanase expression in vivo, blocks spontaneous metastases and enhances overall survival in the 4T1 breast carcinoma model.

    Directory of Open Access Journals (Sweden)

    Edward Hammond

    Full Text Available PG545 is a clinically relevant heparan sulfate (HS mimetic which, in addition to possessing anti-angiogenic properties, also acts as a heparanase inhibitor which may differentiate its mechanism(s of action from approved angiogenesis inhibitors. The degradation of HS by heparanase has been strongly implicated in cell dissemination and the metastatic process. Thus, the anti-metastatic activity of PG545 has been linked to the enzymatic function of heparanase - the only endoglycosidase known to cleave HS, an important component of the extracellular matrix (ECM which represents a potential avenue for therapeutic intervention for certain metastatic cancer indications. Recent concerns raised about the paucity of overall survival as an endpoint in mouse models of clinically relevant metastasis led us to examine the effect of PG545 on the progression of both primary tumor growth and the spontaneously metastasizing disease in the 4T1 syngeneic breast carcinoma model in a non-surgical and surgical (mastectomy setting. PG545 significantly inhibited primary tumor growth but importantly also inhibited lung metastasis in treated mice, an effect not observed with the tyrosine kinase inhibitor sorafenib. Importantly, PG545 significantly enhanced overall survival compared to vehicle control and the sorafenib group, suggesting PG545's inhibitory effect on heparanase is indeed a critical attribute to induce anti-metastatic activity. In addition to blocking a common angiogenic signalling pathway in tumor cells, the expression of heparanase in the primary tumor and lung was also significantly reduced by PG545 treatment. These results support the ongoing development of PG545 and highlight the potential utility in metastatic disease settings.

  4. Analytics of nonpeptidic erythropoietin mimetic agents in sports drug testing employing high-resolution/high-accuracy liquid chromatography-mass spectrometry.

    Science.gov (United States)

    Vogel, Matthias; Dib, Josef; Tretzel, Laura; Piper, Thomas; Thomas, Andreas; Schänzer, Wilhelm; Thevis, Mario

    2016-09-01

    Since its release as anti-anemic drug, recombinant erythropoietin (rEPO) gradually entered the illicit way to sports competitions as endurance-enhancing drug. Novel modifications biopharmaceutically introduced into the rEPO molecule in the form of carbohydrate or polyethylene glycol moieties made robust and sensitive test methods vital to doping controls in order to provide the necessary tools enabling the conviction of dishonest athletes. Modern protein analysis by means of gel electrophoretic separation and western blotting represents the status quo in rEPO anti-doping analysis. However, new therapeutically promising erythropoietin receptor activating compounds have been developed that exhibit cytokine hormone-mimicking properties but lack any protein structure. Progression to evade parenteral application and substitute for rEPO by low molecular mass and orally available compounds is still one of the major objectives in pharmaceutical research. In this approach, four promising in-house synthesized nonpeptidic erythropoietin mimetic agents, namely compound 129, compound 163, A1B10C1, and A5B10C4 were thoroughly evaluated by employing high-resolution/high-accuracy liquid chromatography tandem mass spectrometry experiments. Characteristic product ions were determined supporting the identification of these drugs and putative metabolites as well as related compounds in future doping controls. Test methods employing direct urine injection and receptor affinity purification strategies were assessed, which demonstrated that EPO receptor purification is of limited utility for nonpeptidic EPOR agonists while direct urine injection allowed for comprehensive method characterization. Thereby, achieved limits of detection were 1 ng/mL for compounds 129/163 and 5 ng/mL for A1B10C1/A5B10C4. PMID:27438721

  5. Elicitation of neutralizing antibodies directed against CD4-induced epitope(s using a CD4 mimetic cross-linked to a HIV-1 envelope glycoprotein.

    Directory of Open Access Journals (Sweden)

    Antu K Dey

    Full Text Available The identification of HIV-1 envelope glycoprotein (Env structures that can generate broadly neutralizing antibodies (BNAbs is pivotal to the development of a successful vaccine against HIV-1 aimed at eliciting effective humoral immune responses. To that end, the production of novel Env structure(s that might induce BNAbs by presentation of conserved epitopes, which are otherwise occluded, is critical. Here, we focus on a structure that stabilizes Env in a conformation representative of its primary (CD4 receptor-bound state, thereby exposing highly conserved "CD4 induced" (CD4i epitope(s known to be important for co-receptor binding and subsequent virus infection. A CD4-mimetic miniprotein, miniCD4 (M64U1-SH, was produced and covalently complexed to recombinant, trimeric gp140 envelope glycoprotein (gp140 using site-specific disulfide linkages. The resulting gp140-miniCD4 (gp140-S-S-M64U1 complex was recognized by CD4i antibodies and the HIV-1 co-receptor, CCR5. The gp140-miniCD4 complex elicited the highest titers of CD4i binding antibodies as well as enhanced neutralizing antibodies against Tier 1 viruses as compared to gp140 protein alone following immunization of rabbits. Neutralization against HIV-2(7312/V434M and additional serum mapping confirm the specific elicitation of antibodies directed to the CD4i epitope(s. These results demonstrate the utility of structure-based approach in improving immunogenic response against specific region, such as the CD4i epitope(s here, and its potential role in vaccine application.

  6. Rational design of ApoA-I Mimetic-polypharmacophoric of high free binding energy hopping scaffolds generated by integrating nonlinear scoring functions for similarity-based ligand docking and binding affinity prediction.

    OpenAIRE

    Ioannis Grigoriadis

    2015-01-01

    4F is an anti-inflammatory, apolipoprotein A-I (apoA-I)-mimetic peptide that is active in vivo at nanomolar concentrations in the presence of a large molar excess of apoA-I. Physiologic concentrations (∼35 μM) of human apoA-I did not inhibit the production of LDL-induced monocyte chemotactic activity by human aortic endothelial cell cultures, but adding nanomolar concentrations of 4F in the presence of ∼35 μM apoA-I significantly reduced this inflammatory response. A common stra...

  7. Current guidelines for high-density lipoprotein cholesterol in therapy and future directions

    Directory of Open Access Journals (Sweden)

    Subedi BH

    2014-04-01

    Full Text Available Bishnu H Subedi,1,2 Parag H Joshi,1 Steven R Jones,1 Seth S Martin,1 Michael J Blaha,1 Erin D Michos1 1Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, 2Greater Baltimore Medical Center, Baltimore, MD, USA Abstract: Many studies have suggested that a significant risk factor for atherosclerotic cardiovascular disease (ASCVD is low high-density lipoprotein cholesterol (HDL-C. Therefore, increasing HDL-C with therapeutic agents has been considered an attractive strategy. In the prestatin era, fibrates and niacin monotherapy, which cause modest increases in HDL-C, reduced ASCVD events. Since their introduction, statins have become the cornerstone of lipoprotein therapy, the benefits of which are primarily attributed to decrease in low-density lipoprotein cholesterol. Findings from several randomized trials involving niacin or cholesteryl ester transfer protein inhibitors have challenged the concept that a quantitative elevation of plasma HDL-C will uniformly translate into ASCVD benefits. Consequently, the HDL, or more correctly, HDL-C hypothesis has become more controversial. There are no clear guidelines thus far for targeting HDL-C or HDL due to lack of solid outcomes data for HDL specific therapies. HDL-C levels are only one marker of HDL out of its several structural or functional properties. Novel approaches are ongoing in developing and assessing agents that closely mimic the structure of natural HDL or replicate its various functions, for example, reverse cholesterol transport, vasodilation, anti-inflammation, or inhibition of platelet aggregation. Potential new approaches like HDL infusions, delipidated HDL, liver X receptor agonists, Apo A-I upregulators, Apo A mimetics, and gene therapy are in early phase trials. This review will outline current therapies and describe future directions for HDL therapeutics. Keywords: high-density lipoprotein, lipids, cholesterol, atherosclerosis, cardiovascular disease, therapy

  8. Music Therapy and Music Therapy Research. Response

    DEFF Research Database (Denmark)

    Pedersen, Inge Nygaard

    2002-01-01

    This response to Keynote by Prof. Even Ruud (N)"Music Education and Music Therapy seeks to define these two areas with specific focus on tools and methods for analysis of music as these methods are developed in music therapy. This includes that the music therapist, the music and the client create...

  9. Genes and Gene Therapy

    Science.gov (United States)

    ... correctly, a child can have a genetic disorder. Gene therapy is an experimental technique that uses genes to ... or prevent disease. The most common form of gene therapy involves inserting a normal gene to replace an ...

  10. Hormone Replacement Therapy

    Science.gov (United States)

    ... before and during menopause, the levels of female hormones can go up and down. This can cause ... hot flashes and vaginal dryness. Some women take hormone replacement therapy (HRT), also called menopausal hormone therapy, ...

  11. Adlerian Marriage Therapy.

    Science.gov (United States)

    Carlson, Jon; Dinkmeyer, Don, Sr.

    1987-01-01

    Describes the assumptions, processes, and techniques used in Alderian marriage therapy. Describes purpose of therapy as assessing current beliefs and behaviors while educating the couple in new procedures that can help the couple establish new goals. (Author/ABL)

  12. Therapy and Counseling

    Science.gov (United States)

    ... feelings and behavior. Behavior therapy is sometimes called behavior modification therapy. This kind of treatment focuses on changing unwanted or unhealthy behaviors and replacing them with healthy ones. This treatment ...

  13. Virtual particle therapy centre

    CERN Multimedia

    2015-01-01

    Particle therapy is an advanced technique of cancer radiation therapy, using protons or other ions to target the cancerous mass. This advanced technique requires a multi-disciplinary team working in a specialised centre. 3D animation: Nymus3D

  14. Hyperbaric oxygen therapy

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/002375.htm Hyperbaric oxygen therapy To use the sharing features on this page, please enable JavaScript. Hyperbaric oxygen therapy uses a special pressure chamber to increase ...

  15. 静电纺丝血管组织工程支架构建仿生血管微环境的研究进展%Research advances in construction of mimetic natural blood vessel microenvironment by electrospinning

    Institute of Scientific and Technical Information of China (English)

    王皓; 彭永康; 孔德领; 杨军

    2009-01-01

    静电纺丝是近年来制备纳米纤维组织工程支架的主要技术,可用于多种天然或合成高分子材料的成型加工,其制备的纳米纤维支架具有体内细胞外基质(ECM)的仿生结构和特点,是最有发展前景的仿生构建细胞外基质的新技术.综述了多种静电纺丝技术以及静电纺丝支架的生物活性分子修饰在小口径人工血管的仿生微环境构建研究中的研究进展.%Electrospinning has been, in recent years, a popular choice for producing tissue engineering scaffolds with various natural and synthetic polymers. The structure of nanofibers by electrospun is similar to the extracellular matrix (ECM) in vivo in many characteristics. Electrospinning is a new technique to construct nanofiber scaffolds for mimetic natural ECM. In this paper, review is given on various methods of electrospinning and modifications of nanofibers by bioactive factors which are used in construction of mimetic natural small diameter blood vessel microenvironment.

  16. Combined tumor therapy

    International Nuclear Information System (INIS)

    This comprehensive survey of current methods and achievements first takes a look at the two basic therapies, devoting a chapter each to the surgery and radiotherapy of tumors. The principal subjects of the book, however, are the systemic, adjuvant therapy, biological therapies, hyperthermia and various other therapies (as e.g. treatment with ozone, oxygen, or homeopathic means), and psychotherapy. (MG) With 54 figs., 86 tabs

  17. Venous Thromboembolism Anticoagulation Therapy

    Institute of Scientific and Technical Information of China (English)

    刘泽霖

    2009-01-01

    @@ VTE of the main treatment for anticoagulant thera-py, anticoagulant therapy drug of choice for low molecu-lar weight heparin (LMWH) for the overwhelming major-ity of clinicians agree that long-term oral anticoagulant therapy is still Vit. K antagonist (mainly warfarin).

  18. Musings on Adventure Therapy.

    Science.gov (United States)

    Alvarez, Antonio G.; Stauffer, Gary A.

    2001-01-01

    Critiques various definitions of adventure therapy, then suggests that adventure therapy is any intentional, facilitated use of adventure tools and techniques to guide personal change toward desired therapeutic goals. Reflects on the nature of adventure therapy through a discussion of the application of this definition and its implications for…

  19. Behavior Therapy of Impotence

    Science.gov (United States)

    Dengrove, Edward

    1971-01-01

    Behavior therapy approaches to the treatment of male sexual impotence, specifically premature ejaculation and erective impotence, are discussed. Included in the behavioral therapies are systematic desensitization, active graded therapy, assertive techniques, sexual responses, operant approaches and others. Often marriage counseling is also…

  20. Aquatic Therapy for Children

    Science.gov (United States)

    Kucher, Greta; Moore, Kelsey; Rodia, Rachel; Moser, Christy Szczech

    2015-01-01

    Aquatic therapy has long been highlighted in the literature as a potentially powerful therapeutic intervention. This review will highlight basic definitions of aquatic therapy, review salient research, and identify specific diagnoses that may benefit from aquatic therapy. Online resources, blogs, and books that occupational therapists may find…

  1. Co{sub 3}O{sub 4}-reduced graphene oxide nanocomposite as an effective peroxidase mimetic and its application in visual biosensing of glucose

    Energy Technology Data Exchange (ETDEWEB)

    Xie, Jianxin [The Key Laboratory of Luminescence and Real-time Analysis, Ministry of Education, College of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715 (China); College of Resources and Environment, Yuxi Normal University, Yunnan 653100 (China); Cao, Haiyan; Jiang, Huan; Chen, Yujin [The Key Laboratory of Luminescence and Real-time Analysis, Ministry of Education, College of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715 (China); Shi, Wenbing [College of Chemistry and Chemical Engineering, Yangtze Normal University, Chongqing 408003 (China); Zheng, Huzhi [The Key Laboratory of Luminescence and Real-time Analysis, Ministry of Education, College of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715 (China); Huang, Yuming, E-mail: yuminghuang2000@yahoo.com [The Key Laboratory of Luminescence and Real-time Analysis, Ministry of Education, College of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715 (China)

    2013-09-24

    eyes without any instrumentation or complicated design. Our research results also suggest a simple route for the facile preparation of a highly active nanoparticles-based enzyme mimetics on proper supporting materials.

  2. Music Therapy for Seniors

    OpenAIRE

    SLUNEČKOVÁ, Petra

    2014-01-01

    This bachelor thesis deals with the use of music therapy in the lives of seniors. The target of this thesis is to map the possibilities of using music therapy ways with seniors and to recommend a suitable music therapy resources on the basis of the research and evaluation of obtained dates. The theoretical part describes the term "the music therapy", e.g. concept, definition, types and forms, the development of music therapy, the history, methods and techniques. This age group is defined in t...

