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Sample records for borne therapeutic agents

  1. Fate of water borne therapeutic agents and associated effects on nitrifying biofilters in recirculating aquaculture systems

    DEFF Research Database (Denmark)

    Pedersen, Lars-Flemming

    of these agents on biofilter nitrification performance. All experiments were conducted through addition of chemical additives to closed pilot scale recirculating aquaculture systems (RAS) with fixed media submerged biofilters under controlled operating conditions with rainbow trout (Oncorhynchus mykiss...... to positively correlate to temperature, available biofilter surface-area, and the frequency of FA-exposure. Prolonged biofilter exposure to FA did not negatively affect nitrification, and could therefore be a method to optimize FA treatment in RAS and reduce FA discharge. HP degradation was rapid and could...... prolonged multiple HP dosages at 10 mg/L were found to inhibit nitrite oxidation in systems with low organic loading. PAA decay was found to be concentration-dependent. It had a considerable negative effect on nitrite oxidation over a prolonged period of time when applied at a dosage ≥2 mg/L. PAA and HP...

  2. Applications of inorganic nanoparticles as therapeutic agents

    Science.gov (United States)

    Kim, Taeho; Hyeon, Taeghwan

    2014-01-01

    During the last decade, various functional nanostructured materials with interesting optical, magnetic, mechanical and chemical properties have been extensively applied to biomedical areas including imaging, diagnosis and therapy. In therapeutics, most research has focused on the application of nanoparticles as potential delivery vehicles for drugs and genes, because nanoparticles in the size range of 2-100 nm can interact with biological systems at the molecular level, and allow targeted delivery and passage through biological barriers. Recent investigations have even revealed that several kinds of nanomaterials are intrinsically therapeutic. Not only can they passively interact with cells, but they can also actively mediate molecular processes to regulate cell functions. This can be seen in the treatment of cancer via anti-angiogenic mechanisms as well as the treatment of neurodegenerative diseases by effectively controlling oxidative stress. This review will present recent applications of inorganic nanoparticles as therapeutic agents in the treatment of disease.

  3. Acute Organophosphate Poisonings: Therapeutic Dilemmas and New Potential Therapeutic Agents

    International Nuclear Information System (INIS)

    Vucinic, S.; Jovanovic, D.; Vucinic, Z.; Todorovic, V.; Segrt, Z.

    2007-01-01

    It has been six decades since synthesis of organophosphates, but this chapter has not yet come to a closure. Toxic effects of organophosphates are well known and the current therapeutic scheme includes supportive therapy and antidotes. There is a dilemma on whether and when to apply gastric lavage and activated charcoal. According to Position Statement (by EAPCCT) it should be applied only if the patient presents within one hour of ingestion, with potentially lethal ingested dose. Atropine, a competitive antagonist of acetylcholine at m-receptors, which antagonizes bronchosecretion and bronchoconstriction, is the corner stone of acute organophosphate poisoning therapy. There were many attempts to find a more efficient drug, including glycopyrrolate which has been used even in clinical trials, but it still can not replace atropine. The only dilemma about atropine usage which still exists, concerns usage of high atropine dose and scheme of application. The most efficient atropinization is achieved with bolus doses of 1-2mg of atropine i.v push, with repeating the dose on each 5 minutes until signs of atropinization are registered. Diazepam, with its GABA stabilizing effect, reduces central nervous system damage and central respiratory weakness. Oximes reactivate phosphorylated acetylcholinesterase, which still has not gone ageing, reducing acetylcholine concentration and cholinergic crisis. These effects are clearly demonstrated in experimental conditions, but the clinical significance of oximes is still unclear and there are still those who question oxime therapy. For those who approve it, oxime dosage, duration of therapy, the choice of oxime for certain OP is still an open issue. We need new, more efficient antidotes, and those that are in use are only the small part of the therapy which could be used. Experimental studies show favorable therapeutic effect of many agents, but none of them has been introduced in standard treatment of OPI poisoning in the last 30

  4. Therapeutic neuroprotective agents for amyotrophic lateral sclerosis

    Science.gov (United States)

    Pandya, Rachna S.; Zhu, Haining; Li, Wei; Bowser, Robert; Friedlander, Robert M.

    2014-01-01

    Amyotrophic lateral sclerosis (ALS) is a fatal chronic neurodegenerative disease whose hallmark is proteinaceous, ubiquitinated, cytoplasmic inclusions in motor neurons and surrounding cells. Multiple mechanisms proposed as responsible for ALS pathogenesis include dysfunction of protein degradation, glutamate excitotoxicity, mitochondrial dysfunction, apoptosis, oxidative stress, and inflammation. It is therefore essential to gain a better understanding of the underlying disease etiology and search for neuroprotective agents that might delay disease onset, slow progression, prolong survival, and ultimately reduce the burden of disease. Because riluzole, the only Food and Drug Administration (FDA)-approved treatment, prolongs the ALS patient’s life by only 3 months, new therapeutic agents are urgently needed. In this review, we focus on studies of various small pharmacological compounds targeting the proposed pathogenic mechanisms of ALS and discuss their impact on disease progression. PMID:23864030

  5. Chelating agents in pharmacology, toxicology and therapeutics

    International Nuclear Information System (INIS)

    1988-01-01

    The proceedings contain 71 abstracts of papers. Fourteen abstracts were inputted in INIS. The topics covered include: the effects of chelating agents on the retention of 63 Ni, 109 Cd, 203 Hg, 144 Ce, 95 Nb and the excretion of 210 Po, 63 Ni, 48 V, 239 Pu, 241 Am, 54 Mn; the applications of tracer techniques for studies of the efficacy of chelation therapy in patients with heart and brain disorders; and the treatment of metal poisoning with chelating agents. (J.P.)

  6. Nutraceuticals as therapeutic agents for atherosclerosis.

    Science.gov (United States)

    Moss, Joe W E; Williams, Jessica O; Ramji, Dipak P

    2018-05-01

    Atherosclerosis, a chronic inflammatory disorder of medium and large arteries and an underlying cause of cardiovascular disease (CVD), is responsible for a third of all global deaths. Current treatments for CVD, such as optimized statin therapy, are associated with considerable residual risk and several side effects in some patients. The outcome of research on the identification of alternative pharmaceutical agents for the treatment of CVD has been relatively disappointing with many promising leads failing at the clinical level. Nutraceuticals, products from food sources with health benefits beyond their nutritional value, represent promising agents in the prevention of CVD or as an add-on therapy with current treatments. This review will highlight the potential of several nutraceuticals, including polyunsaturated fatty acids, flavonoids and other polyphenols, as anti-CVD therapies based on clinical and pre-clinical mechanism-based studies. Copyright © 2018 The Author(s). Published by Elsevier B.V. All rights reserved.

  7. New and exploratory therapeutic agents for asthma

    National Research Council Canada - National Science Library

    Yeadon, Michael; Diamant, Zuzana

    2000-01-01

    ... been accomplished. It is well recognized that new drugs are essentially the result of basic and applied research. Early in this century, the advent of a chemical approach to medicine led to many extraordinary developments. The past few decades have been characterized by a search to understand the mechanisms of disease- a quest spurred by the recognition that if pathogenic processes were known, new therapeutic opportunities would ensue. The validity of this concept is beautifully illustrated in the case of asthma. Here is a d...

  8. Peptides as Therapeutic Agents for Dengue Virus.

    Science.gov (United States)

    Chew, Miaw-Fang; Poh, Keat-Seong; Poh, Chit-Laa

    2017-01-01

    Dengue is an important global threat caused by dengue virus (DENV) that records an estimated 390 million infections annually. Despite the availability of CYD-TDV as a commercial vaccine, its long-term efficacy against all four dengue virus serotypes remains unsatisfactory. There is therefore an urgent need for the development of antiviral drugs for the treatment of dengue. Peptide was once a neglected choice of medical treatment but it has lately regained interest from the pharmaceutical industry following pioneering advancements in technology. In this review, the design of peptide drugs, antiviral activities and mechanisms of peptides and peptidomimetics (modified peptides) action against dengue virus are discussed. The development of peptides as inhibitors for viral entry, replication and translation is also described, with a focus on the three main targets, namely, the host cell receptors, viral structural proteins and viral non-structural proteins. The antiviral peptides designed based on these approaches may lead to the discovery of novel anti-DENV therapeutics that can treat dengue patients.

  9. Development of Class IIa Bacteriocins as Therapeutic Agents

    OpenAIRE

    Christopher T. Lohans; John C. Vederas

    2012-01-01

    Class IIa bacteriocins have been primarily explored as natural food preservatives, but there is much interest in exploring the application of these peptides as therapeutic antimicrobial agents. Bacteriocins of this class possess antimicrobial activity against several important human pathogens. Therefore, the therapeutic development of these bacteriocins will be reviewed. Biological and chemical modifications to both stabilize and increase the potency of bacteriocins are discussed, as well as ...

  10. A virtual therapeutic environment with user projective agents.

    Science.gov (United States)

    Ookita, S Y; Tokuda, H

    2001-02-01

    Today, we see the Internet as more than just an information infrastructure, but a socializing place and a safe outlet of inner feelings. Many personalities develop aside from real world life due to its anonymous environment. Virtual world interactions are bringing about new psychological illnesses ranging from netaddiction to technostress, as well as online personality disorders and conflicts in multiple identities that exist in the virtual world. Presently, there are no standard therapy models for the virtual environment. There are very few therapeutic environments, or tools especially made for virtual therapeutic environments. The goal of our research is to provide the therapy model and middleware tools for psychologists to use in virtual therapeutic environments. We propose the Cyber Therapy Model, and Projective Agents, a tool used in the therapeutic environment. To evaluate the effectiveness of the tool, we created a prototype system, called the Virtual Group Counseling System, which is a therapeutic environment that allows the user to participate in group counseling through the eyes of their Projective Agent. Projective Agents inherit the user's personality traits. During the virtual group counseling, the user's Projective Agent interacts and collaborates to recover and increase their psychological growth. The prototype system provides a simulation environment where psychologists can adjust the parameters and customize their own simulation environment. The model and tool is a first attempt toward simulating online personalities that may exist only online, and provide data for observation.

  11. Development of Class IIa Bacteriocins as Therapeutic Agents

    Directory of Open Access Journals (Sweden)

    Christopher T. Lohans

    2012-01-01

    Full Text Available Class IIa bacteriocins have been primarily explored as natural food preservatives, but there is much interest in exploring the application of these peptides as therapeutic antimicrobial agents. Bacteriocins of this class possess antimicrobial activity against several important human pathogens. Therefore, the therapeutic development of these bacteriocins will be reviewed. Biological and chemical modifications to both stabilize and increase the potency of bacteriocins are discussed, as well as the optimization of their production and purification. The suitability of bacteriocins as pharmaceuticals is explored through determinations of cytotoxicity, effects on the natural microbiota, and in vivo efficacy in mouse models. Recent results suggest that class IIa bacteriocins show promise as a class of therapeutic agents.

  12. Applications of inorganic nanoparticles as therapeutic agents

    International Nuclear Information System (INIS)

    Kim, Taeho; Hyeon, Taeghwan

    2014-01-01

    During the last decade, various functional nanostructured materials with interesting optical, magnetic, mechanical and chemical properties have been extensively applied to biomedical areas including imaging, diagnosis and therapy. In therapeutics, most research has focused on the application of nanoparticles as potential delivery vehicles for drugs and genes, because nanoparticles in the size range of 2–100 nm can interact with biological systems at the molecular level, and allow targeted delivery and passage through biological barriers. Recent investigations have even revealed that several kinds of nanomaterials are intrinsically therapeutic. Not only can they passively interact with cells, but they can also actively mediate molecular processes to regulate cell functions. This can be seen in the treatment of cancer via anti-angiogenic mechanisms as well as the treatment of neurodegenerative diseases by effectively controlling oxidative stress. This review will present recent applications of inorganic nanoparticles as therapeutic agents in the treatment of disease. (topical review)

  13. A Zebrafish Heart Failure Model for Assessing Therapeutic Agents.

    Science.gov (United States)

    Zhu, Xiao-Yu; Wu, Si-Qi; Guo, Sheng-Ya; Yang, Hua; Xia, Bo; Li, Ping; Li, Chun-Qi

    2018-03-20

    Heart failure is a leading cause of death and the development of effective and safe therapeutic agents for heart failure has been proven challenging. In this study, taking advantage of larval zebrafish, we developed a zebrafish heart failure model for drug screening and efficacy assessment. Zebrafish at 2 dpf (days postfertilization) were treated with verapamil at a concentration of 200 μM for 30 min, which were determined as optimum conditions for model development. Tested drugs were administered into zebrafish either by direct soaking or circulation microinjection. After treatment, zebrafish were randomly selected and subjected to either visual observation and image acquisition or record videos under a Zebralab Blood Flow System. The therapeutic effects of drugs on zebrafish heart failure were quantified by calculating the efficiency of heart dilatation, venous congestion, cardiac output, and blood flow dynamics. All 8 human heart failure therapeutic drugs (LCZ696, digoxin, irbesartan, metoprolol, qiliqiangxin capsule, enalapril, shenmai injection, and hydrochlorothiazide) showed significant preventive and therapeutic effects on zebrafish heart failure (p failure model developed and validated in this study could be used for in vivo heart failure studies and for rapid screening and efficacy assessment of preventive and therapeutic drugs.

  14. The Born Rule and Free Will: why Libertarian Agent-Causal Free Will is not "antiscientific"

    Science.gov (United States)

    Kastner, Ruth E.

    In the libertarian "agent causation" view of free will, free choices are attributable only to the choosing agent, as opposed to a specific cause or causes outside the agent. An often-repeated claim in the philosophical literature on free will is that agent causation necessarily implies lawlessness, and is therefore "antiscientific." That claim is critiqued and it is argued, on the contrary, that the volitional powers of a free agent need not be viewed as anomic, specifically with regard to the quantum statistical law (the Born Rule). Assumptions about the role and nature of causation, taken as bearing on volitional agency, are examined and found inadequate to the task. Finally, it is suggested that quantum theory may constitute precisely the sort of theory required for a nomic grounding of libertarian free will.

  15. Lipoprotein Nanoplatform for Targeted Delivery of Diagnostic and Therapeutic Agents

    Directory of Open Access Journals (Sweden)

    Jerry D. Glickson

    2008-03-01

    Full Text Available Low-density lipoprotein (LDL provides a highly versatile natural nanoplatform for delivery of visible or near-infrared fluorescent optical and magnetic resonance imaging (MRI contrast agents and photodynamic therapy and chemotherapeutic agents to normal and neoplastic cells that overexpress low-density lipoprotein receptors (LDLRs. Extension to other lipoproteins ranging in diameter from about 10 nm (high-density lipoprotein [HDL] to over a micron (chylomicrons is feasible. Loading of contrast or therapeutic agents onto or into these particles has been achieved by protein loading (covalent attachment to protein side chains, surface loading (intercalation into the phospholipid monolayer, and core loading (extraction and reconstitution of the triglyceride/cholesterol ester core. Core and surface loading of LDL have been used for delivery of optical imaging agents to tumor cells in vivo and in culture. Surface loading was used for delivery of gadolinium-bis-stearylamide contrast agents for in vivo MRI detection in tumor-bearing mice. Chlorin and phthalocyanine near-infrared photodynamic therapy agents (≤ 400/LDL have been attached by core loading. Protein loading was used to reroute the LDL from its natural receptor (LDLR to folate receptors and could be used to target other receptors. A semisynthetic nanoparticle has been constructed by coating magnetite iron oxide nanoparticles with carboxylated cholesterol and overlaying a monolayer of phospholipid to which apolipoprotein A1 or E was adsorbed for targeting HDL or adsorbing synthetic amphipathic helical peptides ltargeting LDL or folate receptors. These particles can be used for in situ loading of magnetite into cells for MRI-monitored cell tracking or gene expression.

  16. Small Scaffolds, Big Potential: Developing Miniature Proteins as Therapeutic Agents.

    Science.gov (United States)

    Holub, Justin M

    2017-09-01

    Preclinical Research Miniature proteins are a class of oligopeptide characterized by their short sequence lengths and ability to adopt well-folded, three-dimensional structures. Because of their biomimetic nature and synthetic tractability, miniature proteins have been used to study a range of biochemical processes including fast protein folding, signal transduction, catalysis and molecular transport. Recently, miniature proteins have been gaining traction as potential therapeutic agents because their small size and ability to fold into defined tertiary structures facilitates their development as protein-based drugs. This research overview discusses emerging developments involving the use of miniature proteins as scaffolds to design novel therapeutics for the treatment and study of human disease. Specifically, this review will explore strategies to: (i) stabilize miniature protein tertiary structure; (ii) optimize biomolecular recognition by grafting functional epitopes onto miniature protein scaffolds; and (iii) enhance cytosolic delivery of miniature proteins through the use of cationic motifs that facilitate endosomal escape. These objectives are discussed not only to address challenges in developing effective miniature protein-based drugs, but also to highlight the tremendous potential miniature proteins hold for combating and understanding human disease. Drug Dev Res 78 : 268-282, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  17. Functional polymers as therapeutic agents: concept to market place.

    Science.gov (United States)

    Dhal, Pradeep K; Polomoscanik, Steven C; Avila, Louis Z; Holmes-Farley, S Randall; Miller, Robert J

    2009-11-12

    Biologically active synthetic polymers have received considerable scientific interest and attention in recent years for their potential as promising novel therapeutic agents to treat human diseases. Although a significant amount of research has been carried out involving polymer-linked drugs as targeted and sustained release drug delivery systems and prodrugs, examples on bioactive polymers that exhibit intrinsic therapeutic properties are relatively less. Several appealing characteristics of synthetic polymers including high molecular weight, molecular architecture, and controlled polydispersity can all be utilized to discover a new generation of therapies. For example, high molecular weight bioactive polymers can be restricted to gastrointestinal tract, where they can selectively recognize, bind, and remove target disease causing substances from the body. The appealing features of GI tract restriction and stability in biological environment render these polymeric drugs to be devoid of systemic toxicity that are generally associated with small molecule systemic drugs. The present article highlights recent developments in the rational design and synthesis of appropriate functional polymers that have resulted in a number of promising polymer based therapies and biomaterials, including some marketed products.

  18. Tetrodotoxin (TTX as a Therapeutic Agent for Pain

    Directory of Open Access Journals (Sweden)

    Cruz Miguel Cendán

    2012-01-01

    Full Text Available Tetrodotoxin (TTX is a potent neurotoxin that blocks voltage-gated sodium channels (VGSCs. VGSCs play a critical role in neuronal function under both physiological and pathological conditions. TTX has been extensively used to functionally characterize VGSCs, which can be classified as TTX-sensitive or TTX-resistant channels according to their sensitivity to this toxin. Alterations in the expression and/or function of some specific TTX-sensitive VGSCs have been implicated in a number of chronic pain conditions. The administration of TTX at doses below those that interfere with the generation and conduction of action potentials in normal (non-injured nerves has been used in humans and experimental animals under different pain conditions. These data indicate a role for TTX as a potential therapeutic agent for pain. This review focuses on the preclinical and clinical evidence supporting a potential analgesic role for TTX. In addition, the contribution of specific TTX-sensitive VGSCs to pain is reviewed.

  19. VIP as a potential therapeutic agent in gram negative sepsis.

    Science.gov (United States)

    Ibrahim, Hiba; Barrow, Paul; Foster, Neil

    2012-12-01

    Gram negative sepsis remains a high cause of mortality and places a great burden on public health finance in both the developed and developing world. Treatment of sepsis, using antibiotics, is often ineffective since pathology associated with the disease occurs due to dysregulation of the immune system (failure to return to steady state conditions) which continues after the bacteria, which induced the immune response, have been cleared. Immune modulation is therefore a rational approach to the treatment of sepsis but to date no drug has been developed which is highly effective, cheap and completely safe to use. One potential therapeutic agent is VIP, which is a natural peptide and is highly homologous in all vertebrates. In this review we will discuss the effect of VIP on components of the immune system, relevant to gram negative sepsis, and present data from animal models. Furthermore we will hypothesise on how these studies could be improved in future and speculate on the possible different ways in which VIP could be used in clinical medicine.

  20. Matricellular proteins in drug delivery: Therapeutic targets, active agents, and therapeutic localization.

    Science.gov (United States)

    Sawyer, Andrew J; Kyriakides, Themis R

    2016-02-01

    Extracellular matrix is composed of a complex array of molecules that together provide structural and functional support to cells. These properties are mainly mediated by the activity of collagenous and elastic fibers, proteoglycans, and proteins such as fibronectin and laminin. ECM composition is tissue-specific and could include matricellular proteins whose primary role is to modulate cell-matrix interactions. In adults, matricellular proteins are primarily expressed during injury, inflammation and disease. Particularly, they are closely associated with the progression and prognosis of cardiovascular and fibrotic diseases, and cancer. This review aims to provide an overview of the potential use of matricellular proteins in drug delivery including the generation of therapeutic agents based on the properties and structures of these proteins as well as their utility as biomarkers for specific diseases. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Prevalence of selected zoonotic and vector-borne agents in dogs and cats in Costa Rica.

    Science.gov (United States)

    Scorza, Andrea V; Duncan, Colleen; Miles, Laura; Lappin, Michael R

    2011-12-29

    To estimate the prevalence of enteric parasites and selected vector-borne agents of dogs and cats in San Isidro de El General, Costa Rica, fecal and serum samples were collected from animals voluntarily undergoing sterilization. Each fecal sample was examined for parasites by microscopic examination after fecal flotation and for Giardia and Cryptosporidium using an immunofluorescence assay (IFA). Giardia and Cryptosporidium IFA positive samples were genotyped after PCR amplification of specific DNA if possible. The seroprevalence rates for the vector-borne agents (Dirofilaria immitis, Borrelia burgdorferi, Ehrlichia canis, and Anaplasma phagocytophilum) were estimated based on results from a commercially available ELISA. Enteric parasites were detected in samples from 75% of the dogs; Ancylostoma caninum, Trichuris vulpis, Giardia, and Toxocara canis were detected. Of the cats, 67.5% harbored Giardia spp., Cryptosporidium spp., Ancylostoma tubaeforme, or Toxocara cati. Both Cryptosporidium spp. isolates that could be sequenced were Cryptosporidium parvum (one dog isolate and one cat isolate). Of the Giardia spp. isolates that were successfully sequenced, the 2 cat isolates were assemblage A and the 2 dog isolates were assemblage D. D. immitis antigen and E. canis antibodies were identified in 2.3% and 3.5% of the serum samples, respectively. The prevalence of enteric zoonotic parasites in San Isidro de El General in Costa Rica is high in companion animals and this information should be used to mitigate public health risks. Copyright © 2011. Published by Elsevier B.V.

  2. Imaging tumor hypoxia: Blood-borne delivery of imaging agents is fundamentally different in hypoxia subtypes

    Directory of Open Access Journals (Sweden)

    Peter Vaupel

    2014-03-01

    Full Text Available Hypoxic tissue subvolumes are a hallmark feature of solid malignant tumors, relevant for cancer therapy and patient outcome because they increase both the intrinsic aggressiveness of tumor cells and their resistance to several commonly used anticancer strategies. Pathogenetic mechanisms leading to hypoxia are diverse, may coexist within the same tumor and are commonly grouped according to the duration of their effects. Chronic hypoxia is mainly caused by diffusion limitations resulting from enlarged intercapillary distances and adverse diffusion geometries and — to a lesser extent — by hypoxemia, compromised perfusion or long-lasting microregional flow stops. Conversely, acute hypoxia preferentially results from transient disruptions in perfusion. While each of these features of the tumor microenvironment can contribute to a critical reduction of oxygen availability, the delivery of imaging agents (as well as nutrients and anticancer agents may be compromised or remain unaffected. Thus, a critical appraisal of the effects of the various mechanisms leading to hypoxia with regard to the blood-borne delivery of imaging agents is necessary to judge their ability to correctly represent the hypoxic phenotype of solid malignancies.

  3. Protein based therapeutic delivery agents: Contemporary developments and challenges.

    Science.gov (United States)

    Yin, Liming; Yuvienco, Carlo; Montclare, Jin Kim

    2017-07-01

    As unique biopolymers, proteins can be employed for therapeutic delivery. They bear important features such as bioavailability, biocompatibility, and biodegradability with low toxicity serving as a platform for delivery of various small molecule therapeutics, gene therapies, protein biologics and cells. Depending on size and characteristic of the therapeutic, a variety of natural and engineered proteins or peptides have been developed. This, coupled to recent advances in synthetic and chemical biology, has led to the creation of tailor-made protein materials for delivery. This review highlights strategies employing proteins to facilitate the delivery of therapeutic matter, addressing the challenges for small molecule, gene, protein and cell transport. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. TRAIL: A Novel Therapeutic Agent for Prostate Cancer

    National Research Council Canada - National Science Library

    Li, Honglin

    2002-01-01

    This study aims to elucidate the signaling pathway of TRAIL-mediated apoptosis in prostate cancer cells, and to examine the therapeutic effect of TRAIL on prostate cancer cells in vitro and in vivo...

  5. TRAIL: A Novel Therapeutic Agent for Prostate Cancer

    National Research Council Canada - National Science Library

    Li, Honglin

    2004-01-01

    This study aims to elucidate the signaling pathway of TRAIL-mediated apoptosis in prostate cancer cells, and to examine the therapeutic effect of TRAIL on prostate cancer cells in vitro and in vivo...

  6. TRAIL: A Novel Therapeutic Agent for Prostate Cancer

    National Research Council Canada - National Science Library

    Li, Honglin

    2003-01-01

    This study aims to elucidate the signaling pathway of TRAIL-mediated apoptosis in prostate cancer cells, and to examine the therapeutic effect of TRAIL on prostate cancer cells in vitro and in vivo...

  7. Development of a Multifaceted Ovarian Cancer Therapeutic and Imaging Agent

    National Research Council Canada - National Science Library

    Markland, Francis S

    2008-01-01

    ...%. This project outlines the development of a recombinant version of a member of a class of proteins known as disintegrins as an innovative imaging and diagnostic agent for ovarian cancer (OC). Vicrostatin (VN...

  8. Cyclic peptides as potential therapeutic agents for skin disorders.

    Science.gov (United States)

    Namjoshi, Sarika; Benson, Heather A E

    2010-01-01

    There is an increasing understanding of the role of peptides in normal skin function and skin disease. With this knowledge, there is significant interest in the application of peptides as therapeutics in skin disease or as cosmeceuticals to enhance skin appearance. In particular, antimicrobial peptides and those involved in inflammatory processes provide options for the development of new therapeutic directions in chronic skin conditions such as psoriasis and dermatitis. To exploit their potential, it is essential that these peptides are delivered to their site of action in active form and in sufficient quantity to provide the desired effect. Many polymers permeate the skin poorly and are vulnerable to enzymatic degradation. Synthesis of cyclic peptide derivatives can substantially alter the physicochemical characteristics of the peptide with the potential to improve its skin permeation. In addition, cyclization can stabilize the peptide structure and thereby increase its stability. This review describes the role of cyclic peptides in the skin, examples of current cyclic peptide therapeutic products, and the potential for cyclic peptides as dermatological therapeutics and cosmeceuticals.

  9. Zoonotic and vector borne agents causing disease in adult patients hospitalized due to fever of unknown origin in Thailand

    Directory of Open Access Journals (Sweden)

    Soawapak Hinjoy

    2017-10-01

    Full Text Available Objective: To determine the etiologic agents of fever of unknown origin among populations in agricultural communities and to assess the possible risk factors for zoonotic infections. Methods: Hospitalized patients with fever of unknown origin under physician care were asked to participate and provide blood samples for laboratory tests and screening for endemic diseases at the hospitals. Samples were stored at –80 °C until they were tested at Chulalongkorn University to identify additional pathogens. Results: We were able to identify the etiologic agents in 24.6% of the 463 enrolled patients. Zoonotic and vector borne agents were confirmed in 59 cases (12.7%. Dengue virus (7.3% was the most frequently detected disease followed by scrub typhus (3.2%. There were two cases of comorbidities of scrub typhus and dengue fever. The other six cases of zoonoses were leptospirosis, melioidosis, and Streptococcus suis infections. Patients with zoonotic/vector borne agents noticed rats in their houses and reported having contact with livestock feces more frequently than those patients without zoonotic/vector borne agents. Conclusions: Dengue virus and scrub typhus were mostly detected in the rainy season. During this specific season, clinicians should raise awareness of those diseases when any patients are admitted to the hospital with fever of an unidentified source.

  10. Towards a Hybrid Agent-based Model for Mosquito Borne Disease.

    Science.gov (United States)

    Mniszewski, S M; Manore, C A; Bryan, C; Del Valle, S Y; Roberts, D

    2014-07-01

    Agent-based models (ABM) are used to simulate the spread of infectious disease through a population. Detailed human movement, demography, realistic business location networks, and in-host disease progression are available in existing ABMs, such as the Epidemic Simulation System (EpiSimS). These capabilities make possible the exploration of pharmaceutical and non-pharmaceutical mitigation strategies used to inform the public health community. There is a similar need for the spread of mosquito borne pathogens due to the re-emergence of diseases such as chikungunya and dengue fever. A network-patch model for mosquito dynamics has been coupled with EpiSimS. Mosquitoes are represented as a "patch" or "cloud" associated with a location. Each patch has an ordinary differential equation (ODE) mosquito dynamics model and mosquito related parameters relevant to the location characteristics. Activities at each location can have different levels of potential exposure to mosquitoes based on whether they are inside, outside, or somewhere in-between. As a proof of concept, the hybrid network-patch model is used to simulate the spread of chikungunya through Washington, DC. Results are shown for a base case, followed by varying the probability of transmission, mosquito count, and activity exposure. We use visualization to understand the pattern of disease spread.

  11. Selective estrogen receptor modulators as brain therapeutic agents

    OpenAIRE

    Arévalo, María Ángeles; Santos-Galindo, María; Lagunas, Natalia; Azcoitia, I.; García-Segura, Luis M.

    2011-01-01

    Selective estrogen receptor modulators (SERMs), used for the treatment of breast cancer, osteoporosis, and menopausal symptoms, affect the nervous system. Some SERMs trigger neuroprotective mechanisms and reduce neural damage in different experimental models of neural trauma, brain inflammation, neurodegenerative diseases, cognitive impairment, and affective disorders. New SERMs with specific actions on neurons and glial cells may represent promising therapeutic tools for the brain. © 2011 So...

  12. Cisplatin encapsulated nanoparticle as a therapeutic agent for anticancer treatment

    Science.gov (United States)

    Eka Putra, Gusti Ngurah Putu; Huang, Leaf; Hsu, Yih-Chih

    2016-03-01

    The knowledge of manipulating size of biomaterials encapsulated drug into nano-scale particles has been researched and developed in treating cancer. Cancer is the second worldwide cause of death, therefore it is critical to treat cancers challenging with therapeutic modality of various mechanisms. Our preliminary investigation has studied cisplatin encapsulated into lipid-based nanoparticle and examined the therapeutic effect on xenografted animal model. We used mice with tumor volume ranging from 195 to 214 mm3 and then few mice were grouped into three groups including: control (PBS), lipid platinum chloride (LPC) nanoparticles and CDDP (cis-diamminedichloroplatinum(II) at dose of 3mg cisplatin /kg body weight. The effect of the treatment was observed for 12 days post-injection. It showed that LPC NPs demonstrated a better therapeutic effect compared to CDDP at same 3mg cisplatin/kg drug dose of tumor size reduction, 96.6% and 11.1% respectively. In addition, mouse body weight loss of LPC, CDDP and PBS treated group are 12.1%, 24.3% and 1.4%. It means that by compared to CDDP group, LPC group demonstrated less side effect as not much reduction of body weight have found. Our findings have shown to be a potential modality to further investigate as a feasible cancer therapy modality.

  13. Development of a Multifaceted Ovarian Cancer Therapeutic and Imaging Agent

    Science.gov (United States)

    2011-04-01

    by 1-ethyl-3- [3-(dimethylamino) propyl ]carbodiimide (EDC) and N-hydroxysulfonosuccinimide (SNHS) at pH 5.5 for 30 min with a molar ratio of...particle-coated migratory substrate that can act as a permanent record of cellular movement. The gold chloride solution was prepared using 0.342 g... Synthesis and clinical Evaluation. Anticancer Agents Med. Chem. McLane, M.A., Joerger, T., Mahmoud, A., 2008. Disintegrins in health and disease. Front

  14. Progranulin as a biomarker and potential therapeutic agent.

    Science.gov (United States)

    Abella, Vanessa; Pino, Jesús; Scotece, Morena; Conde, Javier; Lago, Francisca; Gonzalez-Gay, Miguel Angel; Mera, Antonio; Gómez, Rodolfo; Mobasheri, Ali; Gualillo, Oreste

    2017-10-01

    Progranulin is a cysteine-rich secreted protein with diverse pleiotropic actions and participates in several processes, such as inflammation or tumorigenesis. Progranulin was first identified as a growth factor and, recently, it was characterised as an adipokine implicated in obesity, insulin resistance and rheumatic disease. At a central level, progranulin acts as a neurotropic and neuroprotective factor and protects from neural degeneration. In this review, we summarise the most recent research advances concerning the potential role of progranulin as a therapeutic target and biomarker in cancer, neurodegenerative and inflammatory diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Melatonin and Nitrones As Potential Therapeutic Agents for Stroke

    Directory of Open Access Journals (Sweden)

    Alejandro Romero

    2016-11-01

    Full Text Available Stroke is a disease of aging affecting millions of people worldwide, and recombinant tissue-type plasminogen activator (r-tPA is the only treatment approved. However, r-tPA has a low therapeutic window and secondary effects which limit its beneficial outcome, urging thus the search for new more efficient therapies. Among them, neuroprotection based on melatonin or nitrones, as free radical traps, have arisen as drug candidates due to their strong antioxidant power. In this Perspective article, an update on the specific results of the melatonin and several new nitrones are presented.

  16. Deoxypodophyllotoxin: a promising therapeutic agent from herbal medicine.

    Science.gov (United States)

    Khaled, Meyada; Jiang, Zhen-Zhou; Zhang, Lu-Yong

    2013-08-26

    Recently, biologically active compounds isolated from plants used in herbal medicine have been the center of interest. Deoxypodophyllotoxin (DPT), structurally closely related to the lignan podophyllotoxin, is a potent antitumor and anti-inflammatory agent. However, DPT has not been used clinically yet. Also, DPT from natural sources seems to be unavailable. Hence, it is important to establish alternative resources for the production of such lignan; especially that it is used as a precursor for the semi-synthesis of the cytostatic drugs etoposide phosphate and teniposide. The update paper provides an overview of DPT as an effective anticancer natural compound and a leader for cytotoxic drugs synthesis and development in order to highlight the gaps in our knowledge and explore future research needs. The present review covers the literature available from 1877 to 2012. The information was collected via electronic search using Chinese papers and the major scientific databases including PubMed, Sciencedirect, Web of Science and Google Scholar using the keywords. All abstracts and full-text articles reporting database on the history and current status of DPT were gathered and analyzed. Plants containing DPT have played an important role in traditional medicine. In light of the in vitro pharmacological investigations, DPT is a high valuable medicinal agent that has anti-tumor, anti-proliferative, anti-inflammatory and anti-allergic properties. Further, DPT is an important precursor for the cytotoxic aryltetralin lignan, podophyllotoxin, which is used to obtain semisynthetic derivatives like etoposide and teniposide used in cancer therapy. However, most studies have focused on the in vitro data. Therefore, DPT has not been used clinically yet. DPT has emerged as a potent chemical agent from herbal medicine. Therefore, in vivo studies are needed to carry out clinical trials in humans and enable the development of new anti-cancer agents. In addition, DPT from commercial

  17. Orexin receptor antagonists as therapeutic agents for insomnia

    Directory of Open Access Journals (Sweden)

    Ana Clementina Equihua

    2013-12-01

    Full Text Available Insomnia is a common clinical condition characterized by difficulty initiating or maintaining sleep, or non-restorative sleep with impairment of daytime functioning.Currently, treatment for insomnia involves a combination of cognitive behavioral therapy and pharmacological therapy. Among pharmacological interventions, the most evidence exists for benzodiazepine receptor agonist drugs (GABAA receptor, although concerns persist regarding their safety and their limited efficacy. The use of these hypnotic medications must be carefully monitored for adverse effects.Orexin (hypocretin neuropeptides have been shown to regulate transitions between wakefulness and sleep by promoting cholinergic/monoaminergic neural pathways. This has led to the development of a new class of pharmacological agents that antagonize the physiological effects of orexin. The development of these agents may lead to novel therapies for insomnia without the side effect profile of hypnotics (e.g. impaired cognition, disturbed arousal, and motor balance difficulties. However, antagonizing a system that regulates the sleep-wake cycle may create an entirely different side effect profile. In this review, we discuss the role of orexin and its receptors on the sleep-wake cycle and that of orexin antagonists in the treatment of insomnia.

  18. Resveratrol as a Therapeutic Agent for Alzheimer's Disease

    Science.gov (United States)

    Ma, Teng; Tan, Meng-Shan; Yu, Jin-Tai; Tan, Lan

    2014-01-01

    Alzheimer's disease (AD) is the most common cause of dementia, but there is no effective therapy till now. The pathogenic mechanisms of AD are considerably complex, including Aβ accumulation, tau protein phosphorylation, oxidative stress, and inflammation. Exactly, resveratrol, a polyphenol in red wine and many plants, is indicated to show the neuroprotective effect on mechanisms mostly above. Recent years, there are numerous researches about resveratrol acting on AD in many models, both in vitro and in vivo. However, the effects of resveratrol are limited by its pool bioavailability; therefore researchers have been trying a variety of methods to improve the efficiency. This review summarizes the recent studies in cell cultures and animal models, mainly discusses the molecular mechanisms of the neuroprotective effects of resveratrol, and thus investigates the therapeutic potential in AD. PMID:25525597

  19. Resveratrol as a Therapeutic Agent for Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Teng Ma

    2014-01-01

    Full Text Available Alzheimer’s disease (AD is the most common cause of dementia, but there is no effective therapy till now. The pathogenic mechanisms of AD are considerably complex, including Aβ accumulation, tau protein phosphorylation, oxidative stress, and inflammation. Exactly, resveratrol, a polyphenol in red wine and many plants, is indicated to show the neuroprotective effect on mechanisms mostly above. Recent years, there are numerous researches about resveratrol acting on AD in many models, both in vitro and in vivo. However, the effects of resveratrol are limited by its pool bioavailability; therefore researchers have been trying a variety of methods to improve the efficiency. This review summarizes the recent studies in cell cultures and animal models, mainly discusses the molecular mechanisms of the neuroprotective effects of resveratrol, and thus investigates the therapeutic potential in AD.

  20. Antimicrobial Peptides: An Emerging Category of Therapeutic Agents.

    Science.gov (United States)

    Mahlapuu, Margit; Håkansson, Joakim; Ringstad, Lovisa; Björn, Camilla

    2016-01-01

    Antimicrobial peptides (AMPs), also known as host defense peptides, are short and generally positively charged peptides found in a wide variety of life forms from microorganisms to humans. Most AMPs have the ability to kill microbial pathogens directly, whereas others act indirectly by modulating the host defense systems. Against a background of rapidly increasing resistance development to conventional antibiotics all over the world, efforts to bring AMPs into clinical use are accelerating. Several AMPs are currently being evaluated in clinical trials as novel anti-infectives, but also as new pharmacological agents to modulate the immune response, promote wound healing, and prevent post-surgical adhesions. In this review, we provide an overview of the biological role, classification, and mode of action of AMPs, discuss the opportunities and challenges to develop these peptides for clinical applications, and review the innovative formulation strategies for application of AMPs.

  1. Borrelia miyamotoi, Other Vector-Borne Agents in Cat Blood and Ticks in Eastern Maryland.

    Science.gov (United States)

    Shannon, Avery B; Rucinsky, Renee; Gaff, Holly D; Brinkerhoff, R Jory

    2017-12-01

    We collected blood and tick samples in eastern Maryland to quantify vector-borne pathogen exposure and infection in healthy cats and to assess occupational disease risk to veterinary professionals and others who regularly interact with household pets. Thirty-six percent of healthy cats parasitized by ticks at time of examination (9/25) were exposed to, and 14% of bloods (7/49) tested PCR-positive for, at least one vector-borne pathogen including several bloods and ticks with Borrelia miyamotoi, a recently recognized tick-borne zoonotic bacterium. There was no indication that high tick burdens were associated with exposure to vector-borne pathogens. Our results underscore the potential importance of cats to human vector-borne disease risk.

  2. Investigation of Stilbenoids as Potential Therapeutic Agents for Rotavirus Gastroenteritis

    Directory of Open Access Journals (Sweden)

    Judith M. Ball

    2015-01-01

    Full Text Available Rotavirus (RV infections cause severe diarrhea in infants and young children worldwide. Vaccines are available but cost prohibitive for many countries and only reduce severe symptoms. Vaccinated infants continue to shed infectious particles, and studies show decreased efficacy of the RV vaccines in tropical and subtropical countries where they are needed most. Continuing surveillance for new RV strains, assessment of vaccine efficacy, and development of cost effective antiviral drugs remain an important aspect of RV studies. This study was to determine the efficacy of antioxidant and anti-inflammatory stilbenoids to inhibit RV replication. Peanut (A. hypogaea hairy root cultures were induced to produce stilbenoids, which were purified by high performance countercurrent chromatography (HPCCC and analyzed by HPLC. HT29.f8 cells were infected with RV in the presence stilbenoids. Cell viability counts showed no cytotoxic effects on HT29.f8 cells. Viral infectivity titers were calculated and comparatively assessed to determine the effects of stilbenoid treatments. Two stilbenoids, trans-arachidin-1 and trans-arachidin-3, show a significant decrease in RV infectivity titers. Western blot analyses performed on the infected cell lysates complemented the infectivity titrations and indicated a significant decrease in viral replication. These studies show the therapeutic potential of the stilbenoids against RV replication.

  3. Rituximab: An emerging therapeutic agent for kidney transplantation

    Directory of Open Access Journals (Sweden)

    Joseph Kahwaji

    2009-10-01

    Full Text Available Joseph Kahwaji, Chris Tong, Stanley C Jordan, Ashley A VoComprehensive Transplant Center, Transplant immunology Laboratory, HLA Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA, USAAbstract: Rituximab (anti-CD20, anti-B-cell is now emerging as an important drug for modification of B-cell and antibody responses in solid-organ transplant recipients. Its uses are varied and range from facilitating desensitization and ABO blood group-incompatible transplantation to the treatment of antibody-mediated rejection (AMR, post-transplant lymphoproliferative disorder (PTLD, and recurrent glomerular diseases in the renal allograft. Despite these uses, prospective randomized trials are lacking. Only case reports exist in regards to its use in de novo and recurrent diseases in the renal allograft. Recent reports suggests that the addition of rituximab to intravenous immunoglobulin (IVIG may have significant benefits for desensitization and treatment of AMR and chronic rejection. Current dosing recommendations are based on data from United States Food and Drug Administration-approved indications for treatment of B-cell lymphomas and rheumatoid arthritis. From the initial reported experience in solid organ transplant recipients, the drug is well tolerated and not associated with increased infectious risks. However, close monitoring for viral infections is recommended with rituximab use. The occurrence of progressive multifocal leukoencephalopathy (PML has been reported with rituximab use. However, this is rare and not reported in the renal transplant population. Here we will review current information regarding the effectiveness of rituximab as an agent for desensitization of highly human leukocyte antigen-sensitized and ABO-incompatible transplant recipients and its use in treatment of AMR. In addition, the post-transplant use of rituximab for treatment of PTLD and for recurrent and de novo glomerulonephritis in the allograft will be discussed. In

  4. Therapeutic strategies with oral fluoropyrimidine anticancer agent, S-1 against oral cancer.

    Science.gov (United States)

    Harada, Koji; Ferdous, Tarannum; Ueyama, Yoshiya

    2017-08-01

    Oral cancer has been recognized as a tumor with low sensitivity to anticancer agents. However, introduction of S-1, an oral cancer agent is improving treatment outcome for patients with oral cancer. In addition, S-1, as a main drug for oral cancer treatment in Japan can be easily available for outpatients. In fact, S-1 exerts high therapeutic effects with acceptable side effects. Moreover, combined chemotherapy with S-1 shows higher efficacy than S-1 alone, and combined chemo-radiotherapy with S-1 exerts remarkable therapeutic effects. Furthermore, we should consider the combined therapy of S-1 and molecular targeting agents right now as these combinations were reportedly useful for oral cancer treatment. Here, we describe our findings related to S-1 that were obtained experimentally and clinically, and favorable therapeutic strategies with S-1 against oral cancer with bibliographic considerations.

  5. Nanoparticles as conjugated delivery agents for therapeutic applications

    Science.gov (United States)

    Muroski, Megan Elizabeth

    This dissertation explores the use of nanoparticles as conjugated delivery agents. Chapter 1 is a general introduction. Chapter 2 discusses the delivery by a nanoparticle platform provides a method to manipulate gene activation, by taking advantage of the high surface area of a nanoparticle and the ability to selectively couple a desired biological moiety to the NP surface. The nanoparticle based transfection approach functions by controlled release of gene regulatory elements from a 6 nm AuNP (gold nanoparticle) surface. The endosomal release of the regulatory elements from the nanoparticle surface results in endogenous protein knockdown simultaneously with exogenous protein expression for the first 48 h. The use of fluorescent proteins as the endogenous and exogenous signals for protein expression enables the efficiency of co-delivery of siRNA (small interfering RNA) for GFP (green fluorescent protein) knockdown and a dsRed-express linearized plasmid for induction to be optically analyzed in CRL-2794, a human kidney cell line expressing an unstable green fluorescent protein. Delivery of the bimodal nanoparticle in cationic liposomes results in 20% GFP knockdown within 24 h of delivery and continues exhibiting knockdown for up to 48 h for the bimodal agent. Simultaneous dsRed expression is observed to initiate within the same time frame with expression levels reaching 34% after 25 days although cells have divided approximately 20 times, implying daughter cell transfection has occurred. Fluorescence cell sorting results in a stable colony, as demonstrated by Western blot analysis. The simultaneous delivery of siRNA and linearized plasmid DNA on the surface of a single nanocrystal provides a unique method for definitive genetic control within a single cell and leads to a very efficient cell transfection protocol. In Chapter 3, we wanted to understand the NP complex within the cell, and to look at the dynamics of release utilizing nanometal surface energy transfer as

  6. Multirate delivery of multiple therapeutic agents from metal-organic frameworks

    Directory of Open Access Journals (Sweden)

    Alistair C. McKinlay

    2014-12-01

    Full Text Available The highly porous nature of metal-organic frameworks (MOFs offers great potential for the delivery of therapeutic agents. Here, we show that highly porous metal-organic frameworks can be used to deliver multiple therapeutic agents—a biologically active gas, an antibiotic drug molecule, and an active metal ion—simultaneously but at different rates. The possibilities offered by delivery of multiple agents with different mechanisms of action and, in particular, variable timescales may allow new therapy approaches. Here, we show that the loaded MOFs are highly active against various strains of bacteria.

  7. Fate of water borne therapeutic agents and associated effects on nitrifying biofilters in recirculating aquaculture systems

    DEFF Research Database (Denmark)

    Pedersen, Lars-Flemming

    be described as a concentration-dependent exponential decay. HP was found to be enzymatically eliminated by microorganisms, with degradation rates correlated to organic matter content and microbial abundance. Nitrification performance was not affected by HP when applied in dosages less than 30 mg/L, whereas...... prolonged multiple HP dosages at 10 mg/L were found to inhibit nitrite oxidation in systems with low organic loading. PAA decay was found to be concentration-dependent. It had a considerable negative effect on nitrite oxidation over a prolonged period of time when applied at a dosage ≥2 mg/L. PAA and HP...... decay patterns were significantly affected by water quality parameters, i.e. at low organic matter content HP degradation was impeded due to microbial inhibition. FISH analysis on biofilm samples from two different types of RAS showed that Nitrosomonas oligotropha was the dominant ammonia oxidizing...

  8. RGD-based strategies for selective delivery of therapeutics and imaging agents to the tumour vasculature

    NARCIS (Netherlands)

    Temming, K; Molema, G; Kok, RJ

    2005-01-01

    During the past decade, RGD-peptides have become a popular tool for the targeting of drugs and imaging agents to a(v)beta(3)-integrin expressing tumour vasculature. RGD-peptides have been introduced by recombinant means into therapeutic proteins and viruses. Chemical means have been applied to

  9. 77 FR 62521 - Prospective Grant of Exclusive License: The Development of Therapeutic Agents for the Treatment...

    Science.gov (United States)

    2012-10-15

    ... interleukin-10 (IL-10) inhibitor as a dual-biologic therapy to treat metastatic breast cancer, or ii) incorporating a p53 isoform antisense oligonucleotide as a single biologic therapy to treat T- cell lymphoma... Exclusive License: The Development of Therapeutic Agents for the Treatment of Metastatic Breast Cancer and T...

  10. ATM regulates 3-methylpurine-DNA glycosylase and promotes therapeutic resistance to alkylating agents.

    Science.gov (United States)

    Agnihotri, Sameer; Burrell, Kelly; Buczkowicz, Pawel; Remke, Marc; Golbourn, Brian; Chornenkyy, Yevgen; Gajadhar, Aaron; Fernandez, Nestor A; Clarke, Ian D; Barszczyk, Mark S; Pajovic, Sanja; Ternamian, Christian; Head, Renee; Sabha, Nesrin; Sobol, Robert W; Taylor, Michael D; Rutka, James T; Jones, Chris; Dirks, Peter B; Zadeh, Gelareh; Hawkins, Cynthia

    2014-10-01

    Alkylating agents are a first-line therapy for the treatment of several aggressive cancers, including pediatric glioblastoma, a lethal tumor in children. Unfortunately, many tumors are resistant to this therapy. We sought to identify ways of sensitizing tumor cells to alkylating agents while leaving normal cells unharmed, increasing therapeutic response while minimizing toxicity. Using an siRNA screen targeting over 240 DNA damage response genes, we identified novel sensitizers to alkylating agents. In particular, the base excision repair (BER) pathway, including 3-methylpurine-DNA glycosylase (MPG), as well as ataxia telangiectasia mutated (ATM), were identified in our screen. Interestingly, we identified MPG as a direct novel substrate of ATM. ATM-mediated phosphorylation of MPG was required for enhanced MPG function. Importantly, combined inhibition or loss of MPG and ATM resulted in increased alkylating agent-induced cytotoxicity in vitro and prolonged survival in vivo. The discovery of the ATM-MPG axis will lead to improved treatment of alkylating agent-resistant tumors. Inhibition of ATM and MPG-mediated BER cooperate to sensitize tumor cells to alkylating agents, impairing tumor growth in vitro and in vivo with no toxicity to normal cells, providing an ideal therapeutic window. ©2014 American Association for Cancer Research.

  11. Effect of Some Therapeutic Agents on the Radionuclides Excretion from Internally Contaminated Rats

    International Nuclear Information System (INIS)

    Aziz, M.; Mangood, Sh.A.; Sohsah, M.A.

    2009-01-01

    The present work was oriented to investigate the effectiveness of Prussian blue (PB), vermiculite and diethylenetriaminepentaacetic acid (CaDTPA) as therapeutic agents for the elimination of either 134 Cs or 60 Co from contaminated rats after intake of one of the isotopes. The study was performed by using 48 adult rats divided into 8 identical groups each of six rats having approximately the same body weight. The groups included a reference group, without isotope or therapeutic agent administration, four groups given one of the isotopes and four groups given the isotopes and treated with different therapeutic regimes. The isotope content of the treated and untreated contaminated rats were followed by daily whole body radiometric counting for three weeks. On plotting log % radionuclide retained as a function of time, elapsed between radionuclide administration and radiometric counting, straight lines were obtained. The results indicate that excretion can mostly be represented by two stages; the first is fast followed by a second slow stage. The % radionuclide excreted, the corresponding rate constant and the biological half-life of each stage was estimated. It was found that the application of PB + vermiculite is more efficient, to remove 134 Cs, from contaminated rats, than PB only and CaDTPA is more efficient to remove 60Co. Therefore, it is recommended to use the three therapeutic agents to remove both isotopes when taken simultaneously

  12. Cell targeting peptides as smart ligands for targeting of therapeutic or diagnostic agents: a systematic review.

    Science.gov (United States)

    Mousavizadeh, Ali; Jabbari, Ali; Akrami, Mohammad; Bardania, Hassan

    2017-10-01

    Cell targeting peptides (CTP) are small peptides which have high affinity and specificity to a cell or tissue targets. They are typically identified by using phage display and chemical synthetic peptide library methods. CTPs have attracted considerable attention as a new class of ligands to delivery specifically therapeutic and diagnostic agents, because of the fact they have several advantages including easy synthesis, smaller physical sizes, lower immunogenicity and cytotoxicity and their simple and better conjugation to nano-carriers and therapeutic or diagnostic agents compared to conventional antibodies. In this systematic review, we will focus on the basic concepts concerning the use of cell-targeting peptides (CTPs), following the approaches of selecting them from peptide libraries. We discuss several developed strategies for cell-specific delivery of different cargos by CTPs, which are designed for drug delivery and diagnostic applications. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Targeting Potassium Channels for Increasing Delivery of Imaging Agents and Therapeutics to Brain Tumors

    OpenAIRE

    Nagendra Sanyasihally Ningaraj; Divya eKhaitan

    2013-01-01

    Every year in the US, 20,000 new primary and nearly 200,000 metastatic brain tumor cases are reported. The cerebral microvessels/ capillaries that form the blood–brain barrier (BBB) not only protect the brain from toxic agents in the blood but also pose a significant hindrance to the delivery of small and large therapeutic molecules. Different strategies have been employed to circumvent the physiological barrier posed by blood-brain tumor barrier (BTB). Studies in our laboratory have identifi...

  14. Bacterial and protozoal agents of feline vector-borne diseases in domestic and stray cats from southern Portugal

    Science.gov (United States)

    2014-01-01

    Background Feline vector-borne diseases (FVBD) have emerged in recent years, showing a wider geographic distribution and increased global prevalence. In addition to their veterinary importance, domestic cats play a central role in the transmission cycles of some FVBD agents by acting as reservoirs and sentinels, a circumstance that requires a One Health approach. The aim of the present work was to molecularly detect feline vector-borne bacteria and protozoa with veterinary and zoonotic importance, and to assess associated risk factors in cats from southern Portugal. Methods Six hundred and forty-nine cats (320 domestic and 329 stray), from veterinary medical centres and animal shelters in southern Portugal, were studied. Anaplasma spp./Ehrlichia spp., Babesia spp., Bartonella spp., Borrelia burgdorferi sensu lato, Hepatozoon spp. and Leishmania spp. infections were evaluated by polymerase chain reaction (PCR) in blood samples. Results One hundred and ninety-four (29.9%) cats were PCR-positive to at least one of the tested genera or complex of FVBD agents. Sixty-four (9.9%) cats were positive to Leishmania spp., 56 (8.6%) to Hepatozoon spp., 43 (6.6%) to Babesia spp., 35 (5.4%) to Anaplasma spp./Ehrlichia spp., 19 (2.9%) to Bartonella spp. and 14 (2.2%) to B. burgdorferi s.l. Thirty-three (5.1%) cats were positive to two (n = 29) or three (n = 4) genera/complex. Babesia vogeli, Bartonella clarridgeiae, Bartonella henselae, Ehrlichia canis, Hepatozoon felis and Leishmania infantum were identified by DNA sequencing. Conclusions The occurrence of FVBD agents in southern Portugal, some of them with zoonotic character, emphasizes the need to alert the veterinary community, owners and public health authorities for the risk of infection. Control measures should be implemented to prevent the infection of cats, other vertebrate hosts and people. PMID:24655431

  15. Application of Mesenchymal Stem Cells for Therapeutic Agent Delivery in Anti-tumor Treatment

    Directory of Open Access Journals (Sweden)

    Daria S. Chulpanova

    2018-03-01

    Full Text Available Mesenchymal stem cells (MSCs are non-hematopoietic progenitor cells, which can be isolated from different types of tissues including bone marrow, adipose tissue, tooth pulp, and placenta/umbilical cord blood. There isolation from adult tissues circumvents the ethical concerns of working with embryonic or fetal stem cells, whilst still providing cells capable of differentiating into various cell lineages, such as adipocytes, osteocytes and chondrocytes. An important feature of MSCs is the low immunogenicity due to the lack of co-stimulatory molecules expression, meaning there is no need for immunosuppression during allogenic transplantation. The tropism of MSCs to damaged tissues and tumor sites makes them a promising vector for therapeutic agent delivery to tumors and metastatic niches. MSCs can be genetically modified by virus vectors to encode tumor suppressor genes, immunomodulating cytokines and their combinations, other therapeutic approaches include MSCs priming/loading with chemotherapeutic drugs or nanoparticles. MSCs derived membrane microvesicles (MVs, which play an important role in intercellular communication, are also considered as a new therapeutic agent and drug delivery vector. Recruited by the tumor, MSCs can exhibit both pro- and anti-oncogenic properties. In this regard, for the development of new methods for cancer therapy using MSCs, a deeper understanding of the molecular and cellular interactions between MSCs and the tumor microenvironment is necessary. In this review, we discuss MSC and tumor interaction mechanisms and review the new therapeutic strategies using MSCs and MSCs derived MVs for cancer treatment.

  16. Mesenchymal Stem Cells as New Therapeutic Agents for the Treatment of Primary Biliary Cholangitis

    Directory of Open Access Journals (Sweden)

    Aleksandar Arsenijevic

    2017-01-01

    Full Text Available Primary biliary cholangitis (PBC is a chronic autoimmune cholestatic liver disease characterized by the progressive destruction of small- and medium-sized intrahepatic bile ducts with resultant cholestasis and progressive fibrosis. Ursodeoxycholic acid and obethicholic acid are the only agents approved by the US Food and Drug Administration (FDA for the treatment of PBC. However, for patients with advanced, end-stage PBC, liver transplantation is still the most effective treatment. Accordingly, the alternative approaches, such as mesenchymal stem cell (MSC transplantation, have been suggested as an effective alternative therapy for these patients. Due to their immunomodulatory characteristics, MSCs are considered as promising therapeutic agents for the therapy of autoimmune liver diseases, including PBC. In this review, we have summarized the therapeutic potential of MSCs for the treatment of these diseases, emphasizing molecular and cellular mechanisms responsible for MSC-based effects in an animal model of PBC and therapeutic potential observed in recently conducted clinical trials. We have also presented several outstanding problems including safety issues regarding unwanted differentiation of transplanted MSCs which limit their therapeutic use. Efficient and safe MSC-based therapy for PBC remains a challenging issue that requires continuous cooperation between clinicians, researchers, and patients.

  17. Prevalence of select vector-borne disease agents in owned dogs of Ghana

    Directory of Open Access Journals (Sweden)

    Lorelei L. Clarke

    2014-09-01

    Full Text Available Ticks, sera and ethylenediaminetetraacetic acid (EDTA blood were collected from dogs evaluated at the Amakom Veterinary Clinic in Kumasi, Ghana. Sera were evaluated for Dirofilaria immitis antigen and antibodies against Borrelia burgdorferi, Anaplasma phagocytophilum and Ehrlichia canis. Conventional polymerase chain reaction assays designed to amplify the deoxyribonucleic acid (DNA ofEhrlichia spp. or Anaplasma spp. or Neorickettsia spp. or Wolbachia spp., Babesia spp., Rickettsia spp., Hepatozoon spp., Bartonella spp. and the haemoplasmas were performed on DNA extracted from EDTA blood and all positive amplicons were sequenced. This small survey shows that the following vector-borne pathogens are present in urban Ghanian dogs: Ehrlichia canis, Hepatozoon canis,Dirofilaria immitis and Anaplasma platys. Bartonella henselae was isolated from ticks but not from the dogs.

  18. Perspectives on Phytochemicals as Antibacterial Agents: An Outstanding Contribution to Modern Therapeutics.

    Science.gov (United States)

    Khatri, Savita; Kumar, Manish; Phougat, Neetu; Chaudhary, Renu; Chhillar, Anil Kumar

    2016-01-01

    Despite the considerable advancements in the development of antimicrobial agents, incidents of epidemics due to multi drug resistance in microorganisms have created a massive hazard to mankind. Due to increased resistance against conventional antibiotics, researchers and pharmaceutical industries are more concerned about novel therapeutic agents for the prevention of bacterial infections. Enormous wealth of traditional system of medicine gains importance in health therapies over again. With ancient credentials of potent medicinal plants, various herbal remedies came forward for the management of bacterial infections. The Ayurvedic approach facilitates the development of new therapeutic agents due to structural and functional diversity among phytochemicals. The abundance and diversity is responsible for the characterization of new lead structures from medicinal plants. Industrial interest has increased due to recent research advancements viz. synergistic and high-throughput screening approach for the evaluation of vast variety of phytochemicals. The review certainly emphasizes on the traditional medicines as alternatives to conventional chemotherapeutic drugs. The review briefly describes mode of action of various antibiotics and resistance mechanisms. This review focuses on the chemical diversity and various mechanisms of action of phytochemicals against bacterial pathogens.

  19. Production and evaluation of Lutetium-177 maltolate as a possible therapeutic agent

    International Nuclear Information System (INIS)

    Hakimi, A.; Jalilian, A. R.; Bahrami Samani, A.; Ghannadi Maragheh, M.

    2012-01-01

    Development of oral therapeutic radiopharmaceuticals is a new concept in radiopharmacy. Due to the interesting therapeutic properties of 177 Lu and oral bioavailability of maltolate (MAL) metal complexes, 177 Lu-maltolate ( 177 Lu-MAL) was developed as a possible therapeutic compound for ultimate oral administration. The specific activity of 2.6-3 GBq/mg was obtained by irradiation of natural Lu 2 O 3 sample with thermal neutron flux of 4x10 13 n.cm -2 .s -1 for Lu-177. The product was converted into chloride form which was further used for labeling maltol (MAL). At optimized conditions a radiochemical purity of about >99% was obtained for 177 Lu-MAL shown by ITLC (specific activity, 970-1000 Mbq/mmole). The stability of the labeled compound as well as the partition coefficient was determined in the final solution up to 24h. Biodistribution studies of Lu-177 chloride and 177 Lu-MAL were carried out in wild-type rats for post-oral distribution phase data. Lu-MAL is a possible therapeutic agent in human malignancies for the bone palliation therapy so the efficacy of the compound should be tested in various animal models.

  20. Anti-SEMA3A Antibody: A Novel Therapeutic Agent to Suppress GBM Tumor Growth.

    Science.gov (United States)

    Lee, Jaehyun; Shin, Yong Jae; Lee, Kyoungmin; Cho, Hee Jin; Sa, Jason K; Lee, Sang-Yun; Kim, Seok-Hyung; Lee, Jeongwu; Yoon, Yeup; Nam, Do-Hyun

    2017-11-10

    Glioblastoma (GBM) is classified as one of the most aggressive and lethal brain tumor. Great strides have been made in understanding the genomic and molecular underpinnings of GBM, which translated into development of new therapeutic approaches to combat such deadly disease. However, there are only few therapeutic agents that can effectively inhibit GBM invasion in a clinical framework. In an effort to address such challenges, we have generated anti-SEMA3A monoclonal antibody as a potential therapeutic antibody against GBM progression. We employed public glioma datasets, Repository of Molecular Brain Neoplasia Data and The Cancer Genome Atlas, to analyze SEMA3A mRNA expression in human GBM specimens. We also evaluated for protein expression level of SEMA3A via tissue microarray (TMA) analysis. Cell migration and proliferation kinetics were assessed in various GBM patient-derived cells (PDCs) and U87-MG cell-line for SEMA3A antibody efficacy. GBM patient-derived xenograft (PDX) models were generated to evaluate tumor inhibitory effect of anti-SEMA3A antibody in vivo. By combining bioinformatics and TMA analysis, we discovered that SEMA3A is highly expressed in human GBM specimens compared to non-neoplastic tissues. We developed three different anti-SEMA3A antibodies, in fully human IgG form, through screening phage-displayed synthetic antibody library using a classical panning method. Neutralization of SEMA3A significantly reduced migration and proliferation capabilities of PDCs and U87-MG cell-line in vitro. In PDX models, treatment with anti-SEMA3A antibody exhibited notable tumor inhibitory effect through down-regulation of cellular proliferative kinetics and tumor-associated macrophages recruitment. In present study, we demonstrated tumor inhibitory effect of SEMA3A antibody in GBM progression and present its potential relevance as a therapeutic agent in a clinical framework.

  1. Spherical Nucleic Acids as Intracellular Agents for Nucleic Acid Based Therapeutics

    Science.gov (United States)

    Hao, Liangliang

    Recent functional discoveries on the noncoding sequences of human genome and transcriptome could lead to revolutionary treatment modalities because the noncoding RNAs (ncRNAs) can be applied as therapeutic agents to manipulate disease-causing genes. To date few nucleic acid-based therapeutics have been translated into the clinic due to challenges in the delivery of the oligonucleotide agents in an effective, cell specific, and non-toxic fashion. Unmodified oligonucleotide agents are destroyed rapidly in biological fluids by enzymatic degradation and have difficulty crossing the plasma membrane without the aid of transfection reagents, which often cause inflammatory, cytotoxic, or immunogenic side effects. Spherical nucleic acids (SNAs), nanoparticles consisting of densely organized and highly oriented oligonucleotides, pose one possible solution to circumventing these problems in both the antisense and RNA interference (RNAi) pathways. The unique three dimensional architecture of SNAs protects the bioactive oligonucleotides from unspecific degradation during delivery and supports their targeting of class A scavenger receptors and endocytosis via a lipid-raft-dependent, caveolae-mediated pathway. Owing to their unique structure, SNAs are able to cross cell membranes and regulate target genes expression as a single entity, without triggering the cellular innate immune response. Herein, my thesis has focused on understanding the interactions between SNAs and cellular components and developing SNA-based nanostructures to improve therapeutic capabilities. Specifically, I developed a novel SNA-based, nanoscale agent for delivery of therapeutic oligonucleotides to manipulate microRNAs (miRNAs), the endogenous post-transcriptional gene regulators. I investigated the role of SNAs involving miRNAs in anti-cancer or anti-inflammation responses in cells and in in vivo murine disease models via systemic injection. Furthermore, I explored using different strategies to construct

  2. Silibinin, dexamethasone, and doxycycline as potential therapeutic agents for treating vesicant-inflicted ocular injuries

    International Nuclear Information System (INIS)

    Tewari-Singh, Neera; Jain, Anil K.; Inturi, Swetha; Ammar, David A.; Agarwal, Chapla; Tyagi, Puneet; Kompella, Uday B.; Enzenauer, Robert W.; Petrash, J. Mark; Agarwal, Rajesh

    2012-01-01

    There are no effective and approved therapies against devastating ocular injuries caused by vesicating chemical agents sulfur mustard (SM) and nitrogen mustard (NM). Herein, studies were carried out in rabbit corneal cultures to establish relevant ocular injury biomarkers with NM for screening potential efficacious agents in laboratory settings. NM (100 nmol) exposure of the corneas for 2 h (cultured for 24 h), showed increases in epithelial thickness, ulceration, apoptotic cell death, epithelial detachment microbullae formation, and the levels of VEGF, cyclooxygenase-2 (COX-2) and matrix metalloproteinase-9 (MMP-9). Employing these biomarkers, efficacy studies were performed with agent treatments 2 h and every 4 h thereafter, for 24 h following NM exposure. Three agents were evaluated, including prescription drugs dexamethasone (0.1%; anti-inflammatory steroid) and doxycycline (100 nmol; antibiotic and MMP inhibitor) that have been studied earlier for treating vesicant-induced eye injuries. We also examined silibinin (100 μg), a non-toxic natural flavanone found to be effective in treating SM analog-induced skin injuries in our earlier studies. Treatments of doxycycline + dexamethasone, and silibinin were more effective than doxycycline or dexamethasone alone in reversing NM-induced epithelial thickening, microbullae formation, apoptotic cell death, and MMP-9 elevation. However, dexamethasone and silibinin alone were more effective in reversing NM-induced VEGF levels. Doxycycline, dexamethasone and silibinin were all effective in reversing NM-induced COX-2 levels. Apart from therapeutic efficacy of doxycycline and dexamethasone, these results show strong multifunctional efficacy of silibinin in reversing NM-induced ocular injuries, which could help develop effective and safe therapeutics against ocular injuries by vesicants. -- Highlights: ► Established injury biomarkers in rabbit corneal culture with nitrogen mustard (NM) ► This NM model is a cost effective

  3. Silibinin, dexamethasone, and doxycycline as potential therapeutic agents for treating vesicant-inflicted ocular injuries

    Energy Technology Data Exchange (ETDEWEB)

    Tewari-Singh, Neera, E-mail: Neera.Tewari-Singh@ucdenver.edu [Department of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO 80045 (United States); Jain, Anil K., E-mail: Anil.Jain@ucdenver.edu [Department of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO 80045 (United States); Inturi, Swetha, E-mail: Swetha.Inturi@ucdenver.edu [Department of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO 80045 (United States); Ammar, David A., E-mail: David.Ammar@ucdenver.edu [Department of Ophthalmology, University of Colorado School of Medicine, Aurora, CO 80045 (United States); Agarwal, Chapla, E-mail: Chapla.Agarwal@ucdenver.edu [Department of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO 80045 (United States); Tyagi, Puneet, E-mail: Puneet.Tyagi@ucdenver.edu [Department of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO 80045 (United States); Kompella, Uday B., E-mail: Uday.Kompella@ucdenver.edu [Department of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO 80045 (United States); Enzenauer, Robert W., E-mail: Robert.Enzenauer@ucdenver.edu [Department of Ophthalmology, University of Colorado School of Medicine, Aurora, CO 80045 (United States); Petrash, J. Mark, E-mail: Mark.Petrash@ucdenver.edu [Department of Ophthalmology, University of Colorado School of Medicine, Aurora, CO 80045 (United States); Agarwal, Rajesh, E-mail: Rajesh.Agarwal@ucdenver.edu [Department of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO 80045 (United States)

    2012-10-01

    There are no effective and approved therapies against devastating ocular injuries caused by vesicating chemical agents sulfur mustard (SM) and nitrogen mustard (NM). Herein, studies were carried out in rabbit corneal cultures to establish relevant ocular injury biomarkers with NM for screening potential efficacious agents in laboratory settings. NM (100 nmol) exposure of the corneas for 2 h (cultured for 24 h), showed increases in epithelial thickness, ulceration, apoptotic cell death, epithelial detachment microbullae formation, and the levels of VEGF, cyclooxygenase-2 (COX-2) and matrix metalloproteinase-9 (MMP-9). Employing these biomarkers, efficacy studies were performed with agent treatments 2 h and every 4 h thereafter, for 24 h following NM exposure. Three agents were evaluated, including prescription drugs dexamethasone (0.1%; anti-inflammatory steroid) and doxycycline (100 nmol; antibiotic and MMP inhibitor) that have been studied earlier for treating vesicant-induced eye injuries. We also examined silibinin (100 μg), a non-toxic natural flavanone found to be effective in treating SM analog-induced skin injuries in our earlier studies. Treatments of doxycycline + dexamethasone, and silibinin were more effective than doxycycline or dexamethasone alone in reversing NM-induced epithelial thickening, microbullae formation, apoptotic cell death, and MMP-9 elevation. However, dexamethasone and silibinin alone were more effective in reversing NM-induced VEGF levels. Doxycycline, dexamethasone and silibinin were all effective in reversing NM-induced COX-2 levels. Apart from therapeutic efficacy of doxycycline and dexamethasone, these results show strong multifunctional efficacy of silibinin in reversing NM-induced ocular injuries, which could help develop effective and safe therapeutics against ocular injuries by vesicants. -- Highlights: ► Established injury biomarkers in rabbit corneal culture with nitrogen mustard (NM) ► This NM model is a cost effective

  4. Therapeutic efficacy and mechanism of action of ethamsylate, a long-standing hemostatic agent.

    Science.gov (United States)

    Garay, Ricardo P; Chiavaroli, Carlo; Hannaert, Patrick

    2006-01-01

    Ethamsylate (2,5-dihydroxy-benzene-sulfonate diethylammonium salt) is a synthetic hemostatic drug indicated in cases of capillary bleeding. This review covers more than 40 years of intensive clinical and fundamental research with ethamsylate. First, we summarize the large medical literature concerning its clinical efficacy. Of these, well-controlled clinical trials clearly showed the therapeutic efficacy of ethamsylate in dysfunctional uterine bleeding, with the magnitude of blood-loss reduction being directly proportional to the severity of the menorrhagia. Other well-controlled clinical trials showed therapeutic efficacy of ethamsylate in periventricular hemorrhage in very low birth weight babies and surgical or postsurgical capillary bleeding. Second, we review the numerous investigations performed to elucidate the mechanism of action of ethamsylate. Ethamsylate acts on the first step of hemostasis by improving platelet adhesiveness and restoring capillary resistance. Recent studies showed that ethamsylate promotes P-selectin-dependent, platelet adhesive mechanisms. Finally, we compare ethamsylate with other recent hemostatic agents. It is suggested that the place of ethamsylate as a hemostatic agent is that of a mild but well-tolerated drug, particularly useful in dysfunctional uterine bleeding when contraception is not needed.

  5. Insights into the Antimicrobial Properties of Hepcidins: Advantages and Drawbacks as Potential Therapeutic Agents

    Directory of Open Access Journals (Sweden)

    Lisa Lombardi

    2015-04-01

    Full Text Available The increasing frequency of multi-drug resistant microorganisms has driven research into alternative therapeutic strategies. In this respect, natural antimicrobial peptides (AMPs hold much promise as candidates for the development of novel antibiotics. However, AMPs have some intrinsic drawbacks, such as partial degradation by host proteases or inhibition by host body fluid composition, potential toxicity, and high production costs. This review focuses on the hepcidins, which are peptides produced by the human liver with a known role in iron homeostasis, as well by numerous other organisms (including fish, reptiles, other mammals, and their potential as antibacterial and antifungal agents. Interestingly, the antimicrobial properties of human hepcidins are enhanced at acidic pH, rendering these peptides appealing for the design of new drugs targeting infections that occur in body areas with acidic physiological pH. This review not only considers current research on the direct killing activity of these peptides, but evaluates the potential application of these molecules as coating agents preventing biofilm formation and critically assesses technical obstacles preventing their therapeutic application.

  6. New Therapeutic Agent against Arterial Thrombosis: An Iridium(III-Derived Organometallic Compound

    Directory of Open Access Journals (Sweden)

    Chih-Wei Hsia

    2017-12-01

    Full Text Available Platelet activation plays a major role in cardio and cerebrovascular diseases, and cancer progression. Disruption of platelet activation represents an attractive therapeutic target for reducing the bidirectional cross talk between platelets and tumor cells. Platinum (Pt compounds have been used for treating cancer. Hence, replacing Pt with iridium (Ir is considered a potential alternative. We recently developed an Ir(III-derived complex, [Ir(Cp*1-(2-pyridyl-3-(2-hydroxyphenylimidazo[1,5-a]pyridine Cl]BF4 (Ir-11, which exhibited strong antiplatelet activity; hence, we assessed the therapeutic potential of Ir-11 against arterial thrombosis. In collagen-activated platelets, Ir-11 inhibited platelet aggregation, adenosine triphosphate (ATP release, intracellular Ca2+ mobilization, P-selectin expression, and OH· formation, as well as the phosphorylation of phospholipase Cγ2 (PLCγ2, protein kinase C (PKC, mitogen-activated protein kinases (MAPKs, and Akt. Neither the adenylate cyclase inhibitor nor the guanylate cyclase inhibitor reversed the Ir-11-mediated antiplatelet effects. In experimental mice, Ir-11 prolonged the bleeding time and reduced mortality associated with acute pulmonary thromboembolism. Ir-11 plays a crucial role by inhibiting platelet activation through the inhibition of the PLCγ2–PKC cascade, and the subsequent suppression of Akt and MAPK activation, ultimately inhibiting platelet aggregation. Therefore, Ir-11 can be considered a new therapeutic agent against either arterial thrombosis or the bidirectional cross talk between platelets and tumor cells.

  7. Ultrasound enhanced delivery of molecular imaging and therapeutic agents in Alzheimer's disease mouse models.

    Directory of Open Access Journals (Sweden)

    Scott B Raymond

    Full Text Available Alzheimer's disease is a neurodegenerative disorder typified by the accumulation of a small protein, beta-amyloid, which aggregates and is the primary component of amyloid plaques. Many new therapeutic and diagnostic agents for reducing amyloid plaques have limited efficacy in vivo because of poor transport across the blood-brain barrier. Here we demonstrate that low-intensity focused ultrasound with a microbubble contrast agent may be used to transiently disrupt the blood-brain barrier, allowing non-invasive, localized delivery of imaging fluorophores and immunotherapeutics directly to amyloid plaques. We administered intravenous Trypan blue, an amyloid staining red fluorophore, and anti-amyloid antibodies, concurrently with focused ultrasound therapy in plaque-bearing, transgenic mouse models of Alzheimer's disease with amyloid pathology. MRI guidance permitted selective treatment and monitoring of plaque-heavy anatomical regions, such as the hippocampus. Treated brain regions exhibited 16.5+/-5.4-fold increase in Trypan blue fluorescence and 2.7+/-1.2-fold increase in anti-amyloid antibodies that localized to amyloid plaques. Ultrasound-enhanced delivery was consistently reproduced in two different transgenic strains (APPswe:PSEN1dE9, PDAPP, across a large age range (9-26 months, with and without MR guidance, and with little or no tissue damage. Ultrasound-mediated, transient blood-brain barrier disruption allows the delivery of both therapeutic and molecular imaging agents in Alzheimer's mouse models, which should aid pre-clinical drug screening and imaging probe development. Furthermore, this technique may be used to deliver a wide variety of small and large molecules to the brain for imaging and therapy in other neurodegenerative diseases.

  8. Prevalence of Selected Zoonotic and Vector-Borne Agents in Dogs and Cats on the Pine Ridge Reservation

    Directory of Open Access Journals (Sweden)

    A. Valeria Scorza

    2017-09-01

    Full Text Available The prevalence of intestinal parasites and vector-borne agents of dogs and cats in the Pine Ridge Reservation, South Dakota were determined. Fecal samples (84 dogs, 9 cats were examined by centrifugal floatation and by immunofluorescence assay (FA for Giardia and Cryptosporidium. PCR was performed on Giardia [beta-giardin (bg, triose phosphate isomerase (tpi, glutamate dehydrogenase genes (gdh] and Cryptosporidium [heat shock protein-70 gene (hsp] FA positive samples. Cat sera (n = 32 were tested for antibodies against Bartonella spp., Toxoplasma gondii, and FIV, and antigens of FeLV and Dirofilaria immitis. Dog sera (n = 82 were tested for antibodies against T. gondii, Borrelia burgdorferi, Ehrlichia canis, and Anaplasma phagocytophilum and D. immitis antigen. Blood samples (92 dogs, 39 cats were assessed by PCR for amplification of DNA of Bartonella spp., Ehrlichia spp., Anaplasma spp., haemoplasmas, and Babesia spp. (dogs only. The most significant results were Giardia spp. (32% by FA, Taenia spp. (17.8% and Cryptosporidium spp. (7.1%. The Giardia isolates typed as the dog-specific assemblages C or D and four Cryptosporidium isolates typed as C. canis. Antibodies against T. gondii were detected in 15% of the dogs. Antibodies against Bartonella spp. and against T. gondii were detected in 37.5% and 6% of the cats respectively. FeLV antigen was detected in 10% of the cats.

  9. Recent trends in the transdermal delivery of therapeutic agents used for the management of neurodegenerative diseases.

    Science.gov (United States)

    Ita, Kevin

    2017-06-01

    With the increasing proportion of the global geriatric population, it becomes obvious that neurodegenerative diseases will become more widespread. From an epidemiological standpoint, it is necessary to develop new therapeutic agents for the management of Alzheimer's disease, Parkinson's disease, multiple sclerosis and other neurodegenerative disorders. An important approach in this regard involves the use of the transdermal route. With transdermal drug delivery systems (TDDS), it is possible to modulate the pharmacokinetic profiles of these medications and improve patient compliance. Transdermal drug delivery has also been shown to be useful for drugs with short half-life and low or unpredictable bioavailability. In this review, several transdermal drug delivery enhancement technologies are being discussed in relation to the delivery of medications used for the management of neurodegenerative disorders.

  10. Technical cooperation for the wider uses of Ho-166 therapeutic agents in European countries

    CERN Document Server

    Park, K B; Choi, S M; Han, K H; Hong, Y D; Park, W W; Shin, B C

    2002-01-01

    Czech has put their priority in developing the radiopharmaceuticals based on reactor produced Ho-166 and a related fabrication will be extended to other EU conturies including Germany, France, etc after a development of project. The collaboration will be based on the mutual agreement for developing the between research institutes, industries and academic institutes and further researches should be followed by the issue of developing radiopharmaceuticals using Ho-166. To strengthen the collaboration, detailed discussions for the practical collaboration have been made through the visitation to the research institution of each counter part. For implementing the collaboration between NPI and KAERI, an institutional basis technical cooperation agreement(TCA) will be concluded. Furthermore, agreement for the substantial collaboration on Ho-166 related researches will be made after the conclusion of the TCA. It will accelerate the commercialization of KAERI developed Ho-166 therapeutic agents into other European cou...

  11. Review of therapeutic agents for burns pruritus and protocols for management in adult and paediatric patients using the GRADE classification

    Directory of Open Access Journals (Sweden)

    Goutos Ioannis

    2010-10-01

    Full Text Available To review the current evidence on therapeutic agents for burns pruritus and use the Grading of Recommendations, Assessment, Development and Evaluation (GRADE classification to propose therapeutic protocols for adult and paediatric patients. All published interventions for burns pruritus were analysed by a multidisciplinary panel of burns specialists following the GRADE classification to rate individual agents. Following the collation of results and panel discussion, consensus protocols are presented. Twenty-three studies appraising therapeutic agents in the burns literature were identified. The majority of these studies (16 out of 23 are of an observational nature, making an evidence-based approach to defining optimal therapy not feasible. Our multidisciplinary approach employing the GRADE classification recommends the use of antihistamines (cetirizine and cimetidine and gabapentin as the first-line pharmacological agents for both adult and paediatric patients. Ondansetron and loratadine are the second-line medications in our protocols. We additionally recommend a variety of non-pharmacological adjuncts for the perusal of clinicians in order to maximise symptomatic relief in patients troubled with postburn itch. Most studies in the subject area lack sufficient statistical power to dictate a ′gold standard′ treatment agent for burns itch. We encourage clinicians to employ the GRADE system in order to delineate the most appropriate therapeutic approach for burns pruritus until further research elucidates the most efficacious interventions. This widely adopted classification empowers burns clinicians to tailor therapeutic regimens according to current evidence, patient values, risks and resource considerations in different medical environments.

  12. Preclinical therapeutic potential of a nitrosylating agent in the treatment of ovarian cancer.

    Directory of Open Access Journals (Sweden)

    Shailendra Giri

    Full Text Available This study examines the role of s-nitrosylation in the growth of ovarian cancer using cell culture based and in vivo approaches. Using the nitrosylating agent, S-nitrosoglutathione (GSNO, a physiological nitric oxide molecule, we show that GSNO treatment inhibited proliferation of chemoresponsive and chemoresistant ovarian cancer cell lines (A2780, C200, SKVO3, ID8, OVCAR3, OVCAR4, OVCAR5, OVCAR7, OVCAR8, OVCAR10, PE01 and PE04 in a dose dependent manner. GSNO treatment abrogated growth factor (HB-EGF induced signal transduction including phosphorylation of Akt, p42/44 and STAT3, which are known to play critical roles in ovarian cancer growth and progression. To examine the therapeutic potential of GSNO in vivo, nude mice bearing intra-peritoneal xenografts of human A2780 ovarian carcinoma cell line (2 × 10(6 were orally administered GSNO at the dose of 1 mg/kg body weight. Daily oral administration of GSNO significantly attenuated tumor mass (p<0.001 in the peritoneal cavity compared to vehicle (phosphate buffered saline treated group at 4 weeks. GSNO also potentiated cisplatin mediated tumor toxicity in an A2780 ovarian carcinoma nude mouse model. GSNO's nitrosylating ability was reflected in the induced nitrosylation of various known proteins including NFκB p65, Akt and EGFR. As a novel finding, we observed that GSNO also induced nitrosylation with inverse relationship at tyrosine 705 phosphorylation of STAT3, an established player in chemoresistance and cell proliferation in ovarian cancer and in cancer in general. Overall, our study underlines the significance of S-nitrosylation of key cancer promoting proteins in modulating ovarian cancer and proposes the therapeutic potential of nitrosylating agents (like GSNO for the treatment of ovarian cancer alone or in combination with chemotherapeutic drugs.

  13. Quercetin as an Emerging Anti-Melanoma Agent: A four-focus area therapeutic development strategy

    Directory of Open Access Journals (Sweden)

    Zoey Harris

    2016-10-01

    Full Text Available Replacing current refractory treatments for melanoma with new prevention and therapeutic approaches is crucial in order to successfully treat this aggressive cancer form. Melanoma develops from neural crest cells, which express tyrosinase -- a key enzyme in the pigmentation pathway. The tyrosinase enzyme is highly active in melanoma cells and metabolizes polyphenolic compounds; tyrosinase expression thus makes a feasible a target for polyphenol-based therapies. For example, quercetin (3,3′,4′,5,7-pentahydroxyflavone is a highly ubiquitous and well-classified dietary polyphenol found in various fruits, vegetables and other plant products including onions, broccoli, kale, oranges, blueberries, apples, and tea. Quercetin has demonstrated anti-proliferative and pro-apoptotic activity in various cancer cell types. Quercetin is readily metabolized by tyrosinase into various compounds that promote anti-cancer activity; additionally, given that tyrosinase expression increases during tumorigenesis, and its activity is associated with pigmentation changes in both early- and late-stage melanocytic lesions, it suggests that quercetin can be used to target melanoma. In this review we explore the potential of Quercetin as an anti-melanoma agent utilizing and extrapolating on evidence from previous in vitro studies in various human malignant cell lines and propose a four-focus area strategy to develop quercetin as a targeted anti-melanoma compound for use as either a preventative or therapeutic agent. The four areas of focus include utilizing quercetin to i modulate cellular bioreduction potential and associated signaling cascades, ii affect transcription of relevant genes, iii regulate epigenetic processes, and iv develop effective combination therapies and delivery modalities/protocols. In general, quercetin could be used to exploit tyrosinase activity to prevent, and/or treat, melanoma with minimal additional side effects.

  14. [ManNAc, a new therapeutic agent to reduce Angptl4-induced proteinuria in MCD].

    Science.gov (United States)

    Clément, Lionel; Macé, Camille

    2016-01-01

    Current therapies used in minimal change disease (MCD) were originally designed to cure other diseases. They are only partially efficient, and present inconvenient side effects. Therefore, understanding the molecular mechanisms implicated in the pathogenesis of proteinuria in MCD could lead to new therapeutic strategies. A new experimental transgenic rat model of human MCD was generated. These NPHS2-Angptl4 transgenic rats over-express two different forms of the glycoprotein Angptl4 from the podocyte. The majority of the protein shows a lack of sialylation that is implicated in the pathogenesis of proteinuria. Supplementation of ManNAc, a precursor of sialic acid, significantly reduces albuminuria in those rats by increasing sialylation of the hyposialylated form of Angptl4. After treatment of the first episode of MCD with glucocorticoids in patients, ManNAc could be used as a maintenance drug, especially to reduce the frequency and intensity of relapse. ManNAc is a promising therapeutic agent for patients with MCD. © 2016 médecine/sciences – Inserm.

  15. 166 Ho-HA Evaluation as therapeutic agent for rheumatoid arthritis treatment

    International Nuclear Information System (INIS)

    Chandia, M; Errazu, X; Mendoza, P; Troncoso, F; Jofre, J; Sierralta, P

    2003-01-01

    Aim: Rheumatoid arthritis is a limiting disease having, among its pathological features, the inflammation of synovial tissue with progressive and later destruction of the articulation. This lead to joint deformation and loss of its function, generating pain and reducing the mobility of the affected articulation. The aim was to evaluate 166 Ho-Hydroxyapatite ( 166 Ho-HA) as potential radiopharmaceutical for the syntomatic treatment of chronic and acute arthritis Materials and Methods: 166 Holmiun was produced by irradiation of Ho 2 O 3 at La Reina Research Reactor, Nuclear Chilean Energy Commission. Hydroxyapatite was in-house synthetized. Its labelling and quality controls follows the internationally accepted procedures. An antigen arthritis was induced to eight New Zealand rabbits with the 166 Ho-HA radiochemical being administred thereafter in two dosage modalities (single and double). The compound therapeutic efficiency was evaluated based upon clinical improvement and images from the inflamated articulation using 67 Ga citrate before and after 166 Ho-HA injection. Results: The radiochemical purity of the innoculated compound was greater than 98% as measured under sterility conditions. Clinically, an inflamation reduction (2 cm), appetite improvement and general well being was observed. The 166 Ho-HA distribution and localization was monitored using gamma camera images taken at 4 and 24 h. There was no evidence of extraarticular leakage. From the 67 Ga citrate imaging, the acute group shows an overall improvement of well being corresponding to a lesser uptake at the inflamated articulation, regarding to the chronic group. The 166 Ho-HA double dosis, compared to the single dosis, suggest a reduced uptake of 67 Ga citrate at the inflamated tissue, meaning an increased therapeutic effect. Conclusions: 166 Ho-HA is usefull as therapeutic agent for the syntomatic treatment of rheumatoideal arthritis as shown by imaging and clinical examination (author)

  16. 166Ho-HA evaluation as therapeutic agent for rheumatoid arthritis treatment

    International Nuclear Information System (INIS)

    Chandia, M.C.; Errazu, X.C.; Pinto, L.N.; Godoy, N.O.; Avila, M.J.; Mendoza, P.; Mendoza, J.; Jofre, J.; Sirraalta, P.

    2002-01-01

    Aim: Rheumatoid arthritis is a limiting disease having, among its pathological features, the inflammation of synovial tissue with progressive and later destruction of the articulation. This leads to joint deformation and loss of its function, generating pain and reducing the mobility of the affected articulation. The aim was to evaluate 166 Ho-Hydroxyapatite ( 166 Ho-HA) as potential radiopharmaceutical for the symptomatic treatment of chronic and acute arthritis. Materials and Methods: Holmiun-166 was produced by irradiation of Ho 2 O 3 at La Reina Research Reactor, Nuclear Chilean Energy Commission. Hydroxyapatite was in-house synthesized. Its labelling and quality controls follows the internationally accepted procedures. An antigen's arthritis was induced to eight New Zealand rabbits with the 166 Ho-HA radiochemical being administered thereafter in two dosage modalities (single and double). The compound therapeutic efficiency was evaluated based upon clinical improvement and images from the inflamated articulation using 67 Ga citrate before and after 166 Ho-HA injection. Results: The radiochemical purity of the inoculated compound was greater than 98% as measured under sterility conditions. Clinically, an inflammation reduction (2 cm), appetite improvement and general well being was observed. The 166 Ho-HA distribution and localization was monitored using gamma camera images taken at 4 and 24 h. There was no evidence of extra articular leakage. From the 67 Ga citrate imaging, the acute group shows an overall improvement of well being corresponding to a lesser uptake at the inflamated articulation, regarding to the chronic group. The 166 Ho-HA double doses, compared to the single doses, suggest a reduced uptake of 67 Ga citrate at the inflamated tissue, meaning an increased therapeutic effect. Conclusions: 166 Ho-HA is useful as therapeutic agent for the symptomatic treatment of rheumatoid arthritis as shown by imaging and clinical examination

  17. Therapeutic journery of nitrogen mustard as alkylating anticancer agents: Historic to future perspectives.

    Science.gov (United States)

    Singh, Rajesh K; Kumar, Sahil; Prasad, D N; Bhardwaj, T R

    2018-05-10

    Cancer is considered as one of the most serious health problems today. The discovery of nitrogen mustard as an alkylating agent in 1942, opened a new era in the cancer chemotherapy. This valuable class of alkylating agent exerts its biological activity by binding to DNA, cross linking two strands, preventing DNA replication and ultimate cell death. At the molecular level, nitrogen lone pairs of nitrogen mustard generate a strained intermediate "aziridinium ion" which is very reactive towards DNA of tumor cell as well as normal cell resulting in various adverse side effects alogwith therapeutic implications. Over the last 75 years, due to its high reactivity and peripheral cytotoxicity, numerous modifications have been made in the area of nitrogen mustard to improve its efficacy as well as enhancing drug delivery specifically to tumor cells. This review mainly discusses the medicinal chemistry aspects in the development of various classes of nitrogen mustards (mechlorethamine, chlorambucil, melphalan, cyclophosphamide and steroidal based nitrogen mustards). The literature collection includes the historical and the latest developments in these areas. This comprehensive review also attempted to showcase the recent progress in the targeted delivery of nitrogen mustards that includes DNA directed nitrogen mustards, antibody directed enzyme prodrug therapy (ADEPT), gene directed enzyme prodrug therapy (GDEPT), nitrogen mustard activated by glutathione transferase, peptide based nitrogen mustards and CNS targeted nitrogen mustards. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  18. MUCOLYTIC AGENTS IN PEDIATRICS: RATIONAL SELECTION, THERAPEUTIC EFFECTS AND SPECIFIC ASPECTS OF TREATMENT

    Directory of Open Access Journals (Sweden)

    O. I. Simonova

    2013-01-01

    Full Text Available The article deals with the cough treatment options with mucolytic agents administration at the first several days of acute respiratory tract infections in children. Efficacy of treatment with secretolytic and secretomotoric drugs significantly depends on certain factors. The article contains the criteria of therapeutic efficacy of expectorants. A special attention is given to N-acetylcysteine — a direct acting mucolytic agent, which effect is caused by presence of free sulfhydryl groups, disrupting disulfide bonds between molecules of acid mucopolysaccharides and glycoproteins therefore changing the structure of sputum. Acetylcysteine is active against every type of sputum (mucous, muco-purulent, purulent, that is especially important in treatment of bacterial infections, when it is necessary to quickly decrease sputum thickness, eliminate it from the respiratory tract and prevent dissemination of the infection. High efficacy of acetylcysteine is caused by its unique triple action: mucolytic, antioxidant and antitoxic. Mechanism of action of acetylcysteine is discussed in detail. Timely administered treatment will improve sputum discharge and therefore eliminate one of the main factors of bronchial obstruction and decrease the risk of microbial colonization of the respiratory tract. The article also includes indications, contraindications and dosage regimens of acetylcysteine in children. The most common mistakes and specific aspects of mucolytic drugs in pediatrics are listed in the conclusion. 

  19. Pharmacokinetics of cotinine in rats: a potential therapeutic agent for disorders of cognitive function.

    Science.gov (United States)

    Li, Pei; Beck, Wayne D; Callahan, Patrick M; Terry, Alvin V; Bartlett, Michael G

    2015-06-01

    Attention has been paid to cotinine (COT), one of the major metabolites of nicotine (NIC), for its pro-cognitive effects and potential therapeutic activities against Alzheimer's disease (AD) and other types of cognitive impairment. In order to facilitate pharmacological and toxicological studies on COT for its pro-cognitive activities, we conducted a pharmacokinetic (PK) study of COT in rats, providing important oral and intravenously (iv) PK information. In this study, plasma samples were obtained up to 48 h after COT was dosed to rats orally and iv at a dose of 3mg/kg. Plasma samples were prepared and analyzed using a sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS) bioanalytical method, providing concentration profiles of COT and metabolites after oral and iv administrations. The data were fitted into a one-compartment model and a two-compartment model for the oral and iv groups, respectively, providing important PK information for COT including PK profiles, half-life, clearance and bioavailability. The results suggested fast absorption, slow elimination and high bioavailability of COT in rats. Several important facts about the PK properties in rats suggested COT could be a potential pro-cognitive agent. Information about the pharmacokinetics of COT in rats revealed in this study is of great importance for the future studies on COT or potential COT analogs as agents for improving cognition. Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  20. Targeting Potassium Channels for Increasing Delivery of Imaging Agents and Therapeutics to Brain Tumors

    Directory of Open Access Journals (Sweden)

    Nagendra Sanyasihally Ningaraj

    2013-05-01

    Full Text Available Every year in the US, 20,000 new primary and nearly 200,000 metastatic brain tumor cases are reported. The cerebral microvessels/ capillaries that form the blood–brain barrier (BBB not only protect the brain from toxic agents in the blood but also pose a significant hindrance to the delivery of small and large therapeutic molecules. Different strategies have been employed to circumvent the physiological barrier posed by blood-brain tumor barrier (BTB. Studies in our laboratory have identified significant differences in the expression levels of certain genes and proteins between normal and brain tumor capillary endothelial cells. In this study, we validated the non-invasive and clinically relevant Dynamic Contrast Enhancing-Magnetic Resonance Imaging (DCE-MRI method with invasive, clinically irrelevant but highly accurate Quantitative Autoradiography (QAR method using rat glioma model. We also showed that DCE-MRI metric of tissue vessel perfusion-permeability is sensitive to changes in blood vessel permeability following administration of calcium-activated potassium (BKCa channel activator NS-1619. Our results show that human gliomas and brain tumor endothelial cells that overexpress BKCa channels can be targeted for increased BTB permeability for MRI enhancing agents to brain tumors. We conclude that monitoring the outcome of increased MRI enhancing agents’ delivery to microsatellites and leading tumor edges in glioma patients would lead to beneficial clinical outcome.