  3. Music therapy improvisation

    OpenAIRE

    Mira Kuzma

    2001-01-01

    In this article, the technique of music therapy – music therapy improvisation is introduced. In this form of music therapy the improvising partners share meaning through the improvisation: the improvisation is not an end in itself: it portrays meaning that is personal, complex and can be shared with the partner. The therapeutic work, then, is meeting and matching the client's music in order to give the client an experience of "being known", being responded through sounds a...

  4. Hormone therapy in acne

    OpenAIRE

    Chembolli Lakshmi

    2013-01-01

    Underlying hormone imbalances may render acne unresponsive to conventional therapy. Relevant investigations followed by initiation of hormonal therapy in combination with regular anti-acne therapy may be necessary if signs of hyperandrogenism are present. In addition to other factors, androgen-stimulated sebum production plays an important role in the pathophysiology of acne in women. Sebum production is also regulated by other hormones, including estrogens, growth hormone, insulin, insulin-l...

  5. Psychodynamic Music Therapy

    OpenAIRE

    Jinah Kim

    2016-01-01

    This paper introduces and explores the basic principles of psychodynamic approaches in music therapy. Music is used as a means to explore both conscious and unconscious issues as well as the internal world of the individuals involved in music therapy. However, the focus of therapy is on therapeutic relationship, especially the dynamics of transference and counter-transference between the client and the music therapist. Musical experiences, such as music listening, songs, and improvisation, ca...

  6. Journal of Proton Therapy

    OpenAIRE

    Editorial Office

    2015-01-01

    Journal of Proton Therapy (JPT) is an international open access, peer-reviewed journal, which publishes original research, technical reports, reviews, case reports, editorials, and other materials on proton therapy with focus on radiation oncology, medical physics, medical dosimetry, and radiation therapy.No article processing/submission feeNo publication feePeer-review completion within 3-6 weeksImmediate publication after the completion of final author proofreadDOI assignment for each publi...

  7. Writing Music Therapy

    OpenAIRE

    Mary Helena Rykov

    2011-01-01

    Communicating about music therapy is problematic because discursive language fails to convey the nonverbal, embodied essence of experience. I explore the emergence of this problem in the music therapy literature. I discuss the scholarship of phenomenological writing. I provide examples of nondiscursive music therapy writing. I introduce the genre of poetic inquiry.

    Poetry is the most musical form of language. Poetry and music, linked throughout history, share many ...

  8. Principles of gene therapy

    OpenAIRE

    Mammen Biju; Ramakrishnan T; Sudhakar Uma; Vijayalakshmi

    2007-01-01

    Genes are specific sequences of bases that encode instructions to make proteins. When genes are altered so that encoded proteins are unable to carry out their normal functions, genetic disorders can result. Gene therapy is designed to introduce genetic material into cells to compensate for abnormal genes or to make a beneficial protein. This article reviews the fundamentals in gene therapy and its various modes of administration with an insight into the role of gene therapy in Periodontics an...

  9. Cochlear Gene Therapy

    OpenAIRE

    Lustig, Lawrence R.; Akil, Omar

    2012-01-01

    The purpose of this review is to highlight recent advances in cochlear gene therapy over the past several years. Cochlear gene therapy has undergone tremendous advances over the past decade. Beginning with some groundbreaking work in 2005 documenting hair cell regeneration using virallymediated delivery of the mouse atonal 1 gene, gene therapy is now being explored as a possible treatment for a variety of causes of hearing loss.

  10. Unproven (questionable) cancer therapies.

    OpenAIRE

    Brigden, M L

    1995-01-01

    More than half of all cancer patients use some form of alternative treatment during the course of their illness. Alternative therapies are often started early in patients' illness, and their use is frequently not acknowledged to health care professionals. Some alternative therapies are harmful, and their promoters may be fraudulent. Persons who try alternative cancer therapies may not be poorly educated but may ultimately abandon conventional treatment. Recent attention has focused on aspects...

  11. Pain in photodynamic therapy

    OpenAIRE

    Mircea Tampa; Maria Isabela Sârbu; Mădălina-Irina Mitran; Cristina-Iulia Mitran; Adrian Dumitru; Vasile Benea; Simona-Roxana Georgescu

    2016-01-01

    Photodynamic therapy is a modern treatment with applications in several medical specialties, which has been intensely studied in the last years. The main indications in dermatology are actinic keratosis, superficial basal cell carcinoma and Bowen's disease- common skin disorders in which photodynamic therapy proved its efficacy. At present, the use of photodynamic therapy for the treatment of other skin disorders is profoundly researched. Pain is the most common and redoubtable adverse effect...

  12. Nuclear medicine therapy

    CERN Document Server

    Eary, Janet F

    2013-01-01

    One in three of the 30 million Americans who are hospitalized are diagnosed or treated with nuclear medicine techniques. This text provides a succinct overview and detailed set of procedures and considerations for patient therapy with unsealed radioactivity sources.  Serving as a complete literature reference for therapy with radiopharmaceuticals currently utilized in practice, this source covers the role of the physician in radionuclide therapy, and essential procedures and protocols required by health care personnel.

  13. NCAM Mimetic Peptides: An Update

    DEFF Research Database (Denmark)

    Berezin, Vladimir; Bock, Elisabeth

    2008-01-01

    sequences contain one or several NCAM homophilic binding sites involved in NCAM binding to itself, have been identified. By means of NMR titration analysis and molecular modeling a number of peptides derived from NCAM and targeting NCAM heterophilic ligands such as the fibroblast growth factor receptor...... and heparan sulfate proteoglycans (HSPG) have been identified. The FGL, dekaCAM, FRM/EncaminA, BCL, EncaminC and EncaminE peptides all target the FGF receptor whereas the heparin binding peptide HBP targets HSPG. Moreover, a number of NCAM binding peptides have been identified employing screening...

  14. ERP diffusion and mimetic behaviors

    OpenAIRE

    Erick Leroux; Pierre-Charles Pupion; Jean-Michel Sahut

    2013-01-01

    The emergence of enterprise resource planning systems (ERP) has often been presented as one of the main factors of organizational change within companies in the course of the last few years. The neoclassical and socio-rational analyses show that ERP adoption is often a rational choice in that it results from a costbenefit analysis and indeed an optimization calculation. However, as articulated by Rogers’ analysis (1983), firms are also influenced by information on the attributes of innovation...

  15. Medical Art Therapy

    Directory of Open Access Journals (Sweden)

    Birgul Aydin

    2012-03-01

    Full Text Available Art therapy is a form of expressive therapy that uses art materials. Art therapy combines traditional psychotherapeutic theories and techniques with an understanding of the psychological aspects of the creative process, especially the affective properties of the different art materials. Medical art therapy has been defined as the clinical application of art expression and imagery with individuals who are physically ill, experiencing physical trauma or undergoing invasive or aggressive medical procedures such as surgery or chemotherapy and is considered as a form of complementary or integrative medicine. Several studies have shown that patients with physical illness benefit from medical art therapy in different aspects. Unlike other therapies, art therapy can take the patients away from their illness for a while by means of creative activities during sessions, can make them forget the illness or lost abilities. Art therapy leads to re-experiencing normality and personal power even with short creative activity sessions. In this article definition, influence and necessity of medical art therapy are briefly reviewed.

  16. Postmodernism and Music Therapy

    Directory of Open Access Journals (Sweden)

    Eugenia Hernandez-Ruiz

    2005-11-01

    Full Text Available The present essay is a short and probably superficial analysis of music therapy and music therapy research. I have to say that by no means do I consider myself an expert or even experienced enough to provide "critiques" about any area of music therapy. This work is a revised version of a term paper presented at the University of Kansas in 2002, and is just the result of my interest in some recent trends of thoughts (e.g. social constructionism, and their impact, if any, on music therapy. I believe in dialogue as a means to forward knowledge, and so I dare to share this work with colleagues.

  17. Neutron Therapy Facility

    Data.gov (United States)

    Federal Laboratory Consortium — The Neutron Therapy Facility provides a moderate intensity, broad energy spectrum neutron beam that can be used for short term irradiations for radiobiology (cells)...

  18. Principles of gene therapy

    Directory of Open Access Journals (Sweden)

    Mammen Biju

    2007-01-01

    Full Text Available Genes are specific sequences of bases that encode instructions to make proteins. When genes are altered so that encoded proteins are unable to carry out their normal functions, genetic disorders can result. Gene therapy is designed to introduce genetic material into cells to compensate for abnormal genes or to make a beneficial protein. This article reviews the fundamentals in gene therapy and its various modes of administration with an insight into the role of gene therapy in Periodontics and future percepts and the technical and ethical issues of using gene therapy.

  19. Music Therapy with Adolescents

    Directory of Open Access Journals (Sweden)

    Jukko Tervo

    2005-03-01

    Full Text Available The therapeutic community described in this paper was situated at the University of Oulu Central Hospital Department of Psychiatry, Finland, during the years 1979-1989. The ward consisted of eight beds, four for boys and four for girls. The basic emphasis in the treatment was laid on psychoanalytic psychotherapy and music and art therapies suitable for the stage of adolescent development. Adolescent community therapy (psychoanalytic psychotherapy, music therapy, art therapy, special school etc. creates an environment which supports individual growth of the adolescent and youth culture. This, in turn, simultaneously supports psychotherapy.

  20. [Morita therapy over history].

    Science.gov (United States)

    Usa, Shinichi

    2003-01-01

    At Sansei Hospital in Kyoto we performed Morita Therapy not only for Japanese clients but also foreign clients from several countries, like Germany, Switzerland, U.S.A., China, Korea, India and Indonesia. We could treat those foreign clients using Morita Therapy with good success although they came from various cultural backgrounds. One of the characteristic Approaches of Morita Therapy was that it avoided the conceptualization of self-consciousness and self image as a subjective fiction established by abstract and logical thinking. Secondary Morita Therapy moves clients to deal with activities in real life. These 2 approaches help clients not to be involved in symptom development or fixation mechanisms and break through self-centeredness. At the first stage of Morita Therapy, namely in the bed rest period clients can experience his psychic state as if he were a just born baby. The founder of Gestalt Therapy, Frederick S. Perls experienced by himself Morita Therapy. During bed rest therapy he behaved as if he were a baby. This behavior came out not from conscious abstract and logical thinking but from spontaneous "pre-conscious" state of mind. Morita called this "Jun-na-kokoro" (Pure mind). Morita knew that neurotic symptoms come out from those abstract and logical thinking which could lead to fixation of symptoms so that therapy principle might be the de-centralization of self and the pure mind experience which is found in our daily life and also in daily life of foreign people from various cultural backgrounds. PMID:12875225

  1. Visual and quantitative determination of dopamine based on Co{sub x}Fe{sub 3−x}O{sub 4} magnetic nanoparticles as peroxidase mimetics

    Energy Technology Data Exchange (ETDEWEB)

    Niu, Xiaoying; Xu, Yinyin [State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000 (China); Department of Chemistry, Lanzhou University, Lanzhou 730000 (China); Dong, Yalei [College of Chemistry and Chemical Engineering, University of Chinese Academy of Sciences, Beijing 100049 (China); Qi, Liye [Department of Chemistry, Lanzhou University, Lanzhou 730000 (China); Qi, Shengda [State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000 (China); Department of Chemistry, Lanzhou University, Lanzhou 730000 (China); Key Laboratory of Nonferrous Metal Chemistry and Resources Utilization of Gansu Province, Lanzhou 730000 (China); Chen, Hongli, E-mail: hlchen@lzu.edu.cn [State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000 (China); Department of Chemistry, Lanzhou University, Lanzhou 730000 (China); Key Laboratory of Nonferrous Metal Chemistry and Resources Utilization of Gansu Province, Lanzhou 730000 (China); Chen, Xingguo [State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000 (China); Department of Chemistry, Lanzhou University, Lanzhou 730000 (China); Key Laboratory of Nonferrous Metal Chemistry and Resources Utilization of Gansu Province, Lanzhou 730000 (China)

    2014-02-25

    Graphical abstract: Co{sub x}Fe{sub 3−x}O{sub 4} was proved to possess higher peroxidase-like activity comparing with Fe{sub 3}O{sub 4} MNPs. It could effectively catalyze the reaction between 3,3,5,5-tetramethylbenzidine (TMB) and H{sub 2}O{sub 2} under 40 °C within 15 min. So this proposed method was used for measuring dopamine. The color variation was very obvious on visual observation, which offered a convenient approach to detect DA by naked eye. -- Highlights: • The Co{sub x}Fe{sub 3−x}O{sub 4} MNPs were firstly prepared by a simple coprecipitation method. • Co{sub x}Fe{sub 3−x}O{sub 4} MNPs could effectively catalyze the reaction between TMB and H{sub 2}O{sub 2}. • This colorimetric analytical method was convenient, economic and speedy. • The method had been applied to detection of DA in Shan Yao and human serum sample. -- Abstract: In this study, cobalt doped magnetic composite nanoparticles (Co{sub x}Fe{sub 3−x}O{sub 4} MNPs) were firstly prepared through a simple and convenient coprecipitation approach. The characterization results from EDX, ICP-AES, TEM, XRD and XPS showed that the cobalt atoms might be located in the lattice position instead of the part of iron atoms. Co{sub x}Fe{sub 3−x}O{sub 4} MNPs possessed higher peroxidase-like activity comparing with Fe{sub 3}O{sub 4} MNPs, although they were similar in crystal structure, size distribution and morphology. The as-prepared nanomaterials could effectively catalyze the reaction between 3,3,5,5-tetramethylbenzidine (TMB) and H{sub 2}O{sub 2} under 40 °C within 15 min. Dopamine (DA) has some reducibility due to the existence of phenol hydroxyl group, which results in it can consume H{sub 2}O{sub 2} and cause the blue shallowing of the reaction solution between H{sub 2}O{sub 2} and TMB. A visual, sensitive and simple colorimetric method based on Co{sub x}Fe{sub 3−x}O{sub 4} MNPs as peroxidase mimetics was developed for detecting DA. Good linear relationship and recoveries for DA

  2. Therapy with radionuclides. Radionuklid-Therapie

    Energy Technology Data Exchange (ETDEWEB)

    Biersack, H.J.; Hotze, A.L. (Bonn Univ. (Germany). Klinik fuer Nuklearmedizin)

    1992-12-01

    Radioiodine therapy of benign and malignant thyroid diseases is a well-established procedure in Nuclear Medicine. However, the therapeutic use of radioisotopes in other diseases is relatively unknown among our refering physicians. The therapeutic effects of intraarticular (rheumatoid arthritis) and intracavitary (pleural and peritoneal carcinosis) applications yields good results. The radiophosphorus therapy in polycythemia vera rubra has always to be considered as an alternative to chemotherapy. The use of analgetics may be reduced by pain therapy of bone metastasis by injection of bone-seeking beta emitters like Rh-186 HEDP. Other procedures like therapeutic application of meta-iodo-benzylguanidine in neuroblastoma and malignant pheochromocytoma resulted in at least remissions of the disease. Radioimmunotherapy needs further evaluation before it can be recommended as a routine procedure. (orig.).