  1. Formulation and acoustic studies of a new phase-shift agent for diagnostic and therapeutic ultrasound.

    Science.gov (United States)

    Sheeran, Paul S; Luois, Samantha; Dayton, Paul A; Matsunaga, Terry O

    2011-09-06

    Recent efforts in the area of acoustic droplet vaporization with the objective of designing extravascular ultrasound contrast agents has led to the development of stabilized, lipid-encapsulated nanodroplets of the highly volatile compound decafluorobutane (DFB). We developed two methods of generating DFB droplets, the first of which involves condensing DFB gas (boiling point from -1.1 to -2 °C) followed by extrusion with a lipid formulation in HEPES buffer. Acoustic droplet vaporization of micrometer-sized lipid-coated droplets at diagnostic ultrasound frequencies and mechanical indices were confirmed optically. In our second formulation methodology, we demonstrate the formulation of submicrometer-sized lipid-coated nanodroplets based upon condensation of preformed microbubbles containing DFB. The droplets are routinely in the 200-300 nm range and yield microbubbles on the order of 1-5 μm once vaporized, consistent with ideal gas law expansion predictions. The simple and effective nature of this methodology allows for the development of a variety of different formulations that can be used for imaging, drug and gene delivery, and therapy. This study is the first to our knowledge to demonstrate both a method of generating ADV agents by microbubble condensation and formulation of primarily submicrometer droplets of decafluorobutane that remain stable at physiological temperatures. Finally, activation of DFB nanodroplets is demonstrated using pressures within the FDA guidelines for diagnostic imaging, which may minimize the potential for bioeffects in humans. This methodology offers a new means of developing extravascular contrast agents for diagnostic and therapeutic applications. © 2011 American Chemical Society

  2. Kinase inhibitors of the IGF-1R as a potential therapeutic agent for rheumatoid arthritis.

    Science.gov (United States)

    Tsushima, Hiroshi; Morimoto, Shinji; Fujishiro, Maki; Yoshida, Yuko; Hayakawa, Kunihiro; Hirai, Takuya; Miyashita, Tomoko; Ikeda, Keigo; Yamaji, Ken; Takamori, Kenji; Takasaki, Yoshinari; Sekigawa, Iwao; Tamura, Naoto

    2017-08-01

    We have previously shown that the inhibition of connective tissue growth factor (CTGF) is a potential therapeutic strategy against rheumatoid arthritis (RA). CTGF consists of four distinct modules, including the insulin-like growth factor binding protein (IGFBP). In serum, insulin-like growth factors (IGFs) bind IGFBPs, interact with the IGF-1 receptor (IGF-1 R), and regulate anabolic effects and bone metabolism. We investigated the correlation between IGF-1 and the pathogenesis of RA, and the inhibitory effect on osteoclastogenesis and angiogenesis of the small molecular weight kinase inhibitor of the IGF-1 R, NVP-AEW541, against pathogenesis of RA in vitro. Cell proliferation was evaluated by cell count and immunoblotting. The expression of IGF-1 and IGF-1 R was evaluated by RT-PCR. Osteoclastogenesis was evaluated using tartrate-resistant acid phosphatase staining, a bone resorption assay, and osteoclast-specific enzyme production. Angiogenesis was evaluated by a tube formation assay using human umbilical vein endothelial cells (HUVECs). The proliferation of MH7A cells was found to be inhibited in the presence of NVP-AEW541, and the phosphorylation of extracellular signal-regulated kinase (ERK) and Akt was downregulated in MH7A cells. IGF-1 and IGF-1 R mRNA expression levels were upregulated during formation of M-colony stimulating factor (M-CSF) and receptor activator of NF-κB ligand (RANKL)-mediated osteoclast formation. Moreover, osteoclastogenesis was suppressed in the presence of NVP-AEW541. The formation of the tubular network was enhanced by IGF-1, and this effect was neutralized by NVP-ARE541. Our findings suggest that NVP-AEW541 may be utilized as a potential therapeutic agent in the treatment of RA.

  3. [Weighing use and safety of therapeutic agents and feed additives (author's transl)].

    Science.gov (United States)

    van der Wal, P

    1982-02-01

    (1) The pros and cons of using feed additives and therapeutic agents may be successfully weighed in the light of carefully considered consumer requirements. (2) The socio-economic interests of the producer and the welfare of the animal will also determine the response of the production apparatus to consumer requirements. (3) Consumption of the current amounts of products of animal origin and maintenance of price and quality will only be feasible in the event of rational large-scale production in which constituents used in nutrition, prophylaxis and therapeutics are highly important factors. (4) Using these ingredients should be preceded by accurate evaluation of their use and safety. Testing facilities, conduct of studies and reporting should be such as to make the results nationally and internationally acceptable to all those concerned. (5) In deciding whether feed constituents are acceptable in view of the established use and safety, compliance will have to be sought with those standards which are accepted in other fields of society. Measures which result in raising the price of food without actually helping to reduce the risks to the safety of man, animals and environment, are likely to be rejected by any well-informed consumer who is aware of the facts. (6) For accurate weighing of use and safety at a national level, possibilities are hardly adequate in Europe. Decisions reached within the framework of the European Community, also tuned to U.S.A.- conditions are rightly encouraged. A centrally managed professionally staffed and equipped test system in the European Community would appear to be indispensable.

  4. Folic acid tagged nanoceria as a novel therapeutic agent in ovarian cancer

    International Nuclear Information System (INIS)

    Hijaz, Miriana; Das, Soumen; Mert, Ismail; Gupta, Ankur; Al-Wahab, Zaid; Tebbe, Calvin; Dar, Sajad; Chhina, Jasdeep; Giri, Shailendra; Munkarah, Adnan; Seal, Sudipta; Rattan, Ramandeep

    2016-01-01

    Nanomedicine is a very promising field and nanomedical drugs have recently been used as therapeutic agents against cancer. In a previous study, we showed that Nanoceria (NCe), nanoparticles of cerium oxide, significantly inhibited production of reactive oxygen species, cell migration and invasion of ovarian cancer cells in vitro, without affecting cell proliferation and significantly reduced tumor growth in an ovarian cancer xenograft nude model. Increased expression of folate receptor-α, an isoform of membrane-bound folate receptors, has been described in ovarian cancer. To enable NCe to specifically target ovarian cancer cells, we conjugated nanoceria to folic acid (NCe-FA). Our aim was to investigate the pre-clinical efficacy of NCe-FA alone and in combination with Cisplatin. Ovarian cancer cell lines were treated with NCe or NCe-FA. Cell viability was assessed by MTT and colony forming units. In vivo studies were carried in A2780 generated mouse xenografts treated with 0.1 mg/Kg NCe, 0.1 mg/Kg; NCe-FA and cisplatinum, 4 mg/Kg by intra-peritoneal injections. Tumor weights and burden scores were determined. Immunohistochemistry and toxicity assays were used to evaluate treatment effects. We show that folic acid conjugation of NCe increased the cellular NCe internalization and inhibited cell proliferation. Mice treated with NCe-FA had a lower tumor burden compared to NCe, without any vital organ toxicity. Combination of NCe-FA with cisplatinum decreased the tumor burden more significantly. Moreover, NCe-FA was also effective in reducing proliferation and angiogenesis in the xenograft mouse model. Thus, specific targeting of ovarian cancer cells by NCe-FA holds great potential as an effective therapeutic alone or in combination with standard chemotherapy. The online version of this article (doi:10.1186/s12885-016-2206-4) contains supplementary material, which is available to authorized users

  5. Therapeutic potential of thiazolidinedione-8 as an antibiofilm agent against Candida albicans.

    Directory of Open Access Journals (Sweden)

    Mark Feldman

    Full Text Available Candida albicans is known as a commensal microorganism but it is also the most common fungal pathogen in humans, causing both mucosal and systemic infections. Biofilm-associated C. albicans infections present clinically important features due to their high levels of resistance to traditional antifungal agents. Quorum sensing is closely associated with biofilm formation and increasing fungal pathogenicity. We investigated the ability of the novel bacterial quorum sensing quencher thiazolidinedione-8 (S-8 to inhibit the formation of, and eradication of mature C. albicans biofilms. In addition, the capability of S-8 to alter fungal adhesion to mammalian cells was checked. S-8 exhibited specific antibiofilm and antiadhesion activities against C. albicans, at four- to eightfold lower concentrations than the minimum inhibitory concentration (MIC. Using fluorescence microscopy, we observed that S-8 dose-dependently reduces C. albicans-GFP binding to RAW macrophages. S-8 at sub-MICs also interfered with fungal morphogenesis by inhibiting the yeast-to-hyphal form transition. In addition, the tested agent strongly affected fungal cell wall characteristics by modulating its hydrophobicity. We evaluated the molecular mode of S-8 antibiofilm and antiadhesion activities using real-time RT-PCR. The expression levels of genes associated with biofilm formation, adhesion and filamentation, HWP1, ALS3 and EAP1, respectively, were dose-dependently downregulated by S-8. Transcript levels of UME6, responsible for long-term hyphal maintenance, were also significantly decreased by the tested agent. Both signaling pathways of hyphal formation-cAMP-PKA and MAPK-were interrupted by S-8. Their upstream general regulator RAS1 was markedly suppressed by S-8. In addition, the expression levels of MAPK cascade components CST20, HST7 and CPH1 were downregulated by S-8. Finally, transcriptional repressors of filament formation, TUP1 and NRG1, were dramatically upregulated by our

  6. The nitric oxide prodrug JS-K and its structural analogues as cancer therapeutic agents.

    Science.gov (United States)

    Maciag, Anna E; Saavedra, Joseph E; Chakrapani, Harinath

    2009-09-01

    Nitric oxide (NO) prodrugs of the diazeniumdiolate class are routinely used as reliable sources of nitric oxide in chemical and biological laboratory settings. O(2)-(2,4-dinitrophenyl) diazeniumdiolates, which are derivatized forms of ionic diazeniumdiolates, have been found to show potent anti-proliferative activity in a variety of cancer cells, presumably through the effects of NO. One important member of this class of diazeniumdiolates, O(2)-(2,4-dinitrophenyl) 1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate (JS-K), has shown promise as a novel cancer therapeutic agent in a number of animal models. This review describes the developments in chemical and biochemical characterization and structure-activity relationship of JS-K and its analogues. In addition, some molecular mechanistic insights into the observed anti-proliferative activity of JS-K are discussed. Finally, a structural motif is presented for O(2)-(aryl) diazeniumdiolate nitric oxide prodrugs that show potency comparable with that of JS-K.

  7. Argan Oil as an Effective Nutri-Therapeutic Agent in Metabolic Syndrome: A Preclinical Study

    Directory of Open Access Journals (Sweden)

    Adil El Midaoui

    2017-11-01

    Full Text Available The present study aims at examining the effects of argan oil on the three main cardiovascular risk factors associated with metabolic syndrome (hypertension, insulin resistance and obesity and on one of its main complications, neuropathic pain. Male Sprague-Dawley rats had free access to a drinking solution containing 10% d-glucose or tap water for 12 weeks. The effect of argan oil was compared to that of corn oil given daily by gavage during 12 weeks in glucose-fed rats. Glucose-fed rats showed increases in systolic blood pressure, epididymal fat, plasma levels of triglycerides, leptin, glucose and insulin, insulin resistance, tactile and cold allodynia in association with a rise in superoxide anion production and NADPH oxidase activity in the thoracic aorta, epididymal fat and gastrocnemius muscle. Glucose-fed rats also showed rises in B1 receptor protein expression in aorta and gastrocnemius muscle. Argan oil prevented or significantly reduced all those anomalies with an induction in plasma adiponectin levels. In contrast, the same treatment with corn oil had a positive impact only on triglycerides, leptin, adiponectin and insulin resistance. These data are the first to suggest that argan oil is an effective nutri-therapeutic agent to prevent the cardiovascular risk factors and complications associated with metabolic syndrome.

  8. Therapeutic Effect of Novel Single-Stranded RNAi Agent Targeting Periostin in Eyes with Retinal Neovascularization

    Directory of Open Access Journals (Sweden)

    Takahito Nakama

    2017-03-01

    Full Text Available Retinal neovascularization (NV due to retinal ischemia remains one of the principal causes of vision impairment in patients with ischemic retinal diseases. We recently reported that periostin (POSTN may play a role in the development of preretinal fibrovascular membranes, but its role in retinal NV has not been determined. The purpose of this study was to examine the expression of POSTN in the ischemic retinas of a mouse model of oxygen-induced retinal NV. We also studied the function of POSTN on retinal NV using Postn KO mice and human retinal endothelial cells (HRECs in culture. In addition, we used a novel RNAi agent, NK0144, which targets POSTN to determine its effect on the development of retinal NV. Our results showed that the expression of POSTN was increased in the vascular endothelial cells, pericytes, and M2 macrophages in ischemic retinas. POSTN promoted the ischemia-induced retinal NV by Akt phosphorylation through integrin αvβ3. NK0144 had a greater inhibitory effect than canonical double-stranded siRNA on preretinal pathological NV in vivo and in vitro. These findings suggest a causal relationship between POSTN and retinal NV, and indicate a potential therapeutic role of intravitreal injection of NK0144 for retinal neovascular diseases.

  9. Therapeutic infliximab drug level in a child born to a woman with ulcerative colitis treated until gestation week 31

    DEFF Research Database (Denmark)

    Steenholdt, Casper; Al-Khalaf, Magid; Ainsworth, Mark A

    2012-01-01

    A 26 year old woman with ulcerative colitis was treated with regular infliximab (IFX) infusions until gestation week 31, and gave birth to a healthy child at gestation week 37. Maternal IFX trough level was relatively high during the course of pregnancy. In the infant, therapeutic level of IFX...

  10. New therapeutic agent for radiation synovectomy - preparation of {sup 166}Ho-EDTMP-HA particle

    Energy Technology Data Exchange (ETDEWEB)

    Bai, H.; Jin, X.; Du, J.; Wang, F.; Chen, D.; Fan, H.; Cheng, Z.; Zhang, J. [China Institute of Atomic Energy, Beijing (Switzerland). Isotope Department

    1997-10-01

    In order to prepare new therapeutical agent for radiation synovectomy, Hydroxyapatite (HA) was labelled with {sup 166}Ho by EDTMP that had high affinity to HA particles. Radiolabelling of HA particles was divided into two steps, {sup 166}Ho-EDTMP was prepared first; then mixed with HA particles completely and vibrated for 15 minutes on the micromixer at room temperature, washed 3 times with deionized water. Radiolabelling particle was separated from free {sup 166}Ho via centrifugation to determine its radiolabelling efficiency. {sup 166}Ho-EDTMP-HA and {sup 166}Ho-EDTMP were injected into knee joint of normal rabbits respectively, every group was killed at different time postinjection, took out major organ and collected urine and blood, then weighted and determined their radio counts. HA particles, as a natural component of bone was known to have good compatibility with soft tissue and biodegrade into calcium and phosphate in vivo. It was readily prepared from common chemical and formed into particles of desired size range in a controlled process, it had high stability in vitro and vivo. Radiolabelling of HA particle with {sup 166}Ho by EDTMP was simple to perform and provides an excellent labelling yield that was more than 95% under the optimal labelling condition. The optimal labelling condition at room temperature was pH 6.0-8.0 and vibration time 15 minutes. The absorbed capacity of HA particle was 5 mg Ho/g HA particle and size of radiolabelling particle was at range of 2-5,{mu}m that is suitable for therapy of radiation synovectomy. {sup 166}Ho-EDTMP-HA particle demonstrated high in vitro stability in either normal saline or 1% BSA solution, but instability under extremely acidic condition (pH 1-2). The control studies performed with {sup 166}Ho-EDTMP not bound to HA particle provided information on the distribution of radioactivity that would occur upon leakage of the radiochemical compound from joint. Its short half-life, its extremely low leakage from the

  11. New therapeutic agent for radiation synovectomy - preparation of 166Ho-EDTMP-HA particle

    International Nuclear Information System (INIS)

    Bai, H.; Jin, X.; Du, J.; Wang, F.; Chen, D.; Fan, H.; Cheng, Z.; Zhang, J.

    1997-01-01

    In order to prepare new therapeutical agent for radiation synovectomy, Hydroxyapatite (HA) was labelled with 166 Ho by EDTMP that had high affinity to HA particles. Radiolabelling of HA particles was divided into two steps, 166 Ho-EDTMP was prepared first; then mixed with HA particles completely and vibrated for 15 minutes on the micromixer at room temperature, washed 3 times with deionized water. Radiolabelling particle was separated from free 166 Ho via centrifugation to determine its radiolabelling efficiency. 166 Ho-EDTMP-HA and 166 Ho-EDTMP were injected into knee joint of normal rabbits respectively, every group was killed at different time postinjection, took out major organ and collected urine and blood, then weighted and determined their radio counts. HA particles, as a natural component of bone was known to have good compatibility with soft tissue and biodegrade into calcium and phosphate in vivo. It was readily prepared from common chemical and formed into particles of desired size range in a controlled process, it had high stability in vitro and vivo. Radiolabelling of HA particle with 166 Ho by EDTMP was simple to perform and provides an excellent labelling yield that was more than 95% under the optimal labelling condition. The optimal labelling condition at room temperature was pH 6.0-8.0 and vibration time 15 minutes. The absorbed capacity of HA particle was 5 mg Ho/g HA particle and size of radiolabelling particle was at range of 2-5,μm that is suitable for therapy of radiation synovectomy. 166 Ho-EDTMP-HA particle demonstrated high in vitro stability in either normal saline or 1% BSA solution, but instability under extremely acidic condition (pH 1-2). The control studies performed with 166 Ho-EDTMP not bound to HA particle provided information on the distribution of radioactivity that would occur upon leakage of the radiochemical compound from joint. Its short half-life, its extremely low leakage from the joint and its even distribution throughout

  12. Therapeutic benefit in patients switching tolterodine to other novel antimuscarinic agents.

    Science.gov (United States)

    Sánchez-Ballester, F; Miranda, P; Lizarraga, I; Rejas, J; Arumi, D

    2014-04-01

    To explore in the daily clinical practice setting that antimuscarinic, Fesoterodine or Solifenacin, provides a greater clinical benefit after changing their prior Overactive Bladder (OAB) therapy with tolterodine extended-release (ER) to other novel antimuscarinic agents. A post-hoc analysis of data from an observational multicenter, cross-sectional, retrospective study. Adult patients of both sexes, with OAB and OAB-V8 score≥8, who switched to fesoterodine or solifenacin within the 3-4 months before study visit from their prior tolterodine-ER-based therapy due to poor response were included. 92 patients were selected for each treatment group, matched (1:1) according to conditioned probability using the propensity score. Benefit of treatment change perceived by the physician and patient was evaluated by means of the Clinical Global Impression of Improvement subscale (CGI-I) and Treatment Benefit Scale (TBS), respectively. Degree of worry, bother and interference with daily living activities due to urinary symptoms, level of satisfaction, and preference for current treatment were also assessed. Fesoterodine provided a significantly greater improvement than solifenacina in terms of therapeutic benefit perceived by the physician according to ICG-I. 96.7% of the patients on fesoterodine treatment vs. 81.6% of the solifenacin group showed a score of improvement in TBS (P<.05). Fesoterodine was also better rated than solifenacin with regard to satisfaction and preference for the new treatment (93.4 vs. 78.2% P<.05). In daily clinical practice the switch from tolterodine LP to fesoterodine seems to provide greater benefits both from the physician's and the patient's point of view compared with those provided by solifenacin. Copyright © 2013 AEU. Published by Elsevier Espana. All rights reserved.

  13. Evaluation of gloves as a water bag coupling agent for therapeutic ultrasound

    Directory of Open Access Journals (Sweden)

    Lúcio Salustiano de Lima

    2017-03-01

    Full Text Available Abstract Introduction Therapeutic ultrasound (TUS is a widespread modality in physiotherapy, and the water bag technique is a coupling method employed in the presence of anatomical irregularities in the treatment area. The aim of the present study is to evaluate the acoustic attenuation of the water bag and its effectiveness as a TUS coupling agent. Methods The rated output powers (ROPs of the TUS equipment were evaluated based on IEC 61689. Then, a radiation force balance was used to measure ROP with and without a water bag (latex and nitrile gloves filled with deionized water between a TUS transducer and the cone-shaped target of the balance. Each experiment was performed five times for each nominal power (0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 6.0, and 7.0 W and in the following configurations: without the water bag (A, with nitrile gloves and with (B and without (C a height controller, and latex gloves with (D and without (E height controller. ROPs obtained in different media were compared. Results The highest relative error of ROP was 16.72% for 0.5 W. Although the power values of the equipment were within the range recommended by IEC, there was a significant difference between the ROP values measured with A and with B, C and D. Conclusion As intensity differences below 0.5 W/cm2 are considered clinically not relevant, conditions A, B, C, D, or E can be used interchangeably.

  14. The effect of interstitial pressure on therapeutic agent transport: coupling with the tumor blood and lymphatic vascular systems.

    Science.gov (United States)

    Wu, Min; Frieboes, Hermann B; Chaplain, Mark A J; McDougall, Steven R; Cristini, Vittorio; Lowengrub, John S

    2014-08-21

    Vascularized tumor growth is characterized by both abnormal interstitial fluid flow and the associated interstitial fluid pressure (IFP). Here, we study the effect that these conditions have on the transport of therapeutic agents during chemotherapy. We apply our recently developed vascular tumor growth model which couples a continuous growth component with a discrete angiogenesis model to show that hypertensive IFP is a physical barrier that may hinder vascular extravasation of agents through transvascular fluid flux convection, which drives the agents away from the tumor. This result is consistent with previous work using simpler models without blood flow or lymphatic drainage. We consider the vascular/interstitial/lymphatic fluid dynamics to show that tumors with larger lymphatic resistance increase the agent concentration more rapidly while also experiencing faster washout. In contrast, tumors with smaller lymphatic resistance accumulate less agents but are able to retain them for a longer time. The agent availability (area-under-the curve, or AUC) increases for less permeable agents as lymphatic resistance increases, and correspondingly decreases for more permeable agents. We also investigate the effect of vascular pathologies on agent transport. We show that elevated vascular hydraulic conductivity contributes to the highest AUC when the agent is less permeable, but to lower AUC when the agent is more permeable. We find that elevated interstitial hydraulic conductivity contributes to low AUC in general regardless of the transvascular agent transport capability. We also couple the agent transport with the tumor dynamics to simulate chemotherapy with the same vascularized tumor under different vascular pathologies. We show that tumors with an elevated interstitial hydraulic conductivity alone require the strongest dosage to shrink. We further show that tumors with elevated vascular hydraulic conductivity are more hypoxic during therapy and that the response

  15. Development of radiolanthanide labeled porphyrin complexes as possible therapeutic agents in beast carcinoma xenografts

    Energy Technology Data Exchange (ETDEWEB)

    Vahidfar, Nasim; Aghanejad, Ayuob; Beiki, Davood; Khalaj, Ali [Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of). Faculty of Pharmacy; Jalilian, Amir R.; Fazaeli, Yousef; Bahrami-Samani, Ali; Alirezapour, Behrooz; Erfani, Mostafa [Nuclear Science and Technology Research Institute, Tehran (Iran, Islamic Republic of). Radiopharmacy Research Group

    2014-10-01

    Radiolabeled porphyrins are potential tumor avid radiopharmaceuticals because of their behaviour in the human body, ability to complex various radionuclides, water solubility, low toxicity etc., in this work radio ytterbium/samarium porphyrin complexes have been developed. {sup 175}Yb and {sup 153}Sm labeled 5,10,15,20-tetrakis(3,4-dimethoxyphenyl) porphyrins ([{sup 175}Yb]-TDMPP/[{sup 153}Sm]-TDMPP) were prepared using 5,10,15,20-tetrakis(3,4-dimethoxyphenyl) porphyrin (H{sub 2}TDMPP) and [{sup 175}Yb]YbCl{sub 3} or [{sup 153}Sm]SmCl{sub 3} in 12-24 h at 60 C. Stability of the complexes were checked in final formulation and human serum for 24 h, followed by partition coefficient determination and biodistribution studies in wild type and breast carcinoma-bearing mice. The radiocomplexes were obtained with acceptable radiochemical purity (> 95% (paper chromatography) and > 96% (HPLC) for [{sup 175}Yb]-TDMPP and > 97% (paper chromatography) and > 98% (HPLC) for [{sup 153}Sm]-TDMPP) with specific activities of 12-15 GBq/mmol and 278 GBq/mmol at the end of bombardment for [{sup 175}Yb]-TDMPP and [{sup 153}Sm]-TDMPP respectively. The partition coefficients were determined for [{sup 175}Yb]-TDMPP and [{sup 153}Sm]-TDMPP (log P = 0.63 and log P = 0.96 respectively). The [{sup 175}Yb]-TDMPP complex is mostly washed out from the circulation through kidneys. Liver and spleen also demonstrated significant activity uptake in 72 h post injection. Also [{sup 153}Sm]-TDMPP, is mostly washed out from the circulation through kidneys, however lungs are the major accumulation sites. The [{sup 153}Sm]-TDMPP complex demonstrated significant targeted uptake in breast carcinoma xenografts with tumor: blood ratios of 10.67, 10.47 and 19.01 in 24, 48 and 72 h respectively. Also interesting tumor: kidney/liver ratios were obtained. {sup 153}Sm-TDMPP properties suggest an efficient tumor targeting agent with high tumor-avidity. Further investigation on the therapeutic properties must be

  16. Aptámeros: agentes diagnósticos y terapéuticos = Aptamers: diagnostic and therapeutic agents

    Directory of Open Access Journals (Sweden)

    Frank J Hernandez

    2012-04-01

    Full Text Available Los aptámeros son ácidos nucleicos de cadena sencilla, ADN o ARN, que reconocen una gran variedad de moléculas. Cada aptámero posee una estructura tridimensional particular que le permite unirse con afinidad y especificidad altas a la molécula diana. Los aptámeros tienen propiedades de reconocimiento equiparables a las de los anticuerpos; sin embargo, por la naturaleza de su composición tienen ventajas significativas en cuanto a su tamaño, producción y modificación. Estas características los hacen excelentes candidatos para el desarrollo de nuevas plataformas biotecnológicas. Se han identificado aptámeros con propiedades terapéuticas que han sido evaluados exitosamente en modelos animales; entre ellos, algunos se encuentran en fase clínica y uno ya fue aprobado para tratamiento por la FDA (Food and Drug Administration. Todos estos avances ocurridos durante las dos últimas décadas permiten anticipar el protagonismo que tendrán los aptámeros como agentes diagnósticos y terapéuticos en un futuro cercano.

  17. Choline and Geranate Deep Eutectic Solvent as a Broad-Spectrum Antiseptic Agent for Preventive and Therapeutic Applications.

    Science.gov (United States)

    Zakrewsky, Michael; Banerjee, Amrita; Apte, Sanjana; Kern, Theresa L; Jones, Mattie R; Sesto, Rico E Del; Koppisch, Andrew T; Fox, David T; Mitragotri, Samir

    2016-06-01

    Antiseptic agents are the primary arsenal to disinfect skin and prevent pathogens spreading within the host as well as into the surroundings; however the Food and Drug Administration published a report in 2015 requiring additional validation of nearly all current antiseptic agents before their continued use can be allowed. This vulnerable position calls for urgent identification of novel antiseptic agents. Recently, the ability of a deep eutectic, Choline And Geranate (CAGE), to treat biofilms of Pseudomonas aeruginosa and Salmonella enterica was demonstrated. Here it is reported that CAGE exhibits broad-spectrum antimicrobial activity against a number of drug-resistant bacteria, fungi, and viruses including clinical isolates of Mycobacterium tuberculosis, Staphylococcus aureus, and Candida albicans as well as laboratory strains of Herpes Simplex Virus. Studies in human keratinocytes and mice show that CAGE affords negligible local or systemic toxicity, and an ≈180-14 000-fold improved efficacy/toxicity ratio over currently used antiseptic agents. Further, CAGE penetrates deep into the dermis and treats pathogens located in deep skin layers as confirmed by the ability of CAGE in vivo to treat Propionibacterium acnes infection. In combination, the results clearly demonstrate CAGE holds promise as a transformative platform antiseptic agent for preventive as well as therapeutic applications. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Anticonvulsants for Nerve Agent-Induced Seizures: The Influence of the Therapeutic Dose of Atropine

    National Research Council Canada - National Science Library

    Shih, Tsung-Ming; Rowland, Tami C; McDonough, John H

    2007-01-01

    Two guinea pig models were used to study the anticonvulsant potency of diazepam, midazolam, and scopolamine against seizures induced by the nerve agents tabun, sarin, soman, cyclosarin, O-ethyl S-(2-(diisopropylamino)ethyl...

  19. 78 FR 77471 - Prospective Grant of Exclusive License for: Convection Enhanced Delivery of a Therapeutic Agent...

    Science.gov (United States)

    2013-12-23

    ...; nationalized), U.S. Patent Application 7,371,225, European Patent Application 03756863.1, Australian Patent 2003299140, to Medicenna Therapeutics, Inc. having a principle place of business in 1075 West Georgia St... date of this published notice, NIH receives written evidence and argument that establishes that the...

  20. Growth/differentiation factor-5: a candidate therapeutic agent for periodontal regeneration? A review of pre-clinical data.

    Science.gov (United States)

    Moore, Yolanda R; Dickinson, Douglas P; Wikesjö, Ulf M E

    2010-03-01

    Therapeutic concepts involving the application of matrix, growth and differentiation factors have been advocated in support of periodontal wound healing/regeneration. Growth/differentiation factor-5 (GDF-5), a member of the bone morphogenetic protein family, represents one such factor. The purpose of this review is to provide a background of the therapeutic effects of GDF-5 expressed in various musculoskeletal settings using small and large animal platforms. A comprehensive literature search was conducted to identify all reports in the English language evaluating GDF-5 using the PubMed and Google search engines, and a manual search of the reference lists from the electronically retrieved reports. Two reviewers independently screened the titles and abstracts from a total of 69 reports, 22 of which were identified as pre-clinical (in vivo) evaluations of GDF-5. The full-length article of the 22 pre-clinical reports was then reviewed. Various applications including cranial and craniofacial bone formation, spine fusion, long bone fracture healing, cartilage, and tendon/ligament repair using a variety of small and large animal platforms evaluating GDF-5 as a therapeutic agent were identified. A majority of studies, using biomechanical, radiographic, and histological analysis, demonstrated significant dose-dependent effects of GDF-5. These include increased/enhanced local bone formation, fracture healing/repair, and cartilage and tendon/ligament formation. GDF-5 frequently was shown to accelerate wound maturation. Several studies demonstrated GDF-5 to be a realistic alternative to autograft bone. Studies using pre-clinical models and human histology suggest GDF-5 may also increase/enhance periodontal wound healing/regeneration. GDF-5 appears a promising therapeutic agent for periodontal wound healing/regeneration as GDF-5 supports/accelerates bone and tendon/ligament formation in several musculoskeletal settings including periodontal tissues.

  1. The role of wild canids and felids in spreading parasites to dogs and cats in Europe. Part I: Protozoa and tick-borne agents.

    Science.gov (United States)

    Otranto, Domenico; Cantacessi, Cinzia; Pfeffer, Martin; Dantas-Torres, Filipe; Brianti, Emanuele; Deplazes, Peter; Genchi, Claudio; Guberti, Vittorio; Capelli, Gioia

    2015-09-30

    Over the last few decades, the world has witnessed radical changes in climate, landscape, and ecosystems. These events, together with other factors such as increasing illegal wildlife trade and changing human behaviour towards wildlife, are resulting into thinning boundaries between wild canids and felids and their domestic counterparts. As a consequence, the epidemiology of diseases caused by a number of infectious agents is undergoing profound readjustements, as pathogens adapt to new hosts and environments. Therefore, there is a risk for diseases of wildlife to spread to domestic carnivores and vice versa, and for zoonotic agents to emerge or re-emerge in human populations. Hence, the identification of the hazards arising from the co-habitation of these species is critical in order to plan and develop adequate control strategies against these pathogens. In the first of this two-part article, we review the role that wild canids and felids may play in the transmission of protozoa and arthropod-borne agents to dogs and cats in Europe, and provide an account of how current and future progress in our understanding of the ecology and epidemiology of parasites, as well as of host-parasite interactions, can assist efforts aimed at controlling parasite transmission. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Use of flubendazole as a therapeutic agent against rotifers (Brachionus plicatilis) in intensive cultures of the harpacticoid copepod Tisbe holothuriae

    DEFF Research Database (Denmark)

    Steenfeldt, Svend Jørgen; Nielsen, Johan W.

    2010-01-01

    down production and subsequently use a therapeutic agent to eliminate all zooplankton in the system before restart with a stock culture free of rotifers. We tested flubendazole as a mean of controlling rotifers (Brachionus plicatilis) in intensive laboratory cultures of the harpacticoid copepod (Tisbe...... holothuria). Flubendazole was lethal to rotifers in concentrations as low as 0.05 mg L−1. There was no significant effect on the concentration of copepods, even at the highest concentration tested, i.e. 5.0 mg L−1 flubendazole. We conclude that flubendazole is an effective drug for control of B. plicatilis...

  3. Developing Inhibitors of Translesion DNA Synthesis as Therapeutic Agents Against Lung Cancer

    Science.gov (United States)

    2014-10-01

    pol eta when replicating damaged DNA. 1S. SUBJECT TERMS: Mutagenesis, DNA polymerases, nucleoside analogs, chemotherapeutic agents 16. SECURITY ...such as polymerase eta, iota , and kappa that are involved in replicating damaged DNA. Our kinetic data obtained under Task 1B indicates that pol eta

  4. Evolution of and perspectives on therapeutic approaches to nerve agent poisoning.

    Science.gov (United States)

    Masson, Patrick

    2011-09-25

    After more than 70 years of considerable efforts, research on medical defense against nerve agents has come to a standstill. Major progress in medical countermeasures was achieved between the 50s and 70s with the development of anticholinergic drugs and carbamate-based pretreatment, the introduction of pyridinium oximes as antidotes, and benzodiazepines in emergency treatments. These drugs ensure good protection of the peripheral nervous system and mitigate the acute effects of exposure to lethal doses of nerve agents. However, pyridostigmine and cholinesterase reactivators currently used in the armed forces do not protect/reactivate central acetylcholinesterases. Moreover, other drugs used are not sufficiently effective in protecting the central nervous system against seizures, irreversible brain damages and long-term sequelae of nerve agent poisoning.New developments of medical counter-measures focus on: (a) detoxification of organophosphorus molecules before they react with acetylcholinesterase and other physiological targets by administration of stoichiometric or catalytic scavengers; (b) protection and reactivation of central acetylcholinesterases, and (c) improvement of neuroprotection following delayed therapy.Future developments will aim at treatment of acute and long-term effects of low level exposure to nerve agents, research on alternative routes for optimizing drug delivery, and therapies. Though gene therapy for in situ generation of bioscavengers, and cell therapy based on neural progenitor engraftment for neuronal regeneration have been successfully explored, more studies are needed before practical medical applications can be made of these new approaches. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  5. Epigenetic Modulating Agents as a New Therapeutic Approach in Multiple Myeloma

    International Nuclear Information System (INIS)

    Maes, Ken; Menu, Eline; Van Valckenborgh, Els; Van Riet, Ivan; Vanderkerken, Karin; De Bruyne, Elke

    2013-01-01

    Multiple myeloma (MM) is an incurable B-cell malignancy. Therefore, new targets and drugs are urgently needed to improve patient outcome. Epigenetic aberrations play a crucial role in development and progression in cancer, including MM. To target these aberrations, epigenetic modulating agents, such as DNA methyltransferase inhibitors (DNMTi) and histone deacetylase inhibitors (HDACi), are under intense investigation in solid and hematological cancers. A clinical benefit of the use of these agents as single agents and in combination regimens has been suggested based on numerous studies in pre-clinical tumor models, including MM models. The mechanisms of action are not yet fully understood but appear to involve a combination of true epigenetic changes and cytotoxic actions. In addition, the interactions with the BM niche are also affected by epigenetic modulating agents that will further determine the in vivo efficacy and thus patient outcome. A better understanding of the molecular events underlying the anti-tumor activity of the epigenetic drugs will lead to more rational drug combinations. This review focuses on the involvement of epigenetic changes in MM pathogenesis and how the use of DNMTi and HDACi affect the myeloma tumor itself and its interactions with the microenvironment

  6. Multi-agent systems in epidemiology: a first step for computational biology in the study of vector-borne disease transmission

    Directory of Open Access Journals (Sweden)

    Guégan Jean-François

    2008-10-01

    Full Text Available Abstract Background Computational biology is often associated with genetic or genomic studies only. However, thanks to the increase of computational resources, computational models are appreciated as useful tools in many other scientific fields. Such modeling systems are particularly relevant for the study of complex systems, like the epidemiology of emerging infectious diseases. So far, mathematical models remain the main tool for the epidemiological and ecological analysis of infectious diseases, with SIR models could be seen as an implicit standard in epidemiology. Unfortunately, these models are based on differential equations and, therefore, can become very rapidly unmanageable due to the too many parameters which need to be taken into consideration. For instance, in the case of zoonotic and vector-borne diseases in wildlife many different potential host species could be involved in the life-cycle of disease transmission, and SIR models might not be the most suitable tool to truly capture the overall disease circulation within that environment. This limitation underlines the necessity to develop a standard spatial model that can cope with the transmission of disease in realistic ecosystems. Results Computational biology may prove to be flexible enough to take into account the natural complexity observed in both natural and man-made ecosystems. In this paper, we propose a new computational model to study the transmission of infectious diseases in a spatially explicit context. We developed a multi-agent system model for vector-borne disease transmission in a realistic spatial environment. Conclusion Here we describe in detail the general behavior of this model that we hope will become a standard reference for the study of vector-borne disease transmission in wildlife. To conclude, we show how this simple model could be easily adapted and modified to be used as a common framework for further research developments in this field.

  7. Multi-targeting Andrographolide and its Natural Analogs as Potential Therapeutic Agents.

    Science.gov (United States)

    Kishore, V; Yarla, Nagendra Sastry; Bishayee, Anupam; Putta, Swathi; Malla, Ramarao; Neelapu, Nageswara Rao Reddy; Challa, Surekha; Das, Subhasish; Shiralgi, Yallappa; Hegde, Gurumurthy; Dhananjaya, Bhadrapura Lakkappa

    2017-01-01

    Andrographis paniculata (A. paniculata) is a medicinal plant used in the Indian and Chinese traditional medicinal systems for its various beneficial properties of therapeutics. This is due to the presence of a diterpene lactone called 'andrographolide'. Several biological activities like antiinflammatory, antitumour, anti-hyperglycaemic, anti-fertility, antiviral, cardio protective and hepatoprotective properties are attributed to andrographolide and its natural analogs. The studies have shown that not only this diterpene lactone (andrographolide), but also other related terpenoid analogs from A. paniculata could be exploited for disease prevention due to their structural similarity with diverse pharmacological activities. Several scientific groups are trying to unveil the underlying mechanisms involved in these biological actions brough aout by andrographolide and its analogs. This review aims at giving an overview on the therapeutical and/or pharmacological activities of andrographolide and its derivatives and also exemplify the underlying mechanisms involved. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  8. An Overview on Citrus aurantium L.: Its Functions as Food Ingredient and Therapeutic Agent

    Directory of Open Access Journals (Sweden)

    Ipek Suntar

    2018-01-01

    Full Text Available Citrus aurantium L. (Rutaceae, commonly known as bitter orange, possesses multiple therapeutic potentials. These biological credentials include anticancer, antianxiety, antiobesity, antibacterial, antioxidant, pesticidal, and antidiabetic activities. The essential oil of C. aurantium was reported to display marked pharmacological effects and great variation in chemical composition depending on growing locations but mostly contained limonene, linalool, and β-myrcene. Phytochemically, C. aurantium is rich in p-synephrine, an alkaloid, and many health-giving secondary metabolites such as flavonoids. Animal studies have demonstrated a low affinity of p-synephrine for adrenergic receptors and an even lower affinity in human models. The present review focuses on the different biological activities of the C. aurantium in animal and human models in the form of extract and its pure secondary metabolites. Finally, it is concluded that both the extract and isolated compounds have no unwanted effects in human at therapeutic doses and, therefore, can confidently be used in various dietary formulations.

  9. The botulinum toxin as a therapeutic agent: molecular and pharmacological insights

    Directory of Open Access Journals (Sweden)

    Kukreja R

    2015-12-01

    Full Text Available Roshan Kukreja,1 Bal Ram Singh2 1Department of Chemistry and Biochemistry, University of Massachusetts, 2Botulinum Research Center, Institute of Advanced Sciences, Dartmouth, MA, USA Abstract: Botulinum neurotoxins (BoNTs, the most potent toxins known to mankind, are metalloproteases that act on nerve–muscle junctions to block exocytosis through a very specific and exclusive endopeptidase activity against soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE proteins of presynaptic vesicle fusion machinery. This very ability of the toxins to produce flaccid muscle paralysis through chemical denervation has been put to good use, and these potentially lethal toxins have been licensed to treat an ever expanding list of medical disorders and more popularly in the field of esthetic medicine. In most cases, therapeutic BoNT preparations are high-molecular-weight protein complexes consisting of BoNT, complexing proteins, and excipients. There is at least one isolated BoNT, which is free of complexing proteins in the market (Xeomin®. Each commercially available BoNT formulation is unique, differing mainly in molecular size and composition of complexing proteins, biological activity, and antigenicity. BoNT serotype A is marketed as Botox®, Dysport®, and Xeomin®, while BoNT type B is commercially available as Myobloc®. Nerve terminal intoxication by BoNTs is completely reversible, and the duration of therapeutic effects of BoNTs varies for different serotypes. Depending on the target tissue, BoNTs can block the cholinergic neuromuscular or cholinergic autonomic innervation of exocrine glands and smooth muscles. Therapeutic BoNTs exhibit a high safety and very limited adverse effects profile. Despite their established efficacy, the greatest concern with the use of therapeutic BoNTs is their propensity to elicit immunogenic reactions that might render the patient unresponsive to subsequent treatments, particularly in chronic

  10. Possible role of common spices as a preventive and therapeutic agent for Alzheimer′s disease

    Directory of Open Access Journals (Sweden)

    Omid Mirmosayyeb

    2017-01-01

    Full Text Available For centuries, spices have been consumed as food additives or medicinal agents. However, there is increasing evidence indicating the plant-based foods in regular diet may lower the risk of neurodegenerative diseases including Alzheimer disease. Spices, as one of the most commonly used plant-based food additives may provide more than just flavors, but as agents that may prevent or even halt neurodegenerative processes associated with aging. In this article, we review the role and application of five commonly used dietary spices including saffron turmeric, pepper family, zingiber, and cinnamon. Besides suppressing inflammatory pathways, these spices may act as antioxidant and inhibit acetyl cholinesterase and amyloid β aggregation. We summarized how spice-derived nutraceuticals mediate such different effects and what their molecular targets might be. Finally, some directions for future research are briefly discussed.

  11. Poly-S-Nitrosated Albumin as a Safe and Effective Multifunctional Antitumor Agent: Characterization, Biochemistry and Possible Future Therapeutic Applications

    Directory of Open Access Journals (Sweden)

    Yu Ishima

    2013-01-01

    Full Text Available Nitric oxide (NO is a ubiquitous molecule involved in multiple cellular functions. Inappropriate production of NO may lead to disease states. To date, pharmacologically active compounds that release NO within the body, such as organic nitrates, have been used as therapeutic agents, but their efficacy is significantly limited by unwanted side effects. Therefore, novel NO donors with better pharmacological and pharmacokinetic properties are highly desirable. The S-nitrosothiol fraction in plasma is largely composed of endogenous S-nitrosated human serum albumin (Mono-SNO-HSA, and that is why we are testing whether this albumin form can be therapeutically useful. Recently, we developed SNO-HSA analogs such as SNO-HSA with many conjugated SNO groups (Poly-SNO-HSA which were prepared using chemical modification. Unexpectedly, we found striking inverse effects between Poly-SNO-HSA and Mono-SNO-HSA. Despite the fact that Mono-SNO-HSA inhibits apoptosis, Poly-SNO-HSA possesses very strong proapoptotic effects against tumor cells. Furthermore, Poly-SNO-HSA can reduce or perhaps completely eliminate the multidrug resistance often developed by cancer cells. In this review, we forward the possibility that Poly-SNO-HSA can be used as a safe and effective multifunctional antitumor agent.

  12. Development and biological evaluation of {sup 90}Y-BPAMD as a novel bone seeking therapeutic agent

    Energy Technology Data Exchange (ETDEWEB)

    Rabiei, Ali; Shamsaei, Mojtaba [Amir Kabir University of Technology, Tehran (Iran, Islamic Republic of). Energy Engineering and Physics Dept.; Yousefnia, Hassan; Zolghadri, Samaneh; Jalilian, Amir Reza [Nuclear Science and Technology Research Institute (NSTRI), Tehran (Iran, Islamic Republic of); Enayati, Razieh [Islamic Azad Univ. (IAU), Tehran (Iran, Islamic Republic of). Faculty of Engineering

    2016-07-01

    Nowadays, the bone-seeking radiopharmaceuticals play an important role in the treatment of the bone-related pathologies. Whereas various phosphonate ligands have already been identified, a DOTA-based bisphosphonate, 4-{[(bis(phosphonomethyl))carbamoyl]methyl}-7,10-bis(carboxymethyl) -1,4,7,10-tetraazacyclododec-1-yl (BPAMD) with better characteristics has recently been synthesized. In this study, {sup 90}Y-BPAMD was developed with radiochemical purity >98% and the specific activity of 3.52 TBq/mmol in the optimized conditions as a new bone-seeking therapeutic agent. The complex demonstrated significant stability at room temperature and in human serum even after 48 h. At even low amount of hydroxyapatite (5 mg), more than 90% binding to hydroxyapatite was observed. Biodistribution studies after injection of the complex into the Syrian rats showed major accumulation of the labelled compound in the bone tissue and an insignificant uptake in the other organs all the times after injection. Generally, {sup 90}Y-BPAMD demonstrated interesting characteristics compared to the other {sup 90}Y bone-seeking agents and even {sup 166}Ho-BPAMD, and can be considered as a new bone-seeking candidate for therapeutic applications.

  13. Vascular-targeted photodynamic therapy with BF2-chelated Tetraaryl-Azadipyrromethene agents: a multi-modality molecular imaging approach to therapeutic assessment.

    LENUS (Irish Health Repository)

    Byrne, A T

    2009-11-03

    Photodynamic therapy (PDT) is a treatment modality for a range of diseases including cancer. The BF(2)-chelated tetraaryl-azadipyrromethenes (ADPMs) are an emerging class of non-porphyrin PDT agent, which have previously shown excellent photochemical and photophysical properties for therapeutic application. Herein, in vivo efficacy and mechanism of action studies have been completed for the lead agent, ADMP06.

  14. Potential of Icariin Metabolites from Epimedium koreanum Nakai as Antidiabetic Therapeutic Agents

    Directory of Open Access Journals (Sweden)

    Da Hye Kim

    2017-06-01

    Full Text Available The therapeutic properties of Epimedium koreanum are presumed to be due to the flavonoid component icariin, which has been reported to have broad pharmacological potential and has demonstrated anti-diabetic, anti-Alzheimer’s disease, anti-tumor, and hepatoprotective activities. Considering these therapeutic properties of icariin, its deglycosylated icaritin and glycosylated flavonoids (icaeriside II, epimedin A, epimedin B, and epimedin C were evaluated for their ability to inhibit protein tyrosine phosphatase 1B (PTP1B and α-glucosidase. The results show that icaritin and icariside II exhibit potent inhibitory activities, with 50% inhibition concentration (IC50 values of 11.59 ± 1.39 μM and 9.94 ± 0.15 μM against PTP1B and 74.42 ± 0.01 and 106.59 ± 0.44 μM against α-glucosidase, respectively. With the exceptions of icaritin and icariside II, glycosylated flavonoids did not exhibit any inhibitory effects in the two assays. Enzyme kinetics analyses revealed that icaritin and icariside II demonstrated noncompetitive-type inhibition against PTP1B, with inhibition constant (Ki values of 11.41 and 11.66 μM, respectively. Moreover, molecular docking analysis confirmed that icaritin and icariside II both occupy the same site as allosteric ligand. Thus, the molecular docking simulation results were in close agreement with the experimental data with respect to inhibition activity. In conclusion, deglycosylated metabolites of icariin from E. koreanum might offer therapeutic potential for the treatment of type 2 diabetes mellitus.

  15. Application of Disposable Bag Bioreactors in Tissue Engineering and for the Production of Therapeutic Agents

    Science.gov (United States)

    Eibl, R.; Eibl, D.

    In order to increase process efficiency, many pharmaceutical and biotechnology companies have introduced disposable bag technology over the last 10 years. Because this technology also greatly reduces the risk of cross-contamination, disposable bags are preferred in applications in which an absolute or improved process safety is a necessity, namely the production of functional tissue for implantation (tissue engineering), the production of human cells for the treatment of cancer and immune system diseases (cellular therapy), the production of viruses for gene therapies, the production of therapeutic proteins, and veterinary as well as human vaccines.