  3. Chronic stress in adulthood followed by intermittent stress impairs spatial memory and the survival of newborn hippocampal cells in aging animals: prevention by FGL, a peptide mimetic of neural cell adhesion molecule

    DEFF Research Database (Denmark)

    Borcel, Erika; Pérez-Alvarez, Laura; Herrero, Ana Isabel;

    2008-01-01

    In this study, we examined whether chronic stress in adulthood can exert long-term effects on spatial-cognitive abilities and on the survival of newborn hippocampal cells in aging animals. Male Wistar rats were subjected to chronic unpredictable stress at midlife (12 months old) and then reexposed...... each week to a stress stimulus. When evaluated in the water maze at the early stages of aging (18 months old), chronic unpredictable stress accelerated spatial-cognitive decline, an effect that was accompanied by a reduction in the survival of newborn cells and in the number of adult granular cells......, a peptide mimetic of neural cell adhesion molecule, during the 4 weeks of continuous stress not only prevented the deleterious effects of chronic stress on spatial memory, but also reduced the survival of the newly generated hippocampal cells in aging animals. FGL treatment did not, however, prevent...

  4. Cognitive Behavioral Therapy and Motivational Enhancement Therapy.

    Science.gov (United States)

    Wu, Sarah S; Schoenfelder, Erin; Hsiao, Ray Chih-Jui

    2016-10-01

    Although cognitive behavioral therapy (CBT) is widely recognized as the preferred treatment of psychiatric disorders, less is known about the application of CBT to substance use disorders, particularly in adolescence. This article discusses how CBT conceptualizes substance use and how it is implemented as a treatment of adolescent substance abuse. The article draws on several manuals for CBT that implement it as a standalone treatment or in combination with motivational enhancement therapies. Also reviewed are several studies that examined the efficacy of CBT. Finally, the implications are discussed. Numerous starting resources are provided to help a clinician implement CBT.

  5. Mapping the Interaction of B Cell Leukemia 3 (BCL-3) and Nuclear Factor κB (NF-κB) p50 Identifies a BCL-3-mimetic Anti-inflammatory Peptide.

    Science.gov (United States)

    Collins, Patricia E; Grassia, Gianluca; Colleran, Amy; Kiely, Patrick A; Ialenti, Armando; Maffia, Pasquale; Carmody, Ruaidhrí J

    2015-06-19

    The NF-κB transcriptional response is tightly regulated by a number of processes including the phosphorylation, ubiquitination, and subsequent proteasomal degradation of NF-κB subunits. The IκB family protein BCL-3 stabilizes a NF-κB p50 homodimer·DNA complex through inhibition of p50 ubiquitination. This complex inhibits the binding of the transcriptionally active NF-κB subunits p65 and c-Rel on the promoters of NF-κB target genes and functions to suppress inflammatory gene expression. We have previously shown that the direct interaction between p50 and BCL-3 is required for BCL-3-mediated inhibition of pro-inflammatory gene expression. In this study we have used immobilized peptide array technology to define regions of BCl-3 that mediate interaction with p50 homodimers. Our data show that BCL-3 makes extensive contacts with p50 homodimers and in particular with ankyrin repeats (ANK) 1, 6, and 7, and the N-terminal region of Bcl-3. Using these data we have designed a BCL-3 mimetic peptide based on a region of the ANK1 of BCL-3 that interacts with p50 and shares low sequence similarity with other IκB proteins. When fused to a cargo carrying peptide sequence this BCL-3-derived peptide, but not a mutated peptide, inhibited Toll-like receptor-induced cytokine expression in vitro. The BCL-3 mimetic peptide was also effective in preventing inflammation in vivo in the carrageenan-induced paw edema mouse model. This study demonstrates that therapeutic strategies aimed at mimicking the functional activity of BCL-3 may be effective in the treatment of inflammatory disease.

  6. Passive heat therapy improves cutaneous microvascular function in sedentary humans via improved nitric oxide-dependent dilation.

    Science.gov (United States)

    Brunt, Vienna E; Eymann, Taylor M; Francisco, Michael A; Howard, Matthew J; Minson, Christopher T

    2016-09-01

    Passive heat therapy (repeated hot tub or sauna use) reduces cardiovascular risk, but its effects on the mechanisms underlying improvements in microvascular function have yet to be studied. We investigated the effects of heat therapy on microvascular function and whether improvements were related to changes in nitric oxide (NO) bioavailability using cutaneous microdialysis. Eighteen young, sedentary, otherwise healthy subjects participated in 8 wk of heat therapy (hot water immersion to maintain rectal temperature ≥38.5°C for 60 min/session; n = 9) or thermoneutral water immersion (sham, n = 9), and participated in experiments before and after the 8-wk intervention in which forearm cutaneous hyperemia to 39°C local heating was assessed at three microdialysis sites receiving 1) Lactated Ringer's (Control), 2) N(ω)-nitro-l-arginine (l-NNA; nonspecific NO synthase inhibitor), and 3) 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (Tempol), a superoxide dismutase mimetic. The arm used for microdialysis experiments remained out of the water at all times. Data are means ± SE cutaneous vascular conductance (CVC = laser Doppler flux/mean arterial pressure), presented as percent maximal CVC (% CVCmax). Heat therapy increased local heating plateau from 42 ± 6 to 53 ± 6% CVCmax (P effect on the local heating response (P = 0.53 vs. Control). There were no changes at the Tempol site across interventions (P = 0.58). Passive heat therapy improves cutaneous microvascular function by improving NO-dependent dilation, which may have clinical implications. PMID:27418688

  7. Gene therapy for thyroid cancer

    International Nuclear Information System (INIS)

    Gene therapy for thyroid cancer include immunotherapy, suicide gene therapy, tumor suppressor replacement, 131I therapy by sodium/iodide symporter and antisense therapy and so on. Gene therapy has wide perspectives, but there are many problems need to be solved for clinical application

  8. [Dance/Movement Therapy.

    Science.gov (United States)

    Fenichel, Emily, Ed.

    1994-01-01

    This newsletter theme issue focuses on dance, play, and movement therapy for infants and toddlers with disabilities. Individual articles are: "Join My Dance: The Unique Movement Style of Each Infant and Toddler Can Invite Communication, Expression and Intervention" (Suzi Tortora); "Dynamic Play Therapy: An Integrated Expressive Arts Approach to…

  9. What Is Wilderness Therapy?

    Science.gov (United States)

    Russell, Keith C.

    2001-01-01

    Based on the literature and recent research, an integrated, consistent definition of wilderness therapy is presented to differentiate it from other outdoor adventure programs and guide program design and research efforts. Trends in the outdoor industry are explored that suggest that wilderness therapy programs are searching for recognition by…

  10. Therapy of Lies

    Science.gov (United States)

    Price, Sean

    2012-01-01

    Conversion therapy comes in many forms, ranging from informal chats with counselors to aggressive physical coercion, but all are based on the belief that a gay male or a lesbian can be changed "back" to heterosexual behavior. It is not just alarmed parents who turn to this therapy. Many LGBT individuals seek out such treatment in an effort to…

  11. Antiproton Cancer Therapy

    DEFF Research Database (Denmark)

    Bassler, Niels

    An essential part in cancer radiotherapy, is to direct a sufficiently high dose towards the tumour, without damaging the surrounding tissue. Different techniques such as intensity modulated radiation therapy and proton therapy have been developed, in order to reduce the dose to the normal tissue...

  12. Pediatric Music Therapy.

    Science.gov (United States)

    Lathom-Radocy, Wanda B.

    This book on music therapy includes relevant medical, psychological, and developmental information to help service providers, particularly music therapists, and parents to understand children with disabilities. The first two chapters describe the process of assessment and delineation of goals in music therapy that leads to the design of the music…

  13. Boganmeldelse - Music Therapy Research

    DEFF Research Database (Denmark)

    Ridder, Hanne Mette Ochsner

    2006-01-01

    . Alligevel følger her en anbefaling af bogen: for musikterapeuter er det en bog, man ikke kommer uden om. Music Therapy Research, på dansk Musikterapiforskning, er en gennemrevideret, ja faktisk nyudgivelse, af bogen Music Therapy Research: Quantitative and Qualitative Perspectives, som udkom i 1995. Også...

  14. Poetry Therapy: A Bibliography.

    Science.gov (United States)

    Weinstock, Donald J., Comp.

    The 84 entries contained in this bibliography are arranged under three headings: poetry therapy, bibliotherapy, and relevant related items. Representing books, educational journals, popular magazines, and research studies, the titles span a variety of topics, including the following: poetry therapy in psychiatric nursing, poetry programs in mental…

  15. Massage Therapy Research

    Science.gov (United States)

    Field, Tiffany; Diego, Miguel; Hernandez-Reif, Maria

    2007-01-01

    Massage therapy has been notably effective in preventing prematurity, enhancing growth of infants, increasing attentiveness, decreasing depression and aggression, alleviating motor problems, reducing pain, and enhancing immune function. This review covers massage therapy research from the last decade, as an update to the American Psychologist 1998…

  16. Music therapy improvisation

    Directory of Open Access Journals (Sweden)

    Mira Kuzma

    2001-09-01

    Full Text Available In this article, the technique of music therapy – music therapy improvisation is introduced. In this form of music therapy the improvising partners share meaning through the improvisation: the improvisation is not an end in itself: it portrays meaning that is personal, complex and can be shared with the partner. The therapeutic work, then, is meeting and matching the client's music in order to give the client an experience of "being known", being responded through sounds and being able to express things and communicate meaningfully. Rather than the client playing music, the therapy is about developing the engagement through sustained, joint improvisations. In music therapy, music and emotion share fundamental features: one may represent the other, i.e., we hear the music not as music but as dynamic emotional states. The concept of dynamic structure explains why music makes therapeutic sense.

  17. Medical therapy in acromegaly.

    LENUS (Irish Health Repository)

    Sherlock, Mark

    2011-05-01

    Acromegaly is a rare disease characterized by excess secretion of growth hormone (GH) and increased circulating insulin-like growth factor 1 (IGF-1) concentrations. The disease is associated with increased morbidity and premature mortality, but these effects can be reduced if GH levels are decreased to <2.5 μg\\/l and IGF-1 levels are normalized. Therapy for acromegaly is targeted at decreasing GH and IGF-1 levels, ameliorating patients\\' symptoms and decreasing any local compressive effects of the pituitary adenoma. The therapeutic options for acromegaly include surgery, radiotherapy and medical therapies, such as dopamine agonists, somatostatin receptor ligands and the GH receptor antagonist pegvisomant. Medical therapy is currently most widely used as secondary treatment for persistent or recurrent acromegaly following noncurative surgery, although it is increasingly used as primary therapy. This Review provides an overview of current and future pharmacological therapies for patients with acromegaly.

  18. Proton therapy physics

    CERN Document Server

    2012-01-01

    Proton Therapy Physics goes beyond current books on proton therapy to provide an in-depth overview of the physics aspects of this radiation therapy modality, eliminating the need to dig through information scattered in the medical physics literature. After tracing the history of proton therapy, the book summarizes the atomic and nuclear physics background necessary for understanding proton interactions with tissue. It describes the physics of proton accelerators, the parameters of clinical proton beams, and the mechanisms to generate a conformal dose distribution in a patient. The text then covers detector systems and measuring techniques for reference dosimetry, outlines basic quality assurance and commissioning guidelines, and gives examples of Monte Carlo simulations in proton therapy. The book moves on to discussions of treatment planning for single- and multiple-field uniform doses, dose calculation concepts and algorithms, and precision and uncertainties for nonmoving and moving targets. It also exami...

  19. Music therapy in dementia

    DEFF Research Database (Denmark)

    McDermott, Orii; Crellin, Nadia; Ridder, Hanne Mette Ochsner;

    2013-01-01

    Objective Recent reviews on music therapy for people with dementia have been limited to attempting to evaluate whether it is effective, but there is a need for a critical assessment of the literature to provide insight into the possible mechanisms of actions of music therapy. This systematic review......, five studies investigated hormonal and physiological changes, and five studies focused on social and relational aspects of music therapy. The musical interventions in the studies were diverse, but singing featured as an important medium for change. Conclusions Evidence for short-term improvement...... in mood and reduction in behavioural disturbance was consistent, but there were no high-quality longitudinal studies that demonstrated long-term benefits of music therapy. Future music therapy studies need to define a theoretical model, include better-focused outcome measures, and discuss how the findings...

  20. Pain in photodynamic therapy

    Directory of Open Access Journals (Sweden)

    Mircea Tampa

    2016-04-01

    Full Text Available Photodynamic therapy is a modern treatment with applications in several medical specialties, which has been intensely studied in the last years. The main indications in dermatology are actinic keratosis, superficial basal cell carcinoma and Bowen's disease- common skin disorders in which photodynamic therapy proved its efficacy. At present, the use of photodynamic therapy for the treatment of other skin disorders is profoundly researched. Pain is the most common and redoubtable adverse effect of photodynamic therapy and it is the most important factor affecting the patient's adherence to treatment. The aim of this article is to look over the most recent medical studies regarding pain in PDT, with emphasis on the factors affecting the occurrence of pain and the most recent strategies for controlling photodynamic therapy- related pain.

  1. Accelerators for Cancer Therapy

    Science.gov (United States)

    Lennox, Arlene J.

    2000-05-30

    The vast majority of radiation treatments for cancerous tumors are given using electron linacs that provide both electrons and photons at several energies. Design and construction of these linacs are based on mature technology that is rapidly becoming more and more standardized and sophisticated. The use of hadrons such as neutrons, protons, alphas, or carbon, oxygen and neon ions is relatively new. Accelerators for hadron therapy are far from standardized, but the use of hadron therapy as an alternative to conventional radiation has led to significant improvements and refinements in conventional treatment techniques. This paper presents the rationale for radiation therapy, describes the accelerators used in conventional and hadron therapy, and outlines the issues that must still be resolved in the emerging field of hadron therapy.