  16. Bioprospecting the Curculigoside-Cinnamic Acid-Rich Fraction from Molineria latifolia Rhizome as a Potential Antioxidant Therapeutic Agent

    Directory of Open Access Journals (Sweden)

    Der Jiun Ooi

    2016-06-01

    Full Text Available Increasing evidence from both experimental and clinical studies depicts the involvement of oxidative stress in the pathogenesis of various diseases. Specifically, disruption of homeostatic redox balance in accumulated body fat mass leads to obesity-associated metabolic syndrome. Strategies for the restoration of redox balance, potentially by exploring potent plant bioactives, have thus become the focus of therapeutic intervention. The present study aimed to bioprospect the potential use of the curculigoside-cinnamic acid-rich fraction from Molineria latifolia rhizome as an antioxidant therapeutic agent. The ethyl acetate fraction (EAF isolated from M. latifolia rhizome methanolic extract (RME contained the highest amount of phenolic compounds, particularly curculigoside and cinnamic acid. EAF demonstrated glycation inhibitory activities in both glucose- and fructose-mediated glycation models. In addition, in vitro chemical-based and cellular-based antioxidant assays showed that EAF exhibited high antioxidant activities and a protective effect against oxidative damage in 3T3-L1 preadipocytes. Although the efficacies of individual phenolics differed depending on the structure and concentration, a correlational study revealed strong correlations between total phenolic contents and antioxidant capacities. The results concluded that enriched phenolic contents in EAF (curculigoside-cinnamic acid-rich fraction contributed to the overall better reactivity. Our data suggest that this bioactive-rich fraction warrants therapeutic potential against oxidative stress-related disorders.

  17. Novel compounds for the treatment of Duchenne muscular dystrophy: emerging therapeutic agents

    Directory of Open Access Journals (Sweden)

    Steve D Wilton

    2011-03-01

    Full Text Available Steve D Wilton, Sue FletcherCentre for Neuromuscular and Neurological Disorders, University of Western Australia, Crawley, Perth, WA, AustraliaAbstract: The identification of dystrophin and the causative role of mutations in this gene in Duchenne and Becker muscular dystrophies (D/BMD was expected to lead to timely development of effective therapies. Despite over 20 years of research, corticosteroids remain the only available pharmacological treatment for DMD, although significant benefits and extended life have resulted from advances in the clinical care and management of DMD individuals. Effective treatment of DMD will require dystrophin restitution in skeletal, cardiac, and smooth muscles and nonmuscle tissues; however, modulation of muscle loss and regeneration has the potential to play an important role in altering the natural history of DMD, particularly in combination with other treatments. Emerging biological, molecular, and small molecule therapeutics are showing promise in ameliorating this devastating disease, and it is anticipated that regulatory environments will need to display some flexibility in order to accommodate the new treatment paradigms.Keywords: Duchenne muscular dystrophy, molecular therapeutics, small molecules

  18. Development of Novel Therapeutic Agents by Inhibition of Oncogenic MicroRNAs

    Directory of Open Access Journals (Sweden)

    Dinh-Duc Nguyen

    2017-12-01

    Full Text Available MicroRNAs (miRs, miRNAs are regulatory small noncoding RNAs, with their roles already confirmed to be important for post-transcriptional regulation of gene expression affecting cell physiology and disease development. Upregulation of a cancer-causing miRNA, known as oncogenic miRNA, has been found in many types of cancers and, therefore, represents a potential new class of targets for therapeutic inhibition. Several strategies have been developed in recent years to inhibit oncogenic miRNAs. Among them is a direct approach that targets mature oncogenic miRNA with an antisense sequence known as antimiR, which could be an oligonucleotide or miRNA sponge. In contrast, an indirect approach is to block the biogenesis of miRNA by genome editing using the CRISPR/Cas9 system or a small molecule inhibitor. The development of these inhibitors is straightforward but involves significant scientific and therapeutic challenges that need to be resolved. In this review, we summarize recent relevant studies on the development of miRNA inhibitors against cancer.

  19. Acoustically active lipospheres containing paclitaxel: a new therapeutic ultrasound contrast agent.

    Science.gov (United States)

    Unger, E C; McCreery, T P; Sweitzer, R H; Caldwell, V E; Wu, Y

    1998-12-01

    Paclitaxel-carrying lipospheres (MRX-552) were developed and evaluated as a new ultrasound contrast agent for chemotherapeutic drug delivery. Paclitaxel was suspended in soybean oil and added to an aqueous suspension of phospholipids in vials. The headspace of the vials was replaced with perfluorobutane gas; the vials were sealed, and they were agitated at 4200 rpm on a shaking device. The resulting lipospheres containing paclitaxel were studied for concentration, size, acute toxicity in mice, and acoustic activity and drug release with ultrasound. Lipospheres containing sudan black dye were produced to demonstrate the acoustically active liposphere (AAL)-ultrasound release concept. Acoustically active lipospheres containing paclitaxel had a mean particle count of approximately 1 x 10(9) particles per mL and a mean size of 2.9 microns. Acute toxicity studies in mice showed a 10-fold reduction in toxicity for paclitaxel in AALs compared with free paclitaxel. The AALs reflected ultrasound as a contrast agent. Increasing amounts of ultrasound energy selectively ruptured the AALs and released the paclitaxel. Acoustically active lipospheres represent a new class of acoustically active drug delivery vehicles. Future studies will assess efficacy of AALs for ultrasound-mediated drug delivery.

  20. Alpha-1 antitrypsin: a potent anti-inflammatory and potential novel therapeutic agent.

    LENUS (Irish Health Repository)

    Bergin, David A

    2012-04-01

    Alpha-1 antitrypsin (AAT) has long been thought of as an important anti-protease in the lung where it is known to decrease the destructive effects of major proteases such as neutrophil elastase. In recent years, the perception of this protein in this simple one dimensional capacity as an anti-protease has evolved and it is now recognised that AAT has significant anti-inflammatory properties affecting a wide range of inflammatory cells, leading to its potential therapeutic use in a number of important diseases. This present review aims to discuss the described anti-inflammatory actions of AAT in modulating key immune cell functions, delineate known signalling pathways and specifically to identify the models of disease in which AAT has been shown to be effective as a therapy.

  1. Bee Pollen Flavonoids as a Therapeutic Agent in Allergic and Immunological Disorders.

    Science.gov (United States)

    Jannesar, Masoomeh; Sharif Shoushtari, Maryam; Majd, Ahmad; Pourpak, Zahra

    2017-06-01

    Bee pollen grains, as the male reproductive part of seed-bearing plants contain considerable concentrations of various phytochemicals and nutrients. Since antiquity, people throughout the world used pollens to cure colds, flu, ulcers, premature aging, anemia and colitis. It is now well-documented that some bee pollen secondary metabolites (e.g. flavonoid) may have positive health effects. In recent years, the flavonoids have attracted much interest because of their wide range of biological properties and their beneficial effects on human health. The current review, points out potential therapeutic effects of bee pollen flavonoids as one of the main bee pollen bioactive compounds in allergic and immunological diseases. Due to the fact that some types of flavonoid components in bee pollen have anti-allergic, anti-oxidant and anti-inflammatory properties, bee pollen flavonoids can be excellent candidates for future studies including phytotherapy, molecular pharmacology and substitutes for chemicals used in treating allergic and immunological disorders.

  2. Immunomodulators as Therapeutic Agents in Mitigating the Progression of Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Bethany Grimmig

    2016-09-01

    Full Text Available Parkinson’s disease (PD is a common neurodegenerative disorder that primarily afflicts the elderly. It is characterized by motor dysfunction due to extensive neuron loss in the substantia nigra pars compacta. There are multiple biological processes that are negatively impacted during the pathogenesis of PD, and are implicated in the cell death in this region. Neuroinflammation is evidently involved in PD pathology and mitigating the inflammatory cascade has been a therapeutic strategy. Age is the number one risk factor for PD and thus needs to be considered in the context of disease pathology. Here, we discuss the role of neuroinflammation within the context of aging as it applies to the development of PD, and the potential for two representative compounds, fractalkine and astaxanthin, to attenuate the pathophysiology that modulates neurodegeneration that occurs in Parkinson’s disease.

  3. The life cycle of Ascocotyle (Phagicola) longa (Digenea: Heterophyidae), a causative agent of fish-borne trematodosis.

    Science.gov (United States)

    Simões, Susana Balmant Emerique; Barbosa, Helene Santos; Santos, Cláudia Portes

    2010-03-01

    The complete life cycle of the trematode Ascocotyle (Phagicola) longa (Digenea: Heterophyidae) is elucidated by natural observation validated by experimental infections. The natural first intermediate host of A. (P.) longa, an agent of human heterophyiasis in Brazil, is the cochliopid snail Heleobia australis (new first intermediate host). Metacercariae were found encysted in the body musculature, heart, stomach, liver, kidney, spleen, gonads and mesentery of mullets Mugil liza. Hamsters Mesocricetus auratus were experimentally infected with metacercariae of A. (P.) longa obtained from the mullets, and the adults recovered were used to infect the snails H. australis. Rediae and cercariae of A. (P.) longa are described for the first time. The ultrastructure of the tegument of A. (P.) longa shows a change in spination pattern from the cercaria with single-pointed spines to the metacercaria and adult with multipointed, brush-shaped spines. The life cycle of A. (P.) longa is related to estuaries and coastal lagoons where the recruitment of mugilid juveniles occurs. The high prevalence (100%) of A. (P.) longa encysted in the mullets examined within the urban area of Rio de Janeiro indicates the potentially great public health impact of the consumption of raw mullets. Copyright 2009 Elsevier B.V. All rights reserved.

  4. A Novel Therapeutic Agent for Type 2 Diabetes Mellitus: SGLT2 Inhibitor

    Directory of Open Access Journals (Sweden)

    Chang Hee Jung

    2014-08-01

    Full Text Available Type 2 diabetes mellitus (T2DM is a complex endocrine and metabolic disorder, and a major public health problem that is rapidly increasing in prevalence. Although a wide range of pharmacotherapies for glycemic control is now available, management of T2DM remains complex and challenging. The kidneys contribute immensely to glucose homeostasis by reabsorbing glucose from the glomerular filtrate. Sodium-glucose cotransporter 2 (SGLT2 inhibitors, a new class of antidiabetic agents that inhibit glucose absorption from the kidney independent of insulin, offer a unique opportunity to improve the outcomes of patients with T2DM. In this review, we provide an overview of two globally-approved SGLT2 inhibitors, dapagliflozin and canagliflozin, and discuss their effects and safety. This information will help clinicians to decide whether these drugs will benefit their patients.

  5. Heterocyclic N-Oxides – An Emerging Class of Therapeutic Agents

    Science.gov (United States)

    Mfuh, Adelphe M.; Larionov, Oleg V.

    2016-01-01

    Heterocyclic N-oxides have emerged as potent compounds with anticancer, antibacterial, antihypertensive, antiparasitic, anti-HIV, anti-inflammatory, herbicidal, neuroprotective, and procognitive activities. The N-oxide motif has been successfully employed in a number of recent drug development projects. This review surveys the emergence of this scaffold in the mainstream medicinal chemistry with a focus on the discovery of the heterocyclic N-oxide drugs, N-oxide-specific mechanisms of action, drug-receptor interactions and synthetic avenues to these compounds. As the first review on this subject that covers the developments since 1950s to date, it is expected that it will inspire wider implementation of the heterocyclic N-oxide motif in the rational design of new medicinal agents. PMID:26087764

  6. Survey of vector-borne agents in feral cats and first report of Babesia gibsoni in cats on St Kitts, West Indies.

    Science.gov (United States)

    Kelly, Patrick John; Köster, Liza; Li, Jing; Zhang, Jilei; Huang, Ke; Branford, Gillian Carmichael; Marchi, Silvia; Vandenplas, Michel; Wang, Chengming

    2017-11-13

    As there is little data on vector-borne diseases of cats in the Caribbean region and even around the world, we tested feral cats from St Kitts by PCR to detect infections with Babesia, Ehrlichia and spotted fever group Rickettsia (SFGR) and surveyed them for antibodies to Rickettsia rickettsii and Ehrlichia canis. Whole blood was collected from apparently healthy feral cats during spay/ neuter campaigns on St Kitts in 2011 (N = 68) and 2014 (N = 52). Sera from the 52 cats from 2014 were used to detect antibodies to Ehrlichia canis and Rickettsia rickettsii using indirect fluorescent antibody tests and DNA extracted from whole blood of a total of 119 cats (68 from 2011, and 51 from 2014) was used for PCRs for Babesia, Ehrlichia and Rickettsia. We could not amplify DNA of SFG Rickettsia in any of the samples but found DNA of E. canis in 5% (6/119), Babesia vogeli in 13% (15/119), Babesia gibsoni in 4% (5/119), mixed infections with B. gibsoni and B. vogeli in 3% (3/119), and a poorly characterized Babesia sp. in 1% (1/119). Overall, 10% of the 52 cats we tested by IFA for E. canis were positive while 42% we tested by indirect fluorescent antibody (IFA) for R. rickettsii antigens were positive. Our study provides the first evidence that cats can be infected with B. gibsoni and also indicates that cats in the Caribbean may be commonly exposed to other vector-borne agents including SFGR, E. canis and B. vogeli. Animal health workers should be alerted to the possibility of clinical infections in their patients while public health workers should be alerted to the possibility that zoonotic SFGR are likely circulating in the region.

  7. Curcumin: Reintroduced Therapeutic Agent from Traditional Medicine for Alcoholic Liver Disease

    Directory of Open Access Journals (Sweden)

    Hamid Reza Rahimi

    2015-03-01

    Full Text Available Alcoholic liver disease (ALD is the main cause of chronic liver disease across the world and can lead to fibrosis and cirrhosis. The etiopathogenesis of ALD is related to ethanol-induced oxidative stress, glutathione reduction, abnormal methionine metabolism, malnutrition, and production of endotoxins that activate Kupffer cells. Curcumin is an active ingredient of the rhizome of turmeric. The substance is shown to have minor adverse effects. As the substance possess low bioavailability in free formulation, different strategies has been conducted to improve its bioavailability which resulted in production of nanomiscels and nanoparticles. Curcumin can provide protection for the liver against toxic effects of alcohol use. Several studies showed curcumin blocks endotoxin-mediated activation of NF-κB and suppresses the expression of cytokines, chemokines, COX-2, and iNOS in Kupffer cells. According to the molecular studies, curcumin inhibits NF-κB signaling pathway, regulates cytokines production and modulates immune response. It has been shown that curcumin can suppress gene expression, especially cytokines genes resulting in down-regulation of tumor necrosis factor-α (TNF-α, interleukin 1 (IL-1, IL-6, IL-8, adhesion molecules (ICAM, VCAM and C-reactive protein. Hence, curcumin can have therapeutic effects on the majority of chronic inflammatory diseases such as asthma, bronchitis, inflammatory bowel disease, rheumatoid arthritis, ALD, fatty liver, and allergy.

  8. Nanoparticles as potential clinical therapeutic agents in Alzheimer's disease: focus on selenium nanoparticles.

    Science.gov (United States)

    Nazıroğlu, Mustafa; Muhamad, Salina; Pecze, Laszlo

    2017-07-01

    In etiology of Alzheimer's disease (AD), involvement of amyloid β (Aβ) plaque accumulation and oxidative stress in the brain have important roles. Several nanoparticles such as titanium dioxide, silica dioxide, silver and zinc oxide have been experimentally using for treatment of neurological disease. In the last decade, there has been a great interest on combination of antioxidant bioactive compounds such as selenium (Se) and flavonoids with the oxidant nanoparticles in AD. We evaluated the most current data available on the physiological effects of oxidant and antioxidant nanoparticles. Areas covered: Oxidative nanoparticles decreased the activities of reactive oxygen species (ROS) scavenging enzymes such as glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase in the brain of rats and mice. However, Se-rich nanoparticles in small size (5-15 nm) depleted Aβ formation through decreasing ROS production. Reports on low levels of Se in blood and tissue samples and the low activities of GSH-Px, catalase and SOD enzymes in AD patients and animal models support the proposed crucial role of oxidative stress in the pathogenesis of AD. Expert commentary: In conclusion, present literature suggests that Se-rich nanoparticles appeared to be a potential therapeutic compound for the treatment of AD.

  9. Neurotrophin receptor agonists and antagonists as therapeutic agents: An evolving paradigm.

    Science.gov (United States)

    Josephy-Hernandez, Sylvia; Jmaeff, Sean; Pirvulescu, Iulia; Aboulkassim, Tahar; Saragovi, H Uri

    2017-01-01

    Neurodegenerative disorders are prevalent, complex and devastating conditions, with very limited treatment options currently available. While they manifest in many forms, there are commonalities that link them together. In this review, we will focus on neurotrophins - a family of related factors involved in neuronal development and maintenance. Neurodegenerative diseases often present with a neurotrophin imbalance, in which there may be decreases in trophic signaling through Trk receptors for example, and/or increases in pro-apoptotic activity through p75. Clinical trials with neurotrophins have continuously failed due to their poor pharmacological properties as well as the unavoidable activation of p75. Thus, there is a need for drugs without such setbacks. Small molecule neurotrophin mimetics are favorable options since they can selectively activate Trks or inactivate p75. In this review, we will initially present a brief outline of how these molecules are synthesized and their mechanisms of action; followed by an update in the current state of neurotrophins and small molecules in major neurodegenerative diseases. Although there has been significant progress in the development of potential therapeutics, more studies are needed to establish clear mechanisms of action and target specificity in order to transition from animal models to the assessment of safety and use in humans. Copyright © 2016. Published by Elsevier Inc.

  10. Cynaropicrin: a comprehensive research review and therapeutic potential as an anti- hepatitis C virus agent

    Directory of Open Access Journals (Sweden)

    Mahmoud Fahmi Elsebai

    2016-12-01

    Full Text Available The different pharmacologic properties of plants-containing cynaropicrin, especially artichokes, have been known for many centuries. More recently, cynaropicrin exhibited a potential activity against all genotypes of hepatitis C virus (HCV. Cynaropicrin has also shown a wide range of other pharmacologic properties such as anti-hyperlipidemic, anti-trypanosomal, anti-malarial, antifeedant, antispasmodic, anti-photoaging, and anti-tumor action, as well as activation of bitter sensory receptors, and anti-inflammatory properties (e.g., associated with the suppression of the key pro-inflammatory NF-κB pathway. These pharmacological effects are very supportive factors to its outstanding activity against HCV. Structurally, cynaropicrin might be considered as a potential drug candidate, since it has no violations for the rule of five and its water-solubility could allow formulation as therapeutic injections. Moreover, cynaropicrin is a small molecule that can be easily synthesized and as the major constituent of the edible plant artichoke, which has a history of safe dietary use. In summary, cynaropicrin is a promising bioactive natural product that, with minor hit-to-lead optimization, might be developed as a drug for HCV.

  11. Polymer Nanoparticles as Smart Carriers for the Enhanced Release of Therapeutic Agents to the CNS.

    Science.gov (United States)

    Gagliardi, Mariacristina; Borri, Claudia

    2017-01-01

    The brain is the most protected organ in the human body; its protective shield, relying on a complex system of cells, proteins and transporters, prevents potentially harmful substances from entering the brain from the bloodstream but, on the other hand, it also stops drugs administered via the systemic route. To improve the efficacy of pharmacological treatments, targeted drug delivery by means of polymer nanoparticles is a challenging but, at the same time, efficient strategy. Thanks to a highly multidisciplinary approach, several ways to overcome the brain protection have provided effective solutions to treat a large number of diseases. Important advances in polymer science, together with the development of novel techniques for nanocarrier preparation, and the discovery of novel targeting ligands and molecules, allow a fine-tuning of size, shape, chemicophysical properties and surface chemistry of functional particulate systems; it enables the improvement of the therapeutic performances for several drugs, also toward districts that are difficult to be treated, such as the brain. This review focuses on the great strides made from scientists and doctors in the development of polymer nano-sized drug delivery systems for brain diseases. Even though the optimal nanocarrier was not yet discovered, important advances were made to strive for safer, performant and successful systems, with the expectation to find soon better solutions to cure some still untreatable pathologies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  12. Current state of a dual behaviour of antimicrobial peptides-Therapeutic agents and promising delivery vectors.

    Science.gov (United States)

    Piotrowska, Urszula; Sobczak, Marcin; Oledzka, Ewa

    2017-12-01

    Micro-organism resistance is an important challenge in modern medicine due to the global uncontrolled use of antibiotics. Natural and synthetic antimicrobial peptides (AMPs) symbolize a new family of antibiotics, which have stimulated research and clinical interest as new therapeutic options for infections. They represent one of the most promising antimicrobial substances, due to their broad spectrum of biological activity, against bacteria, fungi, protozoa, viruses, yeast and even tumour cells. Besides, being antimicrobial, AMPs have been shown to bind and neutralize bacterial endotoxins, as well as possess immunomodulatory, anti-inflammatory, wound-healing, angiogenic and antitumour properties. In contrast to conventional antibiotics, which have very defined and specific molecular targets, host cationic peptides show varying, complex and very rapid mechanisms of actions that make it difficult to form an effective antimicrobial defence. Importantly, AMPs display their antimicrobial activity at micromolar concentrations or less. To do this, many peptide-based drugs are commercially available for the treatment of numerous diseases, such as hepatitis C, myeloma, skin infections and diabetes. Herein, we present an overview of the general mechanism of AMPs action, along with recent developments regarding carriers of AMPs and their potential applications in medical fields. © 2017 John Wiley & Sons A/S.

  13. Caffeic Acid Phenethyl Ester Is a Potential Therapeutic Agent for Oral Cancer

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    Ying-Yu Kuo

    2015-05-01

    Full Text Available Head and neck cancers, which affect 650,000 people and cause 350,000 deaths per year, is the sixth leading cancer by cancer incidence and eighth by cancer-related death worldwide. Oral cancer is the most common type of head and neck cancer. More than 90% of oral cancers are oral and oropharyngeal squamous cell carcinoma (OSCC. The overall five-year survival rate of OSCC patients is approximately 63%, which is due to the low response rate to current therapeutic drugs. In this review we discuss the possibility of using caffeic acid phenethyl ester (CAPE as an alternative treatment for oral cancer. CAPE is a strong antioxidant extracted from honeybee hive propolis. Recent studies indicate that CAPE treatment can effectively suppress the proliferation, survival, and metastasis of oral cancer cells. CAPE treatment inhibits Akt signaling, cell cycle regulatory proteins, NF-κB function, as well as activity of matrix metalloproteinase (MMPs, epidermal growth factor receptor (EGFR, and Cyclooxygenase-2 (COX-2. Therefore, CAPE treatment induces cell cycle arrest and apoptosis in oral cancer cells. According to the evidence that aberrations in the EGFR/phosphoinositide 3-kinase (PI3K/protein kinase B (Akt signaling, NF-κB function, COX-2 activity, and MMPs activity are frequently found in oral cancers, and that the phosphorylation of Akt, EGFR, and COX-2 correlates to oral cancer patient survival and clinical progression, we believe that CAPE treatment will be useful for treatment of advanced oral cancer patients.

  14. Singing as a Therapeutic Agent, inThe Etude, 1891-1949.

    Science.gov (United States)

    Hunter

    1999-01-01

    The Etude music magazine, founded by Theodore Presser, was one of a number of popular music magazines published in the years prior to the establishment of the music therapy profession in 1950. During its publication run from 1883 to 1957, over 100 music therapy related articles appeared, including 13 on the health benefits of singing published between 1891 and 1949. Written by authors with diverse backgrounds, such as the famous Battle Creek, Michigan physician John Harvey Kellogg and Boston music critic Louis C. Elson, the articles contained consistent and adamant support regarding the health benefits of singing. The advantages described were both physical and psychological, and were recommended prophylactically for well persons and therapeutically for ill persons. Although the articles varied in perspective, from philosophical to theoretical to pedagogical, there is a consistent holistic medicine theme that appeared almost ahead of its time and no doubt linked to the push for vocal music education in that era. The importance of The Etude in promulgating ideas that helped shape the early practice of music therapy should not be underestimated. For much of its publication run The Etude was the largest music periodical in print, reaching its peak circulation of 250,000 copies per month in 1924.

  15. Fetal hemoglobin in sickle cell anemia: The Arab-Indian haplotype and new therapeutic agents.

    Science.gov (United States)

    Habara, Alawi H; Shaikho, Elmutaz M; Steinberg, Martin H

    2017-11-01

    Fetal hemoglobin (HbF) has well-known tempering effects on the symptoms of sickle cell disease and its levels vary among patients with different haplotypes of the sickle hemoglobin gene. Compared with sickle cell anemia haplotypes found in patients of African descent, HbF levels in Saudi and Indian patients with the Arab-Indian (AI) haplotype exceed that in any other haplotype by nearly twofold. Genetic association studies have identified some loci associated with high HbF in the AI haplotype but these observations require functional confirmation. Saudi patients with the Benin haplotype have HbF levels almost twice as high as African patients with this haplotype but this difference is unexplained. Hydroxyurea is still the only FDA approved drug for HbF induction in sickle cell disease. While most patients treated with hydroxyurea have an increase in HbF and some clinical improvement, 10 to 20% of adults show little response to this agent. We review the genetic basis of HbF regulation focusing on sickle cell anemia in Saudi Arabia and discuss new drugs that can induce increased levels of HbF. © 2017 Wiley Periodicals, Inc.

  16. Onconase responsive genes in human mesothelioma cells: implications for an RNA damaging therapeutic agent

    International Nuclear Information System (INIS)

    Altomare, Deborah A; Rybak, Susanna M; Pei, Jianming; Maizel, Jacob V; Cheung, Mitchell; Testa, Joseph R; Shogen, Kuslima

    2010-01-01

    Onconase represents a new class of RNA-damaging drugs. Mechanistically, Onconase is thought to internalize, where it degrades intracellular RNAs such as tRNA and double-stranded RNA, and thereby suppresses protein synthesis. However, there may be additional or alternative mechanism(s) of action. In this study, microarray analysis was used to compare gene expression profiles in untreated human malignant mesothelioma (MM) cell lines and cells exposed to 5 μg/ml Onconase for 24 h. A total of 155 genes were found to be regulated by Onconase that were common to both epithelial and biphasic MM cell lines. Some of these genes are known to significantly affect apoptosis (IL-24, TNFAIP3), transcription (ATF3, DDIT3, MAFF, HDAC9, SNAPC1) or inflammation and the immune response (IL-6, COX-2). RT-PCR analysis of selected up- or down-regulated genes treated with varying doses and times of Onconase generally confirmed the expression array findings in four MM cell lines. Onconase treatment consistently resulted in up-regulation of IL-24, previously shown to have tumor suppressive activity, as well as ATF3 and IL-6. Induction of ATF3 and the pro-apoptotic factor IL-24 by Onconase was highest in the two most responsive MM cell lines, as defined by DNA fragmentation analysis. In addition to apoptosis, gene ontology analysis indicated that pathways impacted by Onconase include MAPK signaling, cytokine-cytokine-receptor interactions, and Jak-STAT signaling. These results provide a broad picture of gene activity after treatment with a drug that targets small non-coding RNAs and contribute to our overall understanding of MM cell response to Onconase as a therapeutic strategy. The findings provide insights regarding mechanisms that may contribute to the efficacy of this novel drug in clinical trials of MM patients who have failed first line chemotherapy or radiation treatment

  17. Lysis-deficient phages as novel therapeutic agents for controlling bacterial infection

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    Kempashanaiah Nanjundappa

    2011-08-01

    Full Text Available Abstract Background Interest in phage therapy has grown over the past decade due to the rapid emergence of antibiotic resistance in bacterial pathogens. However, the use of bacteriophages for therapeutic purposes has raised concerns over the potential for immune response, rapid toxin release by the lytic action of phages, and difficulty in dose determination in clinical situations. A phage that kills the target cell but is incapable of host cell lysis would alleviate these concerns without compromising efficacy. Results We developed a recombinant lysis-deficient Staphylococcus aureus phage P954, in which the endolysin gene was rendered nonfunctional by insertional inactivation. P954, a temperate phage, was lysogenized in S. aureus strain RN4220. The native endolysin gene on the prophage was replaced with an endolysin gene disrupted by the chloramphenicol acetyl transferase (cat gene through homologous recombination using a plasmid construct. Lysogens carrying the recombinant phage were detected by growth in presence of chloramphenicol. Induction of the recombinant prophage did not result in host cell lysis, and the phage progeny were released by cell lysis with glass beads. The recombinant phage retained the endolysin-deficient genotype and formed plaques only when endolysin was supplemented. The host range of the recombinant phage was the same as that of the parent phage. To test the in vivo efficacy of the recombinant endolysin-deficient phage, immunocompromised mice were challenged with pathogenic S. aureus at a dose that results in 80% mortality (LD80. Treatment with the endolysin-deficient phage rescued mice from the fatal S. aureus infection. Conclusions A recombinant endolysin-deficient staphylococcal phage has been developed that is lethal to methicillin-resistant S. aureus without causing bacterial cell lysis. The phage was able to multiply in lytic mode utilizing a heterologous endolysin expressed from a plasmid in the propagation host

  18. Botulinum Toxin Type A as a Therapeutic Agent against Headache and Related Disorders

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    Siro Luvisetto

    2015-09-01

    Full Text Available Botulinum neurotoxin A (BoNT/A is a toxin produced by the naturally-occurring Clostridium botulinum that causes botulism. The potential of BoNT/A as a useful medical intervention was discovered by scientists developing a vaccine to protect against botulism. They found that, when injected into a muscle, BoNT/A causes a flaccid paralysis. Following this discovery, BoNT/A has been used for many years in the treatment of conditions of pathological muscle hyperactivity, like dystonias and spasticities. In parallel, the toxin has become a “glamour” drug due to its power to ward off facial wrinkles, particularly frontal, due to the activity of the mimic muscles. After the discovery that the drug also appeared to have a preventive effect on headache, scientists spent many efforts to study the potentially-therapeutic action of BoNT/A against pain. BoNT/A is effective at reducing pain in a number of disease states, including cervical dystonia, neuropathic pain, lower back pain, spasticity, myofascial pain and bladder pain. In 2010, regulatory approval for the treatment of chronic migraine with BoNT/A was given, notwithstanding the fact that the mechanism of action is still not completely elucidated. In the present review, we summarize experimental evidence that may help to clarify the mechanisms of action of BoNT/A in relation to the alleviation of headache pain, with particular emphasis on preclinical studies, both in animals and humans. Moreover, we summarize the latest clinical trials that show evidence on headache conditions that may obtain benefits from therapy with BoNT/A.

  19. Nanotechnology solutions for Alzheimer's disease: advances in research tools, diagnostic methods and therapeutic agents.

    Science.gov (United States)

    Nazem, Amir; Mansoori, G Ali

    2008-03-01

    A century of research has passed since the discovery and definition of Alzheimer's disease (AD), the primary common dementing disorder worldwide. However, AD lacks definite diagnostic approaches and effective cure at the present. Moreover, the currently available diagnostic tools are not sufficient for an early screening of AD in order to start preventive approaches. Recently the emerging field of nanotechnology has promised new techniques to solve some of the AD challenges. Nanotechnology refers to the techniques of designing and manufacturing nanosize (1-100 nm) structures through controlled positional and/or self-assembly of atoms and molecules. In this report, we present the promises that nanotechnology brings in research on the AD diagnosis and therapy. They include its potential for the better understanding of the AD root cause molecular mechanisms, AD's early diagnoses, and effective treatment. The advances in AD research offered by the atomic force microscopy, single molecule fluorescence microscopy and NanoSIMS microscopy are examined here. In addition, the recently proposed applications of nanotechnology for the early diagnosis of AD including bio-barcode assay, localized surface plasmon resonance nanosensor, quantum dot and nanomechanical cantilever arrays are analyzed. Applications of nanotechnology in AD therapy including neuroprotections against oxidative stress and anti-amyloid therapeutics, neuroregeneration and drug delivery beyond the blood brain barrier (BBB) are discussed and analyzed. All of these applications could improve the treatment approach of AD and other neurodegenerative diseases. The complete cure of AD may become feasible by a combination of nanotechnology and some other novel approaches, like stem cell technology.

  20. Cabazitaxel-loaded human serum albumin nanoparticles as a therapeutic agent against prostate cancer

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    Qu N

    2016-07-01

    Full Text Available Na Qu,1 Robert J Lee,1,2 Yating Sun,1 Guangsheng Cai,1 Junyang Wang,1 Mengqiao Wang,1 Jiahui Lu,1 Qingfan Meng,1 Lirong Teng,1 Di Wang,1 Lesheng Teng1,3 1School of Life Sciences, Jilin University, Changchun, People’s Republic of China; 2Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, OH, USA; 3State Key Laboratory of Long-acting and Targeting Drug Delivery System, Yantai, People’s Republic of China Abstract: Cabazitaxel-loaded human serum albumin nanoparticles (Cbz-NPs were synthesized to overcome vehicle-related toxicity of current clinical formulation of the drug based on Tween-80 (Cbz-Tween. A salting-out method was used for NP synthesis that avoids the use of chlorinated organic solvent and is simpler compared to the methods based on emulsion-solvent evaporation. Cbz-NPs had a narrow particle size distribution, suitable drug loading content (4.9%, and superior blood biocompatibility based on in vitro hemolysis assay. Blood circulation, tumor uptake, and antitumor activity of Cbz-NPs were assessed in prostatic cancer xenograft-bearing nude mice. Cbz-NPs exhibited prolonged blood circulation and greater accumulation of Cbz in tumors along with reduced toxicity compared to Cbz-Tween. Moreover, hematoxylin and eosin histopathological staining of organs revealed consistent results. The levels of blood urea nitrogen and serum creatinine in drug-treated mice showed that Cbz-NPs were less toxic than Cbz-Tween to the kidneys. In conclusion, Cbz-NPs provide a promising therapeutic for prostate cancer. Keywords: cabazitaxel, human serum albumin, nanoparticle, drug delivery, toxicity, pros­tate cancer

  1. Botulinum Toxin Type A as a Therapeutic Agent against Headache and Related Disorders

    Science.gov (United States)

    Luvisetto, Siro; Gazerani, Parisa; Cianchetti, Carlo; Pavone, Flaminia

    2015-01-01

    Botulinum neurotoxin A (BoNT/A) is a toxin produced by the naturally-occurring Clostridium botulinum that causes botulism. The potential of BoNT/A as a useful medical intervention was discovered by scientists developing a vaccine to protect against botulism. They found that, when injected into a muscle, BoNT/A causes a flaccid paralysis. Following this discovery, BoNT/A has been used for many years in the treatment of conditions of pathological muscle hyperactivity, like dystonias and spasticities. In parallel, the toxin has become a “glamour” drug due to its power to ward off facial wrinkles, particularly frontal, due to the activity of the mimic muscles. After the discovery that the drug also appeared to have a preventive effect on headache, scientists spent many efforts to study the potentially-therapeutic action of BoNT/A against pain. BoNT/A is effective at reducing pain in a number of disease states, including cervical dystonia, neuropathic pain, lower back pain, spasticity, myofascial pain and bladder pain. In 2010, regulatory approval for the treatment of chronic migraine with BoNT/A was given, notwithstanding the fact that the mechanism of action is still not completely elucidated. In the present review, we summarize experimental evidence that may help to clarify the mechanisms of action of BoNT/A in relation to the alleviation of headache pain, with particular emphasis on preclinical studies, both in animals and humans. Moreover, we summarize the latest clinical trials that show evidence on headache conditions that may obtain benefits from therapy with BoNT/A. PMID:26404377

  2. Potential therapeutic agents for circulatory diseases from Bauhinia glauca Benth.subsp. pernervosa. (Da Ye Guan Men).

    Science.gov (United States)

    Tang, Yingzhan; Ling, Junhong; Zhang, Peng; Zhang, Xiangrong; Zhang, Na; Wang, Wenli; Li, Jiayuan; Li, Ning

    2015-08-15

    Because of platelets as critical factor in the formation of pathogenic thrombi, anti-platelet activities have been selected as therapeutic target for various circulatory diseases. In order to find potential therapeutic agents, bioassay-directed separation of Bauhinia glauca Benth.subsp. pernervosa. (called Da Ye Guan Men as a traditional Chinese medicine) was performed to get 29 main components (compounds 1-29) from the bioactive part of this herbal. It was the first time to focus on the composition with anti-platelet aggregation activities for this traditional Chinese medicine. The constituents, characterized from the effective extract, were established on the basis of extensive spectral data analysis. Then their anti-platelet aggregation effects were evaluated systematically. On the basis of the chemical profile and biological assay, it was suggested that the flavonoid composition (5 and 18) should be responsible for the anti-platelet aggregation of the herbal because of their significant activities. The primary structure and activity relationship was also discussed briefly. Copyright © 2015. Published by Elsevier Ltd.

  3. Mesenchymal Stem/Stromal Cell-Derived Extracellular Vesicles and Their Potential as Novel Immunomodulatory Therapeutic Agents

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    Verena Börger

    2017-07-01

    Full Text Available Extracellular vesicles (EVs, such as exosomes and microvesicles, have been identified as mediators of a newly-discovered intercellular communication system. They are essential signaling mediators in various physiological and pathophysiological processes. Depending on their origin, they fulfill different functions. EVs of mesenchymal stem/stromal cells (MSCs have been found to promote comparable therapeutic activities as MSCs themselves. In a variety of in vivo models, it has been observed that they suppress pro-inflammatory processes and reduce oxidative stress and fibrosis. By switching pro-inflammatory into tolerogenic immune responses, MSC-EVs very likely promote tissue regeneration by creating a pro-regenerative environment allowing endogenous stem and progenitor cells to successfully repair affected tissues. Accordingly, MSC-EVs provide a novel, very promising therapeutic agent, which has already been successfully applied to humans. However, the MSC-EV production process has not been standardized, yet. Indeed, a collection of different protocols has been used for the MSC-EV production, characterization and application. By focusing on kidney, heart, liver and brain injuries, we have reviewed the major outcomes of published MSC-EV in vivo studies.

  4. Barnase as a new therapeutic agent triggering apoptosis in human cancer cells.

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    Evelina Edelweiss

    Full Text Available BACKGROUND: RNases are currently studied as non-mutagenic alternatives to the harmful DNA-damaging anticancer drugs commonly used in clinical practice. Many mammalian RNases are not potent toxins due to the strong inhibition by ribonuclease inhibitor (RI presented in the cytoplasm of mammalian cells. METHODOLOGY/PRINCIPAL FINDINGS: In search of new effective anticancer RNases we studied the effects of barnase, a ribonuclease from Bacillus amyloliquefaciens, on human cancer cells. We found that barnase is resistant to RI. In MTT cell viability assay, barnase was cytotoxic to human carcinoma cell lines with half-inhibitory concentrations (IC(50 ranging from 0.2 to 13 microM and to leukemia cell lines with IC(50 values ranging from 2.4 to 82 microM. Also, we characterized the cytotoxic effects of barnase-based immunoRNase scFv 4D5-dibarnase, which consists of two barnase molecules serially fused to the single-chain variable fragment (scFv of humanized antibody 4D5 that recognizes the extracellular domain of cancer marker HER2. The scFv 4D5-dibarnase specifically bound to HER2-positive cells and was internalized via receptor-mediated endocytosis. The intracellular localization of internalized scFv 4D5-dibarnase was determined by electronic microscopy. The cytotoxic effect of scFv 4D5-dibarnase on HER2-positive human ovarian carcinoma SKOV-3 cells (IC(50 = 1.8 nM was three orders of magnitude greater than that of barnase alone. Both barnase and scFv 4D5-dibarnase induced apoptosis in SKOV-3 cells accompanied by internucleosomal chromatin fragmentation, membrane blebbing, the appearance of phosphatidylserine on the outer leaflet of the plasma membrane, and the activation of caspase-3. CONCLUSIONS/SIGNIFICANCE: These results demonstrate that barnase is a potent toxic agent for targeting to cancer cells.

  5. A Novel Single-Strand RNAi Therapeutic Agent Targeting the (Pro)renin Receptor Suppresses Ocular Inflammation.

    Science.gov (United States)

    Kanda, Atsuhiro; Ishizuka, Erdal Tan; Shibata, Atsushi; Matsumoto, Takahiro; Toyofuku, Hidekazu; Noda, Kousuke; Namba, Kenichi; Ishida, Susumu

    2017-06-16

    The receptor-associated prorenin system (RAPS) refers to the pathogenic mechanism whereby prorenin binding to the (pro)renin receptor [(P)RR] dually activates the tissue renin-angiotensin system (RAS) and RAS-independent intracellular signaling. Here we revealed significant upregulation of prorenin and soluble (P)RR levels in the vitreous fluid of patients with uveitis compared to non-inflammatory controls, together with a positive correlation between these RAPS components and monocyte chemotactic protein-1 among several upregulated cytokines. Moreover, we developed a novel single-strand RNAi agent, proline-modified short hairpin RNA directed against human and mouse (P)RR [(P)RR-PshRNA], and we determined its safety and efficacy in vitro and in vivo. Application of (P)RR-PshRNA in mice caused significant amelioration of acute (uveitic) and chronic (diabetic) models of ocular inflammation with no apparent adverse effects. Our findings demonstrate the significant implication of RAPS in the pathogenesis of human uveitis and the potential usefulness of (P)RR-PshRNA as a therapeutic agent to reduce ocular inflammation. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  6. Sporothrix chilensis sp. nov. (Ascomycota: Ophiostomatales), a soil-borne agent of human sporotrichosis with mild-pathogenic potential to mammals.

    Science.gov (United States)

    Rodrigues, Anderson Messias; Cruz Choappa, Rodrigo; Fernandes, Geisa Ferreira; de Hoog, G Sybren; de Camargo, Zoilo Pires

    2016-02-01

    A combination of phylogeny, evolution, morphologies and ecologies has enabled major advances in understanding the taxonomy of Sporothrix species, including members exhibiting distinct lifestyles such as saprobes, human/animal pathogens, and insect symbionts. Phylogenetic analyses of ITS1/2 + 5.8s sequences split Sporothrix genus in two well-defined groups with dissimilar ecologies. Species embedded in the Sporothrix schenckii complex are frequently agents of human and animal sporotrichosis, and some of these are responsible for large sapronoses and zoonoses around the warmer temperate regions of the world. At the other extreme, basal saprophytic species evolved in association with decaying wood and soil, and are rarely found to cause human disease. We propose to create a new taxa, Sporothrix chilensis sp. nov., to accommodate strains collected from a clinical case of onychomycosis as well as from environmental origins in Chile. Multigene analyses based on ITS1/2 + 5.8s region, beta-tubulin, calmodulin and translation elongation factor 1α revealed that S. chilensis is a member of the Sporothrix pallida complex, and the nearest taxon is Sporothrix mexicana, a rare soil-borne species, non-pathogenic to humans. The ITS region serves as a primary barcode marker, while each one of the protein-coding loci easily recognized species boundaries providing sufficient information for species identification. A disseminated model of murine sporotrichosis revealed a mild-pathogenic potential, with lung invasion. Although S. chilensis is not a primary pathogen, accidental infection may have an impact in the immunosuppressed population. With the introduction of distinct species with similar routes of transmission but different virulence, identification of Sporothrix agents at the species level is mandatory. Copyright © 2015 The British Mycological Society. Published by Elsevier Ltd. All rights reserved.

  7. Current progress and future perspectives in the development of anti-polo-like kinase 1 therapeutic agents [version 1; referees: 4 approved

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    Jung-Eun Park

    2017-06-01

    Full Text Available Although significant levels of side effects are often associated with their use, microtubule-directed agents that primarily target fast-growing mitotic cells have been considered to be some of the most effective anti-cancer therapeutics. With the hope of developing new-generation anti-mitotic agents with reduced side effects and enhanced tumor specificity, researchers have targeted various proteins whose functions are critically required for mitotic progression. As one of the highly attractive mitotic targets, polo-like kinase 1 (Plk1 has been the subject of an extensive effort for anti-cancer drug discovery. To date, a variety of anti-Plk1 agents have been developed, and several of them are presently in clinical trials. Here, we will discuss the current status of generating anti-Plk1 agents as well as future strategies for designing and developing more efficacious anti-Plk1 therapeutics.

  8. Potencial terapéutico de los canabinoides como neuroprotectores Therapeutical potential of cannabinoids as neuroprotective agents

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    Laymi Martínez García

    2007-12-01

    Full Text Available La planta Cannabis sativa L. o cáñamo ha captado desde tiempos antiquísimos la atención del hombre en el campo de la salud y terapéutica humanas y todavía, a inicios del siglo XXI, continúa despertando polémicas en la comunidad científica como fuente natural y en el estudio y aplicación de sus derivados. Desde el punto de vista fitoquímico se han descrito más de 70 derivados de tipo canabinoide farmacológicamente activos sobre el sistema nervioso central. En la actualidad se han generado valiosísimas fuentes de información que relacionan la especie botánica Cannabis sativa L. y sus metabolitos secundarios con la medicina (tratamiento terapéutico, farmacología (modelos experimentales y química sintética (diseño y generación de nuevas estructuras, las cuales avalan la importancia del estudio de esta planta, sus extractos, metabolitos y precursores como fuente de agentes terapéuticos. Por tal motivo se presenta una revisión de la información existente sobre las potenciales implicaciones terapéuticas de sistemas moleculares canabinoidales (endógenos, naturales y sintéticos en el tratamiento de enfermedades neurodegenerativas del sistema nervioso central, que incluye: conceptos de tipos de canabinoides, sistemas de receptores canabinoides CB1 y CB2 y evidencias preclínicas de los efectos neuroprotectores de canabinoides desde 1970 hasta el 2005Cannabis sativa L. or cáñamo has focused man's attention for its therapeutical and medical application since ancient times, and yet, at the beginning of XXI century, this plant continues being polemic for the scientific community as a natural source and in the study and application of its derivatives. More than 70 cannabinoid compounds with pharmacological action on the central nervous system have been phytochemically described. At present, a great amount of valuable information and experimental data have been generated that correlate Cannabis sativa and its secondary metabolites

  9. Therapeutic response assessment of percutaneous radiofrequency ablation for hepatocellular carcinoma: Utility of contrast-enhanced agent detection imaging

    International Nuclear Information System (INIS)

    Kim, Chan Kyo; Choi, Dongil; Lim, Hyo K.; Kim, Seung Hoon; Lee, Won Jae; Kim, Min Ju; Lee, Ji Yeon; Jeon, Yong Hwan; Lee, Jongmee; Lee, Soon Jin; Lim, Jae Hoon

    2005-01-01

    Purpose: To assess the utility of contrast-enhanced agent detection imaging (ADI) in the assessment of the therapeutic response to percutaneous radiofrequency (RF) ablation in patients with hepatocellular carcinoma (HCC). Materials and methods: Ninety patients with a total of 97 nodular HCCs (mean, 2.1 ± 1.3 cm; range, 1.0-5.0 cm) treated with percutaneous RF ablation under the ultrasound guidance were evaluated with contrast-enhanced ADI after receiving an intravenous bolus injection of a microbubble contrast agent (SH U 508A). We obtained serial contrast-enhanced ADI images during the time period from 15 to 90 s after the initiation of the bolus contrast injection. All of the patients underwent a follow-up four-phase helical CT at 1 month after RF ablation, which was then repeated at 2-4 month intervals during a period of at least 12 months. The results of the contrast-enhanced ADI were compared with those of the follow-up CT in terms of the presence or absence of residual unablated tumor and local tumor progression in the treated lesions. Results: On contrast-enhanced ADI, technical success was obtained in 94 (97%) of the 97 HCCs, while residual unablated tumors were found in three HCCs (3%). Two of the three tumors that were suspicious (was not proven) for incomplete ablation were subjected to additional RF ablation. The remaining one enhancing lesion that was suspicious of a residual tumor on contrast-enhanced ADI was revealed to be reactive hyperemia at the 1-month follow-up CT. Therefore; the diagnostic concordance between the contrast-enhanced ADI and 1-month follow-up CT was 99%. Of the 94 ablated HCCs without residual tumors on both the contrast-enhanced ADI and 1-month follow-up CT after the initial RF ablation, five (5%) had CT findings of local tumor progression at a subsequent follow-up CT. Conclusion: Despite its limitations in predicting local tumor progression in the treated tumors, contrast-enhanced ADI is potentially useful for evaluating the

  10. Concanavalin A: A potential anti-neoplastic agent targeting apoptosis, autophagy and anti-angiogenesis for cancer therapeutics

    International Nuclear Information System (INIS)

    Li, Wen-wen; Yu, Jia-ying; Xu, Huai-long; Bao, Jin-ku

    2011-01-01

    Highlights: → ConA induces cancer cell death targeting apoptosis and autophagy. → ConA inhibits cancer cell angiogenesis. → ConA is utilized in pre-clinical and clinical trials. -- Abstract: Concanavalin A (ConA), a Ca 2+ /Mn 2+ -dependent and mannose/glucose-binding legume lectin, has drawn a rising attention for its remarkable anti-proliferative and anti-tumor activities to a variety of cancer cells. ConA induces programmed cell death via mitochondria-mediated, P73-Foxo1a-Bim apoptosis and BNIP3-mediated mitochondrial autophagy. Through IKK-NF-κB-COX-2, SHP-2-MEK-1-ERK, and SHP-2-Ras-ERK anti-angiogenic pathways, ConA would inhibit cancer cell survival. In addition, ConA stimulates cell immunity and generates an immune memory, resisting to the same genotypic tumor. These biological findings shed light on new perspectives of ConA as a potential anti-neoplastic agent targeting apoptosis, autophagy and anti-angiogenesis in pre-clinical or clinical trials for cancer therapeutics.

  11. Synthetic Curcumin Analogs as Inhibitors of β -Amyloid Peptide Aggregation: Potential Therapeutic and Diagnostic Agents for Alzheimer's Disease.

    Science.gov (United States)

    Bukhari, Syed Nasir Abbas; Jantan, Ibrahim

    2015-01-01

    There is a crucial need to develop new effective drugs for Alzheimer's disease (AD) as the currently available AD treatments provide only momentary and incomplete symptomatic relief. Amongst natural products, curcumin, a major constituent of turmeric, has been intensively investigated for its neuroprotective effect against β-amyloid (Aβ)-induced toxicity in cultured neuronal cells. The ability of curcumin to attach to Aβ peptide and prevent its accumulation is attributed to its three structural characteristics such as the presence of two aromatic end groups and their co-planarity, the length and rigidity of the linker region and the substitution conformation of these aromatics. However, curcumin failed to reach adequate brain levels after oral absorption in AD clinical trials due to its low water solubility and poor oral bioavailability. A number of new curcumin analogs that mimic the active site of the compound along with analogs that mimic the curcumin anti-amyloid effect combined with anticholinesterase effect have been developed to enhance the bioavailability, pharmacokinetics, water solubility, stability at physiological conditions and delivery of curcumin. In this article, we have summarized all reported synthetic analogs of curcumin showing effects on β-amyloid and discussed their potential as therapeutic and diagnostic agents for AD.

  12. Scientific Opinion on Review of the European Union Summary Report on trends and sources of zoonoses, zoonotic agents and food-borne outbreaks—Terms of reference 2 to 7

    OpenAIRE

    EFSA Panel on Animal Health and Welfare (AHAW)

    2013-01-01

    The Animal Health and Welfare (AHAW) Panel of the European Food Safety Authority (EFSA) has evaluated the European Union Summary Report on Trends and Sources of Zoonoses, Zoonotic Agents and Food-borne Outbreaks by EFSA and ECDC (the report) with regard to data needs and subsequent analyses that will minimise the impact of existing data gaps and inconsistencies. Specific assessments performed for bovine tuberculosis, echinococcosis, Q fever, brucellosis, rabies, cysticercosis and tularaemia s...

  13. Vector borne diseases

    OpenAIRE

    Melillo Fenech, Tanya

    2010-01-01

    A vector-borne disease is one in which the pathogenic microorganism is transmitted from an infected individual to another individual by an arthropod or other agent. The transmission depends upon the attributes and requirements of at least three different Iiving organisms : the pathologic agent which is either a virus, protozoa, bacteria or helminth (worm); the vector, which is commonly an arthropod such as ticks or mosquitoes; and the human host.

  14. Preparation of 125IUdR and its evaluation in animal tumour model as a potential therapeutic agent

    International Nuclear Information System (INIS)

    Korde, A.; Venkatesh, M.; Banerjee, S.; Pillai, M.R.A.; Sarma, H.D.

    1998-01-01

    5-Iodo-2'-deoxyuridine or iodoxyuridine (IUdR), an analogue of thymidine, is taken up by the proliferating cells during DNA synthesis. Radioiodinated IUdR is a potential therapeutic agent since radiohalogenated thymidine analogues are used for in-vivo tumour targeting and Auger electrons from radionuclides such as 123 I and 125 I are very effective in cell destruction when internalised. 125 IUdR was prepared and studied for its suitability as an in-vivo tumour therapy agent. 125 IUdR was prepared both by direct iodination of 2'-deoxyuridine and iododemercuration of 5-chloromercury-2'-deoxyuridine. Radioiodination yields were between 60-80% at pH 7. Iododemercuration was preferred since with direct iodination poor yields were observed when high specific activity product was desired and also the purification procedure was lengthier. The identity of 125 IUdR was established by comparison of TLC and HPLC patterns with those of authentic IUdR. The purified 125 IUdR had radiochemical purity >95% and was stable for 20 days at 4 deg. C and for a week at 23 deg. C and 37 deg. C. Bio-uptake of 125 IUdR was studied by injecting the tracer in tumour bearing mice (Sarcoma S-180). The uptake in tumour cells was 4.28 +- 2.7% per gram at 3 h and 1.48 +- 0.19% at 24 h post injection. In-vivo deiodination of the product was observed as seen by the uptake of the activity in the thyroid. About 40% the activity from all other organs was excreted in 70 h. The optimum time for injection of the tracer for therapy was studied by observing the delay in tumour growth and survival rate in mice injected at 0,3,9 and 12 days after tumour induction. Injection of the tracer on the third day was found to be the most beneficial for retardation of tumour growth, while injection of the activity on the zeroth and ninth day had no effect. (author)

  15. In-silico analysis of heat shock protein 47 for identifying the novel therapeutic agents in the management of oral submucous fibrosis

    Directory of Open Access Journals (Sweden)

    Jayasankar P Pillai

    2014-01-01

    Conclusion: HSP47 can be a potential candidate to target, in order to control the production of abundance collagen in OSF. Hence, the binding sites of HSP47 with collagen are identified and some natural compounds with a potential to bind with these binding receptors are also recognized. These natural compounds might act as anti-HSP47 lead molecules in designing novel therapeutic agents for OSF, which are so far unavailable.

  16. pH Dependent Antimicrobial Peptides and Proteins, Their Mechanisms of Action and Potential as Therapeutic Agents

    Directory of Open Access Journals (Sweden)

    Erum Malik

    2016-11-01

    Full Text Available Antimicrobial peptides (AMPs are potent antibiotics of the innate immune system that have been extensively investigated as a potential solution to the global problem of infectious diseases caused by pathogenic microbes. A group of AMPs that are increasingly being reported are those that utilise pH dependent antimicrobial mechanisms, and here we review research into this area. This review shows that these antimicrobial molecules are produced by a diverse spectrum of creatures, including vertebrates and invertebrates, and are primarily cationic, although a number of anionic examples are known. Some of these molecules exhibit high pH optima for their antimicrobial activity but in most cases, these AMPs show activity against microbes that present low pH optima, which reflects the acidic pH generally found at their sites of action, particularly the skin. The modes of action used by these molecules are based on a number of major structure/function relationships, which include metal ion binding, changes to net charge and conformational plasticity, and primarily involve the protonation of histidine, aspartic acid and glutamic acid residues at low pH. The pH dependent activity of pore forming antimicrobial proteins involves mechanisms that generally differ fundamentally to those used by pH dependent AMPs, which can be described by the carpet, toroidal pore and barrel-stave pore models of membrane interaction. A number of pH dependent AMPs and antimicrobial proteins have been developed for medical purposes and have successfully completed clinical trials, including kappacins, LL-37, histatins and lactoferrin, along with a number of their derivatives. Major examples of the therapeutic application of these antimicrobial molecules include wound healing as well as the treatment of multiple cancers and infections due to viruses, bacteria and fungi. In general, these applications involve topical administration, such as the use of mouth washes, cream formulations

  17. [Tick borne diseases].

    Science.gov (United States)

    Holzer, B R

    2005-11-01

    It is known for many years that tick-borne diseases have worldwide a high economical impact on farming industry and veterinary medicine. But only in the last twenty years the importance of such diseases were notified in human medicine by the medical community and the public with emerging of the tick borne encephalitis virus and the description of Borrelia burgdorferi. It is often forgotten that many other infectious agents as bacteria, virus, Rickettsia or protozoa can be transmitted by ticks. Such diseases are rarely diagnosed in Europe either they are overlooked and misdiagnosed or they are connected with special professional activities. The development of new regions for tourism with different out door activities (adventure trips, trekking, hunting) leads to an exposure to different tick borne diseases, which are often misdiagnosed.

  18. MCM-41 mesoporous silica nanoparticles functionalized with aptamer and radiolabelled with 90Y and 159Gd as a potential therapeutic agent against colorectal cancer

    International Nuclear Information System (INIS)

    Ferreira, Carolina de Aguiar

    2014-01-01

    Colorectal cancer (CRC) is a malignancy that affects large intestine and rectum, and it is the most common malignancy of the gastrointestinal tract, the third most commonly diagnosed type of cancer in the world and the second leading cause of cancer-related death in the United States. Nowadays, available therapeutic procedures for this type of cancer are limited and ineffective. Conventional radiotherapy is not an often used approach in the treatment of CRC due to the fact that peristaltic movements hamper the targeting of ionizing radiation and this type of treatment is used as adjuvant and palliative to control symptoms. Therefore, surgical intervention is the primary therapeutic choice against this disease. Researches based on the combination of radioisotopes and nanostructured carriers systems have demonstrated significant results in improving the selectivity action as well as reducing the radiation dose into healthy tissues. MCM-41 mesoporous silica nanoparticles have unique characteristics such as high surface area and well-defined pore diameters making these nanoparticles an ideal candidate of therapeutic agent carrier. Thus, the objective of this work is to synthesize and characterize MCM-41 mesoporous silica nanoparticles conjugated with yttrium-90 and gadolinium-159 and evaluate this system as a potential therapeutic agent. The nanoparticles were synthesized via sol-gel method. The sample was characterized using FTIR, SAXS, PCS, Zeta Potential analysis, Thermal analysis, CHN elemental analysis, nitrogen adsorption, scanning and transmission electron microscopy. The ability to incorporate Y +3 and Gd +3 ion was determined in vitro using different ratios (1:1, 1:3, 1:5 v/v) of YCL 3 and Gd 2 O 3 and silica nanoparticles dispersed in saline, pH 7.4. The non-incorporated Y +3 and Gd +3 ions were removed by ultracentrifugation procedure and the concentration of ions in the supernatant was determined by ICP-AES. Cell viability was assessed by colorimetric MTT

  19. Radiological and physiological studies on the role of some therapeutic agents used for internal decontamination of radionuclides from male albino rats

    International Nuclear Information System (INIS)

    Mangood, S.A.

    2008-01-01

    With the earths increasing nuclear arsenal and the growing use of nuclear energy, the possibility of radiological accidents involving release of radioactive materials, internal contamination may consequently occurs via inhalation, ingestion or absorption of radioisotopes.Therefore, the present work was oriented to deal with four topics related to the internal decontamination of two of the most widely used isotopes, namely 134 Cs and 60 Co from contaminated rats:-In vitro study aimed to select agents that can strongly bind the two metal ions and elucidate the best conditions and the factors affecting this binding. The tested agents were bentonite, vermiculite and Prussian blue (PB). The sorption capacity of PB and vermiculite for both metal ions was high and equivalent to more than 10 11 Bq 137 Cs or 60 Co per gram sorbent. As bentonite has lower capacity to both isotopes, further in vivo experiments were performed with PB and vermiculite.-In vivo studies, via 5 groups of rats, devoted to investigate the kinetics of excretion of 134 Cs and/or 60 Co from contaminated rats. The biological half lives of excretion, excretion stages for both isotopes and the effect of route of entry on the excretion were estimated.-In vivo studies aimed to investigate the effectiveness of PB + vermiculite and CaDTPA as therapeutic agents for accelerating the elimination of 134 Cs and/or 60 Co from contaminated rats. The study was performed via 6 groups of rats given different regimes of therapy. The results showed the high efficiency of PB + vermiculite for accelerating elimination of 134 Cs and orally administrated 60 Co while CaDTPA succeeded in accelerating intraperitoneally administrated 60 Co. The study proved that oral administration of PB + vermiculite and injection with CaDTPA at the same time is very effective in accelerating elimination of both contaminants simultaneously.-The physiological studies aimed to evaluate the hazardous effects of 134 Cs and/or 60 Co incorporation and

  20. The Botulinum Toxin as a Therapeutic Agent: Molecular Structure and Mechanism of Action in Motor and Sensory Systems.

    Science.gov (United States)

    Kumar, Raj; Dhaliwal, Harkiran Preet; Kukreja, Roshan Vijay; Singh, Bal Ram

    2016-02-01

    Botulinum neurotoxin (BoNT) produced by Clostridium botulinum is the most potent molecule known to mankind. Higher potency of BoNT is attributed to several factors, including structural and functional uniqueness, target specificity, and longevity. Although BoNT is an extremely toxic molecule, it is now increasingly used for the treatment of disorders related to muscle hyperactivity and glandular hyperactivity. Weakening of muscles due to peripheral action of BoNT produces a therapeutic effect. Depending on the target tissue, BoNT can block the cholinergic neuromuscular or cholinergic autonomic innervation of exocrine glands and smooth muscles. In recent observations of the analgesic properties of BoNT, the toxin modifies the sensory feedback loop to the central nervous system. Differential effects of BoNT in excitatory and inhibitory neurons provide a unique therapeutic tool. In this review the authors briefly summarize the structure and mechanism of actions of BoNT on motor and sensory neurons to explain its therapeutic effects and future potential. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  1. TIE2-expressing macrophages limit the therapeutic efficacy of the vascular disrupting agent, combretastatin A4 phosphate in mice.

    OpenAIRE

    Welford, Abigail F.; Biziato, Daniela; Coffelt, Seth B.; Nucera, Silvia; Fisher, Matthew; Pucci, Ferdinando; Di Serio, Clelia; Naldini, Luigi; De Palma, Michele; Tozer, Gillian M.; Lewis, Claire E.

    2011-01-01

    Vascular-disrupting agents (VDAs) such as combretastatin A4 phosphate (CA4P) selectively disrupt blood vessels in tumors and induce tumor necrosis. However, tumors rapidly repopulate after treatment with such compounds. Here, we show that CA4P-induced vessel narrowing, hypoxia, and hemorrhagic necrosis in murine mammary tumors were accompanied by elevated tumor levels of the chemokine CXCL12 and infiltration by proangiogenic TIE2-expressing macrophages (TEMs). Inhibiting TEM recruitment to CA...

  2. Management of soil-borne diseases of organic vegetables

    Directory of Open Access Journals (Sweden)

    Shafique Hafiza Asma

    2016-07-01

    Full Text Available With the rising awareness of the adverse effects of chemical pesticides, people are looking for organically grown vegetables. Consumers are increasingly choosing organic foods due to the perception that they are healthier than those conventionally grown. Vegetable crops are vulnerable to a range of pathogenic organisms that reduce yield by killing the plant or damaging the product, thus making it unmarketable. Soil-borne diseases are among the major factors contributing to low yields of organic produce. Apart from chemical pesticides there are several methods that can be used to protect crops from soil-borne pathogens. These include the introduction of biocontrol agents against soil-borne plant pathogens, plants with therapeutic effects and organic soil amendments that stimulate antagonistic activities of microorganisms to soil-borne diseases. The decomposition of organic matter in soil also results in the accumulation of specific compounds that may be antifungal or nematicidal. With the growing interest in organic vegetables, it is necessary to find non chemical means of plant disease control. This review describes the impact of soil-borne diseases on organic vegetables and methods used for their control.

  3. Targeting activator protein 1 signaling pathway by bioactive natural agents: Possible therapeutic strategy for cancer prevention and intervention.

    Science.gov (United States)

    Tewari, Devesh; Nabavi, Seyed Fazel; Nabavi, Seyed Mohammad; Sureda, Antoni; Farooqi, Ammad Ahmad; Atanasov, Atanas G; Vacca, Rosa Anna; Sethi, Gautam; Bishayee, Anupam

    2018-02-01

    Activator protein 1 (AP-1) is a key transcription factor in the control of several cellular processes responsible for cell survival proliferation and differentiation. Dysfunctional AP-1 expression and activity are involved in several severe diseases, especially inflammatory disorders and cancer. Therefore, targeting AP-1 has recently emerged as an attractive therapeutic strategy for cancer prevention and therapy. This review summarizes our current understanding of AP-1 biology and function as well as explores and discusses several natural bioactive compounds modulating AP-1-associated signaling pathways for cancer prevention and intervention. Current limitations, challenges, and future directions of research are also critically discussed. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Development of a series of aryl pyrimidine kynurenine monooxygenase inhibitors as potential therapeutic agents for the treatment of Huntington's disease.

    Science.gov (United States)

    Toledo-Sherman, Leticia M; Prime, Michael E; Mrzljak, Ladislav; Beconi, Maria G; Beresford, Alan; Brookfield, Frederick A; Brown, Christopher J; Cardaun, Isabell; Courtney, Stephen M; Dijkman, Ulrike; Hamelin-Flegg, Estelle; Johnson, Peter D; Kempf, Valerie; Lyons, Kathy; Matthews, Kimberly; Mitchell, William L; O'Connell, Catherine; Pena, Paula; Powell, Kendall; Rassoulpour, Arash; Reed, Laura; Reindl, Wolfgang; Selvaratnam, Suganathan; Friley, Weslyn Ward; Weddell, Derek A; Went, Naomi E; Wheelan, Patricia; Winkler, Christin; Winkler, Dirk; Wityak, John; Yarnold, Christopher J; Yates, Dawn; Munoz-Sanjuan, Ignacio; Dominguez, Celia

    2015-02-12

    We report on the development of a series of pyrimidine carboxylic acids that are potent and selective inhibitors of kynurenine monooxygenase and competitive for kynurenine. We describe the SAR for this novel series and report on their inhibition of KMO activity in biochemical and cellular assays and their selectivity against other kynurenine pathway enzymes. We describe the optimization process that led to the identification of a program lead compound with a suitable ADME/PK profile for therapeutic development. We demonstrate that systemic inhibition of KMO in vivo with this lead compound provides pharmacodynamic evidence for modulation of kynurenine pathway metabolites both in the periphery and in the central nervous system.

  5. Potential Therapeutic Effects of Curcumin, the Anti-inflammatory Agent, Against Neurodegenerative, Cardiovascular, Pulmonary, Metabolic, Autoimmune and Neoplastic Diseases

    Science.gov (United States)

    Aggarwal, Bharat B.; Harikumar, Kuzhuvelil B.

    2009-01-01

    Although safe in most cases, ancient treatments are ignored because neither their active component nor their molecular targets are well defined. This is not the case, however, with curcumin, a yellow-pigment substance and component of turmeric (Curcuma longa), which was identified more than a century ago. For centuries it has been known that turmeric exhibits anti-inflammatory activity, but extensive research performed within the past two decades has shown that the this activity of turmeric is due to curcumin, a diferuloylmethane. This agent has been shown to regulate numerous transcription factors, cytokines, protein kinases, adhesion molecules, redox status and enzymes that have been linked to inflammation. The process of inflammation has been shown to play a major role in most chronic illnesses, including neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases. In the current review, we provide evidence for the potential role of curcumin in the prevention and treatment of various pro-inflammatory chronic diseases. These features, combined with the pharmacological safety and negligible cost, render curcumin an attractive agent to explore further. PMID:18662800

  6. Small molecule inhibitor screening identifified HSP90 inhibitor 17-AAG as potential therapeutic agent for gallbladder cancer.

    Science.gov (United States)

    Weber, Helga; Valbuena, José R; Barbhuiya, Mustafa A; Stein, Stefan; Kunkel, Hana; García, Patricia; Bizama, Carolina; Riquelme, Ismael; Espinoza, Jaime A; Kurtz, Stephen E; Tyner, Jeffrey W; Calderon, Juan Francisco; Corvalán, Alejandro H; Grez, Manuel; Pandey, Akhilesh; Leal-Rojas, Pamela; Roa, Juan C

    2017-04-18

    Gallbladder cancer (GBC) is a lethal cancer with poor prognosis associated with high invasiveness and poor response to chemotherapy and radiotherapy. New therapeutic approaches are urgently needed in order to improve survival and response rates of GBC patients. We screened 130 small molecule inhibitors on a panel of seven GBC cell lines and identified the HSP90 inhibitor 17-AAG as one of the most potent inhibitory drugs across the different lines. We tested the antitumor efficacy of 17-AAG and geldanamycin (GA) in vitro and in a subcutaneous preclinical tumor model NOD-SCID mice. We also evaluated the expression of HSP90 by immunohistochemistry in human GBC tumors.In vitro assays showed that 17-AAG and GA significantly reduced the expression of HSP90 target proteins, including EGFR, AKT, phospho-AKT, Cyclin B1, phospho-ERK and Cyclin D1. These molecular changes were consistent with reduced cell viability and cell migration and promotion of G2/M cell cycle arrest and apoptosis observed in our in vitro studies.In vivo, 17-AAG showed efficacy in reducing subcutaneous tumors size, exhibiting a 69.6% reduction in tumor size in the treatment group compared to control mice (p < 0.05).The HSP90 immunohistochemical staining was seen in 182/209 cases of GBC (87%) and it was strongly expressed in 70 cases (33%), moderately in 58 cases (28%), and weakly in 54 cases (26%).Our pre-clinical observations strongly suggest that the inhibition of HSP90 function by HSP90 inhibitors is a promising therapeutic strategy for gallbladder cancer that may benefit from new HSP90 inhibitors currently in development.

  7. Becoming Therapeutic Agents: A Grounded Theory of Mothers' Process When Implementing Cognitive Behavioural Therapy at Home with an Anxious Child.

    Science.gov (United States)

    Pishva, Rana

    2017-05-01

    The premise of parent-centred programmes for parents of anxious children is to educate and train caregivers in the sustainable implementation of cognitive behaviour therapy (CBT) in the home. The existing operationalization of parent involvement, however, does not address the systemic, parent or child factors that could influence this process. The qualitative approach of grounded theory was employed to examine patterns of action and interaction involved in the complex process of carrying out CBT with one's child in one's home. A grounded theory goes beyond the description of a process, offering an explanatory theory that brings taken-for-granted meanings and processes to the surface. The theory that emerged from the analysis suggests that CBT implementation by mothers of anxious children is characterized by the evolution of mothers' perception of their child and mothers' perception of their role as well as a shift from reacting with emotion to responding pragmatically to the child. Changes occur as mothers recognize the crisis, make links between the treatment rationale, child's symptoms and their own parenting strategies, integrate tenets of CBT for anxiety and eventually focus on sustaining therapeutic gains through natural life transitions. The theory widens our understanding of mothers' role, therapeutic engagement, process, and decision-making. The theory also generates new hypotheses regarding parent involvement in the treatment of paediatric anxiety disorders and proposes novel research avenues that aim to maximize the benefits of parental involvement in the treatment of paediatric anxiety disorders. Copyright © 2016 John Wiley & Sons, Ltd. Mothers of anxious youth who take part in parent-centred programmes experience a shift in their perception of the child and of their role. Parental strategy after CBT implementation shifts from emotional empathy to cognitive empathy. Mothers experience significant challenges and require additional support in prevention

  8. Indications and patterns of therapeutic use of antimicrobial agents in the Danish pig production from 2002 to 2008

    DEFF Research Database (Denmark)

    Jensen, Vibeke Frøkjær; Emborg, Hanne-Dorthe; Aarestrup, Frank Møller

    2011-01-01

    This study describes trends in the use and indications for prescriptions of antimicrobial agents in the Danish pig production in the period between 2002 and 2008 and is the first description of a complete prescription pattern for one animal species in an entire country. Data on all prescription...... for pigs in Denmark were retrieved from the VetStat database. Antimicrobial use was measured in defined animal daily doses (ADD) for the specific age-group and in ADDkg as a measure of amounts used. According to the results of the ADDkg data, 26% of all antimicrobials were prescribed for sows, 38....../piglets, by 141% for weaning pigs, and by 81% for finisher pig. The most commonly used class of antibiotics was tetracycline for all age-groups, replacing the previously used macrolide/lincosamide group. The use of pleuromutilin increased in 2008 to the level of macrolides. In sow/piglets, the second most used...

  9. TIE2-expressing macrophages limit the therapeutic efficacy of the vascular-disrupting agent combretastatin A4 phosphate in mice

    Science.gov (United States)

    Welford, Abigail F.; Biziato, Daniela; Coffelt, Seth B.; Nucera, Silvia; Fisher, Matthew; Pucci, Ferdinando; Di Serio, Clelia; Naldini, Luigi; De Palma, Michele; Tozer, Gillian M.; Lewis, Claire E.

    2011-01-01

    Vascular-disrupting agents (VDAs) such as combretastatin A4 phosphate (CA4P) selectively disrupt blood vessels in tumors and induce tumor necrosis. However, tumors rapidly repopulate after treatment with such compounds. Here, we show that CA4P-induced vessel narrowing, hypoxia, and hemorrhagic necrosis in murine mammary tumors were accompanied by elevated tumor levels of the chemokine CXCL12 and infiltration by proangiogenic TIE2-expressing macrophages (TEMs). Inhibiting TEM recruitment to CA4P-treated tumors either by interfering pharmacologically with the CXCL12/CXCR4 axis or by genetically depleting TEMs in tumor-bearing mice markedly increased the efficacy of CA4P treatment. These data suggest that TEMs limit VDA-induced tumor injury and represent a potential target for improving the clinical efficacy of VDA-based therapies. PMID:21490397

  10. Evaluation of 188Re-labeled PEGylated nanoliposome as a radionuclide therapeutic agent in an orthotopic glioma-bearing rat model

    Directory of Open Access Journals (Sweden)

    Huang FYJ

    2015-01-01

    Full Text Available Feng-Yun J Huang,1 Te-Wei Lee,2 Chih-Hsien Chang,2 Liang-Cheng Chen,2 Wei-Hsin Hsu,2 Chien-Wen Chang,1 Jem-Mau Lo1 1Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, Taiwan; 2Institute of Nuclear Energy Research, Longtan, Taiwan Purpose: In this study, the 188Re-labeled PEGylated nanoliposome (188Re-liposome was prepared and evaluated as a therapeutic agent for glioma.Materials and methods: The reporter cell line, F98luc was prepared via Lentivector expression kit system and used to set up the orthotopic glioma-bearing rat model for non-invasive bioluminescent imaging. The maximum tolerated dose applicable in Fischer344 rats was explored via body weight monitoring of the rats after single intravenous injection of 188Re-liposome with varying dosages before the treatment study. The OLINDA/EXM 1.1 software was utilized for estimating the radiation dosimetry. To assess the therapeutic efficacy, tumor-bearing rats were intravenously administered 188Re-liposome or normal saline followed by monitoring of the tumor growth and animal survival time. In addition, the histopathological examinations of tumors were conducted on the 188Re-liposome-treated rats.Results: By using bioluminescent imaging, the well-established reporter cell line (F98luc showed a high relationship between cell number and its bioluminescent intensity (R2=0.99 in vitro; furthermore, it could also provide clear tumor imaging for monitoring tumor growth in vivo. The maximum tolerated dose of 188Re-liposome in Fischer344 rats was estimated to be 333 MBq. According to the dosimetry results, higher equivalent doses were observed in spleen and kidneys while very less were in normal brain, red marrow, and thyroid. For therapeutic efficacy study, the progression of tumor growth in terms of tumor volume and/or tumor weight was significantly slower for the 188Re-liposome-treated group than the control group (P<0.05. As a result, the

  11. STAT3 inhibitor WP1066 as a novel therapeutic agent for bCCI neuropathic pain rats.

    Science.gov (United States)

    Xue, Zhao-Jing; Shen, Le; Wang, Zhi-Yao; Hui, Shang-Yi; Huang, Yu-Guang; Ma, Chao

    2014-10-02

    Activation of signal transducer and activator of transcription-3 (STAT3) is suggested to be critically involved in the development of chronic pain, but the complex regulation of STAT3-dependent pathway and the functional significance of inhibiting this pathway during the development of neuropathic pain remain elusive. To evaluate the contribution of the JAK2/STAT3 pathway to neuropathic pain and the potentiality of this pathway as a novel therapeutic target, we examined the effects of the STAT3 inhibitor WP1066 by intrathecal administration in a rat model of bilateral chronic constriction injury (bCCI). The pain behavior tests were performed before the surgery and on postoperative day 3, 7, 14 and 21. L4-L6 dorsal spinal cord were harvested at each time point. Both RT-PCR and Western blot were performed to evaluate the activation of JAK2/STAT3 pathway. To observe the influence of WP1066 on neuropathic pain and its molecular mechanism, WP1066 (10 μl, 10 mmol/L in DMSO) or the same capacity of DMSO as the control were applied through the intrathecal tube on the day before bCCI surgery, and on the postoperative day 3 and 5. Behavioral tests were performed to observe the therapeutic effect on mechanical, thermal and cold hyperalgesia. L4-L6 dorsal spinal cord was harvested on postoperative day fourteen, followed by RT-PCR and Western blot evaluation of the JAK2/STAT3 pathway activation. The mechanical, thermal and cold hyperalgesia of the bCCI rats were significantly decreased when compared with the Sham or the Naïve group at each postoperative time point (PbCCI rats, accompanied by SOCS3 mRNA with a similar tendency. Western blot analysis showed that JAK2 and phosphorylated STAT3 increased significantly since 3 days after bCCI. JAK2 peaked on postoperative day 14 while phosphorylated STAT3 peaked on postoperative day 7 and gradually decreased thereafter and SOCS3׳s peak level on postoperative day 3. When WP1066 were administered intrathecally, the pain behaviors of

  12. Vector-borne diseases

    DEFF Research Database (Denmark)

    More, Simon J.; Bicout, Dominique; Bøtner, Anette

    2017-01-01

    After a request from the Europea n Commission, EFSA’s Panel on Animal Health and Welfaresummarised the main characteristics of 36 vector-borne disease s (VBDs) in 36 web-based storymaps.The risk of introduction in the EU through movement of livestock or pets was assessed for eac h of the36 VBDs......-agents for which the rate of introduction wasestimated to be very low, no further asse ssments were made. Due to the uncertainty related to someparameters used for the risk assessment or the instable or unpredictability disease situation in some ofthe source regions, it is recommended to update the assessment when...

  13. Prediction of a Therapeutic Dose for Buagafuran, a Potent Anxiolytic Agent by Physiologically Based Pharmacokinetic/Pharmacodynamic Modeling Starting from Pharmacokinetics in Rats and Human

    Directory of Open Access Journals (Sweden)

    Fen Yang

    2017-10-01

    Full Text Available Physiologically based pharmacokinetic (PBPK/pharmacodynamic (PD models can contribute to animal-to-human extrapolation and therapeutic dose predictions. Buagafuran is a novel anxiolytic agent and phase I clinical trials of buagafuran have been completed. In this paper, a potentially effective dose for buagafuran of 30 mg t.i.d. in human was estimated based on the human brain concentration predicted by a PBPK/PD modeling. The software GastroPlusTM was used to build the PBPK/PD model for buagafuran in rat which related the brain tissue concentrations of buagafuran and the times of animals entering the open arms in the pharmacological model of elevated plus-maze. Buagafuran concentrations in human plasma were fitted and brain tissue concentrations were predicted by using a human PBPK model in which the predicted plasma profiles were in good agreement with observations. The results provided supportive data for the rational use of buagafuran in clinic.

  14. Multi-Targeting Andrographolide, a Novel NF-κB Inhibitor, as a Potential Therapeutic Agent for Stroke.

    Science.gov (United States)

    Yang, Chih-Hao; Yen, Ting-Lin; Hsu, Chia-Yuan; Thomas, Philip-Aloysius; Sheu, Joen-Rong; Jayakumar, Thanasekaran

    2017-07-27

    A key focus in the field of drug discovery has been motivated by the neuroprotection of natural compounds. Cerebral ischemia is a multifaceted pathological process with a series of mechanisms, and a perspective for the development of neuroprotectants from traditional herbal medicine or natural products is a promising treatment for this disease. Natural compounds with the effects of anti-oxidation, anti-inflammation, anti-apoptosis, and neurofunctional regulation exhibit therapeutic effects on experimental ischemic brain injury. Conferring to the pharmacological mechanisms underlying neuroprotection, a study found that androgapholide, a diterpene lactone compound, exhibits varying degrees of neuroprotective activities in both in vitro and in vivo experimental models of stroke. The neuroprotective mechanisms of andrographolide are suggested as: (I) increasing nuclear factor E2-related factor 2-heme oxygenase (Nrf2-HO-1) expression through p38-mitogen activated protein kinase (MAPK) regulation, (II) inducing cerebral endothelial cells (CEC) apoptosis and caspase-3 activation, (III) down regulating Bax, inducible nitric oxide synthase (iNOS), and (IV) inhibiting hydroxyl radical (OH - ) formation, and activating transcription factor NF-κB signaling pathways. Recently, several researchers have also been trying to unveil the principal mechanisms involved in the neuroprotective effects of andrographolide. Therefore, this review aims to summarize an overview on the neuroprotective effects of andrographolide and exemplifies the essential mechanisms involved. This paper can provide information that andrographolide drug discovery may be a promising strategy for the development of a novel class of neuroprotective drug.

  15. Connective tissue growth factor acts as a therapeutic agent and predictor for peritoneal carcinomatosis of colorectal cancer.

    Science.gov (United States)

    Lin, Been-Ren; Chang, Cheng-Chi; Chen, Robert Jeen-Chen; Jeng, Yung-Ming; Liang, Jin-Tung; Lee, Po-Huang; Chang, King-Jen; Kuo, Min-Liang

    2011-05-15

    Here, we aimed to investigate the role of connective tissue growth factor (CTGF) in peritoneal carcinomatosis (PC) associated with colorectal cancer (CRC) and to characterize the underlying mechanism of CTGF mediating adhesion. A cohort of 136 CRC patient specimens was analyzed in this study. CRC cell lines were used for in vitro adhesion assay and in vivo peritoneal dissemination experiment. Recombinant CTGF protein treatment, transfection of CTGF expression plasmids, and knockdown of CTGF expression in CRC cells were utilized to evaluate the integrin α5, which served as a target of CTGF in inhibiting peritoneal seeding. The analysis of CRC tissues revealed an inverse correlation between CTGF expression and prevalence of PC. Lower CTGF level in CRC patients was associated with higher peritoneal recurrence rate after surgery. Inducing CTGF expression in cancer cells resulted in decreased incidence of PC and increased rate of mice survival. The mice received intraperitoneal injection of recombinant CTGF protein simultaneously with cancer cells or following tumor formation; in both cases, peritoneal tumor dissemination was found to be effectively inhibited in the mouse model. Functional assay revealed that CTGF significantly decreased the CRC cell adhesion ability, and integrin α5 was confirmed by reverse transcriptase PCR and functional blocking assay as a downstream effector in the CTGF-mediated inhibition of CRC cell adhesion. CTGF acts as a molecular predictor of PC and could be a potential therapeutic target for the chemoprevention and treatment of PC in CRC patients. ©2011 AACR.

  16. Mononuclear Pd(II) complex as a new therapeutic agent: Synthesis, characterization, biological activity, spectral and DNA binding approaches

    Science.gov (United States)

    Saeidifar, Maryam; Mirzaei, Hamidreza; Ahmadi Nasab, Navid; Mansouri-Torshizi, Hassan

    2017-11-01

    The binding ability between a new water-soluble palladium(II) complex [Pd(bpy)(bez-dtc)]Cl (where bpy is 2,2‧-bipyridine and bez-dtc is benzyl dithiocarbamate), as an antitumor agent, and calf thymus DNA was evaluated using various physicochemical methods, such as UV-Vis absorption, Competitive fluorescence studies, viscosity measurement, zeta potential and circular dichroism (CD) spectroscopy. The Pd(II) complex was synthesized and characterized using elemental analysis, molar conductivity measurements, FT-IR, 1H NMR, 13C NMR and electronic spectra studies. The anticancer activity against HeLa cell lines demonstrated lower cytotoxicity than cisplatin. The binding constants and the thermodynamic parameters were determined at different temperatures (300 K, 310 K and 320 K) and shown that the complex can bind to DNA via electrostatic forces. Furthermore, this result was confirmed by the viscosity and zeta potential measurements. The CD spectral results demonstrated that the binding of Pd(II) complex to DNA induced conformational changes in DNA. We hope that these results will provide a basis for further studies and practical clinical use of anticancer drugs.

  17. A Thermally Stable Form of Bacterial Cocaine Esterase: A Potential Therapeutic Agent for Treatment of Cocaine Abuse

    Energy Technology Data Exchange (ETDEWEB)

    Brim, Remy L.; Nance, Mark R.; Youngstrom, Daniel W.; Narasimhan, Diwahar; Zhan, Chang-Guo; Tesmer, John J.G.; Sunahara, Roger K.; Woods, James H. (Michigan); (Michigan-Med); (Kentucky)

    2010-09-03

    Rhodococcal cocaine esterase (CocE) is an attractive potential treatment for both cocaine overdose and cocaine addiction. CocE directly degrades cocaine into inactive products, whereas traditional small-molecule approaches require blockade of the inhibitory action of cocaine on a diverse array of monoamine transporters and ion channels. The usefulness of wild-type (wt) cocaine esterase is hampered by its inactivation at 37 C. Herein, we characterize the most thermostable form of this enzyme to date, CocE-L169K/G173Q. In vitro kinetic analyses reveal that CocE-L169K/G173Q displays a half-life of 2.9 days at 37 C, which represents a 340-fold improvement over wt and is 15-fold greater than previously reported mutants. Crystallographic analyses of CocE-L169K/G173Q, determined at 1.6-{angstrom} resolution, suggest that stabilization involves enhanced domain-domain interactions involving van der Waals interactions and hydrogen bonding. In vivo rodent studies reveal that intravenous pretreatment with CocE-L169K/G173Q in mice provides protection from cocaine-induced lethality for longer time periods before cocaine administration than wt CocE. Furthermore, intravenous administration (pretreatment) of CocE-L169K/G173Q prevents self-administration of cocaine in a time-dependent manner. Termination of the in vivo effects of CoCE seems to be dependent on, but not proportional to, its clearance from plasma as its half-life is approximately 2.3 h and similar to that of wt CocE (2.2 h). Taken together these data suggest that CocE-L169K/G173Q possesses many of the properties of a biological therapeutic for treating cocaine abuse but requires additional development to improve its serum half-life.

  18. Co-culturing of Fungal Strains Against Botrytis cinerea as a Model for the Induction of Chemical Diversity and Therapeutic Agents

    Directory of Open Access Journals (Sweden)

    Olga Genilloud

    2017-04-01

    Full Text Available New fungal SMs (SMs have been successfully described to be produced by means of in vitro-simulated microbial community interactions. Co-culturing of fungi has proved to be an efficient way to induce cell–cell interactions that can promote the activation of cryptic pathways, frequently silent when the strains are grown in laboratory conditions. Filamentous fungi represent one of the most diverse microbial groups known to produce bioactive natural products. Triggering the production of novel antifungal compounds in fungi could respond to the current needs to fight health compromising pathogens and provide new therapeutic solutions. In this study, we have selected the fungus Botrytis cinerea as a model to establish microbial interactions with a large set of fungal strains related to ecosystems where they can coexist with this phytopathogen, and to generate a collection of extracts, obtained from their antagonic microbial interactions and potentially containing new bioactive compounds. The antifungal specificity of the extracts containing compounds induced after B. cinerea interaction was determined against two human fungal pathogens (Candida albicans and Aspergillus fumigatus and three phytopathogens (Colletotrichum acutatum, Fusarium proliferatum, and Magnaporthe grisea. In addition, their cytotoxicity was also evaluated against the human hepatocellular carcinoma cell line (HepG2. We have identified by LC-MS the production of a wide variety of known compounds induced from these fungal interactions, as well as novel molecules that support the potential of this approach to generate new chemical diversity and possible new therapeutic agents.

  19. Localized sequence-specific release of a chemopreventive agent and an anticancer drug in a time-controllable manner to enhance therapeutic efficacy.

    Science.gov (United States)

    Pan, Wen-Yu; Lin, Kun-Ju; Huang, Chieh-Cheng; Chiang, Wei-Lun; Lin, Yu-Jung; Lin, Wei-Chih; Chuang, Er-Yuan; Chang, Yen; Sung, Hsing-Wen

    2016-09-01

    Combination chemotherapy with multiple drugs commonly requires several injections on various schedules, and the probability that the drug molecules reach the diseased tissues at the proper time and effective therapeutic concentrations is very low. This work elucidates an injectable co-delivery system that is based on cationic liposomes that are adsorbed on anionic hollow microspheres (Lipos-HMs) via electrostatic interaction, from which the localized sequence-specific release of a chemopreventive agent (1,25(OH)2D3) and an anticancer drug (doxorubicin; DOX) can be thermally driven in a time-controllable manner by an externally applied high-frequency magnetic field (HFMF). Lipos-HMs can greatly promote the accumulation of reactive oxygen species (ROS) in tumor cells by reducing their cytoplasmic expression of an antioxidant enzyme (superoxide dismutase) by 1,25(OH)2D3, increasing the susceptibility of cancer cells to the cytotoxic action of DOX. In nude mice that bear xenograft tumors, treatment with Lipos-HMs under exposure to HFMF effectively inhibits tumor growth and is the most effective therapeutic intervention among all the investigated. These empirical results demonstrate that the synergistic anticancer effects of sequential release of 1,25(OH)2D3 and DOX from the Lipos-HMs may have potential for maximizing DOX cytotoxicity, supporting more effective cancer treatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Carbon Nanoparticles decorated with cupric oxide Nanoparticles prepared by laser ablation in liquid as an antibacterial therapeutic agent

    Science.gov (United States)

    Khashan, Khawla S.; Jabir, Majid S.; Abdulameer, Farah A.

    2018-03-01

    Carbon nanoparticles (CNPs) decorated with cupric oxide nanoparticles (CuO NPs) were prepared by laser ablation in water, and their antibacterial activity was examined. X-ray diffraction measurements demonstrated the presence of carbon phases and different CuO phases, and results were confirmed by Fourier transform infrared analysis. Energy- Dispersive spectra showed the presence of C, O, and Cu in the final product. Transmission electron micrographs revealed that the CNPs were 10-80 nm in size and spherical; after being decorated with CuO NPs, particles became 5-50 nm in size and uniform in shape. The absorption spectrum of decorated Nanoparticles indicated the appearance of a new peak at 254-264 nm in addition to the fundamental peak at 228 nm. We then examined the antibacterial activity of the decorated CNPs for both gram-negative and -positive bacteria using the agar-well-diffusion method. The mode of action was determined using acridine orange-ethidium bromide staining to detect reactive oxygen species, and bacterial morphological change was studied by scanning electron microscopy. Results showed that CNPs decorated with 43% CuO NPs had the highest antibacterial activity for gram-positive bacteria. The CNPs acted on the cytoplasmic membrane and nucleic acid of bacteria, which led to a loss of cell-wall integrity, increased cell-wall permeability, and nucleic acid damage. The results offer a novel way to synthesis Carbon nanoparticles decorated with cupric oxide nanoparticles and could use them as novel antibacterial agent in future for pharmaceutical and biomedical applications.

  1. Mir-34a mimics are potential therapeutic agents for p53-mutated and chemo-resistant brain tumour cells.

    Directory of Open Access Journals (Sweden)

    Yuen Ngan Fan

    Full Text Available Chemotherapeutic drug resistance and relapse remains a major challenge for paediatric (medulloblastoma and adult (glioblastoma brain tumour treatment. Medulloblastoma tumours and cell lines with mutations in the p53 signalling pathway have been shown to be specifically insensitive to DNA damaging agents. The aim of this study was to investigate the potential of triggering cell death in p53 mutated medulloblastoma cells by a direct activation of pro-death signalling downstream of p53 activation. Since non-coding microRNAs (miRNAs have the ability to fine tune the expression of a variety of target genes, orchestrating multiple downstream effects, we hypothesised that triggering the expression of a p53 target miRNA could induce cell death in chemo-resistant cells. Treatment with etoposide, increased miR-34a levels in a p53-dependent fashion and the level of miR-34a transcription was correlated with the cell sensitivity to etoposide. miR-34a activity was validated by measuring the expression levels of one of its well described target: the NADH dependent sirtuin1 (SIRT1. Whilst drugs directly targeting SIRT1, were potent to trigger cell death at high concentrations only, introduction of synthetic miR-34a mimics was able to induce cell death in p53 mutated medulloblastoma and glioblastoma cell lines. Our results show that the need of a functional p53 signaling pathway can be bypassed by direct activation of miR-34a in brain tumour cells.

  2. {sup 166} Ho-HA Evaluation as therapeutic agent for rheumatoid arthritis treatment; Evaluacion de {sup 166}Ho-Ha como agente terapeutico en el tratamiento de la artritis reumatoidea

    Energy Technology Data Exchange (ETDEWEB)

    Chandia, M; Errazu, X [Comision Chilena de Energia Nuclear, Santiago (Chile); Mendoza, P [Departamento de Medicina Nuclear, Hospital Militar, Santiago (Chile); Troncoso, F [Comision Chilena de Energia Nuclear, Santiago (Chile); Jofre, J; Sierralta, P [Departamento de Medicina Nuclear, Hospital Militar, Santiago (Chile)

    2003-01-01

    Aim: Rheumatoid arthritis is a limiting disease having, among its pathological features, the inflammation of synovial tissue with progressive and later destruction of the articulation. This lead to joint deformation and loss of its function, generating pain and reducing the mobility of the affected articulation. The aim was to evaluate {sup 166}Ho-Hydroxyapatite ({sup 166} Ho-HA) as potential radiopharmaceutical for the syntomatic treatment of chronic and acute arthritis Materials and Methods: {sup 166}Holmiun was produced by irradiation of Ho{sub 2}O{sub 3} at La Reina Research Reactor, Nuclear Chilean Energy Commission. Hydroxyapatite was in-house synthetized. Its labelling and quality controls follows the internationally accepted procedures. An antigen arthritis was induced to eight New Zealand rabbits with the {sup 166}Ho-HA radiochemical being administred thereafter in two dosage modalities (single and double). The compound therapeutic efficiency was evaluated based upon clinical improvement and images from the inflamated articulation using {sup 67}Ga citrate before and after {sup 166} Ho-HA injection. Results: The radiochemical purity of the innoculated compound was greater than 98% as measured under sterility conditions. Clinically, an inflamation reduction (2 cm), appetite improvement and general well being was observed. The {sup 166} Ho-HA distribution and localization was monitored using gamma camera images taken at 4 and 24 h. There was no evidence of extraarticular leakage. From the {sup 67}Ga citrate imaging, the acute group shows an overall improvement of well being corresponding to a lesser uptake at the inflamated articulation, regarding to the chronic group. The {sup 166}Ho-HA double dosis, compared to the single dosis, suggest a reduced uptake of {sup 67}Ga citrate at the inflamated tissue, meaning an increased therapeutic effect. Conclusions: {sup 166} Ho-HA is usefull as therapeutic agent for the syntomatic treatment of rheumatoideal arthritis

  3. Pharmacological prevention of reperfusion injury in acute myocardial infarction. A potential role for adenosine as a therapeutic agent.

    Science.gov (United States)

    Quintana, Miguel; Kahan, Thomas; Hjemdahl, Paul

    2004-01-01

    last years, three relatively large placebo-controlled clinical trials have been conducted: Acute Myocardial Infarction Study of Adenosine Trial (AMISTAD) I and II and Attenuation by Adenosine of Cardiac Complications (ATTACC). In the AMISTAD trials, the final infarct size was reduced and the LV systolic function was improved by adenosine treatment, mainly in patients with anterior MI localization. However, morbidity and mortality were not affected. In the ATTACC study, the LV systolic function was not affected by adenosine, however, trends towards improved survival were observed in patients with anterior MI localization. The possibility of obtaining a Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow in the infarct-related artery in up to 95% of patients with acute MI (increasing the occurrence of reperfusion injury) has turned back the interest towards the protection of myocardial cells from the impending ischemic and reperfusion injury in which adenosine alone or together with other cardio-protective agents may exert important clinical effects.

  4. The influence of polymeric excipients on the process of pharmaceutical availability of therapeutic agents from a model drug form. Part I. In formulations with controlled disintegration and release time.

    Science.gov (United States)

    Nachajski, Michal Jakub; Zgoda, Marian Mikołaj

    2010-01-01

    Pre-formulation research was conducted on the application of Ex. Echinaceae aq. siccum in the production of a quickly disintegrating suspension tablet, a lozenge with kariostatic sugar alcohols (mannitol, sorbitol), and, above all, a solid drug form with controlled release of therapeutic agents included in the extract. Morphological parameters of tablets obtained in the course of experiment were estimated and the profiles of the release (diffusion) ofhydrophilic therapeutic agents into model receptor fluids with varying values of osmolarity (0.1 mol HCl approximately 200 mOsm/l, hypotonic hydrating fluid approximately 143 mOsm/l, and compensatory paediatric fluid approximately 272 mOsm/l) were examined. The study focused on the technological problem of determining the effect of hydrogel Carbopol structure on the ordering of diffusion ofhydrophilic therapeutic agents from a model drug form (a tablet) into model fluids with variable osmolarity.