  2. 75 FR 50880 - TRICARE: Non-Physician Referrals for Physical Therapy, Occupational Therapy, and Speech Therapy

    Science.gov (United States)

    2010-08-18

    ..., Occupational Therapy, and Speech Therapy AGENCY: Office of the Secretary, Department of Defense. ACTION: Final... engage in referrals of beneficiaries to the Military Health System for physical therapy, occupational..., occupational therapy, and speech therapy without having the patient see a physician. This rule will...

  3. How Does Oxygen Therapy Work?

    Science.gov (United States)

    ... page from the NHLBI on Twitter. How Does Oxygen Therapy Work? Oxygen therapy provides you with extra ... be delivered to your lungs in several ways. Oxygen Therapy Systems Oxygen is supplied in three forms: ...

  4. Gene Therapy of Cancerous Diseases

    OpenAIRE

    Valenčáková, A.; Dziaková, A.; Hatalová, E.

    2015-01-01

    Gene therapy of cancerous diseases provides new means of curing patients with oncologic illnesses. There are several approaches in treating cancer by gene therapy. Most commonly used methods are: cancer immunogene therapy, suicide gene therapy, application of tumor-suppressor genes, antiangiogenic therapy, mesenchymal stem cells used as vectors, gene directed enzyme/prodrug therapy and bacteria used as anti-cancer agents. Cancer gene immunotherapy uses several immunologic agents for the purp...

  5. Massage therapy research review.

    Science.gov (United States)

    Field, Tiffany

    2016-08-01

    In this review, massage therapy has been shown to have beneficial effects on varying conditions including prenatal depression, preterm infants, full-term infants, autism, skin conditions, pain syndromes including arthritis and fibromyalgia, hypertension, autoimmune conditions including asthma and multiple sclerosis, immune conditions including HIV and breast cancer and aging problems including Parkinson's and dementia. Although many of the studies have involved comparisons between massage therapy and standard treatment control groups, several have compared different forms of massage (e.g. Swedish versus Thai massage), and different active therapies such as massage versus exercise. Typically, the massage therapy groups have experienced more positive effects than the control or comparison groups. This may relate to the massage therapy providing more stimulation of pressure receptors, in turn enhancing vagal activity and reducing cortisol levels. Some of the researchers have assessed physical, physiological and biochemical effects, although most have relied exclusively on self-report measures. Despite these methodological problems and the dearth of research from the U.S., the massage therapy profession has grown significantly and massage therapy is increasingly practiced in traditional medical settings, highlighting the need for more rigorous research. PMID:27502797

  6. Targeted Therapies for Kidney Cancer

    Science.gov (United States)

    ... for kidney cancer Targeted therapies for kidney cancer Biologic therapy (immunotherapy) for kidney cancer Chemotherapy for kidney cancer Pain control for kidney cancer Treatment choices by stage for ...

  7. Radiation therapy physics

    CERN Document Server

    Hendee, William R; Hendee, Eric G

    2013-01-01

    The Third Edition of Radiation Therapy Physics addresses in concise fashion the fundamental diagnostic radiologic physics principles as well as their clinical implications. Along with coverage of the concepts and applications for the radiation treatment of cancer patients, the authors have included reviews of the most up-to-date instrumentation and critical historical links. The text includes coverage of imaging in therapy planning and surveillance, calibration protocols, and precision radiation therapy, as well as discussion of relevant regulation and compliance activities. It contains an upd

  8. Medical Therapy of Acromegaly

    Directory of Open Access Journals (Sweden)

    U. Plöckinger

    2012-01-01

    Full Text Available This paper outlines the present status of medical therapy of acromegaly. Indications for permanent postoperative treatment, postirradiation treamtent to bridge the interval until remission as well as primary medical therapy are elaborated. Therapeutic efficacy of the different available drugs—somatostatin receptor ligands (SRLs, dopamine agonists, and the GH antagonist Pegvisomant—is discussed, as are the indications for and efficacy of their respective combinations. Information on their mechanism of action, and some pharmakokinetic data are included. Special emphasis is given to the difficulties to define remission criteria of acromegaly due to technical assay problems. An algorithm for medical therapy in acromegaly is provided.

  9. Drug therapies in dermatology.

    Science.gov (United States)

    Aslam, Arif; Griffiths, Christopher E M

    2014-02-01

    This article explores the current and emerging therapies for skin disease, with a particular focus on chronic plaque psoriasis and metastatic malignant melanoma. We discuss the current biological therapies used for psoriasis and those on the horizon, including small molecules and biosimilars. We also summarise the recent advances in the use of novel therapeutic agents in other dermatological diseases and outline the promise of translational research and stratified medicine approaches in dermatology. Better matching of patients with therapies is anticipated to have a major effect on both clinical practice and the development of new drugs and diagnostics. PMID:24532745

  10. Vitamin therapy in schizophrenia.

    Science.gov (United States)

    Hoffer, Leonard John

    2008-01-01

    Schizophrenia is a devastating and poorly understood disease for which the only accepted therapy is nonspecific antipsychotic and anti-seizure medication. This article summarizes the evidence that certain vitamin deficiencies likely worsen the symptoms of schizophrenia, and the evidence that large doses of certain vitamins could improve the core metabolic abnormalities that predispose some people to develop it; it recounts the history of a controversial vitamin-based therapy for schizophrenia called orthomolecular psychiatry; and it concludes by advocating a process for discovering promising new schizophrenia therapies that involves small, carefully conducted clinical trials of nutrient combinations in appropriately selected patients. PMID:18587164

  11. Collaboration in experiential therapy.

    Science.gov (United States)

    Berdondini, Lucia; Elliott, Robert; Shearer, Joan

    2012-02-01

    We offer a view of the nature and role of client-therapist collaboration in experiential psychotherapy, focusing on Gestalt and emotion-focused therapy (EFT). We distinguish between the necessary condition of mutual trust (the emotional bond between client and therapist) and effective collaboration (regarding the goals and tasks of therapy). Using a case study of experiential therapy for social anxiety, we illustrate how the development of collaboration can be both complex and pivotal for therapeutic success, and how it can involve client and therapist encountering one another through taking risks by openly and nonjudgementally disclosing difficult experiences in order to enrich and advance the work. PMID:23616296

  12. Complications of cancer therapy

    International Nuclear Information System (INIS)

    The purpose of this chapter is to review systematically the toxicity of contemporary chemotherapy and irradiation on normal tissues of growing children. Whenever possible, the separate toxicity of chemotherapy, irradiation, and combination therapy is addressed. However, it is not always possible to quantitate specifically such reactions in the face of multiple drug therapy, which may enhance radiation injury or reactivate prior radiation injury. Prior detailed reviews have provided important sources of information concerning radiation injury for this more general discussion. The information provided will assist both the clinician and the radiologist in the recognition of early and late complications of therapy in pediatric oncology

  13. Feminist music therapy pedagogy

    DEFF Research Database (Denmark)

    Hahna, Nicole; Swantes, Melody

    2011-01-01

    ) participatory learning, (b) validation of personal experience/development of confidence, (c) political/social activism, and (d) critical thinking/ open-mindedness. The results revealed that 46% (n = 32) of participants identified as feminist music therapists and 67% (n = 46) of participants identified as using......This study surveyed 188 music therapy educators regarding their views and use of feminist pedagogy and feminist music therapy. The purpose of this study was two-fold: (a) to determine how many music therapy educators used feminist pedagogy and (b) to determine if there was a relationship between...

  14. Electroconvulsive therapy revisited.

    Science.gov (United States)

    Atkinson, S D; Smith, C; Smith, E M; Miller, J M

    1991-05-01

    Electroconvulsive therapy (ECT) remains an extremely valuable tool in the treatment of certain psychiatric disorders. Despite the sensationalism of the past decade, ECT is the treatment of choice in severe depression that is unresponsive to other therapies or in patients who are overtly suicidal. In addition, ECT is particularly valuable in the elderly population, who are at risk for serious complications from the side effects associated with drug therapy. This report describes a case of recurrent depression in which ECT was successfully used. PMID:2072186

  15. Radiation Therapy (For Parents)

    Science.gov (United States)

    ... be some permanent changes to the color and elasticity of the skin. How can you help? Dress ... to Home and School Cancer Center Cancer Basics Types of Cancer Teens Get Radiation Therapy Chemotherapy Dealing ...

  16. External Radiation Therapy

    Medline Plus

    Full Text Available ... frequently used is radiation therapy. Gunnar Zagars, M.D.: There are different forms of radiation for prostate ... typical treatment takes seven weeks. Gunnar Zagars, M.D.: A patient comes in every day, Monday to ...

  17. Targeted therapies for cancer

    Science.gov (United States)

    ... to be untrue. Possible side effects from targeted therapies include: Diarrhea Liver problems Skin problems such as rash, dry skin, and nail changes Problems with blood clotting and wound healing High blood pressure As with any treatment, you ...

  18. Targeted Thrombolytic Therapy

    Institute of Scientific and Technical Information of China (English)

    胡豫

    2004-01-01

    @@ Venous and arterial thrombosis are closely related to many severe diseases, especially to cardiovascular and cerebrovasular disorders. Thrombolytic therapy has been proven to be an effective method to treat such disease, which decreased the mortality and morbidity greatly.

  19. [Physiotherapy as manual therapy].

    Science.gov (United States)

    Torstensen, T A; Nielsen, L L; Jensen, R; Reginiussen, T; Wiesener, T; Kirkesola, G; Mengshoel, A M

    1999-05-30

    Manual therapy includes methods where the therapist's hands are used to stretch, mobilize or manipulate the spinal column, paravertebral structures or extremity joints. The aims of these methods are to relieve pain and improve function. In Norway only specially qualified physiotherapists and chiropractors are authorized to perform manipulation of joints (high velocity thrust techniques). To become a qualified manual therapist in Norway one must have a minimum of two years of clinical practice as physiotherapist followed by two year full time postgraduate training in manual therapy (a total of six years). Historically the Norwegian manual therapy system was developed in the 1950s by physiotherapists and medical doctors in England (James Cyriax and James Mennell) and Norway. As a result doctors allowed physiotherapists to use manipulation as a treatment method of both spinal and peripheral joints. In 1957 the Norwegian health authorities introduced reimbursement for manual therapy performed by physiotherapists.

  20. Drug therapy smartens up

    Science.gov (United States)

    Martin, Christian

    2015-11-01

    The submission of the first 'smart pill' for market approval, combined with progress in the European nanomedicine landscape, illustrates the positive outlook for drug therapy and health monitoring, explains Christian Martin.

  1. External Radiation Therapy

    Medline Plus

    Full Text Available ... the treatment that is frequently used is radiation therapy. Gunnar Zagars, M.D.: There are different forms of radiation for prostate cancer. They really boil down to two different types. ...

  2. Home Oxygen Therapy

    Science.gov (United States)

    ... Oxygen Therapy Font: Aerosol Delivery Oxygen Resources Immunizations Pollution Nutrition Exercise Coming Of Age Older Adults Allergy ... oxygen is so cold it can hurt your skin. Keep a fire extinguisher close by, and let ...

  3. Interactional Gestalt Therapy.

    Science.gov (United States)

    Warehime, Robert G.

    1981-01-01

    Group gestalt therapy in which the leader facilitates the development of helping capacity in group members is described. The general characteristics of this approach are discussed and ground rules concerning leader and member behaviors are suggested. (RC)

  4. Occupational therapy evaluation

    DEFF Research Database (Denmark)

    Nielsen, Kristina Tomra; Wæhrens, Eva Ejlersen

    2014-01-01

    Background: The Occupational Therapy Intervention Process Model (OTIPM) serves to guide occupational therapists in their professional reasoning. The OTIPM prescribes evaluation of task performance based on both self-report and observation. Although this approach seems ideal, many clinicians raise...

  5. Therapy Provider Phase Information

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Therapy Provider Phase Information dataset is a tool for providers to search by their National Provider Identifier (NPI) number to determine their phase for...

  6. Photodynamic therapy in dermatology

    Directory of Open Access Journals (Sweden)

    Nayak Chitra

    2005-01-01

    Full Text Available Photodynamic therapy is a new modality of therapy being used for the diagnosis and treatment of many tumors. It is now being increasingly used for skin tumors and other dermatological disorders. With its range of application it is certainly the therapy of the future. Its mechanism of action is by the Type II photo-oxidative reaction. The variables are the photosensitizer, the tissue oxygenation and the light source. It has been used to treat various disorders including Bowen′s disease, actinic keratoses, squamous cell carcinomas, basal cell carcinomas, and mycosis fungoides. The side-effects are fortunately mild and transient. Newer photosensitisers like methyl aminolevulinate hold a lot of promise for better therapy.

  7. Proton beam therapy

    OpenAIRE

    Levin, W P; Kooy, H; Loeffler, J S; T. F. DeLaney

    2005-01-01

    Conventional radiation therapy directs photons (X-rays) and electrons at tumours with the intent of eradicating the neoplastic tissue while preserving adjacent normal tissue. Radiation-induced damage to healthy tissue and second malignancies are always a concern, however, when administering radiation. Proton beam radiotherapy, one form of charged particle therapy, allows for excellent dose distributions, with the added benefit of no exit dose. These characteristics make this form of radiother...

  8. Nanomedicine and cancer therapies

    CERN Document Server

    Sebastian, Mathew; Elias, Eldho

    2012-01-01

    Introduction Nanotechnological-Based Systems for CancerIn vivo Spectroscopy for Detection and Treatment of GBM with NPt® ImplantationNanobiotechnology for Antibacterial Therapy and DiagnosisChitosan NanoparticlesSynthesis and Biomedical Application of Silver NanoparticlesRecent Advances in Cancer Therapy Using PhytochemicalsMitochondrial Dysfunction and Cancer: Modulation by Palladium-Lipoic Acid ComplexUnity of Mind and Body: The Concept of Life Purpose DominantThuja Occidentalis and Breast Cancer ChemopreventionAntioxidants and Com

  9. Who needs pharmacologic therapy?

    Directory of Open Access Journals (Sweden)

    Christopher Porterfield; Rohit Malhotra

    2014-06-01

    Full Text Available Treatment of atrial fibrillation has evolved significantly in the last ten years, with ablation becoming a far more common form of treatment for this most common of arrhythmias. However, while ablation has become more common, certain populations derive continued benefit from the use of pharmacologic therapy for treatment. We review the use of pharmacologic therapy and novel considerations for treatment of atrial fibrillation.

  10. Intraoperative Stem Cell Therapy

    OpenAIRE

    Coelho, Mónica Beato; Cabral, Joaquim M. S.; Karp, Jeffrey M.