  5. A Multi-Host Agent-Based Model for a Zoonotic, Vector-Borne Disease. A Case Study on Trypanosomiasis in Eastern Province, Zambia.

    Directory of Open Access Journals (Sweden)

    Simon Alderton

    2016-12-01

    Full Text Available This paper presents a new agent-based model (ABM for investigating T. b. rhodesiense human African trypanosomiasis (rHAT disease dynamics, produced to aid a greater understanding of disease transmission, and essential for development of appropriate mitigation strategies.The ABM was developed to model rHAT incidence at a fine spatial scale along a 75 km transect in the Luangwa Valley, Zambia. The method offers a complementary approach to traditional compartmentalised modelling techniques, permitting incorporation of fine scale demographic data such as ethnicity, age and gender into the simulation.Through identification of possible spatial, demographic and behavioural characteristics which may have differing implications for rHAT risk in the region, the ABM produced output that could not be readily generated by other techniques. On average there were 1.99 (S.E. 0.245 human infections and 1.83 (S.E. 0.183 cattle infections per 6 month period. The model output identified that the approximate incidence rate (per 1000 person-years was lower amongst cattle owning households (0.079, S.E. 0.017, than those without cattle (0.134, S.E. 0.017. Immigrant tribes (e.g. Bemba I.R. = 0.353, S.E.0.155 and school-age children (e.g. 5-10 year old I.R. = 0.239, S.E. 0.041 were the most at-risk for acquiring infection. These findings have the potential to aid the targeting of future mitigation strategies.ABMs provide an alternative way of thinking about HAT and NTDs more generally, offering a solution to the investigation of local-scale questions, and which generate results that can be easily disseminated to those affected. The ABM can be used as a tool for scenario testing at an appropriate spatial scale to allow the design of logistically feasible mitigation strategies suggested by model output. This is of particular importance where resources are limited and management strategies are often pushed to the local scale.

  6. Rhodium complexes as therapeutic agents.

    Science.gov (United States)

    Ma, Dik-Lung; Wang, Modi; Mao, Zhifeng; Yang, Chao; Ng, Chan-Tat; Leung, Chung-Hang

    2016-02-21

    The landscape of inorganic medicinal chemistry has been dominated by the investigation of platinum, and to a lesser extent ruthenium, complexes over the past few decades. Recently, complexes based on other metal centers such as rhodium have attracted attention due to their tunable chemical and biological properties as well as distinct mechanisms of action. This perspective highlights recent examples of rhodium complexes that show diverse biological activities against various targets, including enzymes and protein-protein interactions.

  7. Early quantification of the therapeutic efficacy of the vascular disrupting agent, CKD-516, using dynamic contrast-enhanced ultrasonography in rabbit VX2 liver tumors

    Energy Technology Data Exchange (ETDEWEB)

    Joo, Ijin; Kim, Jung Hoon; Lee, Jeong Min; Choi, Jin Woo; Han, Joon Koo; Choi, Byung Ihn [Dept. of Radiology, Seoul National University Hospital, Seoul (Korea, Republic of)

    2014-03-15

    To evaluate the usefulness of dynamic contrast-enhanced ultrasonography (DCE-US) in the early quantification of hemodynamic change following administration of the vascular disrupting agent (VDA) CKD-516 using a rabbit VX2 liver tumor model. This study was approved by our institutional animal care and use committee. Eight VX2 liver-tumor-bearing rabbits were treated with intravenous CKD-516, and all underwent DCE-US using SonoVue before and again 2, 4, 6, and 24 hours following their treatment. The tumor perfusion parameters were obtained from the time-intensity curve of the DCE-US data. Repeated measures analysis of variance was performed to assess any significant change in tumor perfusion over time. Relative changes in the DCE-US parameters between the baseline and follow-up assessments were correlated with the relative changes in tumor size over the course of seven days using Pearson correlation. CKD-516 treatment resulted in significant changes in the DCE-US parameters, including the peak intensity, total area under the time-intensity curve (AUCtotal), and AUC during wash-out (AUCout) over time (P<0.05). Pairwise comparison tests revealed that the AUCtotal and AUC during wash-in (AUCin) seen on the two-hour follow-up were significantly lower than the baseline values (P<0.05). However, none of early changes in the DCE-US parameters until 24-hour follow-up showed a significant correlation with the relative changes in tumor size during seven days after CKD-516 treatment. Our results suggest that a novel VDA (CKD-516) can cause disruption of tumor perfusion as early as two hours after treatment and that the therapeutic effect of CKD-516 treatment can be effectively quantified using DCE-US.

  8. Evaluation of the therapeutic efficacy of high-intensity focused ultrasound ablation of hepatocellular carcinoma by three-dimensional sonography with a perflubutane-based contrast agent

    International Nuclear Information System (INIS)

    Numata, Kazushi; Fukuda, Hiroyuki; Ohto, Masao; Itou, Ryu; Nozaki, Akito; Kondou, Masaaki; Morimoto, Manabu; Karasawa, Eii; Tanaka, Katsuaki

    2010-01-01

    Objective: We performed contrast-enhanced three-dimensional sonography (CE 3D US) with a perflubutane-based contrast agent to immediately evaluate the completeness of ablation of small hepatocellular carcinoma (HCC) lesions by extracorporeal high-intensity focused ultrasound (HIFU). Subjects and methods: Twenty-one HCC lesions were treated by a single ultrasound-guided HIFU ablation session, and CE 3D US was performed before, immediately after, and 1 week, and 1 month after HIFU, and contrast-enhanced CT (CE CT) or contrast-enhanced MRI (CE MRI) was performed before HIFU, 1 week and 1 month after HIFU, and during the follow-up period. Results: Immediately and 1 month after HIFU, 17 lesions were evaluated as adequately ablated by CE 3D US, and the other 4 lesions as residual tumors. One month after HIFU, 18 were evaluated as adequately ablated by CE CT or CE MRI, and the other 3 as residual tumors. The evaluation by CE 3D US immediately after HIFU and by CE CT or CE MRI 1 month after HIFU was concordant with 20 lesions. The kappa value for agreement between the findings of CE 3D US and other modalities by two blinded observers was 0.83. When the 1-month CE CT or CE MRI findings were used as the reference standard, the sensitivity, specificity, and accuracy of CE 3D US immediately after HIFU for the diagnosis of the adequate ablation were 100%, 75%, and 95%, respectively. Conclusion: CE 3D US appears to be a useful method for immediate evaluation of therapeutic efficacy of HIFU ablation of HCC lesions.

  9. Evaluation of the therapeutic efficacy of high-intensity focused ultrasound ablation of hepatocellular carcinoma by three-dimensional sonography with a perflubutane-based contrast agent

    Energy Technology Data Exchange (ETDEWEB)

    Numata, Kazushi, E-mail: kz-numa@urahp.yokohama-cu.ac.j [Gastroenterological Center, Yokohama City University Medical Center, 4-57 Urafune-cho, Minami-ku, Yokohama, Kanagawa 232-0024 (Japan); Fukuda, Hiroyuki; Ohto, Masao; Itou, Ryu [Department of Internal Medicine, Naruto General Hospital, 167 Naruto, Sanbu, Chiba 289-1326 (Japan); Nozaki, Akito; Kondou, Masaaki; Morimoto, Manabu [Gastroenterological Center, Yokohama City University Medical Center, 4-57 Urafune-cho, Minami-ku, Yokohama, Kanagawa 232-0024 (Japan); Karasawa, Eii [Department of Gastroenterology, International University of Health and Welfare Atami Hospital, 13-1 Higashi Kaigan-cho, Atami, Shizuoka 413-0012 (Japan); Tanaka, Katsuaki [Gastroenterological Center, Yokohama City University Medical Center, 4-57 Urafune-cho, Minami-ku, Yokohama, Kanagawa 232-0024 (Japan)

    2010-08-15

    Objective: We performed contrast-enhanced three-dimensional sonography (CE 3D US) with a perflubutane-based contrast agent to immediately evaluate the completeness of ablation of small hepatocellular carcinoma (HCC) lesions by extracorporeal high-intensity focused ultrasound (HIFU). Subjects and methods: Twenty-one HCC lesions were treated by a single ultrasound-guided HIFU ablation session, and CE 3D US was performed before, immediately after, and 1 week, and 1 month after HIFU, and contrast-enhanced CT (CE CT) or contrast-enhanced MRI (CE MRI) was performed before HIFU, 1 week and 1 month after HIFU, and during the follow-up period. Results: Immediately and 1 month after HIFU, 17 lesions were evaluated as adequately ablated by CE 3D US, and the other 4 lesions as residual tumors. One month after HIFU, 18 were evaluated as adequately ablated by CE CT or CE MRI, and the other 3 as residual tumors. The evaluation by CE 3D US immediately after HIFU and by CE CT or CE MRI 1 month after HIFU was concordant with 20 lesions. The kappa value for agreement between the findings of CE 3D US and other modalities by two blinded observers was 0.83. When the 1-month CE CT or CE MRI findings were used as the reference standard, the sensitivity, specificity, and accuracy of CE 3D US immediately after HIFU for the diagnosis of the adequate ablation were 100%, 75%, and 95%, respectively. Conclusion: CE 3D US appears to be a useful method for immediate evaluation of therapeutic efficacy of HIFU ablation of HCC lesions.

  10. A stable explant culture of HER2/neu invasive carcinoma supported by alpha-Smooth Muscle Actin expressing stromal cells to evaluate therapeutic agents

    Directory of Open Access Journals (Sweden)

    Piechocki Marie P

    2008-04-01

    Full Text Available Abstract Background To gain a better understanding of the effects of therapeutic agents on the tumor microenvironment in invasive cancers, we developed a co-culture model from an invasive lobular carcinoma. Tumor cells expressing HER2/neu organize in nests surrounded by alpha-Smooth Muscle Actin (α-SMA expressing tumor stroma to resemble the morphology of an invading tumor. This co-culture, Mammary Adenocarcinoma Model (MAM-1 maintains a 1:1 ratio of HER2/neu positive tumor cells to α-SMA-reactive stromal cells and renews this configuration for over 20 passages in vitro. Methods We characterized the cellular elements of the MAM-1 model by microarray analysis, and immunocytochemistry. We developed flow cytometric assays to evaluate the relative responses of the tumor and stroma to the tyrosine kinase inhibitor, Iressa. Results The MAM-1 gene expression profile contains clusters that represent the ErbB-2 breast cancer signature and stroma-specific clusters associated with invasive breast cancers. The stability of this model and the ability to antigenically label the tumor and stromal fractions allowed us to determine the specificity of Iressa, a receptor tyrosine kinase inhibitor, for targeting the tumor cell population. Treatment resulted in a selective dose-dependent reduction in phospho-pMEK1/2 and pp44/42MAPK in tumor cells. Within 24 h the tumor cell fraction was reduced 1.9-fold while the stromal cell fraction increased >3-fold, consistent with specific reductions in phospho-pp44/42 MAPK, MEK1/2 and PCNA in tumor cells and reciprocal increases in the stromal cells. Erosion of the tumor cell nests and augmented growth of the stromal cells resembled a fibrotic response. Conclusion This model demonstrates the specificity of Iressa for HER2/neu expressing tumor cells versus the tumor associated myofibroblasts and is appropriate for delineating effects of therapy on signal transduction in the breast tumor microenvironment and improving

  11. A stable explant culture of HER2/neu invasive carcinoma supported by alpha-Smooth Muscle Actin expressing stromal cells to evaluate therapeutic agents

    International Nuclear Information System (INIS)

    Piechocki, Marie P

    2008-01-01

    To gain a better understanding of the effects of therapeutic agents on the tumor microenvironment in invasive cancers, we developed a co-culture model from an invasive lobular carcinoma. Tumor cells expressing HER2/neu organize in nests surrounded by alpha-Smooth Muscle Actin (α-SMA) expressing tumor stroma to resemble the morphology of an invading tumor. This co-culture, Mammary Adenocarcinoma Model (MAM-1) maintains a 1:1 ratio of HER2/neu positive tumor cells to α-SMA-reactive stromal cells and renews this configuration for over 20 passages in vitro. We characterized the cellular elements of the MAM-1 model by microarray analysis, and immunocytochemistry. We developed flow cytometric assays to evaluate the relative responses of the tumor and stroma to the tyrosine kinase inhibitor, Iressa. The MAM-1 gene expression profile contains clusters that represent the ErbB-2 breast cancer signature and stroma-specific clusters associated with invasive breast cancers. The stability of this model and the ability to antigenically label the tumor and stromal fractions allowed us to determine the specificity of Iressa, a receptor tyrosine kinase inhibitor, for targeting the tumor cell population. Treatment resulted in a selective dose-dependent reduction in phospho-pMEK1/2 and pp44/42MAPK in tumor cells. Within 24 h the tumor cell fraction was reduced 1.9-fold while the stromal cell fraction increased >3-fold, consistent with specific reductions in phospho-pp44/42 MAPK, MEK1/2 and PCNA in tumor cells and reciprocal increases in the stromal cells. Erosion of the tumor cell nests and augmented growth of the stromal cells resembled a fibrotic response. This model demonstrates the specificity of Iressa for HER2/neu expressing tumor cells versus the tumor associated myofibroblasts and is appropriate for delineating effects of therapy on signal transduction in the breast tumor microenvironment and improving strategies that can dually or differentially target the tumor and stromal

  12. Assessment of oxytetracycline baths as therapeutic treatment for the control of the agent of withering syndrome (WS) in red abalone (Haliotis rufescens).

    Science.gov (United States)

    Winkler, Federico M; García, Ricardo; Valdivia, María Vicenta; Lohrmann, Karin B

    2018-03-01

    Withering Syndrome (WS) is a lethal disease that affects abalone species in both wild and farmed populations. This infection, caused by the rickettsial-like intracellular organism (RLO) Candidatus Xenohaliotis californiensis, can severely impair the normal development of affected animals, and ultimately, their survival. The most common line of action against the WS has been the use of antibiotics, specifically oxytetracycline (OTC), administered via intramuscular injection and per os via medicated feed. In the present study, we have assessed the effectiveness of OTC baths as therapeutic treatment for the control of the WS agent in H. rufescens. Clinical signs of infection were monitored for 11 months in treated juveniles, in addition to feed consumption rate, growth patterns and gonad development. Abalones were asymptomatic until the end of the experiment, when a small number of non-treated animals exhibited clinical signs of infection. Gonad maturity was not observed. OTC treated animals grew significantly less than their non-treated counterparts, being 4.3% shorter and 13.6% lighter at the end of the experiment. They also displayed negative allometry, i.e. for the same shell length, they were lighter than non-treated groups. Furthermore, the weight of muscle and soft tissues in OTC treated animals was lighter than in the other groups, while no differences were found in shell weight. The feed consumption rate was the same for all groups, thus the observed growth patterns cannot be attributed to a decreased feed intake. One possible explanation is that antibiotic treatment may have impacted gut microflora, thus preventing efficient nutrient digestion and absorption and, indirectly, reducing growth. Prevalence of RLOs causing WS (WS-RLO) and the variant form (RLOv), infected with a bacteriophague and non virulent, were significantly lower in the OTC-treated group than in the other groups. Similar results were observed for the mean intensity of RLOv, while for WS

  13. To Investigate the Therapeutic Efforts of the COX-2 Inhibitor NS-398 as a Single Agent, and in Combination with Vitamin D, in Vitro and in Vivo

    National Research Council Canada - National Science Library

    Lee, Yi-Fen

    2008-01-01

    .... We have identified a cross-talk between vitamin D and COX-2 inhibitor, two chemopreventative agents for prostate cancer, and conducted series investigations of their anti-prostate cancer effects...

  14. [Tick-borne diseases].

    Science.gov (United States)

    Tissot Dupont, H; Raoult, D

    1993-05-01

    Due to their worldwide distribution, from hottest to coldest climates, and due to their behaviour, ticks are capable of transmitting numerous human and animal bacterial viral or parasitous diseases. Depending on the disease, they play the role of biological vector or intermediate host. In France, six tick borne diseases are of epidemiologic importance. Q fever (not often tick-borne), Mediterranean Spotted Fever, Lyme disease, Turalemia (human and animal), Babesiosis and Tick-borne Viral Encephalitis.

  15. Possíveis etapas na patogênese da cefaléia tensional e indicações de tratamento Tension headache: possible pathogenic stages and its relations with therapeutic agents

    Directory of Open Access Journals (Sweden)

    Ceme Ferreira Jordy

    1995-09-01

    Full Text Available Análise de resultados obtidos no estudo de uma série de 100 pacientes com diagnóstico de cefaléia tensional permitem sugerir 5 etapas de um processo fisiopatogênico implicado. Com base nesta sugestão, a indicação para o tratamento e respectiva eficácia, dependerão da etapa patogênica sobre a qual se pretenda fazer incidir a ação terapêutica.Five steps in the pathogenic process involved in the tension headache pathogenesis are suggested from a 100 patients clinical study. Therapeutic efficacy in the treatment of the tension headache is considered to be linked to the relation between the therapeutic agent and the stage in which it has focused its effect, in the pathogenic process.

  16. Evaluation of real-time data obtained from gravimetric preparation of antineoplastic agents shows medication errors with possible critical therapeutic impact: Results of a large-scale, multicentre, multinational, retrospective study.

    Science.gov (United States)

    Terkola, R; Czejka, M; Bérubé, J

    2017-08-01

    Medication errors are a significant cause of morbidity and mortality especially with antineoplastic drugs, owing to their narrow therapeutic index. Gravimetric workflow software systems have the potential to reduce volumetric errors during intravenous antineoplastic drug preparation which may occur when verification is reliant on visual inspection. Our aim was to detect medication errors with possible critical therapeutic impact as determined by the rate of prevented medication errors in chemotherapy compounding after implementation of gravimetric measurement. A large-scale, retrospective analysis of data was carried out, related to medication errors identified during preparation of antineoplastic drugs in 10 pharmacy services ("centres") in five European countries following the introduction of an intravenous workflow software gravimetric system. Errors were defined as errors in dose volumes outside tolerance levels, identified during weighing stages of preparation of chemotherapy solutions which would not otherwise have been detected by conventional visual inspection. The gravimetric system detected that 7.89% of the 759 060 doses of antineoplastic drugs prepared at participating centres between July 2011 and October 2015 had error levels outside the accepted tolerance range set by individual centres, and prevented these doses from reaching patients. The proportion of antineoplastic preparations with deviations >10% ranged from 0.49% to 5.04% across sites, with a mean of 2.25%. The proportion of preparations with deviations >20% ranged from 0.21% to 1.27% across sites, with a mean of 0.71%. There was considerable variation in error levels for different antineoplastic agents. Introduction of a gravimetric preparation system for antineoplastic agents detected and prevented dosing errors which would not have been recognized with traditional methods and could have resulted in toxicity or suboptimal therapeutic outcomes for patients undergoing anticancer treatment.

  17. Equine tick-borne infections in the Netherlands

    NARCIS (Netherlands)

    Butler, C.M.

    2012-01-01

    This thesis focuses on the emergence and establishment of equine tick-borne infections in the Netherlands, with particular attention to their diagnosis, clinical relevance and treatment. Four tick-borne agents (Borrelia burgdorferi, Theileria equi, Babesia caballi and Anaplasma phagocytophilum)

  18. The role of lipid and carbohydrate digestive enzyme inhibitors in the management of obesity: a review of current and emerging therapeutic agents

    Directory of Open Access Journals (Sweden)

    Tucci S

    2010-05-01

    Full Text Available Sonia A Tucci, Emma J Boyland, Jason CG HalfordKissileff Laboratory for the Study of Human Ingestive Behaviour, School of Psychology, University of Liverpool, Liverpool, UKAbstract: Obesity is a global epidemic associated with significant morbidity and mortality in adults and ill health in children. A proven successful approach in weight management has been the disruption of nutrient digestion, with orlistat having been used to treat obesity for the last 10 years. Although orlistat-induced weight loss remains modest, it produces meaningful reductions in risk factors for obesity-related conditions such as diabetes and cardiovascular disease. Moreover, this lipase inhibitor is free of the serious side effects that have dogged appetite-suppressing drugs. This success had driven investigation into new generation nutraceuticals, supplements and pharmaceutical agents that inhibit the breakdown of complex carbohydrates and fats within the gut. This review focuses on agents purported to inhibit intestinal enzymes responsible for macronutrient digestion. Except for some synthetic products, the majority of agents reviewed are either botanical extracts or bacterial products. Currently, carbohydrate digestion inhibitors are under development to improve glycemic control and these may also induce some weight loss. However, colonic fermentation induced side effects, such as excess gas production, remain an issue for these compounds. The α-glucosidase inhibitor acarbose, and the α-amylase inhibitor phaseolamine, have been used in humans with some promising results relating to weight loss. Nonetheless, few of these agents have made it into clinical studies and without any clinical proof of concept or proven efficacy it is unlikely any will enter the market soon.Keywords: lipase, amylase, saccharidases, overweight, orlistat, Alli®, digestion, body weight

  19. Synthetic miR-34a mimics as a novel therapeutic agent for multiple myeloma: in vitro and in vivo evidence.

    Science.gov (United States)

    Di Martino, Maria T; Leone, Emanuela; Amodio, Nicola; Foresta, Umberto; Lionetti, Marta; Pitari, Maria R; Cantafio, Maria E Gallo; Gullà, Annamaria; Conforti, Francesco; Morelli, Eugenio; Tomaino, Vera; Rossi, Marco; Negrini, Massimo; Ferrarini, Manlio; Caraglia, Michele; Shammas, Masood A; Munshi, Nikhil C; Anderson, Kenneth C; Neri, Antonino; Tagliaferri, Pierosandro; Tassone, Pierfrancesco

    2012-11-15

    Deregulated expression of miRNAs has been shown in multiple myeloma (MM). A promising strategy to achieve a therapeutic effect by targeting the miRNA regulatory network is to enforce the expression of miRNAs that act as tumor suppressor genes, such as miR-34a. Here, we investigated the therapeutic potential of synthetic miR-34a against human MM cells in vitro and in vivo. Either transient expression of miR-34a synthetic mimics or lentivirus-based miR-34a-stable enforced expression triggered growth inhibition and apoptosis in MM cells in vitro. Synthetic miR-34a downregulated canonic targets BCL2, CDK6, and NOTCH1 at both the mRNA and protein level. Lentiviral vector-transduced MM xenografts with constitutive miR-34a expression showed high growth inhibition in severe combined immunodeficient (SCID) mice. The anti-MM activity of lipidic-formulated miR-34a was further shown in vivo in two different experimental settings: (i) SCID mice bearing nontransduced MM xenografts; and (ii) SCID-synth-hu mice implanted with synthetic 3-dimensional scaffolds reconstituted with human bone marrow stromal cells and then engrafted with human MM cells. Relevant tumor growth inhibition and survival improvement were observed in mice bearing TP53-mutated MM xenografts treated with miR-34a mimics in the absence of systemic toxicity. Our findings provide a proof-of-principle that formulated synthetic miR-34a has therapeutic activity in preclinical models and support a framework for development of miR-34a-based treatment strategies in MM patients. ©2012 AACR.

  20. The influence of AT1002 on the nasal absorption of molecular weight markers and therapeutic agents when co-administered with bioadhesive polymers and an AT1002 antagonist, AT1001.

    Science.gov (United States)

    Song, Keon-Hyoung; Eddington, Natalie D

    2012-01-01

    The purpose of this study was to demonstrate the effects of the tight junction permeation enhancer, AT1002, on the nasal absorption of molecular weight markers and low bioavailable therapeutic agents co-administered with bioadhesive polymers or zonulin antagonist. The bioadhesive polymers, carrageenan and Na-CMC, were prepared with AT1002 to examine the permeation-enhancing effect of AT1002 on the nasal absorption of inulin, calcitonin and saquinavir after nasal administration to Sprague-Dawley rats. Blood samples were collected over a 6-hour period from a jugular cannula. In addition, we determined whether AT1002 exerts a permeation-enhancing effect via activation of PAR-2 specific binding to a putative receptor of zonulin. To examine this zonulin antagonist, AT1001, was administered 30 min prior to dosing with an AT1002/inulin solution and blood samples were collected over a 6-hour period. The bioadhesive polymers did not directly increase the absorption of inulin, calcitonin and saquinavir, but promoted the permeation-enhancing effect of AT1002 when delivered nasally, thereby significantly increasing the absorption of each drug. Pre-treatment with AT1001 antagonized the zonulin receptor and significantly minimized the permeation-enhancing effect of AT1002. These findings will assist in understanding the permeation-enhancing capability of and the receptor binding of AT1002. Further, combining AT1002 with carrageenan supports the development of the mucosal delivery of therapeutic agents that have low bioavailability even with bioadhesive agents. © 2011 The Authors. JPP © 2011 Royal Pharmaceutical Society.

  1. Development of oral agent in the treatment of multiple sclerosis: how the first available oral therapy, Fingolimod will change therapeutic paradigm approach

    Directory of Open Access Journals (Sweden)

    Gasperini C

    2012-07-01

    Full Text Available Claudio Gasperini,1 Serena Ruggieri21Department of Neurosciences, S Camillo Forlanini Hospital, 2Department of Neurology and Psychiatry, University of Rome “Sapienza,” Rome, ItalyAbstract: Multiple sclerosis (MS is a chronic inflammatory disorder of the central nervous system, traditionally considered to be an autoimmune, demyelinating disease. Based on this understanding, the initial therapeutic strategies were directed at immune modulation and inflammation control. At present, there are five licensed first-line disease-modifying drugs and two second-line treatments in MS. Currently available MS therapies have shown significant efficacy throughout many trials, but they produce different side-effect profiles in patients. Since they are well known and safe, they require regular and frequent parenteral administration and are associated with limited long-term treatment adherence. Thus, there is an important need for the development of new therapeutic strategies. Several oral compounds are in late-stage development for treating MS. Fingolimod (FTY720; Novartis, Basel, Switzerland is an oral sphingosine-1-phosphase receptor modulator which has demonstrated superior efficacy compared with placebo and interferon β-1a in Phase III studies and has been approved in the treatment of MS. We summarily review the oral compounds in study, focusing on the recent development, approval and the clinical experience with FTY720.Keywords: multiple sclerosis, oral compounds, fingolimod, fty720, sphingosine 1, phosphate, patient satisfaction

  2. Innovative Born Globals

    DEFF Research Database (Denmark)

    Kraus, Sascha; Brem, Alexander; Muench, Miriam

    2017-01-01

    Internationalization is a hot topic in innovation management, whereby the phenomenon of “Born Globals” is still limited to research in the domains of Entrepreneurship and International Management. As business model design plays a key role for Born Globals, we link these two concepts. For this, we...... propose hypotheses about the influence of efficiency-centered and novelty-entered business model design on international firm performance. To test these hypotheses, we performed a quantitative survey with 252 founders of international companies in Germany, Switzerland and Liechtenstein. Additionally, we...... gained further insights through a case study analysis of 11 Born Globals. The results show that business model design matters to international firm performance and the business model design of Born Globals tends to be more efficiency-centered. Based on a multiple case study, we analyzed business models...

  3. A born dreamer

    Indian Academy of Sciences (India)

    Lawrence

    encouraged me to believe that education was the only way to fulfil one's dreams ... liant student, financial constraints prevented him from pursuing. A born ... higher education. .... to fulfil one's dream despite difficulties, which women face. How-.

  4. Treatment outcomes regarding the addition of targeted agents in the therapeutic portfolio for stage II-III rectal cancer undergoing neoadjuvant chemoradiation.

    Science.gov (United States)

    Liang, Jin-Tung; Chen, Tzu-Chun; Huang, John; Jeng, Yung-Ming; Cheng, Jason Chia-Hsien

    2017-11-24

    To evaluate the impact of targeted agents in stage II-III rectal cancer undergoing neoadjuvant concurrent chemoradiation therapy (CCRT). A retrospective study was performed in 124 consecutive patients with clinically T 3 N 0-2 M 0 -staged rectal cancer incorporating targeted agents in CCRT. Pathologic complete response was detected in 34.2% (n=26) of bevacizumab+FOLFOX-treated patients (n=76), which was significantly higher (p=0.019, post-hoc statistical power =35.87%) than that (n=10, 20.8%) of the cetuximab+FOLFOX-treated patients (n=48). Patients receiving cetuximab+FOLFOX therapy tended to develop severe liver toxicity (91.7%, n=44 versus 17.1%, n=13, panalysis within bevacizumab+FOLFOX-treated patients with either wild-type (n=36) or mutant (n=40) K-ras status indicated K-ras status did not significantly influence the treatment outcomes. The addition of bevacizumab instead of cetuximab to FOLFOX in the neoadjuvant settings for T 3 N 0-2 M 0 -staged rectal cancer could induce a promising rate of pathologic complete response and lesser hepatotoxicity.

  5. Supramolecular interaction of 6-shogaol, a therapeutic agent of Zingiber officinale with human serum albumin as elucidated by spectroscopic, calorimetric and molecular docking methods.

    Science.gov (United States)

    Feroz, S R; Mohamad, S B; Lee, G S; Malek, S N A; Tayyab, S

    2015-06-01

    6-Shogaol, one of the main bioactive constituents of Zingiber officinale has been shown to possess various therapeutic properties. Interaction of a therapeutic compound with plasma proteins greatly affects its pharmacokinetic and pharmacodynamic properties. The present investigation was undertaken to characterize the interaction between 6-shogaol and the main in vivo transporter, human serum albumin (HSA). Various binding characteristics of 6-shogaol-HSA interaction were studied using fluorescence spectroscopy. Thermal stability of 6-shogaol-HSA system was determined by circular dichroism (CD) and differential scanning calorimetric (DSC) techniques. Identification of the 6-shogaol binding site on HSA was made by competitive drug displacement and molecular docking experiments. Fluorescence quench titration results revealed the association constant, Ka of 6-shogaol-HSA interaction as 6.29 ± 0.33 × 10(4) M(-1) at 25 ºC. Values of the enthalpy change (-11.76 kJ mol(-1)) and the entropy change (52.52 J mol(-1) K(-1)), obtained for the binding reaction suggested involvement of hydrophobic and van der Waals forces along with hydrogen bonds in the complex formation. Higher thermal stability of HSA was noticed in the presence of 6-shogaol, as revealed by DSC and thermal denaturation profiles. Competitive ligand displacement experiments along with molecular docking results suggested the binding preference of 6-shogaol for Sudlow's site I of HSA. All these results suggest that 6-shogaol binds to Sudlow's site I of HSA through moderate binding affinity and involves hydrophobic and van der Waals forces along with hydrogen bonds. Copyright © 2015 Elsevier GmbH. All rights reserved.

  6. MCM-41 mesoporous silica nanoparticles functionalized with aptamer and radiolabelled with {sup 90}Y and {sup 159}Gd as a potential therapeutic agent against colorectal cancer; Nanoparticulas de silica mesoporosa MCM-41 funcionalizadas com aptamero e radiomarcadas com {sup 90}Y e {sup 159}Gd como um potencial agente terapeutico contra cancer colorretal

    Energy Technology Data Exchange (ETDEWEB)

    Ferreira, Carolina de Aguiar

    2014-06-01

    Colorectal cancer (CRC) is a malignancy that affects large intestine and rectum, and it is the most common malignancy of the gastrointestinal tract, the third most commonly diagnosed type of cancer in the world and the second leading cause of cancer-related death in the United States. Nowadays, available therapeutic procedures for this type of cancer are limited and ineffective. Conventional radiotherapy is not an often used approach in the treatment of CRC due to the fact that peristaltic movements hamper the targeting of ionizing radiation and this type of treatment is used as adjuvant and palliative to control symptoms. Therefore, surgical intervention is the primary therapeutic choice against this disease. Researches based on the combination of radioisotopes and nanostructured carriers systems have demonstrated significant results in improving the selectivity action as well as reducing the radiation dose into healthy tissues. MCM-41 mesoporous silica nanoparticles have unique characteristics such as high surface area and well-defined pore diameters making these nanoparticles an ideal candidate of therapeutic agent carrier. Thus, the objective of this work is to synthesize and characterize MCM-41 mesoporous silica nanoparticles conjugated with yttrium-90 and gadolinium-159 and evaluate this system as a potential therapeutic agent. The nanoparticles were synthesized via sol-gel method. The sample was characterized using FTIR, SAXS, PCS, Zeta Potential analysis, Thermal analysis, CHN elemental analysis, nitrogen adsorption, scanning and transmission electron microscopy. The ability to incorporate Y{sup +3} and Gd{sup +3} ion was determined in vitro using different ratios (1:1, 1:3, 1:5 v/v) of YCL{sub 3} and Gd{sub 2}O{sub 3} and silica nanoparticles dispersed in saline, pH 7.4. The non-incorporated Y{sup +3} and Gd{sup +3} ions were removed by ultracentrifugation procedure and the concentration of ions in the supernatant was determined by ICP-AES. Cell viability

  7. Trafficking of drug candidates relevant for sports drug testing: detection of non-approved therapeutics categorized as anabolic and gene doping agents in products distributed via the Internet.

    Science.gov (United States)

    Thevis, Mario; Geyer, Hans; Thomas, Andreas; Schänzer, Wilhelm

    2011-05-01

    Identifying the use of non-approved drugs by cheating athletes has been a great challenge for doping control laboratories. This is due to the additional complexities associated with identifying relatively unknown and uncharacterized compounds and their metabolites as opposed to known and well-studied therapeutics. In 2010, the prohibited drug candidates and gene doping substances AICAR and GW1516, together with the selective androgen receptor modulator (SARM) MK-2866 were obtained by the Cologne Doping Control Laboratory from Internet suppliers and their structure, quantity, and formulation elucidated. All three compounds proved authentic as determined by liquid chromatography-high resolution/high accuracy (tandem) mass spectrometry and comparison to reference material. While AICAR was provided as a colourless powder in 100 mg aliquots, GW1516 was obtained as an orange/yellow suspension in water/glycerol (150 mg/ml), and MK-2866 (25 mg/ml) was shipped dissolved in polyethylene glycol (PEG) 300. In all cases, the quantified amounts were considerably lower than indicated on the label. The substances were delivered via courier, with packaging identifying them as containing 'amino acids' and 'green tea extract', arguably to circumvent customs control. Although all of the substances were declared 'for research only', their potential misuse in illicit performance-enhancement cannot be excluded; moreover sports drug testing authorities should be aware of the facile availability of black market copies of these drug candidates. Copyright © 2011 John Wiley & Sons, Ltd.

  8. Structure-based development of small molecule PFKFB3 inhibitors: a framework for potential cancer therapeutic agents targeting the Warburg effect.

    Directory of Open Access Journals (Sweden)

    Minsuh Seo

    Full Text Available Cancer cells adopt glycolysis as the major source of metabolic energy production for fast cell growth. The HIF-1-induced PFKFB3 plays a key role in this adaptation by elevating the concentration of Fru-2,6-BP, the most potent glycolysis stimulator. As this metabolic conversion has been suggested to be a hallmark of cancer, PFKFB3 has emerged as a novel target for cancer chemotherapy. Here, we report that a small molecular inhibitor, N4A, was identified as an initial lead compound for PFKFB3 inhibitor with therapeutic potential. In an attempt to improve its potency, we determined the crystal structure of the PFKFB3•N4A complex to 2.4 Å resolution and, exploiting the resulting molecular information, attained the more potent YN1. When tested on cultured cancer cells, both N4A and YN1 inhibited PFKFB3, suppressing the Fru-2,6-BP level, which in turn suppressed glycolysis and, ultimately, led to cell death. This study validates PFKFB3 as a target for new cancer therapies and provides a framework for future development efforts.

  9. Climatic Droplet Keratopathy in Argentina: Involvement of Environmental Agents in Its Genesis Which Would Open the Prospect for New Therapeutic Interventions.

    Science.gov (United States)

    Suárez, María Fernanda; Correa, Leandro; Crim, Nicolás; Espósito, Evangelina; Monti, Rodolfo; Urrets-Zavalía, Julio Alberto; Serra, Horacio Marcelo

    2015-01-01

    Climatic droplet keratopathy (CDK) is a degenerative corneal disease of unknown etiology. We described CDK for the first time in Latin America in the Argentinean Patagonia (El Cuy). A deeper knowledge of CDK pathogenic mechanisms will provide new therapeutic strategies. For that reason we investigated the prevalence of CDK in El Cuy and its existence in other 3 provinces with similar climate. Patients eyes were examined, habits throughout lives were inquired about, and serum ascorbate (sAA) was determined. All individuals work outdoors for most of the day. All regions had normal O3 levels. Individuals from regions 1, 2, and 3 had very low consumption of vegetables/fruits and low sAA levels. Conversely, region 4 individuals had balanced diet and higher sAA concentrations. CDK was only found in region 3 where individuals had partial deficiency of sAA and did not use eye protection. No CDK was found in regions 1 and 2 where individuals had similar work activities and dietary habits to those in region 3 but wear eye protection. No disease was found in region 4 where individuals work outdoors, have balanced diet, and use eye protection. To summarize, the CDK existence was related not only to climate but also to the dietary habits and lack of protection from sunlight.

  10. Climatic Droplet Keratopathy in Argentina: Involvement of Environmental Agents in Its Genesis Which Would Open the Prospect for New Therapeutic Interventions

    Directory of Open Access Journals (Sweden)

    María Fernanda Suárez

    2015-01-01

    Full Text Available Climatic droplet keratopathy (CDK is a degenerative corneal disease of unknown etiology. We described CDK for the first time in Latin America in the Argentinean Patagonia (El Cuy. A deeper knowledge of CDK pathogenic mechanisms will provide new therapeutic strategies. For that reason we investigated the prevalence of CDK in El Cuy and its existence in other 3 provinces with similar climate. Patients eyes were examined, habits throughout lives were inquired about, and serum ascorbate (sAA was determined. All individuals work outdoors for most of the day. All regions had normal O3 levels. Individuals from regions 1, 2, and 3 had very low consumption of vegetables/fruits and low sAA levels. Conversely, region 4 individuals had balanced diet and higher sAA concentrations. CDK was only found in region 3 where individuals had partial deficiency of sAA and did not use eye protection. No CDK was found in regions 1 and 2 where individuals had similar work activities and dietary habits to those in region 3 but wear eye protection. No disease was found in region 4 where individuals work outdoors, have balanced diet, and use eye protection. To summarize, the CDK existence was related not only to climate but also to the dietary habits and lack of protection from sunlight.

  11. Terlipressina como novo recurso terapêutico no choque séptico Terlipressin as a new therapeutic agent in septic shock

    Directory of Open Access Journals (Sweden)

    Valter Nilton Felix

    2006-06-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: A terlipressina tem sido inserida em protocolos de suporte hemodinâmico da sepse, como recurso em casos de choque refratário, o que motiva análise crítica a respeito do assunto. CONTEÚDO: Foram revistas para a análise terapias hemodinâmicas com objetivos finais bem delineados e novas recomendações para reanimação volêmica, uso de vasopressores e agentes inotrópicos em adultos e crianças sépticos. CONCLUSÕES: A terlipressina tem sido considerada nova alternativa nos cuidados intensivos da sepse, embora ainda controversa.BACKGROUND AND OBJECTIVES: The hemodynamic support of sepsis is now formulated trying to insert terlipressin as salvage drug in catecholamine resistant shock, justifying a broad critical analysis. CONTENTS: The analysis included hemodynamic therapies with defined specific goals and new recommendations for fluid resuscitation, vasopressor therapy, and inotropic therapy of septic in adult and pediatric patients. CONCLUSIONS: Terlipressin appears as a new but controversial alternative for vasopressor therapy in sepsis.

  12. Effect of Gamma-Oryzanol as Therapeutic Agent to Prevent Cardiorenal Metabolic Syndrome in Animals Submitted to High Sugar-Fat Diet

    Directory of Open Access Journals (Sweden)

    Fabiane Valentini Francisqueti

    2017-11-01

    Full Text Available Background: The high consumption of fat and sugar contributes to the development of obesity and co-morbidities, such as diabetes, and cardiovascular and kidney diseases. Different strategies have been used to prevent these diseases associated with obesity, such as changes in eating habits and/or the addition of dietary components with anti-inflammatory and anti-oxidant properties, such as gamma-oryzanol (γOz present mainly in bran layers and rice germ. Methods: Animals were randomly divided into four experimental groups and fed ad libitum for 20 weeks with control diet (C, n = 8, control diet + γOz (C + γOz, n = 8, high-sugar and high-fat diet (HSF, n = 8, and high-sugar and high-fat diet + γOz (HSF + γOz, n = 8. HSF groups also received water + sucrose (25%. The dose of γOz was added to diets to reach 0.5% of final concentration (w/w. Evaluation in animals included food and caloric intake, body weight, plasma glucose, insulin, triglycerides, uric acid, HOMA-IR, glomerular filtration rate, protein/creatinine ratio, systolic blood pressure, and Doppler echocardiographic. Results: Animals that consumed the HSF diet had weight gain compared to group C, increased insulin, HOMA, glucose and triglycerides, there were also atrial and ventricular structural alterations, deterioration of systolic and diastolic function, decreased glomerular filtration rate, and proteinuria. Gamma-oryzanol is significantly protective against effects on body weight, hypertriglyceridemia, renal damage, and against structural and functional alteration of the heart. Conclusion: Gamma-oryzanol shows potential as a therapeutic to prevent Cardiorenal Metabolic Syndrome.

  13. Bio-synthesis of silver nanoparticles using Potentilla fulgens Wall. ex Hook. and its therapeutic evaluation as anticancer and antimicrobial agent

    International Nuclear Information System (INIS)

    Mittal, Amit Kumar; Tripathy, Debabrata; Choudhary, Alka; Aili, Pavan Kumar; Chatterjee, Anupam; Singh, Inder Pal; Banerjee, Uttam Chand

    2015-01-01

    The present study aims to develop an easy and eco-friendly method for the synthesis of silver nanoparticles using extracts from the medicinal plant, Potentilla fulgens and evaluation of its anticancer and antimicrobial properties. The various parts of P. fulgens were screened and the root extract was found to have the highest potential for the synthesis of nanoparticles. The root extracts were able to quickly reduce Ag + to Ag 0 and stabilized the nanoparticles. The synthesis of nanoparticles was confirmed by UV–Visible spectrophotometry and further characterized using Zeta sizer, Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), transmission electron microscope (TEM) and X-ray diffraction (XRD). Electron microscopic study showed that the size of the nanoparticle was in the range of 10 to 15 nm and spherical in shape. The studies of phytochemical analysis of nanoparticles indicated that the adsorbed components on the surface of nanoparticles were mainly flavonoid in nature. Furthermore, nanoparticles were evaluated as cytotoxic against various cancer cell lines and 0.2 to 12 μg/mL nanoparticles showed good toxicity. The IC 50 value of nanoparticles was found to be 4.91 and 8.23 μg/mL against MCF-7 and U-87 cell lines, respectively. Additionally, the apoptotic effect of synthesized nanoparticles on normal and cancer cells was studied using trypan blue assay and flow-cytometric analysis. The results indicate the synthesized nanoparticle ability to kill cancer cells compared to normal cells. The nanoparticles also exhibited comparable antimicrobial activity against both Gram-positive and Gram-negative bacteria. - Highlights: • Bio-synthesis of AgNPs using a medicinal plant Potentilla fulgens Wall. ex Hook. • Optimization of NP synthesis and its characterization using various techniques • Determination of therapeutic potential in terms of anticancer and antimicrobial properties • To know the mechanistic apoptosis effect of

  14. Bio-synthesis of silver nanoparticles using Potentilla fulgens Wall. ex Hook. and its therapeutic evaluation as anticancer and antimicrobial agent

    Energy Technology Data Exchange (ETDEWEB)

    Mittal, Amit Kumar [Department of Pharmaceutical Technology Biotechnology, National Institute of Pharmaceutical Education and Research, Sector-67, S.A.S. Nagar, 160062 Punjab (India); Tripathy, Debabrata [Department of Biotechnology and Bioinformatics, North Eastern Hill University, Shillong, 793002 Meghalaya (India); Choudhary, Alka [Department of Natural Products, National Institute of Pharmaceutical Education and Research, Sector-67, S.A.S. Nagar, 160062 Punjab (India); Aili, Pavan Kumar [Department of Pharmaceutical Technology Biotechnology, National Institute of Pharmaceutical Education and Research, Sector-67, S.A.S. Nagar, 160062 Punjab (India); Chatterjee, Anupam [Department of Biotechnology and Bioinformatics, North Eastern Hill University, Shillong, 793002 Meghalaya (India); Singh, Inder Pal [Department of Natural Products, National Institute of Pharmaceutical Education and Research, Sector-67, S.A.S. Nagar, 160062 Punjab (India); Banerjee, Uttam Chand, E-mail: ucbanerjee@niper.ac.in [Department of Pharmaceutical Technology Biotechnology, National Institute of Pharmaceutical Education and Research, Sector-67, S.A.S. Nagar, 160062 Punjab (India)

    2015-08-01

    The present study aims to develop an easy and eco-friendly method for the synthesis of silver nanoparticles using extracts from the medicinal plant, Potentilla fulgens and evaluation of its anticancer and antimicrobial properties. The various parts of P. fulgens were screened and the root extract was found to have the highest potential for the synthesis of nanoparticles. The root extracts were able to quickly reduce Ag{sup +} to Ag{sup 0} and stabilized the nanoparticles. The synthesis of nanoparticles was confirmed by UV–Visible spectrophotometry and further characterized using Zeta sizer, Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), transmission electron microscope (TEM) and X-ray diffraction (XRD). Electron microscopic study showed that the size of the nanoparticle was in the range of 10 to 15 nm and spherical in shape. The studies of phytochemical analysis of nanoparticles indicated that the adsorbed components on the surface of nanoparticles were mainly flavonoid in nature. Furthermore, nanoparticles were evaluated as cytotoxic against various cancer cell lines and 0.2 to 12 μg/mL nanoparticles showed good toxicity. The IC{sub 50} value of nanoparticles was found to be 4.91 and 8.23 μg/mL against MCF-7 and U-87 cell lines, respectively. Additionally, the apoptotic effect of synthesized nanoparticles on normal and cancer cells was studied using trypan blue assay and flow-cytometric analysis. The results indicate the synthesized nanoparticle ability to kill cancer cells compared to normal cells. The nanoparticles also exhibited comparable antimicrobial activity against both Gram-positive and Gram-negative bacteria. - Highlights: • Bio-synthesis of AgNPs using a medicinal plant Potentilla fulgens Wall. ex Hook. • Optimization of NP synthesis and its characterization using various techniques • Determination of therapeutic potential in terms of anticancer and antimicrobial properties • To know the mechanistic

  15. 3H-1,2-Dithiole-3-thione as a novel therapeutic agent for the treatment of ischemic stroke through Nrf2 defense pathway.

    Science.gov (United States)

    Kuo, Ping-Chang; Yu, I-Chen; Scofield, Barbara A; Brown, Dennis A; Curfman, Eric T; Paraiso, Hallel C; Chang, Fen-Lei; Yen, Jui-Hung

    2017-05-01

    Cerebral ischemic stroke accounts for more than 80% of all stroke cases. During cerebral ischemia, reactive oxygen species produced in brain tissue induce oxidative stress and inflammatory responses. D3T, the simplest compound of the cyclic, sulfur-containing dithiolethiones, is found in cruciferous vegetables and has been reported to induce antioxidant genes and glutathione biosynthesis through activation of Nrf2. In addition to antioxidant activity, D3T was also reported to possess anti-inflammatory effects. In this study, we evaluated the therapeutic potential of D3T for the treatment of ischemic stroke and investigated the mechanisms underlying the protective effects of D3T in ischemic stroke. Mice subjected to transient middle cerebral artery occlusion/reperfusion (tMCAO/R) were administered with vehicle or D3T to evaluate the effect of D3T in cerebral brain injury. We observed D3T reduced infarct size, decreased brain edema, lessened blood-brain barrier disruption, and ameliorated neurological deficits. Further investigation revealed D3T suppressed microglia (MG) activation and inhibited peripheral inflammatory immune cell infiltration of CNS in the ischemic brain. The protective effect of D3T in ischemic stroke is mediated through Nrf2 induction as D3T-attenuated brain injury was abolished in Nrf2 deficient mice subjected to tMCAO/R. In addition, in vitro results indicate the induction of Nrf2 by D3T is required for its suppressive effect on MG activation and cytokine production. In summary, we demonstrate for the first time that D3T confers protection against ischemic stroke, which is mediated through suppression of MG activation and inhibition of CNS peripheral cell infiltration, and that the protective effect of D3T in ischemic stroke is dependent on the activation of Nrf2. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Identification of the factors that govern the ability of therapeutic antibodies to provide postchallenge protection against botulinum toxin: a model for assessing postchallenge efficacy of medical countermeasures against agents of bioterrorism and biological warfare.

    Science.gov (United States)

    Al-Saleem, Fetweh H; Nasser, Zidoon; Olson, Rebecca M; Cao, Linsen; Simpson, Lance L

    2011-08-01

    Therapeutic antibodies are one of the major classes of medical countermeasures that can provide protection against potential bioweapons such as botulinum toxin. Although a broad array of antibodies are being evaluated for their ability to neutralize the toxin, there is little information that defines the circumstances under which these antibodies can be used. In the present study, an effort was made to quantify the temporal factors that govern therapeutic antibody use in a postchallenge scenario. Experiments were done involving inhalation administration of toxin to mice, intravenous administration to mice, and direct application to murine phrenic nerve-hemidiaphragm preparations. As part of this study, several pharmacokinetic characteristics of botulinum toxin and neutralizing antibodies were measured. The core observation that emerged from the work was that the window of opportunity within which postchallenge administration of antibodies exerted a beneficial effect increased as the challenge dose of toxin decreased. The critical factor in establishing the window of opportunity was the amount of time needed for fractional redistribution of a neuroparalytic quantum of toxin from the extraneuronal space to the intraneuronal space. This redistribution event was a dose-dependent phenomenon. It is likely that the approach used to identify the factors that govern postchallenge efficacy of antibodies against botulinum toxin can be used to assess the factors that govern postchallenge efficacy of medical countermeasures against any agent of bioterrorism or biological warfare.

  17. Therapeutic potential of a non-steroidal bifunctional anti-inflammatory and anti-cholinergic agent against skin injury induced by sulfur mustard

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Yoke-Chen; Wang, James D.; Hahn, Rita A.; Gordon, Marion K.; Joseph, Laurie B. [Department of Pharmacology and Toxicology, Rutgers University, Piscataway, NJ (United States); Heck, Diane E. [Department of Environmental Science, New York Medical College, Valhalla, NY (United States); Heindel, Ned D. [Department of Chemistry, Lehigh University, Bethlehem, PA (United States); Young, Sherri C. [Department of Chemistry, Muhlenberg College, Allentown, PA (United States); Sinko, Patrick J. [Department of Pharmaceutics, Rutgers University, Piscataway, NJ (United States); Casillas, Robert P. [MRIGlobal, Kansas City, MO (United States); Laskin, Jeffrey D. [Environmental and Occupational Medicine, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ (United States); Laskin, Debra L. [Department of Pharmacology and Toxicology, Rutgers University, Piscataway, NJ (United States); Gerecke, Donald R., E-mail: gerecke@eohsi.rutgers.edu [Department of Pharmacology and Toxicology, Rutgers University, Piscataway, NJ (United States)

    2014-10-15

    Sulfur mustard (bis(2-chloroethyl) sulfide, SM) is a highly reactive bifunctional alkylating agent inducing edema, inflammation, and the formation of fluid-filled blisters in the skin. Medical countermeasures against SM-induced cutaneous injury have yet to be established. In the present studies, we tested a novel, bifunctional anti-inflammatory prodrug (NDH 4338) designed to target cyclooxygenase 2 (COX2), an enzyme that generates inflammatory eicosanoids, and acetylcholinesterase, an enzyme mediating activation of cholinergic inflammatory pathways in a model of SM-induced skin injury. Adult SKH-1 hairless male mice were exposed to SM using a dorsal skin vapor cup model. NDH 4338 was applied topically to the skin 24, 48, and 72 h post-SM exposure. After 96 h, SM was found to induce skin injury characterized by edema, epidermal hyperplasia, loss of the differentiation marker, keratin 10 (K10), upregulation of the skin wound marker keratin 6 (K6), disruption of the basement membrane anchoring protein laminin 322, and increased expression of epidermal COX2. NDH 4338 post-treatment reduced SM-induced dermal edema and enhanced skin re-epithelialization. This was associated with a reduction in COX2 expression, increased K10 expression in the suprabasal epidermis, and reduced expression of K6. NDH 4338 also restored basement membrane integrity, as evidenced by continuous expression of laminin 332 at the dermal–epidermal junction. Taken together, these data indicate that a bifunctional anti-inflammatory prodrug stimulates repair of SM induced skin injury and may be useful as a medical countermeasure. - Highlights: • Bifunctional anti-inflammatory prodrug (NDH4338) tested on SM exposed mouse skin • The prodrug NDH4338 was designed to target COX2 and acetylcholinesterase. • The application of NDH4338 improved cutaneous wound repair after SM induced injury. • NDH4338 treatment demonstrated a reduction in COX2 expression on SM injured skin. • Changes of skin repair

  18. Transient receptor potential ankyrin 1 receptor activation in vitro and in vivo by pro-tussive agents: GRC 17536 as a promising anti-tussive therapeutic.

    Directory of Open Access Journals (Sweden)

    Indranil Mukhopadhyay

    Full Text Available Cough is a protective reflex action that helps clear the respiratory tract which is continuously exposed to airborne environmental irritants. However, chronic cough presents itself as a disease in its own right and despite its global occurrence; the molecular mechanisms responsible for cough are not completely understood. Transient receptor potential ankyrin1 (TRPA1 is robustly expressed in the neuronal as well as non-neuronal cells of the respiratory tract and is a sensor of a wide range of environmental irritants. It is fast getting acceptance as a key biological sensor of a variety of pro-tussive agents often implicated in miscellaneous chronic cough conditions. In the present study, we demonstrate in vitro direct functional activation of TRPA1 receptor by citric acid which is routinely used to evoke cough in preclinical and clinical studies. We also show for the first time that a potent and selective TRPA1 antagonist GRC 17536 inhibits citric acid induced cellular Ca(+2 influx in TRPA1 expressing cells and the citric acid induced cough response in guinea pigs. Hence our data provides a mechanistic link between TRPA1 receptor activation in vitro and cough response induced in vivo by citric acid. Furthermore, we also show evidence for TRPA1 activation in vitro by the TLR4, TLR7 and TLR8 ligands which are implicated in bacterial/respiratory virus pathogenesis often resulting in chronic cough. In conclusion, this study highlights the potential utility of TRPA1 antagonist such as GRC 17536 in the treatment of miscellaneous chronic cough conditions arising due to diverse causes but commonly driven via TRPA1.

  19. In vitro and in vivo anti-tumor effect of metformin as a novel therapeutic agent in human oral squamous cell carcinoma

    International Nuclear Information System (INIS)

    Luo, Qingqiong; Hu, Dan; Hu, Shuiqing; Yan, Ming; Sun, Zujun; Chen, Fuxiang

    2012-01-01

    Metformin, which is widely used as an antidiabetic agent, has recently been reported to reduce cancer risk and improve prognosis in certain malignancies. However, the specific mechanisms underlying the effect of metformin on the development and progression of several cancers including oral squamous cell carcinoma (OSCC) remain unclear. In the present study, we investigated the effects of metformin on OSCC cells in vitro and in vivo. OSCC cells treated with or without metformin were counted using a hemocytometer. The clonogenic ability of OSCC cells after metformin treatment was determined by colony formation assay. Cell cycle progression and apoptosis were assessed by flow cytometry, and the activation of related signaling pathways was examined by immunoblotting. The in vivo anti-tumor effect of metformin was examined using a xenograft mouse model. Immunohistochemistry and TUNEL staining were used to determine the expression of cyclin D1 and the presence of apoptotic cells in tumors from mice treated with or without metformin. Metformin inhibited proliferation in the OSCC cell lines CAL27, WSU-HN6 and SCC25 in a time- and dose-dependent manner, and significantly reduced the colony formation of OSCC cells in vitro. Metformin induced an apparent cell cycle arrest at the G0/G1 phase, which was accompanied by an obvious activation of the AMP kinase pathway and a strongly decreased activation of mammalian target of rapamycin and S6 kinase. Metformin treatment led to a remarkable decrease of cyclin D1, cyclin-dependent kinase (CDK) 4 and CDK6 protein levels and phosphorylation of retinoblastoma protein, but did not affect p21 or p27 protein expression in OSCC cells. In addition, metformin induced apoptosis in OSCC cells, significantly down-regulating the anti-apoptotic proteins Bcl-2 and Bcl-xL and up-regulating the pro-apoptotic protein Bax. Metformin also markedly reduced the expression of cyclin D1 and increased the numbers of apoptotic cells in vivo, thus inhibiting

  20. EFSA Panel on Biological Hazards (BIOHAZ); Scientific Opinion on a review on the European Union Summary reports on trends and sources zoonoses, zoonotic agents and food-borne outbreaks in 2009 and 2010 – specifically for the data on Salmonella, Campylobacter, verotoxigenic Escherichia coli

    DEFF Research Database (Denmark)

    Hald, Tine

    health problems related to food and animal sources in the EU, it is desirable to differentiate between travel within and outside the EU. This would also be useful to better evaluate the public health impact of EU-wide food safety measures. Whenever possible the data/results should be analysed using......The European Union (EU) Summary Reports on trends and sources of zoonoses, zoonotic agents and food-borne outbreaks in 2009 and 2010 – specifically for the data on Salmonella, Campylobacter, verotoxigenic Escherichia coli, Listeria monocytogenes and foodborne outbreaks was reviewed. The main...... insight. Ultimately, summary measures of public health such as disability adjusted life years (DALYs) and cost-of-illness estimates should be presented. Travel information was found to be still incomplete in many MSs. For many pathogens this hampers source attribution. To better understand the public...

  1. Vector-borne Infections

    Centers for Disease Control (CDC) Podcasts

    2011-04-18

    This podcast discusses emerging vector-borne pathogens, their role as prominent contributors to emerging infectious diseases, how they're spread, and the ineffectiveness of mosquito control methods.  Created: 4/18/2011 by National Center for Emerging Zoonotic and Infectious Diseases (NCEZID).   Date Released: 4/27/2011.

  2. Tick-borne disease.

    Science.gov (United States)

    Bratton, Robert L; Corey, Ralph

    2005-06-15

    Tick-borne diseases in the United States include Rocky Mountain spotted fever, Lyme disease, ehrlichiosis, tularemia, babesiosis, Colorado tick fever, and relapsing fever. It is important for family physicians to consider these illnesses when patients present with influenza-like symptoms. A petechial rash initially affecting the palms and soles of the feet is associated with Rocky Mountain spotted fever, whereas erythema migrans (annular macule with central clearing) is associated with Lyme disease. Various other rashes or skin lesions accompanied by fever and influenza-like illness also may signal the presence of a tick-borne disease. Early, accurate diagnosis allows treatment that may help prevent significant morbidity and possible mortality. Because 24 to 48 hours of attachment to the host are required for infection to occur, early removal can help prevent disease. Treatment with doxycycline or tetracycline is indicated for Rocky Mountain spotted fever, Lyme disease, ehrlichiosis, and relapsing fever. In patients with clinical findings suggestive of tick-borne disease, treatment should not be delayed for laboratory confirmation. If no symptoms follow exposure to tick bites, empiric treatment is not indicated. The same tick may harbor different infectious pathogens and transmit several with one bite. Advising patients about prevention of tick bites, especially in the summer months, may help prevent exposure to dangerous vector-borne diseases.

  3. Tick-Borne Encephalitis (TBE)

    Science.gov (United States)

    ... virus, Siberian tick-borne encephalitis virus, and Far eastern Tick-borne encephalitis virus (formerly known as Russian ... viruses are closely related to TBEV and Far-eastern TBE, and include Omsk hemorrhagic fever virus in ...

  4. Frontiers in nano-therapeutics

    CERN Document Server

    Tasnim, Nishat; Sai Krishna, Katla; Kalagara, Sudhakar; Narayan, Mahesh; Noveron, Juan C; Joddar, Binata

    2017-01-01

    This brief highlights recent research advances in the area of nano-therapeutics. Nanotechnology holds immense potential for application in a wide range of biological and engineering applications such as molecular sensors for disease diagnosis, therapeutic agents for the treatment of diseases, a vehicle for delivering therapeutics and imaging agents for theranostic applications, both in-vitro and in-vivo. The brief is grouped into the following sections namely, A) Discrete Nanosystems ; B) Anisotropic Nanoparticles; C) Nano-films/coated/layered and D) Nano-composites.

  5. Where was Joseph Babinski born?

    Directory of Open Access Journals (Sweden)

    H A G Teive

    2011-01-01

    Full Text Available There is controversy in the neurological literature about where Joseph Babinski was born, including a myth propounded by various important authors that he was born in Lima, Peru. However, according to the most consistent biographical data, he was in fact born in Paris, France, and became a medical celebrity there and in Poland as well as around the world.

  6. VECTOR BORNE TRANSMISSIBLE ZOONOSES IN MONTENEGRO

    Directory of Open Access Journals (Sweden)

    Gordana Mijovic

    2012-02-01

    Full Text Available Vector borne transmissible zoonoses are becoming more and more important in the group of emerging and re-emerging infections. We present the characteristics and actuality of this group of infectious diseases in Montenegro for the period 1998 - 2011. In examinations, standard epidemiological, clinical, serological, pathohistological diagnostic methods are employed. Natural conditions in Montenegro make it an important endemic area for more vector borne transmissible zoonoses. The changes of ecological characteristics, the vectors and infective agents, present the accidence for expansion and increasing importance of these infections in national pathology. According to the fact that it is an international port of nautical, continental and air traffic, Montenegro has responsibility for control and management of diseases belonging to the group of the travel and tropical diseases.

  7. Therapeutic Potential of HDPs as Immunomodulatory Agents

    DEFF Research Database (Denmark)

    Jenssen, Håvard; Hancock, Robert E.W.

    2010-01-01

    One of the most significant advances in medical history is the discovery and development of antibiotics, which in the middle of last century was flourishing and appeared to be the ultimate solution to the treatment of life-threatening human bacterial diseases. However, lately there has been a huge...... decline in the rate of discovery of new antimicrobial intervention strategies in parallel with an increasing incidence of multidrug-resistant pathogens; if these circumstances do not change we will continue to approach the end of the antibiotic era. Facing this dark future, scientists are considering new...... strategies for intervention tailored around the appropriate (selective) stimulation of the host’s immune system, and particularly rapid acting innate immunity, as an alternative to direct targeting of microbial pathogens. One recent player in such an immunomodulatory strategy is the naturally occurring host...

  8. Development of Targeted Therapeutic Agents for Botulism

    National Research Council Canada - National Science Library

    Dolly, Oliver

    1998-01-01

    .... Therefore, an ELISA was optimised and standardised for measuring their proteolysis of immobilised, bacterially-expressed SNAP-25, using purified IgGs reactive solely with full-length or BoNT/A-truncated SNAP-25...

  9. Therapeutic management of inflammatory bowel disease in real-life practice in the current era of anti-TNF agents: analysis of the French administrative health databases 2009-2014.

    Science.gov (United States)

    Kirchgesner, J; Lemaitre, M; Rudnichi, A; Racine, A; Zureik, M; Carbonnel, F; Dray-Spira, R

    2017-01-01

    Management of inflammatory bowel disease (IBD) has evolved in the last decade. To assess IBD therapeutic management, including treatment withdrawal and early treatment use in the current era of anti-TNF agents (anti-TNFs). All patients affiliated to the French national health insurance diagnosed with IBD were included from 2009 to 2013 and followed up until 31 December 2014. Medication uses, treatment sequences after introduction of thiopurine or anti-TNF monotherapies or both (combination therapy), surgical procedures and hospitalisations were assessed. A total of 210 001 patients were diagnosed with IBD [Crohn's disease (CD), 100 112; ulcerative colitis (UC), 109 889]. Five years after diagnosis, cumulative probabilities of anti-TNF monotherapy and combination therapy exposures were 33.8% and 18.3% in CD patients and 12.9% and 7.4% in UC patients, respectively. Among incident patients who received thiopurines or anti-TNFs, the first treatment was thiopurine in 69.1% of CD and 78.2% of UC patients. Among patients treated with anti-TNFs, 45.2% and 54.5% of CD patients and 38.2% and 39.9% of UC patients started monotherapy and combination therapy within 3 months after diagnosis, respectively; 31.3% of CD and 27.1% of UC incident patients withdrew from thiopurine or anti-TNFs for more than 3 months after their first course of treatment. Five years after diagnosis, the cumulative risks of first intestinal resection in CD patients and colectomy in UC patients were 11.9% and 5.7%, respectively. Step-up approach remains the predominant strategy, while exposure to anti-TNFs is high. Surgery rates are low. Treatment withdrawal in IBD is more common than expected. © 2016 John Wiley & Sons Ltd.

  10. Tick-borne encephalitis.

    Science.gov (United States)

    Dumpis, U; Crook, D; Oksi, J

    1999-04-01

    Tick-borne encephalitis (TBE) is a zoonotic arbovirus infection endemic to Russia and Eastern and Central Europe. Despite being a common and serious life-threatening disease for which a mass vaccination program was implemented in Austria, there is only limited reference to this disease in the English-language literature. TBE is transmitted to humans usually by the bite of a tick (either Ixodes persulcatus or Ixodes ricinus); occasionally, cases occur following consumption of infected unpasteurized milk. Transmission is seasonal and occurs in spring and summer, particularly in rural areas favored by the vector. TBE is a serious cause of acute central nervous system disease, which may result in death or long-term neurological sequelae. Effective vaccines are available in a few countries. The risk for travelers of acquiring TBE is increasing with the recent rise in tourism to areas of endemicity during spring and summer.

  11. Recent characterization of cowpea aphid-borne mosaic virus ...

    African Journals Online (AJOL)

    Woodiness disease is the most important disorder of passion fruit worldwide. The causal agent in Brazil is the Cowpea aphid-borne mosaic virus (CABMV), and despite the economic relevance of passion fruit for agriculture there have been recently very few studies about this virus in Brazil and worldwide. This work reveals ...

  12. Biological Agents

    Science.gov (United States)

    ... E-Tools Safety and Health Topics / Biological Agents Biological Agents This page requires that javascript be enabled ... 202) 693-2300 if additional assistance is required. Biological Agents Menu Overview In Focus: Ebola Frederick A. ...

  13. Topical antifungal agents: an update.

    Science.gov (United States)

    Diehl, K B

    1996-10-01

    So many topical antifungal agents have been introduced that it has become very difficult to select the proper agent for a given infection. Nonspecific agents have been available for many years, and they are still effective in many situations. These agents include Whitfield's ointment, Castellani paint, gentian violet, potassium permanganate, undecylenic acid and selenium sulfide. Specific antifungal agents include, among others, the polyenes (nystatin, amphotericin B), the imidazoles (metronidazole, clotrimazole) and the allylamines (terbinafine, naftifine). Although the choice of an antifungal agent should be based on an accurate diagnosis, many clinicians believe that topical miconazole is a relatively effective agent for the treatment of most mycotic infections. Terbinafine and other newer drugs have primary fungicidal effects. Compared with older antifungal agents, these newer drugs can be used in lower concentrations and shorter therapeutic courses. Studies are needed to evaluate the clinical efficacies and cost advantages of both newer and traditional agents.

  14. Behavior of platelets stained by 5,6-CF-encapsulated PEGylated liposomes after laser irradiation of vessel wall: an in-vivo model for studying site-selective delivery of diagnostic or therapeutic agents

    Science.gov (United States)

    Mordon, Serge R.; Begu, Sylvie; Buys, Bruno; Tourne-Peteilh, Corine; Devoisselle, Jean-Marie

    2001-05-01

    Vascular endothelium serves as an extensive interface between circulating blood and various tissues and organs of the body. As such, it offers an accessible target for blood-borne pharmacological and genetic manipulations that can mediate both local and systemic effects. Thus, targeting of liposomes to activated vascular endothelial cells may provide a strategy for site-selective delivery in the vascular system with broad therapeutic applicability. This study aimed to evaluate an intravital fluorescence imaging technique to visualize in-situ and in real-time the activation of platelets after staining by 5,6-CF- encapsulated PEGylated liposomes injected intravenously. The study was performed on skin by using a dorsal skin-fold chamber implanted in golden hamsters using intravital microscopy. The skin micro circulation was observed with an intravital microscope (using x25 and x40 magnification) fitted with a Xenon light source and an epi-fluorescence assembly. An ultra-high sensitivity video-camera mounted on the microscope projected the image onto a monitor, and the images were recorded for play-back analysis with a digital video cassette recorder. An inflammatory response was induced by an Argon laser emitting at 514.5nm. The 80micrometers laser beam was focused on a vessel and its position was controlled with the microscope imaging system, it was possible to see individual platelets flowing in blood vessels. As liposomes were labeled with a fluorescent probe which was hydrophilic (located in the aqueous phase), the fluorescence of platelets was due only to the uptake of liposomes. After laser irradiation, platelets activation at sites of vascular injury was obtained. Tethering, translocation of some platelets inside the irradiated zone were clearly seen. At last, detachment and extravasation of platelets were observed. A perivascular fluorescence confirmed that platelets migrated across the basal lamina into the dermal connective tissue. In conclusion, staining of

  15. Macromolecular therapeutics.

    Science.gov (United States)

    Yang, Jiyuan; Kopeček, Jindřich

    2014-09-28

    This review covers water-soluble polymer-drug conjugates and macromolecules that possess biological activity without attached low molecular weight drugs. The main design principles of traditional and backbone degradable polymer-drug conjugates as well as the development of a new paradigm in nanomedicines - (low molecular weight) drug-free macromolecular therapeutics are discussed. To address the biological features of cancer, macromolecular therapeutics directed to stem/progenitor cells and the tumor microenvironment are deliberated. Finally, the future perspectives of the field are briefly debated. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. PYTHIOSIS: A THERAPEUTIC APPROACH

    Directory of Open Access Journals (Sweden)

    C. M. C. Falcão

    2015-10-01

    Full Text Available Pythiosis, a disease caused by the oomycete Pythium insidiosum, often presents inefficient response to chemotherapy. It is a consensus that, in spite the several therapeutic protocols, a combination of surgery, chemotherapy and immunotherapy should be used. Surgical excision requires the removal of the entire affected area, with a wide margin of safety. The use of antifungal drugs has resulted in variable results, both in vitro and in vivo, and presents low therapeutic efficiency due to differences in the agent characteristics, which differ from true fungi. Immunotherapy is a non-invasive alternative for the treatment of pythiosis, which aims at modifying the immune response of the host, thereby producing an effective response to the agent. Photodynamic therapy has emerged as a promising technique, with good activity against P. insidiosum in vitro and in vivo. However, more studies are necessary to increase the efficiency of the current treatment protocols and consequently improve the cure rates. This paper aims to conduct a review covering the conventional and recent therapeutic methods against P. insidiosum infections

  17. Born Again Heathenism

    DEFF Research Database (Denmark)

    Grodal, Torben Kragh

    2008-01-01

    The article discusses films with fantastic elements using evolutionary psychology. The fascination with the fantastic on film is a by-product of different evolutionary mental adaptations, like the interest in causality with the purpose of control that create interest in fantastic violation...... by invention of supernatural agents. The prominence of supernaturalism in media is not necessarily linked to an increase in religious interest vis à vis science but could also be caused by a diminished 'heresy control' allowing media to exploit a range of innate dispositions of being intrigued by different...... supernatural phenomena that might be called 'heathen' because it often reuses all kinds of folk superstitions....

  18. Therapeutic Nanodevices

    Science.gov (United States)

    Lee, Stephen; Ruegsegger, Mark; Barnes, Philip; Smith, Bryan; Ferrari, Mauro

    Therapeutic nanotechnology offers minimally invasive therapies with high densities of function concentrated in small volumes, features that may reduce patient morbidity and mortality. Unlike other areas of nanotechnology, novel physical properties associated with nanoscale dimensionality are not the raison d'être of therapeutic nanotechnology, whereas the aggregation of multiple biochemical (or comparably precise) functions into controlled nanoarchitectures is. Multifunctionality is a hallmark of emerging nanotherapeutic devices, and multifunctionality can allow nanotherapeutic devices to perform multistep work processes, with each functional component contributing to one or more nanodevice subroutine such that, in aggregate, subroutines sum to a cogent work process. Cannonical nanotherapeutic subroutines include tethering (targeting) to sites of disease, dispensing measured doses of drug (or bioactive compound), detection of residual disease after therapy and communication with an external clinician/operator. Emerging nanotherapeutics thus blur the boundaries between medical devices and traditional pharmaceuticals. Assembly of therapeutic nanodevices generally exploits either (bio)material self-assembly properties or chemoselective bioconjugation techniques, or both. Given the complexity, composition, and the necessity for their tight chemical and structural definition inherent in the nature of nanotherapeutics, their cost of goods (COGs) might exceed that of (already expensive) biologics. Early therapeutic nanodevices will likely be applied to disease states which exhibit significant unmet patient need (cancer and cardiovascular disease), while application to other disease states well-served by conventional therapy may await perfection of nanotherapeutic design and assembly protocols.

  19. Plasma and tissue insulin-like growth factor-I receptor (IGF-IR) as a prognostic marker for prostate cancer and anti-IGF-IR agents as novel therapeutic strategy for refractory cases: a review.

    Science.gov (United States)

    Ozkan, Emine Elif

    2011-09-15

    Cancer database analysis indicates that prostate cancer is one of the most seen cancers in men meanwhile composing the leading cause of morbidity and mortality among developed countries. Current available therapies are surgery, radiotherapy and androgene ablation for prostate carcinoma. The response rate is as high nearly 90% however, most of these recur or become refractory and androgene independent (AI). Therefore recent studies intensified on molecular factors playing role on development of prostate carcinoma and novel treatment strategies targetting these factors and their receptors. Insulin-like growth factor-I (IGF-I) and its primary receptor insulin-like growth factor receptor-I (IGF-IR) are among these factors. Biologic functions and role in malign progression are primarily achieved via IGF-IR which is a type 2 tyrosine kinase receptor. IGF-IR plays an important role in mitogenesis, angiogenesis, transformation, apoptosis and cell motility. It also generates intensive proliferative signals leading to carcinogenesis in prostate tissue. So IGF-IR and its associated signalling system have provoked considerable interest over recent years as a novel therapeutic target in cancer. In this paper it is aimed to sum up the lately published literature searching the relation of IGF-IR and prostate cancer in terms of incidence, pathologic features, and prognosis. This is followed by a discussion of the different possible targets within the IGF-1R system, and drugs developed to interact at each target. A systems-based approach is then used to review the in vitro and in vivo data in the published literature of the following compounds targeting IGF-1R components using specific examples: growth hormone releasing hormone antagonists (e.g. JV-1-38), growth hormone receptor antagonists (e.g. pegvisomant), IGF-1R antibodies (e.g. CP-751,871, AVE1642/EM164, IMC-A12, SCH-717454, BIIB022, AMG 479, MK-0646/h7C10), and IGF-1R tyrosine kinase inhibitors (e.g. BMS-536942, BMS-554417

  20. Early Recollections of First-Borns.

    Science.gov (United States)

    Fakouri, M. Ebrahim; Hafner, James L.

    1984-01-01

    Compared the early recollections of 50 first-borns and 98 later-borns. The first-borns mentioned significantly more nonfamily members, illness/injury, hospital/doctor's office. Later-borns mentioned significantly more siblings than did first-borns. Findings were discussed in the context of Adler's personality theory. (JAC)

  1. Born : vastutustundlikud tulevikus edukad / Kerstin Born ; interv. Kristo Kiviorg

    Index Scriptorium Estoniae

    Born, Kerstin

    2007-01-01

    Vastutustundliku ettevõtluse Euroopa organisatsiooni CSR Europe'i juht Kerstin Born vastab küsimustele ettevõtete vastutustundlikkuse kohta ühiskonnas. Vt. samas: Käivitus vastutustundliku ettevõtluse indeks

  2. Born-Infeld Nonlinear Electrodynamics

    International Nuclear Information System (INIS)

    Bialynicki-Birula, I.

    1999-01-01

    This is only a summary of a lecture delivered at the Infeld Centennial Meeting. In the lecture the history of the Born-Infeld nonlinear electrodynamics was presented and some general features of the theory were discussed. (author)

  3. Strategies Used by Foreign-Born Family Therapists to Connect Across Cultural Differences: A Thematic Analysis.

    Science.gov (United States)

    Niño, Alba; Kissil, Karni; Davey, Maureen P

    2016-01-01

    With the growing diversity in the United States among both clinicians and clients, many therapeutic encounters are cross-cultural, requiring providers to connect across cultural differences. Foreign-born therapists have many areas of differences to work through. Thus, exploring how foreign-born family therapists in the United States connect to their clients can uncover helpful strategies that all therapists can use to establish stronger cross-cultural therapeutic connections. A thematic analysis was conducted to understand strategies 13 foreign-born therapists used during therapeutic encounters. Four themes were identified: making therapy a human-to-human connection, dealing with stereotypes, what really matters, and flexibility. Findings suggest that developing a deep therapeutic connection using emotional attunement and human-to-human engagement is crucial for successful cross-cultural therapy. Clinical and training implications are provided. © 2015 American Association for Marriage and Family Therapy.

  4. Therapeutic ultrasound

    International Nuclear Information System (INIS)

    Crum, Lawrence A

    2004-01-01

    The use of ultrasound in medicine is now quite commonplace, especially with the recent introduction of small, portable and relatively inexpensive, hand-held diagnostic imaging devices. Moreover, ultrasound has expanded beyond the imaging realm, with methods and applications extending to novel therapeutic and surgical uses. These applications broadly include: tissue ablation, acoustocautery, lipoplasty, site-specific and ultrasound mediated drug activity, extracorporeal lithotripsy, and the enhancement of natural physiological functions such as wound healing and tissue regeneration. A particularly attractive aspect of this technology is that diagnostic and therapeutic systems can be combined to produce totally non-invasive, imageguided therapy. This general lecture will review a number of these exciting new applications of ultrasound and address some of the basic scientific questions and future challenges in developing these methods and technologies for general use in our society. We shall particularly emphasize the use of High Intensity Focused Ultrasound (HIFU) in the treatment of benign and malignant tumors as well as the introduction of acoustic hemostasis, especially in organs which are difficult to treat using conventional medical and surgical techniques. (amum lecture)

  5. Optimal vaccination strategies against vector-borne diseases

    DEFF Research Database (Denmark)

    Græsbøll, Kaare; Enøe, Claes; Bødker, Rene

    2014-01-01

    Using a process oriented semi-agent based model, we simulated the spread of Bluetongue virus by Culicoides, biting midges, between cattle in Denmark. We evaluated the minimum vaccination cover and minimum cost for eight different preventive vaccination strategies in Denmark. The simulation model ...... results when index cases were in the vaccinated areas. However, given that the long-range spread of midge borne disease is still poorly quantified, more robust national vaccination schemes seem preferable....

  6. Biomedical and therapeutic applications of biosurfactants

    OpenAIRE

    Rodrigues, L. R.; Teixeira, J. A.

    2010-01-01

    During the last years, several applications of biosurfactants with medical purposes have been reported. Biosurfactants are considered relevant molecules for applications in combating many diseases and as therapeutic agents due to their antibacterial, antifungal and antiviral activities. Furthermore, their role as anti-adhesive agents against several pathogens illustrate their utility as suitable anti-adhesive coating agents for medical insertional materials leading to a reduction of a large n...

  7. Arthropod-borne disease in Canada: A clinician’s perspective from the ‘Cold Zone’

    OpenAIRE

    Artsob, Harvey

    2000-01-01

    Arthropod-borne diseases do not occur commonly in Canada. Nevertheless, Canadians run the risk of contracting certain infections within the country during arthropod season, as well as when travelling abroad. Therefore, it is important that clinicians are aware of the possible occurrence of arthropod-borne diseases, and consider them in their differential diagnoses. The present review is divided into two sections: arthropod-borne diseases or disease agents documented in Canada, and imported ar...

  8. [Alkylating agents].

    Science.gov (United States)

    Pourquier, Philippe

    2011-11-01

    With the approval of mechlorethamine by the FDA in 1949 for the treatment of hematologic malignancies, alkylating agents are the oldest class of anticancer agents. Even though their clinical use is far beyond the use of new targeted therapies, they still occupy a major place in specific indications and sometimes represent the unique option for the treatment of refractory diseases. Here, we are reviewing the major classes of alkylating agents and their mechanism of action, with a particular emphasis for the new generations of alkylating agents. As for most of the chemotherapeutic agents used in the clinic, these compounds are derived from natural sources. With a complex but original mechanism of action, they represent new interesting alternatives for the clinicians, especially for tumors that are resistant to conventional DNA damaging agents. We also briefly describe the different strategies that have been or are currently developed to potentiate the use of classical alkylating agents, especially the inhibition of pathways that are involved in the repair of DNA lesions induced by these agents. In this line, the development of PARP inhibitors is a striking example of the recent regain of interest towards the "old" alkylating agents.

  9. Therapeutic and diagnostic nanomaterials

    CERN Document Server

    Devasena T

    2017-01-01

    This brief highlights nanoparticles used in the diagnosis and treatment of prominent diseases and toxic conditions. Ecofriendly methods which are ideal for the synthesis of medicinally valued nanoparticles are explained and the characteristic features of these particles projected. The role of these particles in the therapeutic field, and the induced biological changes in some diseases are discussed. The main focus is on inflammation, oxidative stress and cellular membrane integrity alterations. The effect of nanoparticles on these changes produced by various agents are highlighted using in vitro and in vivo models. The mechanism of nanoparticles in ameliorating the biological changes is supported by relevant images and data. Finally, the brief demonstrates recent developments on the use of nanoparticles in diagnosis or sensing of some biological materials and biologically hazardous environmental materials.

  10. Inferences from the collaboration in the field of pharmaco-chemical protection and treatment of radiation injury according to the 'Intercosmos' program. Study of new prophylactic and therapeutic agents to manage radiation disease from protracted exposure. Topic 5

    Energy Technology Data Exchange (ETDEWEB)

    Rogozkin, D D [Institut Biofiziki, Moscow (USSR)

    1976-01-01

    Primary consideration was given to agents promoting general systemic resistance. In short-term or protracted irradiation experiments, confirmatory evidence was obtained for antiradiation effects produced by amitetravit, urease, and yeast polysaccharides. On Ehrlich ascites tumor cells and lymphosarcoma cells, exogenous DNA was shown to enhance repair of the DNA molecule, even with regard to double-strand breaks. Usefulness of serum globulins as an antiradiation agent was substantiated in acute experiments on rabbits, where survival of animals was seen to rise and natural immunity factors to be normalized and stimulated. A similar favorable effect of serum globulins was demonstrated on hemopoiesis in mice, where incidence of autoinfections was also decreased. Studies are continuing to elucidate mechanisms underlying hemopoiesis protection by hypoxic hypoxia and hypoxic hypothermy in mice. Minimum amounts of protective preparations needed to produce an appreciable effect on mouse stem cells were determined. ATP and noradrenalin were found to act largely through their influence on blood formation.

  11. [New agents for hypercholesterolemia].

    Science.gov (United States)

    Pintó, Xavier; García Gómez, María Carmen

    2016-02-19

    An elevated proportion of high cardiovascular risk patients do not achieve the therapeutic c-LDL goals. This owes to physicians' inappropriate or insufficient use of cholesterol lowering medications or to patients' bad tolerance or therapeutic compliance. Another cause is an insufficient efficacy of current cholesterol lowering drugs including statins and ezetimibe. In addition, proprotein convertase subtilisin kexin type 9 inhibitors are a new cholesterol lowering medications showing safety and high efficacy to reduce c-LDL in numerous already performed or underway clinical trials, potentially allowing an optimal control of hypercholesterolemia in most patients. Agents inhibiting apolipoprotein B synthesis and microsomal transfer protein are also providing a new potential to decrease cholesterol in patients with severe hypercholesterolemia and in particular in homozygote familial hypercholesterolemia. Last, cholesteryl ester transfer protein inhibitors have shown powerful effects on c-HDL and c-LDL, although their efficacy in cardiovascular prevention and safety has not been demonstrated yet. We provide in this article an overview of the main characteristics of therapeutic agents for hypercholesterolemia, which have been recently approved or in an advanced research stage. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

  12. First-In-Class Small Molecule ONC201 Induces DR5 and Cell Death in Tumor but Not Normal Cells to Provide a Wide Therapeutic Index as an Anti-Cancer Agent.

    Science.gov (United States)

    Allen, Joshua E; Crowder, Roslyn N; Crowder, Roslyn; El-Deiry, Wafik S

    2015-01-01

    We previously identified ONC201 (TIC10) as a first-in-class orally active small molecule with robust antitumor activity that is currently in clinical trials in advanced cancers. Here, we further investigate the safety characteristics of ONC201 in preclinical models that reveal an excellent safety profile at doses that exceed efficacious doses by 10-fold. In vitro studies indicated a strikingly different dose-response relationship when comparing tumor and normal cells where maximal effects are much stronger in tumor cells than in normal cells. In further support of a wide therapeutic index, investigation of tumor and normal cell responses under identical conditions demonstrated large apoptotic effects in tumor cells and modest anti-proliferative effects in normal cells that were non-apoptotic and reversible. Probing the underlying mechanism of apoptosis indicated that ONC201 does not induce DR5 in normal cells under conditions that induce DR5 in tumor cells; DR5 is a pro-apoptotic TRAIL receptor previously linked to the anti-tumor mechanism of ONC201. GLP toxicology studies in Sprague-Dawley rats and beagle dogs at therapeutic and exaggerated doses revealed no dose-limiting toxicities. Observations in both species at the highest doses were mild and reversible at doses above 10-fold the expected therapeutic dose. The no observed adverse event level (NOAEL) was ≥42 mg/kg in dogs and ≥125 mg/kg in rats, which both correspond to a human dose of approximately 1.25 g assuming standard allometric scaling. These results provided the rationale for the 125 mg starting dose in dose escalation clinical trials that began in 2015 in patients with advanced cancer.

  13. First-In-Class Small Molecule ONC201 Induces DR5 and Cell Death in Tumor but Not Normal Cells to Provide a Wide Therapeutic Index as an Anti-Cancer Agent.

    Directory of Open Access Journals (Sweden)

    Joshua E Allen

    Full Text Available We previously identified ONC201 (TIC10 as a first-in-class orally active small molecule with robust antitumor activity that is currently in clinical trials in advanced cancers. Here, we further investigate the safety characteristics of ONC201 in preclinical models that reveal an excellent safety profile at doses that exceed efficacious doses by 10-fold. In vitro studies indicated a strikingly different dose-response relationship when comparing tumor and normal cells where maximal effects are much stronger in tumor cells than in normal cells. In further support of a wide therapeutic index, investigation of tumor and normal cell responses under identical conditions demonstrated large apoptotic effects in tumor cells and modest anti-proliferative effects in normal cells that were non-apoptotic and reversible. Probing the underlying mechanism of apoptosis indicated that ONC201 does not induce DR5 in normal cells under conditions that induce DR5 in tumor cells; DR5 is a pro-apoptotic TRAIL receptor previously linked to the anti-tumor mechanism of ONC201. GLP toxicology studies in Sprague-Dawley rats and beagle dogs at therapeutic and exaggerated doses revealed no dose-limiting toxicities. Observations in both species at the highest doses were mild and reversible at doses above 10-fold the expected therapeutic dose. The no observed adverse event level (NOAEL was ≥42 mg/kg in dogs and ≥125 mg/kg in rats, which both correspond to a human dose of approximately 1.25 g assuming standard allometric scaling. These results provided the rationale for the 125 mg starting dose in dose escalation clinical trials that began in 2015 in patients with advanced cancer.

  14. Bacterial food-borne zoonoses.

    Science.gov (United States)

    Thorns, C J

    2000-04-01

    In many countries of the world, bacterial food-borne zoonotic infections are the most common cause of human intestinal disease. Salmonella and Campylobacter account for over 90% of all reported cases of bacteria-related food poisoning world-wide. Poultry and poultry products have been incriminated in the majority of traceable food-borne illnesses caused by these bacteria, although all domestic livestock are reservoirs of infection. In contrast to the enzootic nature of most Salmonella and Campylobacter infections, Salmonella Enteritidis caused a pandemic in both poultry and humans during the latter half of the 20th Century. Salmonella Typhimurium and Campylobacter appear to be more ubiquitous in the environment, colonising a greater variety of hosts and environmental niches. Verocytotoxin-producing Escherichia coli O157 (VTEC O157) also emerged as a major food-borne zoonotic pathogen in the 1980s and 1990s. Although infection is relatively rare in humans, clinical disease is often severe, with a significant mortality rate among the young and elderly. The epidemiology of VTEC O157 is poorly understood, although ruminants, especially cattle and sheep, appear to be the major source of infection. The dissemination of S. Enteritidis along the food chain is fairly well understood, and control programmes have been developed to target key areas of poultry meat and egg production. Recent evidence indicates that these control programmes have been associated with an overall reduction of S. Enteritidis along the food chain. Unfortunately, existing controls do not appear to reduce the levels of Campylobacter and VTEC O157 infections. Future control strategies need to consider variations in the epidemiologies of food-borne zoonotic infections, and apply a quantitative risk analysis approach to ensure that the most cost-effective programmes are developed.

  15. Emerging Vector-Borne Diseases.

    Science.gov (United States)

    Huntington, Mark K; Allison, Jay; Nair, Dilip

    2016-10-01

    Several mosquito-borne viral infections have recently emerged in North America; West Nile virus is the most common in the United States. Although West Nile virus generally causes a self-limited, flulike febrile illness, a serious neuroinvasive form may occur. Dengue is the most common vector-borne viral disease worldwide, and it has been a significant public health threat in the United States since 2009. Known as breakbone fever for its severe myalgias and arthralgias, dengue may cause a hemorrhagic syndrome. Chikungunya also causes flulike febrile illness and disabling arthralgias. Although meningoencephalitis may occur with chikungunya, bleeding is uncommon. Symptoms of Zika virus infection are similar to those of dengue, but milder. Zika virus increases the risk of fetal brain abnormalities, including microcephaly, if a pregnant woman is infected. Zika virus is spread through Aedes albopictus mosquito bites, is transmitted sexually, and may rarely spread nonsexually from person to person. Diagnosis of these vectorborne infections is clinical and serologic, and treatment is supportive. Other, well-established vector-borne diseases are also important. Ehrlichiosis is a tick-borne bacterial disease that presents as a nonspecific syndrome of fever, headache, malaise, and myalgias. It is diagnosed via blood smear testing, with confirmatory serology. Ehrlichiosis is treated with doxycycline. Rickettsial infections are transmitted by fleas, mites, and ticks, and severity ranges from mild to life threatening. Rocky Mountain spotted fever, the most significant rickettsial infection, is primarily a clinical diagnosis that presents as fever, headache, myalgias, petechial rash, and tick exposure. Doxycycline is effective for rickettsial infections if administered promptly. Vector avoidance strategies are critical to the prevention of all of these infections.

  16. Bacterial agents and sensitivity pattern of neonatal conjuctivitis in ...

    African Journals Online (AJOL)

    Introduction: In Africa alone, between 1000 – 4000 children are blinded annually by conjunctivitis. In view of the changing aetiological agents documented in other parts of the world and evolving resistance of infective agents to therapeutic agents, the present study was designed to define the bacterial agents, their antibiotic ...

  17. Chemical Agents

    Science.gov (United States)

    ... CR) see Riot Control Agents Digitalis Distilled mustard (HD) see Sulfur mustard E Ethylene glycol F Fentanyls and other opioids H Hydrazine Hydrofluoric acid (hydrogen fluoride) Hydrogen chloride Hydrogen cyanide (AC) Hydrogen ...

  18. GRASP agents: social first, intelligent later

    NARCIS (Netherlands)

    Hofstede, G.J.

    2017-01-01

    This paper urges that if we wish to give social intelligence to our agents, it pays to look at how we acquired our social intelligence ourselves. We are born with drives and motives that are innate and deeply social. Next, as children we are socialized to acquire norms and values and to understand

  19. The Leeds Evaluation of Efficacy of Detoxification Study (LEEDS project: An open-label pragmatic randomised control trial comparing the efficacy of differing therapeutic agents for primary care detoxification from either street heroin or methadone [ISRCTN07752728

    Directory of Open Access Journals (Sweden)

    Sheard Laura

    2004-04-01

    Full Text Available Abstract Background Heroin is a synthetic opioid with an extensive illicit market leading to large numbers of people becoming addicted. Heroin users often present to community treatment services requesting detoxification and in the UK various agents are used to control symptoms of withdrawal. Dissatisfaction with methadone detoxification 8 has lead to the use of clonidine, lofexidine, buprenorphine and dihydrocodeine; however, there remains limited evaluative research. In Leeds, a city of 700,000 people in the North of England, dihydrocodeine is the detoxification agent of choice. Sublingual buprenorphine, however, is being introduced. The comparative value of these two drugs for helping people successfully and comfortably withdraw from heroin has never been compared in a randomised trial. Additionally, there is a paucity of research evaluating interventions among drug users in the primary care setting. This study seeks to address this by randomising drug users presenting in primary care to receive either dihydrocodeine or buprenorphine. Methods/design The Leeds Evaluation of Efficacy of Detoxification Study (LEEDS project is a pragmatic randomised trial which will compare the open use of buprenorphine with dihydrocodeine for illicit opiate detoxification, in the UK primary care setting. The LEEDS project will involve consenting adults and will be run in specialist general practice surgeries throughout Leeds. The primary outcome will be the results of a urine opiate screening at the end of the detoxification regimen. Adverse effects and limited data to three and six months will be acquired.

  20. Depletion of mammalian O6-alkylguanine-DNA alkyltransferase activity by O6-benzylguanine provides a means to evaluate the role of this protein in protection against carcinogenic and therapeutic alkylating agents

    International Nuclear Information System (INIS)

    Dolan, M.E.; Pegg, A.E.; Moschel, R.

    1990-01-01

    O 6 -Alkylguanine-DNA alkyltransferase was rapidly and irreversibly inactivated by exposure to O 6 -benzylguanine or the p-chlorobenzyl and p-methylbenzyl analogues. This inactivation was much more rapid than with O 6 -methylguanine: incubation with 2.5 μM O 6 -benzylguanine led to more than a 90% loss of activity within 10 min, whereas 0.2 mM O 6 -methylguanine for 60 min was required for the same reduction. O 6 -Benzylguanine was highly effective in depleting the alkyltransferase activity of cultured human colon tumor (HT29) cells. Complete loss of activity was produced within 15 min after addition of O 6 -benzylguanine to the culture medium and a maximal effect was obtained with 5 μM. In contrast, at least 100 μM O 6 -methylguanine for 4 hr was needed to get a maximal effect, and this reduced the alkyltransferase by only 80%. Pretreatment of HT29 cells with 10 μM O 6 -benzylguanine for 2 hr led to a dramatic increase in the cytotoxicity produced by the chemotherapeutic agents 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) or 2-chloroethyl(methylsulfonyl)methanesulfonate (Clomesone). Administration of O 6 -benzylguanine to mice at a dose of 10 mg/kg reduced alkyltransferase levels by more than 95% in both liver and kidney. These results indicate that depletion of the alkyltransferase by O 6 -benzylguanine may be used to investigate the role of the DNA repair protein in carcinogenesis and mutagensis and that this treatment may be valuable to increase the chemotherapeutic effectiveness of chloroethylating agents

  1. Nanoparticles for therapeutic and diagnostic applications

    OpenAIRE

    Chiu, Yin To

    2014-01-01

    Nanomedicine focuses on the development and engineering of novel and unique therapeutic and diagnostic agents that can overcome the challenges associated with using traditional modalities. Nanoparticles (NPs) in the size range between 1 and 1000 nm have many advantages for use in these applications, such as, low polydispersity, established characterization methodologies, and the ability to be loaded with therapeutics for diseases, conjugated to targeting ligands to enhance specificity, and co...