    2012-01-01

    Stem cells hold significant promise for regeneration of tissue defects and disease-modifying therapies. Although numerous promising stem cell approaches are advancing in clinical trials, intraoperative stem cell therapies offer more immediate hope by integrating an autologous cell source with a well-established surgical intervention in a single procedure. Herein, the major developments in intraoperative stem cell approaches, from in vivo models to clinical studies, are reviewed, and the poten...

  11. Antisense Therapy in Neurology

    OpenAIRE

    Lee, Joshua J.A.; Toshifumi Yokota

    2013-01-01

    Antisense therapy is an approach to fighting diseases using short DNA-like molecules called antisense oligonucleotides. Recently, antisense therapy has emerged as an exciting and promising strategy for the treatment of various neurodegenerative and neuromuscular disorders. Previous and ongoing pre-clinical and clinical trials have provided encouraging early results. Spinal muscular atrophy (SMA), Huntington’s disease (HD), amyotrophic lateral sclerosis (ALS), Duchenne muscular dystrophy (DMD)...

  12. Yoga therapy for Schizophrenia

    OpenAIRE

    N Gangadhar Bangalore; Shivarama Varambally

    2012-01-01

    Schizophrenia is one of the most severe mental disorders. Despite significant advances in pharmacotherapy, treatment remains sub-optimal, with many patients having persisting deficits, especially in cognitive and social functioning. Yoga as a therapy has proven to be effective as a sole or additional intervention in psychiatric disorders such as depression and anxiety. Recently, there has been significant interest in the application of yoga therapy in psychosis and schizophrenia. To review a)...

  13. YOGA THERAPY AND DISABILITY

    OpenAIRE

    Belia Méndez Rial

    2015-01-01

    Yoga is a useful supportive intervention for a broad range of pain-associated diseases. It is often recommended as therapy for a variety of medical conditions and it is rising popularity as therapy (Verrastro, 2014). Yoga is a system of movement and breathing exercises meant to foster mind-body connection. It creates inner, physical and emotional balance through the use of postures, called asanas, combined with breathing techniques or pranayama (Posadzki et al, 2011). Benefits are found in di...

  14. Practical procedures: oxygen therapy.

    Science.gov (United States)

    Olive, Sandra

    Knowing when to start patients on oxygen therapy can save lives, but ongoing assessment and evaluation must be carried out to ensure the treatment is safe and effective. This article outlines when oxygen therapy should be used and the procedures to follow. It also describes the delivery methods applicable to different patient groups, along with the appropriate target saturation ranges, and details relevant nurse competencies.

  15. Cognitive behavioural therapies versus other psychological therapies for depression.

    Science.gov (United States)

    Churchill, Rachel; Moore, Theresa Hm; Caldwell, Deborah; Davies, Philippa; Jones, Hannah; Furukawa, Toshi A; Lewis, Glyn; Hunot, Vivien

    2010-01-01

    This is the protocol for a review and there is no abstract. The objectives are as follows: To examine the effectiveness and acceptability of all CBT approaches compared with all other psychological therapy approaches for acute depressionTo examine the effectiveness and acceptability of different CBT approaches (cognitive therapy, rational emotive behaviour therapy, problem-solving therapy, self-control therapy and Coping with Depression course) compared with all other psychological therapy approaches for acute depression.To examine the effectiveness and acceptability of all CBT approaches compared with different psychological therapy approaches (psychodynamic, behavioural, humanistic, integrative, third wave CBT) for acute depression.

  16. Humanistic therapies versus other psychological therapies for depression.

    Science.gov (United States)

    Churchill, Rachel; Davies, Philippa; Caldwell, Deborah; Moore, Theresa Hm; Jones, Hannah; Lewis, Glyn; Hunot, Vivien

    2010-01-01

    This is the protocol for a review and there is no abstract. The objectives are as follows: To examine the effectiveness and acceptability of all humanistic therapies compared with all other psychological therapy approaches for acute depression.To examine the effectiveness and acceptability of different humanistic therapy models (person-centred, gestalt, process-experiential, transactional analysis, existential and non-directive therapies) compared with all other psychological therapy approaches for acute depression.To examine the effectiveness and acceptability of all humanistic therapies compared with different psychological therapy approaches (psychodynamic, behavioural, humanistic, integrative, cognitive-behavioural) for acute depression. PMID:25278809

  17. Concept Analysis: Music Therapy.

    Science.gov (United States)

    Murrock, Carolyn J; Bekhet, Abir K

    2016-01-01

    Down through the ages, music has been universally valued for its therapeutic properties based on the psychological and physiological responses in humans. However, the underlying mechanisms of the psychological and physiological responses to music have been poorly identified and defined. Without clarification, a concept can be misused, thereby diminishing its importance for application to nursing research and practice. The purpose of this article was for the clarification of the concept of music therapy based on Walker and Avant's concept analysis strategy. A review of recent nursing and health-related literature covering the years 2007-2014 was performed on the concepts of music, music therapy, preferred music, and individualized music. As a result of the search, the attributes, antecedents, and consequences of music therapy were identified, defined, and used to develop a conceptual model of music therapy. The conceptual model of music therapy provides direction for developing music interventions for nursing research and practice to be tested in various settings to improve various patient outcomes. Based on Walker and Avant's concept analysis strategy, model and contrary cases are included. Implications for future nursing research and practice to use the psychological and physiological responses to music therapy are discussed. PMID:27024999

  18. Psychodynamic Music Therapy

    Directory of Open Access Journals (Sweden)

    Jinah Kim

    2016-07-01

    Full Text Available This paper introduces and explores the basic principles of psychodynamic approaches in music therapy. Music is used as a means to explore both conscious and unconscious issues as well as the internal world of the individuals involved in music therapy. However, the focus of therapy is on therapeutic relationship, especially the dynamics of transference and counter-transference between the client and the music therapist. Musical experiences, such as music listening, songs, and improvisation, can be used to facilitate the therapeutic processes, and to achieve individualized therapeutic goals. When clinically appropriate, verbal processing might play as crucial a role as the musical processing. Practitioners of psychodynamic approaches often strive to gain meaning and in-depth understandings from therapeutic experiences, and the approach is therefore suitable for individuals who are ready to work through their personal issues within a therapeutic relationship. Various approaches and techniques have been developed in psychotherapy as well as in music therapy. Perhaps the only commonality in these approaches is that psychodynamic thinking informs the direction of the therapy and therapeutic processes. Clinical vignettes will be introduced within the article to highlight a triadic dynamic—the client, the music therapist, and the music—in order to illustrate the core aspects of psychodynamic music therapy.

  19. Cellular therapy in Tuberculosis

    Directory of Open Access Journals (Sweden)

    Shreemanta K. Parida

    2015-03-01

    Full Text Available Cellular therapy now offer promise of potential adjunct therapeutic options for treatment of drug-resistant tuberculosis (TB. We review here the role of Mesenchymal stromal cells, (MSCs, as well as other immune effector cells in the therapy of infectious diseases with a focus on TB. MSCs represent a population of tissue-resident non-hematopoietic adult progenitor cells which home into injured tissues increase the proliferative potential of broncho-alveolar stem cells and restore lung epithelium. MSCs have been shown to be immune-modulatory and anti-inflammatory mediated via cell-cell contacts as well as soluble factors. We discuss the functional profile of MSCs and their potential use for adjunct cellular therapy of multi-drug resistant TB, with the aim of limiting tissue damage, and to convert unproductive inflammatory responses into effective anti-pathogen directed immune responses. Adjunct cellular therapy could potentially offer salvage therapy options for patients with drug-resistant TB, increase clinically relevant anti-M.tuberculosis directed immune responses and possibly shorten the duration of anti-TB therapy.

  20. Fertility and cancer therapy

    Energy Technology Data Exchange (ETDEWEB)

    Maguire, L.C.

    1979-05-01

    With increased survival of increasing numbers of cancer patients as a result of therapy, the consequences, early and late, of the therapies must be realized. It is the treating physician's duty to preserve as much reproductive potential as possible for patients, consistent with adequate care. With radiotherapy this means shielding the gonads as much as possible, optimal but not excessive doses and fields, oophoropexy, or sperm collection and storage prior to irradiation. With chemotherapy it means the shortest exposure to drugs consistent with best treatment and prior to therapy the collection and storage of sperm where facilities are available. At present this is still an experimental procedure. Artificial insemination for a couple when the male has received cancer therapy is another alternative. Finally, it is the responsibility of physicians caring for patients with neoplasms to be knowledgeable about these and all other effects of therapy so that patients may be counseled appropriately and understand the implications of therapy for their life.

  1. Concept Analysis: Music Therapy.

    Science.gov (United States)

    Murrock, Carolyn J; Bekhet, Abir K

    2016-01-01

    Down through the ages, music has been universally valued for its therapeutic properties based on the psychological and physiological responses in humans. However, the underlying mechanisms of the psychological and physiological responses to music have been poorly identified and defined. Without clarification, a concept can be misused, thereby diminishing its importance for application to nursing research and practice. The purpose of this article was for the clarification of the concept of music therapy based on Walker and Avant's concept analysis strategy. A review of recent nursing and health-related literature covering the years 2007-2014 was performed on the concepts of music, music therapy, preferred music, and individualized music. As a result of the search, the attributes, antecedents, and consequences of music therapy were identified, defined, and used to develop a conceptual model of music therapy. The conceptual model of music therapy provides direction for developing music interventions for nursing research and practice to be tested in various settings to improve various patient outcomes. Based on Walker and Avant's concept analysis strategy, model and contrary cases are included. Implications for future nursing research and practice to use the psychological and physiological responses to music therapy are discussed.

  2. Adenovirus Vectors for Gene Therapy, Vaccination and Cancer Gene Therapy

    OpenAIRE

    Wold, William S.M.; Toth, Karoly

    2013-01-01

    Adenovirus vectors are the most commonly employed vector for cancer gene therapy. They are also used for gene therapy and as vaccines to express foreign antigens. Adenovirus vectors can be replication-defective; certain essential viral genes are deleted and replaced by a cassette that expresses a foreign therapeutic gene. Such vectors are used for gene therapy, as vaccines, and for cancer therapy. Replication-competent (oncolytic) vectors are employed for cancer gene therapy. Oncolytic vector...

  3. Application research on preparation of fat-mimetics by extruding corn starch starch with enzyme in ice cream%玉米淀粉基脂肪模拟物在冰淇淋中的应用研究

    Institute of Scientific and Technical Information of China (English)

    郭艳莉; 肖志刚; 王利民; 郑广钊; 严棣

    2012-01-01

    Aiming at the problems of various diseases on humans caused by long-term eating high-fat food, solution plan was put forward combined with the application of fat-mimetics in food. The application of fat-mimetics in ice cream showed that with the increase of fat substitution rate the index such as hardness, flexibility, cohesive-ness, gumminess and chewiness in ice cream sample increased gradually, expansion rate of ice cream decreased gradually, ant melting property in ice cream increased gradually. When fat substitution rate was 0%, G" (viscous modulus) of ice cream was bigger than G' . When fat substitution rate was 25% , 50% and 75%, G" of ice cream sample was bigger than G (elastic modulus) in low frequency area, while was smaller in high frequency area. When fat substitution rate was 100% , G' of ice cream was bigger than G" in frenquency range. There was a significant dependence between viscoelastic and frenquency in ice cream added fat-mimetics. With the increasement of frenquency, viscous and elastic both increased, as well as the development of fat substitution rate. The order of sensory evaluatin index of ice cream by principal component analysis was mouth melt>soapy feeling>-fatty sense>milk powder taste>ropiness sense. The order of five ice cream samples by fuzzymathematics analysis was M1 > M2 > M3> M4> M5.%针对人类长期食用高脂肪类食品而引起的各种疾病的问题,文章结合脂肪模拟物在食品中的应用,提出解决方案.利用加酶挤压的方法制备脂肪模拟物,将玉米淀粉基脂肪模拟物应用到冰淇淋中可知,随着冰淇淋中脂肪替代率的增加,不同冰淇淋样品的硬度、弹性、黏聚性、黏合性、咀嚼性逐渐增加,膨胀率越来越低,冰淇淋的抗融化性逐渐增强,脂肪替代率为0%的全脂冰淇淋的G″(黏性模量)大于G ′(弹性模量),脂肪替代率为25%,50%,75%的冰淇淋样品在低频率区域G″大于G ′,在高频率区域内G″大于G

  4. Application on mimetic fat with mung bean starch as matrix in low-fat clyster%绿豆淀粉模拟脂肪在低脂灌肠中的应用

    Institute of Scientific and Technical Information of China (English)

    毛迪锐; 岳云蛟

    2011-01-01

    Fat pork, mung starch mimetic fat. Starch, and water were used as the raw material of low-fat clyster . Through orthogonal experiment, the effectors on products quality were discussed, such as the ratio of mung bean starch mimetic fat to fat pork, the additive a-■nounts of water and starch. The results was showed: As a benchmark in the adding amount of meat,the best formula is starch 15%, water 18%, salt 2. 5%, simulated fat to the pork fat 40%. Fat pork ratio 3 : 7. Compared to the non-simulated fat sausage, the cooking loss of the low-fat clyster decreased, adhesion increased, water retention rate increased, fst content reduced. Freeze-thaw stability has increased, which avoids sausage retrogradation and increases the storage stability of the products.%以肥瘦猪肉、绿豆淀粉模拟脂肪、水、淀粉等为原料研制低脂灌肠,通过正交试验,分别讨论绿豆淀粉模拟脂肪占猪肥臊的比例、水和淀粉的添加量对产品品质的影响.结果表明,低脂灌肠的最佳配方:以肉的添加量为基准,淀粉的添加量为15%、水为18%、盐为2.5%、模拟脂肪添加量为猪肥膘的40%、肥瘦猪肉比例为3;7,所得到的灌肠与未添加模拟脂肪的灌肠相比较,其蒸煮损失减少,黏着性增加,保水率增加,脂肪含量减少,冻融稳定性有所提高,使得灌肠不易发生回生,增加了产品的储藏稳定性.

  5. Depigmentation therapies in vitiligo

    Directory of Open Access Journals (Sweden)

    Divya Gupta

    2012-01-01

    Full Text Available Depigmentation therapy in vitiligo is an option in those with extensive vitiligo who have failed to respond to medical therapy and have obvious cosmetic disfigurement due to intervening patchy pigmented areas. Various aspects of this therapy such as the cost, treatment time, course, permanency of depigmentation, side effects, and the possibility of repigmentation should first be discussed with the patient. At present, there is no ideal depigmenting therapy available, but many agents in the market have been in use for many years. Monobenzyl ether of hydroquinone (MBEH is the mainstay and Food and Drug Administration (FDA approved in USA but takes many months to depigment and is associated with local side effects and risk of repigmentation. Other agents which are also used are 4-methoxy phenol and 88% phenol. Physical therapies for depigmentation include Q-switched ruby and alexandrite lasers and cryotherapy. Second-line agents which can be explored for depigmentation include imatinib mesylate, imiquimod, and diphencyprone. Many possible experimental agents are being explored like various phenol derivatives, melanoma vaccines, interferon gamma, busulfan, etc. A major lacuna still exists in this area and a lot more research is desirable to give satisfactory cosmesis to these patients with extensive vitiligo.

  6. [Systemic therapy of rosacea].

    Science.gov (United States)

    Schaller, M; Belge, K

    2013-07-01

    The only medication which is authorized for therapy of rosacea is doxycycline. It is usually administered at a dose of 40-100 mg daily for 3-6 months. In case of a lack of efficacy or in case of contraindications (e.g. pregnancy, children below 8 years), azithromycin or metronidazole are alternative systemic therapies. Those forms of rosacea which involve hyperplasia of sebaceous glands respond well to retinoids such as isotretinoin. Dapsone has been successfully used for the treatment of granulomatous rosacea and rosacea fulminans. Erythema can be reduced by use of beta blockers. If patients do not respond to various therapies or if they are immunocompromised, the differential diagnosis of demodicosis should be considered; here the treatment is oral ivermectin. Some forms of rosacea (rosacea fulminans and granulomatous rosacea) may be treated initially with oral corticosteroids. Ophthalmic rosacea is treated topically as well as with tetracyclines or macrolides.

  7. Hormonal therapy for acne.

    Science.gov (United States)

    George, Rosalyn; Clarke, Shari; Thiboutot, Diane

    2008-09-01

    Acne affects more than 40 million people, of which more than half are women older than 25 years of age. These women frequently fail traditional therapy and have high relapse rates even after isotretinoin. Recent advances in research have helped to delineate the important role hormones play in the pathogenesis of acne. Androgens such as dihydrotestosterone and testosterone, the adrenal precursor dehydroepiandrosterone sulfate, estrogens, growth hormone, and insulin-like growth factors may all contribute to the development of acne. Hormonal therapy remains an important part of the arsenal of acne treatments available to the clinician. Women dealing with acne, even those without increased serum androgens, may benefit from hormonal treatments. The mainstays of hormonal therapy include oral contraceptives and antiandrogens such as spironolactone, cyproterone acetate, or flutamide. In this article, we discuss the effects of hormones on the pathogenesis of acne, evaluation of women with suspected endocrine abnormalities, and the myriad of treatment options available. PMID:18786497

  8. Bacteriophage therapy against Enterobacteriaceae

    Institute of Scientific and Technical Information of China (English)

    Youqiang; Xu; Yong; Liu; Yang; Liu; Jiangsen; Pei; Su; Yao; Chi; Cheng

    2015-01-01

    The Enterobacteriaceae are a class of gram-negative facultative anaerobic rods, which can cause a variety of diseases, such as bacteremia, septic arthritis, endocarditis, osteomyelitis, lower respiratory tract infections, skin and soft-tissue infections, urinary tract infections, intra-abdominal infections and ophthalmic infections, in humans, poultry, animals and fish. Disease caused by Enterobacteriaceae cause the deaths of millions of people every year, resulting in enormous economic loss. Drug treatment is a useful and efficient way to control Enterobacteriaceae infections. However, with the abuse of antibiotics, drug resistance has been found in growing number of Enterobacteriaceae infections and, as such, there is an urgent need to find new methods of control. Bacteriophage therapy is an efficient alternative to antibiotics as it employs a different antibacterial mechanism. This paper summarizes the history of bacteriophage therapy, its bacteriallytic mechanisms, and the studies that have focused on Enterobacteriaceae and bacteriophage therapy.

  9. Targeted cancer therapies

    Institute of Scientific and Technical Information of China (English)

    Li Yan; Neal Rosen; Carlos Arteaga

    2011-01-01

    With unprecedented understanding of molecular events underlying human cancer in this genomic era, a large number of drugs specifically targeting hypothesized oncogenic drivers to which tumors are potentially addicted to have been developed and continue to be developed. These targeted cancer therapies are being actively tested in clinical trials with mixed successes. This editorial provides an overview on successful targeted cancer drugs on the market and those drugs that are in late clinical development stages. Importantly, the article lays out main challenges in developing molecular targeted therapies and potential path forward to overcome these challenges, as well as opportunities for China in this new era of targeted agents. The editorial serves as an introduction to the Targeted Cancer Therapies serias that will review in depth of major pathways and drugs targeting these pathways to be published in the coming issues of the Chinese Journal of Cancer.

  10. Laser therapy for periodontitis

    Science.gov (United States)

    Efanov, O. I.

    2001-04-01

    An investigation was made of applying pulsed (lambda) equals 0.89 micrometers laser radiation in the treatment for early diagnosed periodontitis. The investigation was made on 65 patients (47 patients constituted the experimental group and 18 patients constituted a control group) affected by periodontitis. Clinical and functional tests revealed that laser therapy produced a string effect on the course of the illness. It reduced bleeding, inflammation, and pruritus. However, it did not produce an affect on electroexcitation. Biomicroscopic examinations and periodontium rheography revealed that the gingival blood flow became normal after the course of laser therapy. The capillary permeability and venous congestion decreased, which was confirmed by the increased time of vacuum tests, raised gingival temperature, reduced tissue clearance, and increased oxygen tension. Apart from that, laser therapy subsided fibrinolysis, proteolytic tissue activity, and decreased the exudative inflammation of periodontium.

  11. Music Therapy in Europe

    DEFF Research Database (Denmark)

    2015-01-01

    Professional development and recognition is an 'old' issue in music therapy but still a relevant, complex and crucial one. Burning questions regarding professionalisation are at the forefront of most music therapy associations’ agendas across Europe and beyond, and feed back directly to the work...... of the EMTC. Considering the wider political, socio-economic, cultural and disciplinary aspects of professionalisation, different development pathways impact directly on music therapy practice, training, ethics, professional collaboration and employment conditions. Although a number of endeavours have been...... implemented regarding music therapy’s professional development and recognition in different countries, documentation and sharing of such endeavours on international level has been limited and scattered. Drawing from the EMTC’s work since the early ‘90s, as well as from colleagues’ experiences (and struggles...

  12. [Therapy and suggestion].

    Science.gov (United States)

    Barrucand, D; Paille, F

    1986-12-01

    Therapy and suggestion are closely related. That is clear for the ancient time: primitive medicine gives a good place to the Word. In plant, animal or mineral remedies, the suggestion is clearly preponderant. Towards the end of the 19th century, the "Ecole de Nancy" sets up a real theory of the suggestion, and Bernheim, its leader, bases hypnosis, then psychotherapy on this concept. Thereafter Coué will bring up the "conscious autosuggestion". Today, despite the progress of scientific medicine, the part of suggestion is still very important in medical therapy (with or without drugs), or in chirurgical therapy; this part is also very important in psychotherapies, whatever has been said in this field. This has to be known and used consciously in the doctor-patient relation, which is always essential in the therapeutic effectiveness.

  13. Psychodynamic therapies versus other psychological therapies for depression.

    Science.gov (United States)

    Churchill, Rachel; Moore, Theresa Hm; Davies, Philippa; Caldwell, Deborah; Jones, Hannah; Lewis, Glyn; Hunot, Vivien

    2010-01-01

    This is the protocol for a review and there is no abstract. The objectives are as follows: To examine the effectiveness and acceptability of all psychodynamic therapy approaches compared with all other psychological therapy approaches for acute depression.To examine the effectiveness and acceptability of different psychodynamic therapy approaches (drive/structural, relational and integrative analytic models) compared with all other psychological therapy approaches for acute depression.To examine the effectiveness and acceptability of all psychodynamic therapy approaches compared with different psychological therapy approaches (behavioural, humanistic, integrative, cognitive-behavioural, 'third-wave' CBT) for acute depression.

  14. Pharmacologic Therapies in Anticoagulation.

    Science.gov (United States)

    Ferreira, Joana Lima; Wipf, Joyce E

    2016-07-01

    Anticoagulants are beneficial for prevention and treatment of venous thromboembolism and stroke prevention in atrial fibrillation. The development of target-specific oral anticoagulants is changing the landscape of anticoagulation therapy and created growing interest on this subject. Understanding the pharmacology of different anticoagulants is the first step to adequately treat patients with best available therapy while avoiding serious bleeding complications. This article reviews the pharmacology of the main anticoagulant classes (vitamin K antagonists, direct oral anticoagulants, and heparins) and their clinical indications based on evidence-based data currently available in the literature. PMID:27235611

  15. Anticholinerge Therapie der OAB

    Directory of Open Access Journals (Sweden)

    Hampel C

    2007-01-01

    Full Text Available Kenntnisse über Differentialdiagnostik und Pathophysiologie des Blasenüberaktivitäts-Syndroms sind essentiell für eine erfolgreiche Therapie. Obwohl Verhaltenstraining und Elektrostimulation ihre Wirksamkeit bei OAB bewiesen haben, ist die Therapie der ersten Wahl nach wie vor die anticholinerge Behandlung. Dessen ungeachtet ist die Einnahmetreue der Patienten unbefriedigend, was in der letzten Zeit zu verschiedenen Medikamentenneuentwicklungen mit verbesserter Verträglichkeit bei gleichbleibend hoher Effektivität geführt hat. Retard-Formulierungen, extraenterale Applikationswege und Rezeptor-Subselektivität sind hierbei die Prinzipien, welche die Behandlungsakzeptanz und Patientenzufriedenheit steigern sollen.

  16. Spa therapy in dermatology

    Directory of Open Access Journals (Sweden)

    Najeeba Riyaz

    2011-01-01

    Full Text Available Spa therapy constitutes the use of mineral springs and thermal mud to soothe and heal various ailments. Like the mineral springs, seas and oceans are also important centers for spa therapy of which the most important is Dead Sea (DS. DS has been famous for thousands of years for its miraculous curative and cosmetic properties. Intensive research is going on using DS minerals in a wide range of dermatological conditions especially psoriasis, atopic dermatitis, vitiligo and other eczemas and several papers have been published in various international and pharmacological journals.

  17. Gene therapy for brain tumors.

    Science.gov (United States)

    Bansal, K; Engelhard, H H

    2000-09-01

    "Gene therapy" can be defined as the transfer of genetic material into a patient's cells for therapeutic purposes. To date, a diverse and creative assortment of treatment strategies utilizing gene therapy have been devised, including gene transfer for modulating the immune system, enzyme prodrug ("suicide gene") therapy, oncolytic therapy, replacement/therapeutic gene transfer, and antisense therapy. For malignant glioma, gene-directed prodrug therapy using the herpes simplex virus thymidine kinase gene was the first gene therapy attempted clinically. A variety of different strategies have now been pursued experimentally and in clinical trials. Although, to date, gene therapy for brain tumors has been found to be reasonably safe, concerns still exist regarding issues related to viral delivery, transduction efficiency, potential pathologic response of the brain, and treatment efficacy. Improved viral vectors are being sought, and potential use of gene therapy in combination with other treatments is being investigated.

  18. A Special Extract of Bacopa monnieri (CDRI-08-Restored Memory in CoCl2-Hypoxia Mimetic Mice Is Associated with Upregulation of Fmr-1 Gene Expression in Hippocampus

    Directory of Open Access Journals (Sweden)

    Anupama Rani

    2015-01-01

    Full Text Available Fragile X mental retardation protein (FMRP is a neuronal translational repressor and has been implicated in learning, memory, and cognition. However, the role of Bacopa monnieri extract (CDRI-08 in enhancing cognitive abilities in hypoxia-induced memory impairment via Fmr-1 gene expression is not known. Here, we have studied effects of CDRI-08 on the expression of Fmr-1 gene in the hippocampus of well validated cobalt chloride (CoCl2-induced hypoxia mimetic mice and analyzed the data with alterations in spatial memory. Results obtained from Morris water maze test suggest that CoCl2 treatment causes severe loss of spatial memory and CDRI-08 is capable of reversing it towards that in the normal control mice. Our semiquantitative RT-PCR, Western blot, and immunofluorescence microscopic data reveal that CoCl2-induced hypoxia significantly upregulates the expression of Hif-1α and downregulates the Fmr-1 expression in the hippocampus, respectively. Further, CDRI-08 administration reverses the memory loss and this is correlated with significant downregulation of Hif-1α and upregulation of Fmr-1 expression. Our data are novel and may provide mechanisms of hypoxia-induced impairments in the spatial memory and action of CDRI-08 in the recovery of hypoxia led memory impairment involving Fmr-1 gene encoded protein called FMRP.

  19. Gene therapy: An overview

    Directory of Open Access Journals (Sweden)

    Sudip Indu

    2013-01-01

    Full Text Available Gene therapy "the use of genes as medicine" involves the transfer of a therapeutic or working copy of a gene into specific cells of an individual in order to repair a faulty gene copy. The technique may be used to replace a faulty gene, or to introduce a new gene whose function is to cure or to favorably modify the clinical course of a condition. The objective of gene therapy is to introduce new genetic material into target cells while causing no damage to the surrounding healthy cells and tissues, hence the treatment related morbidity is decreased. The delivery system includes a vector that delivers a therapeutic gene into the patient′s target cell. Functional proteins are created from the therapeutic gene causing the cell to return to a normal stage. The vectors used in gene therapy can be viral and non-viral. Gene therapy, an emerging field of biomedicine, is still at infancy and much research remains to be done before this approach to the treatment of condition will realize its full potential.

  20. Sex Therapy and Mastectomy

    Science.gov (United States)

    Witkin, Mildred Hope

    1975-01-01

    Because the emotional trauma associated with a mastectomy exceeds the physical trauma, the recovery of the woman is greatly affected by the response of her husband or lover. Sex therapy, therefore, involves the couple. The approach described is aimed at assisting the couple to confront and integrate the mastectomy experience. (Author)

  1. Adjuvant Therapy: Melanoma

    Directory of Open Access Journals (Sweden)

    Diwakar Davar

    2011-01-01

    Full Text Available With an incidence that is increasing at 2–5% per year, cutaneous melanoma is an international scourge that disproportionately targets young individuals. Despite much research, the treatment of advanced disease is still quite challenging. Immunotherapy with high-dose interferon-α2b or interleukin-2 benefits a select group of patients in the adjuvant and metastatic settings, respectively, with significant attendant toxicity. Advances in the biology of malignant melanoma and the role of immunomodulatory therapy have produced advances that have stunned the field. In this paper, we review the data for the use of interferon-α2b in various dosing ranges, vaccine therapy, and the role of radiotherapy in the adjuvant setting for malignant melanoma. Recent trials in the metastatic setting using anticytoxic T-lymphocyte antigen-4 (anti-CTLA-4 monoclonal antibody therapy and BRAF inhibitor therapy have demonstrated clear benefit with prolongation of survival. Trials investigating combinations of these novel agents with existing immunomodulators are at present underway.

  2. Advances in Antiplatelet Therapy

    Institute of Scientific and Technical Information of China (English)

    包承鑫

    2006-01-01

    @@ Platelets play a central role in hemostasis and thrombosis but also in the initation of atherosclerosis making platelet receptors and there intracellular signaling pathways important molecular targets for antithrombotic and anti-inflammatory therapy.Therapeutic targeting of platelets has two objectives:prevention of vessel occlusion and inhibition of the platelet contribution to lesion progression.

  3. Adventure Therapy with Youth

    Science.gov (United States)

    Norton, Christine Lynn; Tucker, Anita; Russell, Keith C.; Bettmann, Joanna E.; Gass, Michael A.; Gillis, H. L.; Behrens, Ellen

    2014-01-01

    This state of knowledge article provides an overview of Adventure Therapy (AT) as it is practiced with adolescents in North America, presenting (a) current findings in AT research with adolescents, (b) critical issues in AT, (c) the need for training and professional development in AT, and (d) professionalization in AT. Implications of current…

  4. Antiproton Cancer Therapy

    DEFF Research Database (Denmark)

    Bassler, Niels

    Antiprotons are interesting as a modality in radiation therapy for the following reasons: When fast antiprotons penetrate matter, they behave as protons. Well before the Bragg-peak, protons and antiprotons have near identical stopping powers exhibit equal radiobiology. But when the antiprotons co...

  5. Tumor therapy evaluation

    International Nuclear Information System (INIS)

    The aim of this program is to acquire data in order to evaluate the advantages of the proton spot scan technique compared to other forefront radiotherapy procedures, and to integrate the diagnostic and therapeutic possibilities of the life science department for human cancer therapy by testing it in veterinary radio-oncology. (author) 1 fig., 2 tab., 2 refs

  6. Botulinum Toxin Therapy

    Science.gov (United States)

    ... resources Meet our partners Español Donate Diseases and treatments Acne and rosacea Bumps and growths Color problems Contagious skin diseases ... toxin therapy public SPOT Skin Cancer™ Diseases and treatments Acne and rosacea Bumps and growths Color problems Contagious skin diseases ...

  7. Marketing occupational therapy.

    Science.gov (United States)

    Jacobs, K

    1987-05-01

    Marketing is emerging as an important aspect of the delivery of health care services, including occupational therapy. An understanding of marketing and a knowledge of how to apply its principles will permit therapists to keep pace with the changing health care environment. This article introduces terminology, strategies, and applications of marketing. PMID:3688145

  8. Weekend therapy in diabetes.

    Science.gov (United States)

    Kalra, Sanjay; Gupta, Yashdeep

    2016-05-01

    This article introduces the concept of "weekend therapy", which has now become reality in diabetes. It briefly describes injectable and oral drugs which are currently available, or are in advanced stages of development, for use in once weekly administration. These include dulaglutide, exenatide QW, semaglutide, omarigliptin and trelagliptin. PMID:27183953

  9. Medical nutrition therapy planning

    Directory of Open Access Journals (Sweden)

    Torović Ljilja

    2010-01-01

    Full Text Available Introduction. Diet has vital, preventive and therapeutic functions. Medical nutrition therapy is a part of the Standardized Nutrition Care Process integrated in health care systems. Material and methods. An overview of the Nutrition Care Process model and the application of nutrition guidelines based on literature, reports, documents and programmes of international health, food and physical activity authorities was done. Results. The Nutrition Care Process model requires registered dieticians, standardized terminology as well as nutrition diagnosis categorization. It consists of four distinct, but interrelated and connected steps: (a nutrition assessment, (b nutrition diagnosis, (c nutrition intervention, and (d nutrition monitoring and evaluation. An individual approach is essential for successful medical nutrition therapy. Nutrition guidelines facilitate the process of understanding and application of medical nutrition therapy. Conclusion. The Nutrition Care process provides dietetic professionals information on high-quality client nutrition care. The success of medical nutrition therapy rests not only upon the advice of the dietician, but also upon the client’s compliance.

  10. Obstructive sleep apnea therapy

    NARCIS (Netherlands)

    Hoekema, A.; Stegenga, B.; Wijkstra, P. J.; van der Hoeven, J. H.; Meinesz, A. F.; de Bont, L. G. M.

    2008-01-01

    In clinical practice, oral appliances are used primarily for obstructive sleep apnea patients who do not respond to continuous positive airway pressure (CPAP) therapy. We hypothesized that an oral appliance is not inferior to CPAP in treating obstructive sleep apnea effectively. We randomly assigned

  11. Yoga therapy for Schizophrenia

    Directory of Open Access Journals (Sweden)

    N Gangadhar Bangalore

    2012-01-01

    Full Text Available Schizophrenia is one of the most severe mental disorders. Despite significant advances in pharmacotherapy, treatment remains sub-optimal, with many patients having persisting deficits, especially in cognitive and social functioning. Yoga as a therapy has proven to be effective as a sole or additional intervention in psychiatric disorders such as depression and anxiety. Recently, there has been significant interest in the application of yoga therapy in psychosis and schizophrenia. To review a the evidence for the use of yoga therapy in patients with schizophrenia b studies which have been done in this area, c the barriers for reaching yoga to patients, and d future directions, an English language literature search of PubMed/MEDLINE, Google Scholar, and EBSCO as well as grey literature was done. Research reports have demonstrated the feasibility and efficacy of yoga as an add-on therapy in schizophrenia, particularly in improving negative symptomatology and social cognition. However, the biological underpinnings of this effect remain unclear, although there are some indications that hormones like oxytocin may contribute to the changes in social cognition.

  12. YOGA THERAPY AND DISABILITY

    Directory of Open Access Journals (Sweden)

    Belia Méndez Rial

    2015-05-01

    Full Text Available Yoga is a useful supportive intervention for a broad range of pain-associated diseases. It is often recommended as therapy for a variety of medical conditions and it is rising popularity as therapy (Verrastro, 2014. Yoga is a system of movement and breathing exercises meant to foster mind-body connection. It creates inner, physical and emotional balance through the use of postures, called asanas, combined with breathing techniques or pranayama (Posadzki et al, 2011. Benefits are found in different areas: Physical benefits (e.g.: flexibility, coordination, strength, endurance mental benefits (e.g.: to develop greater awareness, diminish anxiety and reduction of distress, positive behavioural changes, improvement mood, facilitate positive emotions and optimism, broaden cognitive processes and enhance self- efficacy for pain control or social (e.g.: to reduce isolation, to foster social networks and reinforce social support. Researches show that even despite persistent pain symptoms, patients recognize that they are able to be physically active, they experience higher self-competence and self-awareness, which contributes to higher quality of life. Moreover, yoga therapy is a safe and beneficial supportive treatment, relatively cheap, it requires just the motivation of patients (Posadzki et al, 2011; Büsing et al, 2012 and a good professional support. Objectives: The aim of this review it is to determine what are the topics of the researches about Yoga therapy and disability.   

  13. Principles of radiation therapy

    International Nuclear Information System (INIS)

    This chapter reviews (a) the natural history of metastatic bone disease in general terms and as it impacts on the use of radiation as therapy; (b) the clinical and radiographic evaluations used to guide the application of irradiation; and (c) the methods, results, and toxicities of various techniques of irradiation

  14. External Radiation Therapy

    Medline Plus

    Full Text Available ... prostate or when the patient is older the treatment that is frequently used is radiation therapy. Gunnar Zagars, M.D.: There are different forms ... different types. There's what we call external beam treatment, which is given from an x-ray machine, ...

  15. Indomethacin therapy in hydramnios.

    Directory of Open Access Journals (Sweden)

    Abhyankar S

    2000-07-01

    Full Text Available AIM: The use of indomethacin in treatment of hydramnios was evaluated. SUBJECTS & METHODS: Twelve patients with symptomatic hydramnios were treated with indomethacin (2.2- 3.0 mg/kg body weight/day. RESULTS: The treatment was started at a gestational age of 31.17-/+7.94 weeks and continued for 3.74-/+2.3 weeks. Eleven patients responded to the therapy both subjectively and objectively and pregnancies were prolonged by 4.6-/+3.1 weeks (range 0.1-10 weeks. Five women had term deliveries. Six patients had a favourable perinatal outcome. Four patients who had a known congenital anomaly in the foetus, delivered stillborn babies or had an early neonatal death. One patient who did not follow up after commencing therapy delivered a full-term stillbirth. One patient delivered within 1 day of starting therapy. Indomethacin therapy caused no maternal complications. CONCLUSION: Indomethacin was effective in the management of hydramnios and preventing it′s complications.

  16. Adlerian Family Therapy.

    Science.gov (United States)

    Dinkmeyer, Don; Dinkmeyer, Don, Jr.

    1981-01-01

    Discusses the competencies basic to Adlerian therapy--including influencing psychological movement, working with the family communication system, focusing on the real issue, aligning goals and dealing with resistance, stimulating social interest, encouragement, and tentative hypotheses, and antisuggestion. A specific process for helping the family…

  17. Complementary and Integrative Therapies

    Science.gov (United States)

    ... claims. No complementary therapy has been proven to cure cancer. If this claim is made, it’s not true. Find out what research has been done. Your doctor can be a good source of this information. 5 Natural does not mean safe. While the idea of ...

  18. Cybernetics of Brief Family Therapy.

    Science.gov (United States)

    Keeney, Bradford P.; Ross, Jeffrey M.

    1983-01-01

    Presents a cybernetic view of brief family therapy. Includes a historical discussion of the key ideas underlying brief family therapy, a cybernetic model of therapeutic change, and a clinical case for exemplification. (Author/JAC)

  19. Targeted therapy for pediatric glioma

    NARCIS (Netherlands)

    A.K. Olow

    2015-01-01

    This thesis assesses molecular underpinnings of responses to promising targeted agents for pediatric tumors of Central Nervous System (CNS), incorporating preclinical testing of novel and translatable combination therapies to define the best therapy for each tumor cell specific molecular aberration.

  20. [Manual therapy in general practice].

    Science.gov (United States)

    Березуцкий, Владимир И

    2016-01-01

    The article is devoted to manual therapy practice for diagnostics and treatment of vertebrogenic pain syndrome in general practice. Analytical roundup of sources proves medical advantage of implementation of manual therapy basic methods by general practice specialists.

  1. Radiation Therapy for Skin Cancer

    Science.gov (United States)

    ... skin cells called melanocytes that produce skin color ( melanin ). Radiation therapy is used mostly for melanomas that ... in addition to surgery, chemotherapy or biologic therapy. Hair Epidermis Dermis Subcutaneous Hair Follicle Vein Artery © ASTRO ...

  2. Population Health and Occupational Therapy.

    Science.gov (United States)

    Braveman, Brent

    2016-01-01

    Occupational therapy practitioners play an important role in improving the health of populations through the development of occupational therapy interventions at the population level and through advocacy to address occupational participation and the multiple determinants of health. This article defines and explores population health as a concept and describes the appropriateness of occupational therapy practice in population health. Support of population health practice as evidenced in the official documents of the American Occupational Therapy Association and the relevance of population health for occupational therapy as a profession are reviewed. Recommendations and directions for the future are included related to celebration of the achievements of occupational therapy practitioners in the area of population health, changes to the Occupational Therapy Practice Framework and educational accreditation standards, and the importance of supporting, recognizing, rewarding, and valuing occupational therapy practitioners who assume roles in which direct care is not their primary function.

  3. Screening for the mimetic homologous oligopeptides of keratins 14 and 17 related with psoriasis from phage random peptide library%应用噬菌体肽库研究银屑病相关的角蛋白K14,K17模拟表位

    Institute of Scientific and Technical Information of China (English)

    张亮; 刘玉峰; 杨乔欣; 任君萍; 黎志东

    2001-01-01

    目的获得与银屑病相关的角蛋白K14和K17同源序列的模拟表位,评估含有此基序的短肽与银屑病发病的关系. 方法将1株抗角蛋白K14和K17同源序列的单克隆抗体(mAb)5G5经亲和层析纯化后进行生物素标记,对噬菌体递呈的随机6肽库进行3轮淘洗并进行ELISA检测. 挑取10个阳性克隆进行DNA测序,分析所获数据,并进行竞争阻断实验. 结果氨基酸序列分析表明模拟短肽的基序为VL(x)AG,角蛋白K14、K17的同源序列及链球菌M蛋白均含有此基序. 携有这些短肽的噬菌体可与mAb 5G5特异结合,并可阻断单抗与角蛋白反应. 结论含有此基序的短肽可以模拟mAb 5G5识别的与银屑病相关的角蛋白K14和K17同源序列的抗原表位,为银屑病特异性短肽的研究提供了一个新途径,同时也为肽疫苗用于银屑病的治疗提供了崭新的思路.%AIM To acquire the mimetic homologous oligopeptides of human epidermal keratins 14 and 17 related with psoriasis and evaluate the effect of the oligopeptides on the pathogenesis of psoriasis. METHODS The mAb 5G5 recognizing the common epitope of human epidermal keratin K14 and K17 was purified by HiTrap Protein G affinity column, and was biotinylated by the biotin ester. A 6-mer phage random peptide library was biopanned for 3 cycles, then positive clones were identified by ELISA and DNA were extracted for sequencing. RESULTS Amino acid sequence analysis showed that 10 positive clones selected randomly had the consensus Amino acid sequence (motif) VL(x)AG. The motif VL(x)AG could be detected in the homologous amino acid sequence of keratins 14 and 17, and streptococcal M protein contained the motif too. The phages of positive clones reacted with mAb 5G5 specifically and prevented the interaction between mAb 5G5 and keratins with dose-dependent effects. CONCLUSION The motif could mimic the common epitope on human epidermal keratins 14,17 and streptococcal M protein, perhaps the

  4. Bioinspired Gold Nanorod Functionalization Strategies for MUC1-Targeted Imaging and Photothermal Therapy

    Science.gov (United States)

    Zelasko-Leon, Daria Cecylia

    The majority of cancers diagnosed in 2016 are epithelial in origin, constituting 85% of all new cases and predicted to account for 78% of all cancer deaths this year. Given these statistics, improving patient outcomes by providing personalized, multimodal, and minimally invasive medical interventions is critically needed. Mucin 1 (MUC1), a transmembrane glycoprotein, extends over 100 nm from cell membranes and is a key marker promoting epithelial carcinogenesis. Due to its antenna-like manifestation, MUC1 is a unique yet underexplored candidate for targeted cancer therapy, with overexpression in >64% of epithelial cancers. To overcome the limitations of existing treatment strategies for epithelial cancer, this dissertation describes a novel platform for nanomedicine, highlighting bioinspired modifications of gold nanorod (AuNR) surfaces for diagnostic cancer imaging and photothermal therapy. An ongoing challenge in the field of nanomedicine is the need for simple and effective strategies for simple surface modification of nanoparticles to facilitate targeting and enhance efficacy. Here, biofunctionalization of AuNRs was achieved with polydopamine (PD) and tannic acid (TA), polyphenolic compounds found in the marine mussel and throughout the plant kingdom that exhibit promiscuous interfacial binding properties. AuNR stabilization was achieved via PD or TA coatings followed by secondary modification with the serum protein, bovine serum albumin (BSA), or glycoprotein-mimetic polymers. The resultant constructs demonstrated good biocompatibility, enabled diagnostic imaging, and facilitated MUC1-specific photothermal treatment of breast and oral cancer cells. The in vivo performance of BSA and PD modified AuNRs was evaluated in two orthotopic animal models of breast cancer. Clinically relevant hyperthermia and high response rates with MUC1-targeted formulations were found, with significant enhancement of progression-free survival and several complete tumor regressions

  5. Lower Superoxide Dismutase 2 (SOD2) Protein Content in Mononuclear Cells Is Associated with Better Survival in Patients with Hemodialysis Therapy

    Science.gov (United States)

    Shen, Jianlin

    2016-01-01

    Mitochondrial superoxide dismutase 2 (SOD2) converts superoxide anions to hydrogen peroxide and oxygen. Human data on SOD2 protein content in chronic kidney disease (CKD) are sparse and mortality data are lacking. We investigated SOD2 protein content in monocytes from patients with hemodialysis therapy (n = 81), CKD stage 1–5 (n = 120), and healthy controls (n = 13) using in-cell Western assays. SOD2 protein decreased from CKD stage 1 until stage 4 whereas it increased again in stage 5 with and without hemodialysis. SOD2 gene expression, analyzed by quantitative real-time PCR, was not significantly different between the groups. Elevating cellular superoxide production reduced SOD2 protein content. This effect was abolished by the superoxide dismutase mimetic Tempol. Using gelelectrophoresis and Western blot we did not detect nitrotyrosine modifications of SOD2 in CKD. Finally, in patients with CKD stage 5 with hemodialysis therapy higher than median SOD2 protein content was associated with higher all-cause mortality. In conclusion, SOD2 protein content declined in CKD until stage 4 while SOD2 gene expression did not. Increased cellular superoxide anion production might affect SOD2 protein content. In advanced CKD (stage 5) SOD2 protein content increased again, but higher than median SOD2 protein content in these patients did not confer a survival benefit. PMID:27630759

  6. Lower Superoxide Dismutase 2 (SOD2 Protein Content in Mononuclear Cells Is Associated with Better Survival in Patients with Hemodialysis Therapy

    Directory of Open Access Journals (Sweden)

    Katharina Krueger

    2016-01-01

    Full Text Available Mitochondrial superoxide dismutase 2 (SOD2 converts superoxide anions to hydrogen peroxide and oxygen. Human data on SOD2 protein content in chronic kidney disease (CKD are sparse and mortality data are lacking. We investigated SOD2 protein content in monocytes from patients with hemodialysis therapy (n=81, CKD stage 1–5 (n=120, and healthy controls (n=13 using in-cell Western assays. SOD2 protein decreased from CKD stage 1 until stage 4 whereas it increased again in stage 5 with and without hemodialysis. SOD2 gene expression, analyzed by quantitative real-time PCR, was not significantly different between the groups. Elevating cellular superoxide production reduced SOD2 protein content. This effect was abolished by the superoxide dismutase mimetic Tempol. Using gelelectrophoresis and Western blot we did not detect nitrotyrosine modifications of SOD2 in CKD. Finally, in patients with CKD stage 5 with hemodialysis therapy higher than median SOD2 protein content was associated with higher all-cause mortality. In conclusion, SOD2 protein content declined in CKD until stage 4 while SOD2 gene expression did not. Increased cellular superoxide anion production might affect SOD2 protein content. In advanced CKD (stage 5 SOD2 protein content increased again, but higher than median SOD2 protein content in these patients did not confer a survival benefit.

  7. New Oral Therapies for Psoriasis

    Science.gov (United States)

    Lanoue, Julien; Dong, Joanna

    2016-01-01

    Conventional oral therapies for psoriasis, including methotrexate, cyclosporine, and acitretin, have generally unfavorable safety profiles and are not ideal for long-standing use. Thus, new oral therapies are necessary for patients with more moderate disease, patients who prefer oral treatments to injectable biologies, and patients who failed conventional therapies. The authors review here the clinical and safety evidence of phosphodiesterase 4 inhibitor, apremilast, janus kinase inhibitors, including tofacitinib, and fumarie acid esters as additional options in oral psoriasis therapy. PMID:27672415

  8. Adventure Therapy--Critical Questions.

    Science.gov (United States)

    Itin, Christian M.

    2001-01-01

    Defining adventure therapy involves considering the level of change attempted; the degree held by practitioners; the population served; and whether "adventure" refers to activities used, philosophy of adventure, or both. Deciding whether adventure therapy is a profession or a set of tools and techniques depends on the place of adventure therapy in…

  9. What makes internet therapy work?

    NARCIS (Netherlands)

    Andersson, G.; Carlbring, P.; Berger, T.; Almlov, J.; Cuijpers, P.

    2009-01-01

    Abstract Internet therapy is a novel treatment approach that is used to deliver cognitive behaviour therapy. Treatment components are mainly delivered in the form of texts presented via webpages, and support is provided via e-mail. A growing number of controlled trials suggest that Internet therapy

  10. LASER THERAPY IN CHILD NEUROLOGY

    OpenAIRE

    D. A. Prityko

    2012-01-01

    The current review of studies devoted to efficacy and safety of laser therapy in the treatment of neurological diseases in children is proposed. The author discusses pathophysiological background of this method of therapy, general therapeutic approaches and definite schemes of therapy in different diseases.

  11. Cardiac resynchronization therapy in China

    Institute of Scientific and Technical Information of China (English)

    Wei HUA

    2006-01-01

    @@ Congestive heart failure (HF) is a major and growing public health problem. The therapeutic approach includes non-pharmacological measures, pharmacological therapy,mechanical devices, and surgery. Despite the benefits of optimal pharmacologic therapy, the prognosis is still not ideal. At this time, cardiac resynchronization therapy (CRT)has gained wide acceptance as an alternative treatment for HF patients with conduction delay.1

  12. Schema Therapy in Sex Therapy: A Theoretical Conceptualization.

    Science.gov (United States)

    Derby, Danny S; Peleg-Sagy, Tal; Doron, Guy

    2016-10-01

    Schema therapy is an integrative approach of psychotherapy developed by Jeffrey E. Young. Its aim is to help clients explore and understand their deep emotional needs and meet them in a healthy manner. It is suitable for complex pathologies, such as comorbidities and personality disorders. In sex therapy, schema therapy can serve as a method for a deep, evidence-based, integrative conceptualization of a client's difficulties and needs. However, its principles have never been demonstrated in sex therapy. In this paper, we briefly review schema therapy and introduce schema domains. We bring a case study of a couple undergoing sex therapy from the cognitive-behavioral perspective. We then return to the same case study, in order to demonstrate the usefulness of a schema therapy conceptualization.

  13. Gestalt Therapy and Cognitive Therapy - Contrasts or Complementarities?

    DEFF Research Database (Denmark)

    Tønnesvang, Jan; Sommer, Ulla; Hammink, James;

    2010-01-01

    The article investigates the relationship between crucial concepts and understandings in gestalt therapy and cognitive therapy aiming at discussing if and how they can be mutually enriching when considered as complementary parts in a more encompassing integrative therapeutic approach. It is argued...... that gestalt therapy, defined as a fieldtheoretical approach to the study of gestalt formation process, can complement the schema-based understanding and practice in cognitive therapy. The clinical benefits from a complementary view of the two approaches will be a wider scope of awareness toward individual...... between fundamental awareness work in gestalt therapy and the tendency within cognitive therapy toward incorporating mindfulness as a therapeutic tool. In the conclusion of the article, additional complementary points between the two approaches are outlined. Keywords: integrative therapy, gestalt...

  14. Biological therapy of psoriasis

    Directory of Open Access Journals (Sweden)

    Sivamani Raja

    2010-01-01

    Full Text Available The treatment of psoriasis has undergone a revolution with the advent of biologic therapies, including infliximab, etanercept, adalimumab, efalizumab, and alefacept. These medications are designed to target specific components of the immune system and are a major technological advancement over traditional immunosuppressive medications. These usually being well tolerated are being found useful in a growing number of immune-mediated diseases, psoriasis being just one example. The newest biologic, ustekinumab, is directed against the p40 subunit of the IL-12 and IL-23 cytokines. It has provided a new avenue of therapy for an array of T-cell-mediated diseases. Biologics are generally safe; however, there has been concern over the risk of lymphoma with use of these agents. All anti-TNF-α agents have been associated with a variety of serious and "routine" opportunistic infections.

  15. Hormonal therapies in acne.

    Science.gov (United States)

    Shaw, James C

    2002-07-01

    Hormones, in particular androgen hormones, are the main cause of acne in men, women, children and adults, in both normal states and endocrine disorders. Therefore, the use of hormonal therapies in acne is rational in concept and gratifying in practice. Although non-hormonal therapies enjoy wide usage and continue to be developed, there is a solid place for hormonal approaches in women with acne, especially adult women with persistent acne. This review covers the physiological basis for hormonal influence in acne, the treatments that are in use today and those that show promise for the future. The main treatments to be discussed are oral contraceptives androgen receptor blockers like spironolactone and flutamide, inhibitors of the enzyme 5 alpha-reductase and topical hormonal treatments. PMID:12083987

  16. Radionuclide therapy revisited

    Energy Technology Data Exchange (ETDEWEB)

    Hoefnagel, C.A. (Nederlands Kanker Inst., Amsterdam (Netherlands). Dept. of Nuclear Medicine)

    1991-06-01

    Apart from its use in endocrinology and rheumatology, therapeutic nuclear medicine is developing rapidly as an additional treatment modality in oncology. Many different specific tumour-seeking radiopharmaceuticals are being applied both for diagnostic scintigraphy and treatment, using multiple routes and mechanisms to target radionuclides at tumours. After a brief introduction of some basic principles of radionuclide targeting, the therapeutic radiopharmaceuticals available are reviewed according to the accumulation site in relation to the cell nucleus; the results of their current clinical use for therapy are also reviewed. The response observed to a number of these applications, the non-invasiveness of the procedure and the relative lack of toxicity and late effects in comparison with chemotherapy and external beam radiotherapy make radionuclide therapy an attractive and realistic alternative in the management of malignant disease, as well as in the treatment of a few benign disorders. (orig.).

  17. Regenerative photonic therapy: Review

    Science.gov (United States)

    Salansky, Natasha; Salansky, Norman

    2012-09-01

    After four decades of research of photobiomodulation phenomena in mammals in vitro and in vivo, a solid foundation is created for the use of photobiomodulation in regenerative medicine. Significant accomplishments are achieved in animal models that demonstrate opportunities for photo-regeneration of injured or pathological tissues: skin, muscles and nerves. However, the use of photobiomodulation in clinical studies leads to controversial results while negative or marginal clinical efficacy is reported along with positive findings. A thor ough analysis of requirements to the optical parameters (dosimetry) for high efficacy in photobimodulation led us to the conclusion that there are several misconceptions in the clinical applications of low level laser therapy (LLLT). We present a novel appr oach of regenerative photonic therapy (RPT) for tissue healing and regeneration that overcomes major drawbacks of LLLT. Encouraging clinical results on RPT efficacy are presented. Requirements for RPT approach and vision for its future development for tissue regeneration is discussed.

  18. Medical leech therapy (Hirudotherapy

    Directory of Open Access Journals (Sweden)

    Uwe Wollina

    2016-01-01

    Full Text Available Leeches have been used in medicine long time before BC. In recent years medical leech therapy has gained increasing interest in reconstructive surgery and pain management and other medical fields. The possible indications and success rates of this treatment are discussed. There is a special interest in salvage of flaps and grafts by the use of medical leeches. Retrospective analysis indicates a success rate of >80%. Randomized controlled trials have been performed in osteoarthritis. Case reports and smaller series are available for the treatment of chronic wounds, post-phlebitic syndrome and inflammatory skin diseases. The most common adverse effects are prolonged bleeding and infection by saprophytic intestinal bacteria of leeches. Medical leech therapy is a useful adjunct to other measures wound management.

  19. Marketing occupational therapy services.

    Science.gov (United States)

    Kautzmann, L N

    1985-01-01

    The ability to understand and appropriately apply business skills is a key component in the development of a successful private practice. Marketing is one of the business skills occupational therapists need to have in order to take full advantage of the opportunities available to entrepeneurs in the health care industry. The purpose of this article is to present a structured approach to marketing occupational therapy services through the use of a marketing plan. The four components of a marketing plan, a situation analysis, the identification of problems, opportunities, and target markets, the development of a marketing strategy for each targeted market, and a method to monitor the plan, are discussed. Applications to occupational therapy practice are suggested. The use of a marketing plan as a method for organizing and focusing marketing efforts is an effective means of supporting and enhancing the development of a private practice.

  20. Iron replacement therapy

    DEFF Research Database (Denmark)

    Nielsen, Ole Haagen; Coskun, Mehmet; Weiss, Günter

    2016-01-01

    PURPOSE OF REVIEW: Approximately, one-third of the world's population suffers from anemia, and at least half of these cases are because of iron deficiency. With the introduction of new intravenous iron preparations over the last decade, uncertainty has arisen when these compounds should...... be administered and under which circumstances oral therapy is still an appropriate and effective treatment. RECENT FINDINGS: Numerous guidelines are available, but none go into detail about therapeutic start and end points or how iron-deficiency anemia should be best treated depending on the underlying cause...... of iron deficiency or in regard to concomitant underlying or additional diseases. SUMMARY: The study points to major issues to be considered in revisions of future guidelines for the true optimal iron replacement therapy, including how to assess the need for treatment, when to start and when to stop...