  2. We have "born digital" - now what about "born semantic"?

    Science.gov (United States)

    Leadbetter, Adam; Fredericks, Janet

    2014-05-01

    The phrase "born-digital" refers to those materials which originate in a digital form. In Earth and Space Sciences, this is now very much the norm for data: analogue to digital converters sit on instrument boards and produce a digital record of the observed environment. While much effort has been put in to creating and curating these digital data, there has been little work on using semantic mark up of data from the point of collection - what we term 'born semantic'. In this presentation we report on two efforts to expand this area: Qartod-to-OGC (Q2O) and SenseOCEAN. These projects have taken a common approach to 'born semantic': create or reuse appropriate controlled vocabularies, published to World Wide Web Commission (W3C) standards use standards from the Open Geospatial Consortium's Sensor Web Enablement (SWE) initiative to describe instrument setup, deployment and/or outputs using terms from those controlled vocabularies embed URLs from the controlled vocabularies within the SWE documents in a "Linked Data" conformant approach Q2O developed best practices examples of SensorML descriptions of Original Equipment Manufacturers' metadata (model characteristics, capabilities, manufacturer contact, etc ...) set-up and deployment SensorML files; and data centre process-lineage using registered vocabularies to describe terms (including input, output, processes, parameters, quality control flags) One Q2O use case, the Martha's Vineyard Coastal Observatory ADCP Waves instance, uses SensorML and registered vocabularies to fully describe the process of computing wave parameters from sensed properties, including quality control tests and associated results. The European Commission Framework Programme 7 project SenseOCEAN draws together world leading marine sensor developers to create a highly integrated multifunction and cost-effective in situ marine biogeochemical sensor system. This project will provide a quantum leap in the ability to measure crucial biogeochemical

  3. Surgical experts: born or made?

    Science.gov (United States)

    Sadideen, Hazim; Alvand, Abtin; Saadeddin, Munir; Kneebone, Roger

    2013-01-01

    The concept of surgical expertise and the processes involved in its development are topical, and there is a constant drive to identify reliable measures of expert performance in surgery. This review explores the notion of whether surgical experts are "born" or "made", with reference to educational theory and pertinent literature. Peer-reviewed publications, books, and online resources on surgical education, expertise and training were reviewed. Important themes and aspects of expertise acquisition were identified in order to better understand the concept of a surgical expert. The definition of surgical expertise and several important aspects of its development are highlighted. Innate talent plays an important role, but is insufficient on its own to produce a surgical expert. Multiple theories that explore motor skill acquisition and memory are relevant, and Ericsson's theory of the development of competence followed by deliberate self-practice has been especially influential. Psychomotor and non-technical skills are necessary for progression in the current climate in light of our training curricula; surgical experts are adaptive experts who excel in these. The literature suggests that surgical expertise is reached through practice; surgical experts are made, not born. A deeper understanding of the nature of expert performance and its development will ensure that surgical education training programmes are of the highest possible quality. Surgical educators should aim to develop an expertise-based approach, with expert performance as the benchmark. Copyright © 2013 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

  4. An Overview of Animal Models for Arthropod-Borne Viruses.

    Science.gov (United States)

    Reynolds, Erin S; Hart, Charles E; Hermance, Meghan E; Brining, Douglas L; Thangamani, Saravanan

    2017-06-01

    Arthropod-borne viruses (arboviruses) have continued to emerge in recent years, posing a significant health threat to millions of people worldwide. The majority of arboviruses that are pathogenic to humans are transmitted by mosquitoes and ticks, but other types of arthropod vectors can also be involved in the transmission of these viruses. To alleviate the health burdens associated with arbovirus infections, it is necessary to focus today's research on disease control and therapeutic strategies. Animal models for arboviruses are valuable experimental tools that can shed light on the pathophysiology of infection and will enable the evaluation of future treatments and vaccine candidates. Ideally an animal model will closely mimic the disease manifestations observed in humans. In this review, we outline the currently available animal models for several viruses vectored by mosquitoes, ticks, and midges, for which there are no standardly available vaccines or therapeutics.

  5. Molecular detection of vector-borne bacteria and protozoa in healthy hunting dogs from Central Italy

    Directory of Open Access Journals (Sweden)

    Valentina Virginia Ebani

    2015-02-01

    Conclusions:: The results demonstrated that several vector-borne pathogens were circulating in this region and dogs infected by these agents were usually asymptomatic. A relevant finding was the presence of DNA of C. burnetii, a severe zoonotic agent, in the 5.1% of tested dogs, which can be source of infection for their owners not only through tick bites, but also directly with urine, feces and birth products.

  6. Reactor-produced therapeutic radioisotopes

    International Nuclear Information System (INIS)

    Knapp, F.F. Jr.

    2002-01-01

    The significant worldwide increase in therapeutic radioisotope applications in nuclear medicine, oncology and interventional cardiology requires the dependable production of sufficient levels of radioisotopes for these applications (Reba, 2000; J. Nucl. Med., 1998; Nuclear News, 1999; Adelstein and Manning, 1994). The issues associated with both accelerator- and reactor-production of therapeutic radioisotopes is important. Clinical applications of therapeutic radioisotopes include the use of both sealed sources and unsealed radiopharmaceutical sources. Targeted radiopharmaceutical agents include those for cancer therapy and palliation of bone pain from metastatic disease, ablation of bone marrow prior to stem cell transplantation, treatment modalities for mono and oligo- and polyarthritis, for cancer therapy (including brachytherapy) and for the inhibition of the hyperplastic response following coronary angioplasty and other interventional procedures (For example, see Volkert and Hoffman, 1999). Sealed sources involve the use of radiolabeled devices for cancer therapy (brachytherapy) and also for the inhibition of the hyperplasia which is often encountered after angioplasty, especially with the exponential increase in the use of coronary stents and stents for the peripheral vasculature and other anatomical applications. Since neutron-rich radioisotopes often decay by beta decay or decay to beta-emitting daughter radioisotopes which serve as the basis for radionuclide generator systems, reactors are expected to play an increasingly important role for the production of a large variety of therapeutic radioisotopes required for these and other developing therapeutic applications. Because of the importance of the availability of reactor-produced radioisotopes for these applications, an understanding of the contribution of neutron spectra for radioisotope production and determination of those cross sections which have not yet been established is important. This

  7. Conceptualizing Innovation in Born Global Firms

    DEFF Research Database (Denmark)

    Zijdemans, Erik; Tanev, Stoyan

    2014-01-01

    This research provides insights from recent literature on innovativeness in the environment of born globals. This article will be relevant to researchers interested in born globals and their business environments and, more specifically, the role that innovation plays in their foundation and devel...... of knowledge acquisition, networking capabilities and the lean startup approach in born global innovation. Finally, the article addresses the issue of quantifying and measuring innovativeness....

  8. [Therapeutic use of cannabis derivatives].

    Science.gov (United States)

    Benyamina, Amine; Reynaud, Michel

    2014-02-01

    The therapeutic use of cannabis has generated a lot of interest in the past years, leading to a better understanding of its mechanisms of action. Countries like the United States and Canada have modified their laws in order to make cannabinoid use legal in the medical context. It's also the case in France now, where a recent decree was issued, authorizing the prescription of medication containing "therapeutic cannabis" (decree no. 2013-473, June 5, 2013). Cannabinoids such as dronabinol, Sativex and nabilone have been tested for the treatment of acute and chronic pain. These agents are most promising to relieve chronic pain associated with cancer, with human immunodeficiency virus infection and with multiple sclerosis. However, longer-term studies are required to determine potential long-term adverse effects and risks of misuse and addiction.

  9. Repositioning of Memantine as a Potential Novel Therapeutic Agent against Meningitic E. coli-Induced Pathogenicities through Disease-Associated Alpha7 Cholinergic Pathway and RNA Sequencing-Based Transcriptome Analysis of Host Inflammatory Responses.

    Directory of Open Access Journals (Sweden)

    Jing-Yi Yu

    Full Text Available Neonatal sepsis and meningitis (NSM remains a leading cause worldwide of mortality and morbidity in newborn infants despite the availability of antibiotics over the last several decades. E. coli is the most common gram-negative pathogen causing NSM. Our previous studies show that α7 nicotinic receptor (α7 nAChR, an essential regulator of inflammation, plays a detrimental role in the host defense against NSM. Despite notable successes, there still exists an unmet need for new effective therapeutic approaches to treat this disease. Using the in vitro/in vivo models of the blood-brain barrier (BBB and RNA-seq, we undertook a drug repositioning study to identify unknown antimicrobial activities for known drugs. We have demonstrated for the first time that memantine (MEM, a FDA-approved drug for treatment of Alzheimer's disease, could very efficiently block E. coli-caused bacteremia and meningitis in a mouse model of NSM in a manner dependent on α7 nAChR. MEM was able to synergistically enhance the antibacterial activity of ampicillin in HBMEC infected with E. coli K1 (E44 and in neonatal mice with E44-caused bacteremia and meningitis. Differential gene expression analysis of RNA-Seq data from mouse BMEC infected with E. coli K1 showed that several E44-increased inflammatory factors, including IL33, IL18rap, MMP10 and Irs1, were significantly reduced by MEM compared to the infected cells without drug treatment. MEM could also significantly up-regulate anti-inflammatory factors, including Tnfaip3, CISH, Ptgds and Zfp36. Most interestingly, these factors may positively and negatively contribute to regulation of NF-κB, which is a hallmark feature of bacterial meningitis. Furthermore, we have demonstrated that circulating BMEC (cBMEC are the potential novel biomarkers for NSM. MEM could significantly reduce E44-increased blood level of cBMEC in mice. Taken together, our data suggest that memantine can efficiently block host inflammatory responses to

  10. Interactions of ionic and nonionic contrast agents with thrombolytic agents

    International Nuclear Information System (INIS)

    Fareed, J.; Moncada, R.; Scanlon, P.; Hoppensteadt, D.; Huan, X.; Walenga, J.M.

    1987-01-01

    Both the ionic and nonionic intravascular contrast media have been used before and after the administration of thrombolytic agents to evaluate clot lysis during angioplasty and the treatment of myocardial infarction. In experimental animal models, the authors found that the clot lytic efficacy of streptokinase, streptokinase-plasminogen complex, and tissue plasminogen activator (t-PA) is markedly augmented if these agents are administered within 1 hour after the angiographic producers. Furthermore, contrast agents injected after the administration of t-Pa exhibit a synergistic action. In stimulated models administration of one ionic contrast medium (Angiovist, Berlex, Wayne, NJ) and two nonionic contrast agents (Isovue-370, Squibb Diagnostics, New Brunswick, NJ; Omnipaque-350, Winthrop, NY) 15 minutes before the administration of t-PA resulted in marked enhancement of the lytic activity. Although the mechanism of this interaction is unknown at this time, it should be taken into consideration in the treatment of patients with myocardial infarction, in whom contrast agents are continually used to evaluate the therapeutic lysis. Furthermore, this interaction may be partly related to the therapeutic efficacy and/or hemorrhagic actions observed

  11. [Biological agents].

    Science.gov (United States)

    Amano, Koichi

    2009-03-01

    There are two types of biological agents for the treatment of rheumatoid arthritis (RA); monoclonal antibodies and recombinant proteins. Among the latter, etanercept, a recombinant fusion protein of soluble TNF receptor and IgG was approved in 2005 in Japan. The post-marketing surveillance of 13,894 RA patients revealed the efficacy and safety profiles of etanercept in the Japanese population, as well as overseas studies. Abatacept, a recombinant fusion protein of CTLA4 and IgG, is another biological agent for RA. Two clinical trials disclosed the efficacy of abatacept for difficult-to-treat patients: the AIM for MTX-resistant cases and the ATTAIN for patients who are resistant to anti-TNF. The ATTEST trial suggested abatacept might have more acceptable safety profile than infliximab. These biologics are also promising for the treatment of RA for not only relieving clinical symptoms and signs but retarding structural damage.

  12. Vector-Borne Infections in Tornado-Displaced and Owner-Relinquished Dogs in Oklahoma, USA.

    Science.gov (United States)

    Barrett, Anne W; Little, Susan E

    2016-06-01

    To determine the prevalence of infection with vector-borne agents in a cross-section of dogs from Oklahoma, where canine vector-borne diseases are common, blood samples were evaluated through serology and molecular analysis. Antibodies reactive to Ehrlichia spp., Rickettsia rickettsii, R. montanensis, and "R. amblyommii" were detected in 10.5% (11/105), 74.3% (78/105), 58.1% (61/105), and 55.2% (58/105) of dogs, respectively. Presence of spotted fever group Rickettsia spp. DNA was identified in 13.1% (8/61) of shelter dogs but not in any pet dogs (0/44). DNA of "R. amblyommii" was confirmed by sequencing, constituting the first report of this agent in a naturally infected dog. Antigen of Dirofilaria immitis was detected in 10.5% (11/105) and 16.2% (17/105) of samples before and after heat treatment, respectively. In total, 87.6% (92/105) of the dogs had evidence of infection with at least one vector-borne disease agent, confirming high risk of exposure to multiple vector-borne disease agents, several of which are zoonotic.

  13. Non- chemical methods of seed treatment for control of seed- borne pathogens on vegetables

    NARCIS (Netherlands)

    Amein, T.; Wright, S.A.I.; Wickstrom, M.; Schmitt, A.; Koch, E.; Wolf, van der J.M.; Groot, S.P.C.; Werner, S.; Jahn, M.

    2006-01-01

    The aim of EU-project "Seed Treatments for Organic Vegetable Production" (STOVE) was to evaluate non-chemical methods for control of seed-borne pathogens in organic vegetable production. Physical (hot air, hot water and electron) and biologi-cal (microorganisms and different agents of natural

  14. [Antiangiogenic agents in ARMD treatment].

    Science.gov (United States)

    Coroi, Mihaela-Cristiana; Demea, Sorina; Todor, Meda; Apopei, Emmanuela

    2012-01-01

    The aim of antiangiogenic agents in the treatment of age related senile macular degeneration is to destroy coroidian neoformation vessels by minimally affecting the central vision. We present a case of important central vision recovery after 3 intravitreal injections of Avastin. The therapeutic decision and patient monitoring have been made using imaging studies, such as OCT and AFG. A modern therapeutic approach of neovascular forms of age related macular degeneration, backed up by AFG and OCT is a modern treatment method of this disabling illness which brings patients optimal functional and structural improvement.

  15. Immunological effects of hypomethylating agents.

    Science.gov (United States)

    Lindblad, Katherine E; Goswami, Meghali; Hourigan, Christopher S; Oetjen, Karolyn A

    2017-08-01

    Epigenetic changes resulting from aberrant methylation patterns are a recurrent observation in hematologic malignancies. Hypomethylating agents have a well-established role in the management of patients with high-risk myelodysplastic syndrome or acute myeloid leukemia. In addition to the direct effects of hypomethylating agents on cancer cells, there are several lines of evidence indicating a role for immune-mediated anti-tumor benefits from hypomethylating therapy. Areas covered: We reviewed the clinical and basic science literature for the effects of hypomethylating agents, including the most commonly utilized therapeutics azacitidine and decitabine, on immune cell subsets. We summarized the effects of hypomethylating agents on the frequency and function of natural killer cells, T cells, and dendritic cells. In particular, we highlight the effects of hypomethylating agents on expression of immune checkpoint inhibitors, leukemia-associated antigens, and endogenous retroviral elements. Expert commentary: In vitro and ex vivo studies indicate mixed effects on the function of natural killer, dendritic cells and T cells following treatment with hypomethylating agents. Clinical correlates of immune function have suggested that hypomethylating agents have immunomodulatory functions with the potential to synergize with immune checkpoint therapy for the treatment of hematologic malignancy, and has become an active area of clinical research.

  16. Inhibiting DNA Polymerases as a Therapeutic Intervention against Cancer

    Directory of Open Access Journals (Sweden)

    Anthony J. Berdis

    2017-11-01

    Full Text Available Inhibiting DNA synthesis is an important therapeutic strategy that is widely used to treat a number of hyperproliferative diseases including viral infections, autoimmune disorders, and cancer. This chapter describes two major categories of therapeutic agents used to inhibit DNA synthesis. The first category includes purine and pyrmidine nucleoside analogs that directly inhibit DNA polymerase activity. The second category includes DNA damaging agents including cisplatin and chlorambucil that modify the composition and structure of the nucleic acid substrate to indirectly inhibit DNA synthesis. Special emphasis is placed on describing the molecular mechanisms of these inhibitory effects against chromosomal and mitochondrial DNA polymerases. Discussions are also provided on the mechanisms associated with resistance to these therapeutic agents. A primary focus is toward understanding the roles of specialized DNA polymerases that by-pass DNA lesions produced by DNA damaging agents. Finally, a section is provided that describes emerging areas in developing new therapeutic strategies targeting specialized DNA polymerases.

  17. Food-borne pathogens, health and role of dietary phytochemicals.

    Science.gov (United States)

    Shetty, K; Labbe, R G

    1998-12-01

    Infectious diseases transmitted by food have become a major public health concern in recent years. In the USA alone, there are an estimated 6-33 million cases each year. The list of responsible agents continues to grow. In the past 20 years some dozen new pathogens that are primarily food-borne have been identified. Fruits and vegetables, often from the global food market, have been added to the traditional vehicles of food-borne illness; that is, undercooked meat, poultry, seafood, or unpasteurized milk. Such products are minimally processed and have fewer barriers to microbial growth such as salt, sugar or preservatives. The evolution of the epidemiology of food-borne illness requires a rethinking of traditional, though still valid, solutions for their prevention. Among various strategies to prevent food-borne pathogens, use of dietary phytochemicals is promising. The major obstacle in the use of dietary phytochemical is the consistency of phytochemicals in different foods due to their natural genetic variation. We have developed a novel tissue-culture-based selection strategy to isolate elite phenolic phytochemical-producing clonal lines of species belonging to the family Lamiaceae. Among several species we have targeted elite clonal lines of thyme (Thymus vulgaris) and oregano (Origanum vulgare) against Escherichia coli and Clostridium perfrigens in fresh and processed meats. We are also evaluating high phenolic profile-containing clonal lines of basil (Ocimum basilicum) to inhibit gastric ulcer-causing Helicobacter pylori. Other elite lines of the members of the family Lamiaceae, rosemary (Rosmarinus officinalis) and salvia (Salvia officinalis) also hold promise against a wide range of food pathogens such as Salmonella species in poultry products and Vibrio species in seafood.

  18. Trading Agents

    CERN Document Server

    Wellman, Michael

    2011-01-01

    Automated trading in electronic markets is one of the most common and consequential applications of autonomous software agents. Design of effective trading strategies requires thorough understanding of how market mechanisms operate, and appreciation of strategic issues that commonly manifest in trading scenarios. Drawing on research in auction theory and artificial intelligence, this book presents core principles of strategic reasoning that apply to market situations. The author illustrates trading strategy choices through examples of concrete market environments, such as eBay, as well as abst

  19. Non-abelian Born-Infeld revisited

    NARCIS (Netherlands)

    Roo, M. de

    2002-01-01

    We discuss the non-abelian Born-Infeld action, including fermions, as a series in α'. We review recent work establishing the complete result to α'2, and its impact on our earlier attempts to derive the Born-Infeld action using κ-symmetry.

  20. [Climate- and vector-borne diseases

    DEFF Research Database (Denmark)

    Bygbjerg, I.C.; Schioler, K.L.; Konradsen, F.

    2009-01-01

    The predicted changes in climate have raised concerns that vector-borne diseases may emerge or expand in tempered regions. Malaria, leishmaniasis and tick-borne illnesses are discussed in terms of climate change and their endemic potential, especially in Denmark. While climate may play an important...

  1. Therapeutic improvement of colonic anastomotic healing under complicated conditions

    DEFF Research Database (Denmark)

    Nerstrøm, Malene; Krarup, Peter-Martin; Jørgensen, Lars Nannestad

    2016-01-01

    AIM: To identify therapeutic agents for the prophylaxis of gastrointestinal anastomotic leakage (AL) under complicated conditions. METHODS: The PubMed and EMBASE databases were searched for English articles published between January 1975 and September 2014. Studies with the primary purpose of imp...... controls in experimental chemotherapeutic models. CONCLUSION: This systematic review identified potential therapeutic agents, but more studies are needed before concluding that any of these are useful for AL prophylaxis....

  2. Purinergic Signalling: Therapeutic Developments

    Directory of Open Access Journals (Sweden)

    Geoffrey Burnstock

    2017-09-01

    Full Text Available Purinergic signalling, i.e., the role of nucleotides as extracellular signalling molecules, was proposed in 1972. However, this concept was not well accepted until the early 1990’s when receptor subtypes for purines and pyrimidines were cloned and characterised, which includes four subtypes of the P1 (adenosine receptor, seven subtypes of P2X ion channel receptors and 8 subtypes of the P2Y G protein-coupled receptor. Early studies were largely concerned with the physiology, pharmacology and biochemistry of purinergic signalling. More recently, the focus has been on the pathophysiology and therapeutic potential. There was early recognition of the use of P1 receptor agonists for the treatment of supraventricular tachycardia and A2A receptor antagonists are promising for the treatment of Parkinson’s disease. Clopidogrel, a P2Y12 antagonist, is widely used for the treatment of thrombosis and stroke, blocking P2Y12 receptor-mediated platelet aggregation. Diquafosol, a long acting P2Y2 receptor agonist, is being used for the treatment of dry eye. P2X3 receptor antagonists have been developed that are orally bioavailable and stable in vivo and are currently in clinical trials for the treatment of chronic cough, bladder incontinence, visceral pain and hypertension. Antagonists to P2X7 receptors are being investigated for the treatment of inflammatory disorders, including neurodegenerative diseases. Other investigations are in progress for the use of purinergic agents for the treatment of osteoporosis, myocardial infarction, irritable bowel syndrome, epilepsy, atherosclerosis, depression, autism, diabetes, and cancer.

  3. Dental therapeutic systems.

    Science.gov (United States)

    Iqbal, Zeenat; Jain, Nilu; Jain, Gaurav K; Talegaonkar, Sushama; Ahuja, Alka; Khar, Roop K; Ahmad, Farhan J

    2008-01-01

    The recognition of periodontal diseases as amenable to local antibiotherapy has resulted in a paradigmatic shift in treatment modalities of dental afflictions. Moreover the presence of antimicrobial resistance, surfacing of untoward reactions owing to systemic consumption of antibiotics has further advocated the use of local delivery of physiologically active substances into the periodontal pocket. While antimicrobials polymerized into acrylic strips, incorporated into biodegradable collagen and hollow permeable cellulose acetate fibers, multiparticulate systems, bio-absorbable dental materials, biodegradable gels/ointments, injectables, mucoadhesive microcapsules and nanospheres will be more amenable for direct placement into the periodontal pockets the lozenges, buccoadhesive tablets, discs or gels could be effectively used to mitigate the overall gingival inflammation. Whilst effecting controlled local delivery of a few milligram of an antibacterial agent within the gingival crevicular fluid for a longer period of time, maintaining therapeutic concentrations such delivery devices will circumvent all adverse effects to non- oral sites. Since the pioneering efforts of Goodson and Lindhe in 1989, delivery at gingival and subgingival sites has witnessed a considerable progress. The interest in locally active systems is evident from the patents being filed and granted. The present article shall dwell in reviewing the recent approaches being proffered in the field. Patents as by Shefer, et al. US patent, 6589562 dealing with multicomponent biodegradable bioadhesive controlled release system for oral care products, Lee, et al. 2001, US patent 6193994, encompassing a locally administrable, biodegradable and sustained-release pharmaceutical composition for periodontitis and process for preparation thereof and method of treating periodontal disease as suggested by Basara in 2004via US patent 6830757, shall be the types of intellectual property reviewed and presented in

  4. Radioprotective Agents

    Directory of Open Access Journals (Sweden)

    Ilker Kelle

    2008-01-01

    Full Text Available Since1949, a great deal of research has been carried out on the radioprotective activity of various chemical substances. Thiol compounds, compounds which contain –SH radical, different classes of pharmacological agents and other compounds such as vitamine C and WR-2721 have been shown to reduce mortality when administered prior to exposure to a lethal dose of radiation. Recently, honey bee venom as well as that of its components melittin and histamine have shown to be valuable in reduction of radiation-induced damage and also provide prophylactic alternative treatment for serious side effects related with radiotherapy. It has been suggested that the radioprotective activity of bee venom components is related with the stimulation of the hematopoetic system.

  5. Validation of Born Traveltime Kernels

    Science.gov (United States)

    Baig, A. M.; Dahlen, F. A.; Hung, S.

    2001-12-01

    Most inversions for Earth structure using seismic traveltimes rely on linear ray theory to translate observed traveltime anomalies into seismic velocity anomalies distributed throughout the mantle. However, ray theory is not an appropriate tool to use when velocity anomalies have scale lengths less than the width of the Fresnel zone. In the presence of these structures, we need to turn to a scattering theory in order to adequately describe all of the features observed in the waveform. By coupling the Born approximation to ray theory, the first order dependence of heterogeneity on the cross-correlated traveltimes (described by the Fréchet derivative or, more colourfully, the banana-doughnut kernel) may be determined. To determine for what range of parameters these banana-doughnut kernels outperform linear ray theory, we generate several random media specified by their statistical properties, namely the RMS slowness perturbation and the scale length of the heterogeneity. Acoustic waves are numerically generated from a point source using a 3-D pseudo-spectral wave propagation code. These waves are then recorded at a variety of propagation distances from the source introducing a third parameter to the problem: the number of wavelengths traversed by the wave. When all of the heterogeneity has scale lengths larger than the width of the Fresnel zone, ray theory does as good a job at predicting the cross-correlated traveltime as the banana-doughnut kernels do. Below this limit, wavefront healing becomes a significant effect and ray theory ceases to be effective even though the kernels remain relatively accurate provided the heterogeneity is weak. The study of wave propagation in random media is of a more general interest and we will also show our measurements of the velocity shift and the variance of traveltime compare to various theoretical predictions in a given regime.

  6. Avian Diagnostic and Therapeutic Antibodies

    Energy Technology Data Exchange (ETDEWEB)

    Bradley, David Sherman [UND SMHS

    2012-12-31

    A number of infectious agents have the potential of causing significant clinical symptomology and even death, but dispite this, the number of incidence remain below the level that supports producing a vaccine. Therapeutic antibodies provide a viable treatment option for many of these diseases. We proposed that antibodies derived from West Nile Virus (WNV) immunized geese would be able to treat WNV infection in mammals and potential humans. We demonstrated that WNV specific goose antibodies are indeed successful in treating WNV infection both prophylactically and therapeutically in a golden hamster model. We demonstrated that the goose derived antibodies are non-reactogenic, i.e. do not cause an inflammatory response with multiple exposures in mammals. We also developed both a specific pathogen free facility to house the geese during the antibody production phase and a patent-pending purification process to purify the antibodies to greater than 99% purity. Therefore, the success of these study will allow a cost effective rapidly producible therapeutic toward clinical testing with the necessary infrastructure and processes developed and in place.

  7. Physical Fitness in Young Adults Born Preterm.

    Science.gov (United States)

    Tikanmäki, Marjaana; Tammelin, Tuija; Sipola-Leppänen, Marika; Kaseva, Nina; Matinolli, Hanna-Maria; Miettola, Satu; Eriksson, Johan G; Järvelin, Marjo-Riitta; Vääräsmäki, Marja; Kajantie, Eero

    2016-01-01

    Young adults born preterm have higher levels of cardiometabolic risk factors than their term-born peers. Muscular and cardiorespiratory fitness have important cardiometabolic and other health benefits. We assessed muscular, cardiorespiratory, and self-rated fitness in preterm-born young adults. We studied unimpaired participants of the ESTER (Ennenaikainen syntymä ja aikuisiän terveys [Preterm Birth and Early-Life Programming of Adult Health and Disease]) birth cohort study at age 23.3 (SD: 1.2) years: 139 born early preterm (EPT; Young adults born EPT (-0.8; 95% confidence interval: -1.5 to -0.1; adjusted for gender, age, and source cohort) and LPT (-0.8; -1.4 to -0.3) performed fewer modified push-ups than controls. Handgrip strength was 23.8 (0.9-46.8) N lower in EPT participants. Cardiorespiratory fitness, measured by submaximal step test, was similar. On a self-rated fitness scale (1-5), the EPT adults reported 0.2 (0.0-0.4) lower scores than controls. After adjustment for early-life confounders, the results remained. They attenuated after further adjustment for mediating factors. Young adults born EPT and LPT had lower muscular fitness than controls, which may predispose them to cardiometabolic and other chronic diseases. Adults born EPT also perceived themselves as less fit than controls. Copyright © 2016 by the American Academy of Pediatrics.

  8. [Climate- and vector-borne diseases

    DEFF Research Database (Denmark)

    Bygbjerg, I.C.; Schioler, K.L.; Konradsen, F.

    2009-01-01

    The predicted changes in climate have raised concerns that vector-borne diseases may emerge or expand in tempered regions. Malaria, leishmaniasis and tick-borne illnesses are discussed in terms of climate change and their endemic potential, especially in Denmark. While climate may play an important...... role in disease patterns, it is evident that transmission potential is governed by a complex of factors, including socio-economy, health-care capacity and ecology. In Denmark, malaria and leishmaniasis are unlikely to become public health problems, whereas the potential for tick-borne illnesses may...

  9. Pathogenic agents in freshwater resources

    Science.gov (United States)

    Geldreich, Edwin E.

    1996-02-01

    Numerous pathogenic agents have been found in freshwaters used as sources for water supplies, recreational bathing and irrigation. These agents include bacterial pathogens, enteric viruses, several protozoans and parasitic worms more common to tropical waters. Although infected humans are a major source of pathogens, farm animals (cattle, sheep, pigs), animal pets (dogs, cats) and wildlife serve as significant reservoirs and should not be ignored. The range of infected individuals within a given warm-blooded animal group (humans included) may range from 1 to 25%. Survival times for pathogens in the water environment may range from a few days to as much as a year (Ascaris, Taenia eggs), with infective dose levels varying from one viable cell for several primary pathogenic agents to many thousands of cells for a given opportunistic pathogen.As pathogen detection in water is complex and not readily incorporated into routine monitoring, a surrogate is necessary. In general, indicators of faecal contamination provide a positive correlation with intestinal pathogen occurrences only when appropriate sample volumes are examined by sensitive methodology.Pathways by which pathogens reach susceptible water users include ingestion of contaminated water, body contact with polluted recreational waters and consumption of salad crops irrigated by polluted freshwaters. Major contributors to the spread of various water-borne pathogens are sewage, polluted surface waters and stormwater runoff. All of these contributions are intensified during periods of major floods. Several water-borne case histories are cited as examples of breakdowns in public health protection related to water supply, recreational waters and the consumption of contaminated salad crops. In the long term, water resource management must focus on pollution prevention from point sources of waste discharges and the spread of pathogens in watershed stormwater runoff.

  10. Oncolytic Viruses: Therapeutics With an Identity Crisis

    Directory of Open Access Journals (Sweden)

    Caroline J. Breitbach

    2016-07-01

    Full Text Available Oncolytic viruses (OV are replicating viral therapeutics for the treatment of cancer and have been in laboratory development for about twenty years. Recently, the FDA approved Imlygic, a herpes virus based therapeutic for the treatment of melanoma and thus OVs have entered a new era where they are a weapon in the armament of the oncologist. OVs are unique therapeutics with multiple mechanisms of therapeutic activity. The exact path for their development and eventual uptake by pharmaceutical companies is somewhat clouded by an uncertain identity. Are they vaccines, tumour lysing therapeutics, inducers of innate immunity, gene therapy vectors, anti-vascular agents or all of the above? Should they be developed as stand-alone loco-regional therapeutics, systemically delivered tumour hunters or immune modulators best tested as combination therapeutics? We summarize data here supporting the idea, depending upon the virus, that OVs can be any or all of these things. Pursuing a “one-size fits all” approach is counter-productive to their clinical development and instead as a field we should build on the strengths of individual virus platforms.

  11. Nutraceuticals as potential therapeutic agents for colon cancer: a review

    OpenAIRE

    Kuppusamy, Palaniselvam; Yusoff, Mashitah M.; Maniam, Gaanty Pragas; Ichwan, Solachuddin Jauhari Arief; Soundharrajan, Ilavenil; Govindan, Natanamurugaraj

    2014-01-01

    Colon cancer is a world-wide health problem and the second-most dangerous type of cancer, affecting both men and women. The modern diet and lifestyles, with high meat consumption and excessive alcohol use, along with limited physical activity has led to an increasing mortality rate for colon cancer worldwide. As a result, there is a need to develop novel and environmentally benign drug therapies for colon cancer. Currently, nutraceuticals play an increasingly important role in the treatment o...

  12. Nutraceuticals as potential therapeutic agents for colon cancer: a review.

    Science.gov (United States)

    Kuppusamy, Palaniselvam; Yusoff, Mashitah M; Maniam, Gaanty Pragas; Ichwan, Solachuddin Jauhari Arief; Soundharrajan, Ilavenil; Govindan, Natanamurugaraj

    2014-06-01

    Colon cancer is a world-wide health problem and the second-most dangerous type of cancer, affecting both men and women. The modern diet and lifestyles, with high meat consumption and excessive alcohol use, along with limited physical activity has led to an increasing mortality rate for colon cancer worldwide. As a result, there is a need to develop novel and environmentally benign drug therapies for colon cancer. Currently, nutraceuticals play an increasingly important role in the treatment of various chronic diseases such as colon cancer, diabetes and Alzheimer׳s disease. Nutraceuticals are derived from various natural sources such as medicinal plants, marine organisms, vegetables and fruits. Nutraceuticals have shown the potential to reduce the risk of colon cancer and slow its progression. These dietary substances target different molecular aspects of colon cancer development. Accordingly, this review briefly discusses the medicinal importance of nutraceuticals and their ability to reduce the risk of colorectal carcinogenesis.

  13. Tanshinones as Effective Therapeutic Agents for Prostate Cancer

    Science.gov (United States)

    2011-06-01

    Y. Tian, T.-F. Chen, W. Ye, L. Li, F. Ni, J.-R. Zhou: Construction and screening of fractional library of Salvia Miltiorrhiza for the rapid...glutathione perturbation. Food Chem Toxicol 2008;46: 328–38. 19. Singh AV, Franke AA, Blackburn GL, Zhou JR. Soy phytochemicals prevent orthotopic growth and

  14. The Chemistry of Curcumin: From Extraction to Therapeutic Agent

    Directory of Open Access Journals (Sweden)

    Kavirayani Indira Priyadarsini

    2014-12-01

    Full Text Available Curcumin, a pigment from turmeric, is one of the very few promising natural products that has been extensively investigated by researchers from both the biological and chemical point of view. While there are several reviews on the biological and pharmacological effects of curcumin, chemistry reviews are comparatively scarcer. In this article, an overview of different aspects of the unique chemistry research on curcumin will be discussed. These include methods for the extraction from turmeric, laboratory synthesis methods, chemical and photochemical degradation and the chemistry behind its metabolism. Additionally other chemical reactions that have biological relevance like nucleophilic addition reactions, and metal chelation will be discussed. Recent advances in the preparation of new curcumin nanoconjugates with metal and metal oxide nanoparticles will also be mentioned. Directions for future investigations to be undertaken in the chemistry of curcumin have also been suggested.

  15. Flavonoids as Chemopreventive and Therapeutic Agents Against Lung Cancer

    Directory of Open Access Journals (Sweden)

    Albert Cabrera

    2014-05-01

    Full Text Available The objective of the present review is to study the relationship between flavonoids and lung cancer, proposing that their regular consumption in Western diets could be beneficial for protecting patients against lung cancer. An extensive search of the scientific literature was performed in the following electronic specialized databases (PubMed central (PMC-NBCI, Elsevier Journal, SciELO Spain, Scirus, Science Direct, including studies in animals, cells, and humans, in order to establish the effect of flavonoids in the prevention and development of lung cancer. Although in vitro and animal studies show the potential ability of flavonoids to act against different types of cancers, especially against lung cancers, the diverse results reported within epidemiological studies, together with the lack of experiments in humans, are the major factors in limiting making dietary recommendations based on scientific evidence for the management of patients with lung cancer. Therefore, the authors of the present study recommend following the dietary health practice guidelines which promotes the consumption of food enriched in flavonoids and reflects the current state of knowledge of an effective and appropriate diet in lung cancer patients.Erratum in: Rev Esp Nutr Hum Diet. 2013;17(2:91-92Link: http://www.renhyd.org/index.php/renhyd/article/view/6/17

  16. Nutraceuticals as potential therapeutic agents for colon cancer: a review

    Directory of Open Access Journals (Sweden)

    Palaniselvam Kuppusamy

    2014-06-01

    Full Text Available Colon cancer is a world-wide health problem and the second-most dangerous type of cancer, affecting both men and women. The modern diet and lifestyles, with high meat consumption and excessive alcohol use, along with limited physical activity has led to an increasing mortality rate for colon cancer worldwide. As a result, there is a need to develop novel and environmentally benign drug therapies for colon cancer. Currently, nutraceuticals play an increasingly important role in the treatment of various chronic diseases such as colon cancer, diabetes and Alzheimer׳s disease. Nutraceuticals are derived from various natural sources such as medicinal plants, marine organisms, vegetables and fruits. Nutraceuticals have shown the potential to reduce the risk of colon cancer and slow its progression. These dietary substances target different molecular aspects of colon cancer development. Accordingly, this review briefly discusses the medicinal importance of nutraceuticals and their ability to reduce the risk of colorectal carcinogenesis.

  17. Polyphenols as potential therapeutical agents against cardiovascular diseases.

    Science.gov (United States)

    Curin, Yann; Andriantsitohaina, Ramaroson

    2005-01-01

    Increasing evidence suggests that polyphenols from fruits, vegetables and beverages such as wine and tea may exert protective effects on the cardiovascular system. Indeed, research in the field of polyphenols points out their antioxidant and free radical scavenging properties, leading to lower low-density lipoprotein (LDL) oxidation and platelet aggregation. These compounds are also able to modulate the generation of nitric oxide (NO) from vascular endothelium and to interfere with the mechanisms leading to inflammation and endothelial apoptosis, contributing to the prevention of the endothelial dysfunction, known to play a central role in the pathogenesis of cardiovascular diseases. This article reviews the potential targets of polyphenols involved in the complex pathophysiological events occurring in cardiovascular diseases, such as hypertension, atherosclerosis and stroke.

  18. [Phenibut potentiation of the therapeutic action of antiparkinson agents].

    Science.gov (United States)

    Gol'dblat, Iu V; Lapin, I P

    1986-01-01

    It was observed in experiments on mice that the central action of phenibut (beta-phenyl-gamma-aminobutyric acid) diminished after destruction of brain dopaminergic neurons by 6-hydroxydopamine and after pretreatment with the dopamine receptor blocker haloperidol which suggests the dopaminergic component in the action of phenibut. In 13 of 16 patients receiving long-term treatment with antiparkinsonic drugs, addition of phenibut (0.25 g thrice daily for 10 days) resulted in marked clinical improvement with a significant increase of motor activity, as well as diminution of both rigidity and tremor. Follow-up showed a significant lowering of muscle tone of rigid muscles, augmentation of their strength and amplitude of movements. In 8 patients receiving phenibut without antiparkinsonic drugs the results were negligible.

  19. Wortmannin as Targeted Therapeutic Agent for the Treatment of ...

    African Journals Online (AJOL)

    (7 mg/kg) in DMSO daily intraperitoneally whereas the animals in control groups received an equal volume of DMSO for 21 days after the cancer attained palpable stage. Western blot analysis was carried out using enhanced chemiluminescence reagent while Protean IEF cell unit was used for 1-D electrophoresis. Results: ...

  20. Structure-borne noise at hotels

    Science.gov (United States)

    Wilson, George Paul; Jue, Deborah A.

    2002-11-01

    Hotels present a challenging environment for building designers to provide suitable noise and vibration isolation between very incompatible uses. While many are familiar with ways to reduce traditional sources of airborne noise and vibration, structure-borne noise and vibration are often overlooked, often with costly repercussions. Structure-borne noise can be very difficult to pinpoint, and troubleshooting the sources of the vibration can be a tedious process. Therefore, the best approach is to avoid the problem altogether during design, with attention to the building construction, potential vibration sources, building uses and equipment locations. In this paper, the relationship between structure-borne vibration and noise are reviewed, typical vibration sources discussed (e.g., aerobic rooms, laundry rooms, mechanical equipment/building services, and subway rail transit), and key details and design guidance to minimize structure-borne noise provided.

  1. On Born approximation in black hole scattering

    Science.gov (United States)

    Batic, D.; Kelkar, N. G.; Nowakowski, M.

    2011-12-01

    A massless field propagating on spherically symmetric black hole metrics such as the Schwarzschild, Reissner-Nordström and Reissner-Nordström-de Sitter backgrounds is considered. In particular, explicit formulae in terms of transcendental functions for the scattering of massless scalar particles off black holes are derived within a Born approximation. It is shown that the conditions on the existence of the Born integral forbid a straightforward extraction of the quasi normal modes using the Born approximation for the scattering amplitude. Such a method has been used in literature. We suggest a novel, well defined method, to extract the large imaginary part of quasinormal modes via the Coulomb-like phase shift. Furthermore, we compare the numerically evaluated exact scattering amplitude with the Born one to find that the approximation is not very useful for the scattering of massless scalar, electromagnetic as well as gravitational waves from black holes.

  2. Pap Tests and Foreign-Born Women

    Centers for Disease Control (CDC) Podcasts

    Foreign-born women living in the U.S. are less likely to have Pap tests to detect cervical cancer than women born in this country. The problem is worse for women from certain countries or regions. Find out why this is a disturbing trend, who these women are and why they are less likely to get a Pap test, and what CDC is doing about it.

  3. Foreign-born Peers and Academic Performance.

    Science.gov (United States)

    Conger, Dylan

    2015-04-01

    The academic performance of foreign-born youth in the United States is well studied, yet little is known about whether and how foreign-born students influence their classmates. In this article, I develop a set of expectations regarding the potential consequences of immigrant integration across schools, with a distinction between the effects of sharing schools with immigrants who are designated as English language learners (ELL) and those who are not. I then use administrative data on multiple cohorts of Florida public high school students to estimate the effect of immigrant shares on immigrant and native-born students' academic performance. The identification strategy pays careful attention to the selection problem by estimating the effect of foreign-born peers from deviations in the share foreign-born across cohorts of students attending the same school in different years. The assumption underlying this approach is that students choose schools based on the composition of the entire school, not on the composition of each entering cohort. The results of the analysis, which hold under several robustness checks, indicate that foreign-born peers (both those who are ELL and those who are non-ELL) have no effect on their high school classmates' academic performance.

  4. Dendrimer Advances for the Central Nervous System Delivery of Therapeutics

    Science.gov (United States)

    2013-01-01

    The effectiveness of noninvasive treatment for central nervous system (CNS) diseases is generally limited by the poor access of therapeutic agents into the CNS. Most CNS drugs cannot permeate into the brain parenchyma because of the blood-brain barrier (BBB), and overcoming this has become one of the most significant challenges in the development of CNS therapeutics. Rapid advances in nanotechnology have provided promising solutions to this challenge. This review discusses the latest applications of dendrimers in the treatment of CNS diseases with an emphasis on brain tumors. Dendrimer-mediated drug delivery, imaging, and diagnosis are also reviewed. The toxicity, biodistribution, and transport mechanisms in dendrimer-mediated delivery of CNS therapeutic agents bypassing or crossing the BBB are also discussed. Future directions and major challenges of dendrimer-mediated delivery of CNS therapeutic agents are included. PMID:24274162

  5. Dendrimer advances for the central nervous system delivery of therapeutics.

    Science.gov (United States)

    Xu, Leyuan; Zhang, Hao; Wu, Yue

    2014-01-15

    The effectiveness of noninvasive treatment for central nervous system (CNS) diseases is generally limited by the poor access of therapeutic agents into the CNS. Most CNS drugs cannot permeate into the brain parenchyma because of the blood-brain barrier (BBB), and overcoming this has become one of the most significant challenges in the development of CNS therapeutics. Rapid advances in nanotechnology have provided promising solutions to this challenge. This review discusses the latest applications of dendrimers in the treatment of CNS diseases with an emphasis on brain tumors. Dendrimer-mediated drug delivery, imaging, and diagnosis are also reviewed. The toxicity, biodistribution, and transport mechanisms in dendrimer-mediated delivery of CNS therapeutic agents bypassing or crossing the BBB are also discussed. Future directions and major challenges of dendrimer-mediated delivery of CNS therapeutic agents are included.

  6. Sonochemically born proteinaceous micro- and nanocapsules.

    Science.gov (United States)

    Vassileva, Elena D; Koseva, Neli S

    2010-01-01

    The use of proteins as a substrate in the fabrication of micro- and nanoparticulate systems has attracted the interest of scientists, manufactures, and consumers. Albumin-derived particles were commercialized as contrast agents or anticancer therapeutics. Food proteins are widely used in formulated dietary products. The potential benefits of proteinaceous micro- and nanoparticles in a wide range of biomedical applications are indisputable. Protein-based particles are highly biocompatible and biodegradable structures that can impart bioadhesive properties or mediate particle uptake by specific interactions with the target cells. Currently, protein microparticles are engineered as vehicles for covalent attachment and/or encapsulation of bioactive compounds, contrast agents for magnetic resonance imaging, thermometric and oximetric imaging, sonography and optical coherence tomography, etc. Ultrasound irradiation is a versatile technique which is widely used in many and different fields as biology, biochemistry, dentistry, geography, geology, medicine, etc. It is generally recognized as an environmental friendly, cost-effective method which is easy to be scaled up. Currently, it is mainly applied for homogenization, drilling, cleaning, etc. in industry, as well for noninvasive scanning of the human body, treatment of muscle strains, dissolution of blood clots, and cancer therapy. Proteinaceous micro- and nanocapsules could be easily produced in a one-step process by applying ultrasound to an aqueous protein solution. The origin of this process is in the chemical changes, for example, sulfhydryl groups oxidation, that takes place as a result of acoustically generated cavitation. Partial denaturation of the protein most probably occurs which makes the hydrophobic interactions dominant and also responsible for the formation of stable capsules. This chapter aims to present the current state-of-the-art in the field of sonochemically produced protein micro- and nanocapsules

  7. Gallium a unique anti-resorptive agent in bone: Preclinical studies on its mechanisms of action

    International Nuclear Information System (INIS)

    Bockman, R.; Adelman, R.; Donnelly, R.; Brody, L.; Warrell, R.; Jones, K.W.

    1990-01-01

    The discovery of gallium as a new and unique agent for the treatment of metabolic bone disorders was in part fortuitous. Gallium is an exciting new therapeutic agent for the treatment of pathologic states characterized by accelerated bone resorption. Compared to other therapeutic metal compounds containing platinum or germanium, gallium affects its antiresorptive action without any evidence of a cytotoxic effect on bone cells. Gallium is unique amongst all therapeutically available antiresorptive agents in that it favors bone formation. 18 refs., 1 fig

  8. Urbanization, land tenure security and vector-borne Chagas disease

    Science.gov (United States)

    Levy, Michael Z.; Barbu, Corentin M.; Castillo-Neyra, Ricardo; Quispe-Machaca, Victor R.; Ancca-Juarez, Jenny; Escalante-Mejia, Patricia; Borrini-Mayori, Katty; Niemierko, Malwina; Mabud, Tarub S.; Behrman, Jere R.; Naquira-Velarde, Cesar

    2014-01-01

    Modern cities represent one of the fastest growing ecosystems on the planet. Urbanization occurs in stages; each stage characterized by a distinct habitat that may be more or less susceptible to the establishment of disease vector populations and the transmission of vector-borne pathogens. We performed longitudinal entomological and epidemiological surveys in households along a 1900 × 125 m transect of Arequipa, Peru, a major city of nearly one million inhabitants, in which the transmission of Trypanosoma cruzi, the aetiological agent of Chagas disease, by the insect vector Triatoma infestans, is an ongoing problem. The transect spans a cline of urban development from established communities to land invasions. We find that the vector is tracking the development of the city, and the parasite, in turn, is tracking the dispersal of the vector. New urbanizations are free of vector infestation for decades. T. cruzi transmission is very recent and concentrated in more established communities. The increase in land tenure security during the course of urbanization, if not accompanied by reasonable and enforceable zoning codes, initiates an influx of construction materials, people and animals that creates fertile conditions for epidemics of some vector-borne diseases. PMID:24990681

  9. Angiogenesis and Its Therapeutic Opportunities

    Directory of Open Access Journals (Sweden)

    So Young Yoo

    2013-01-01

    Full Text Available Angiogenesis plays critical roles in human physiology that range from reproduction and fetal growth to wound healing and tissue repair. The sophisticated multistep process is tightly regulated in a spatial and temporal manner by “on-off switch signals” between angiogenic factors, extracellular matrix components, and endothelial cells. Uncontrolled angiogenesis may lead to several angiogenic disorders, including vascular insufficiency (myocardial or critical limb ischemia and vascular overgrowth (hemangiomas, vascularized tumors, and retinopathies. Thus, numerous therapeutic opportunities can be envisaged through the successful understanding and subsequent manipulation of angiogenesis. Here, we review the clinical implications of angiogenesis and discuss pro- and antiangiogenic agents that offer potential therapy for cancer and other angiogenic diseases.

  10. Therapeutic Plasmapheresis in Kidney Transplantation

    Directory of Open Access Journals (Sweden)

    Zeynep Kendi Celebi

    2013-02-01

    Full Text Available In 1960's, with succesfully renal transplantations, acute rejection became to be a serious problem for graft survival. From 1965 to 2010, with the introduction of new immunosuppressant agents such as cyclosporine, mycophenolate mofetile and tacrolimus, the acute rejection rates declined from 80% to 10% . There is an ongoing gradual improvement in allograft survival. Use of Therapeutic plasma exchange (TPE is not evidence based treatment, but TPE is necessary for pre- and also post transplantation in patients with DSA. TPE is also a main treatment for antibody mediated rejection (AMR , but in clinical practice the duration and frequency of TPE and individual difference of antibody production is unclear. There is a requirement for more specific antibody elimination. Further randomised controlled studies are needed to elucidate TPE use before and after kidney transplantation. [Dis Mol Med 2013; 1(1.000: 8-10

  11. Guidelines for Rational Cancer Therapeutics

    Directory of Open Access Journals (Sweden)

    Byunghee Yoo

    2017-12-01

    Full Text Available Traditionally, cancer therapy has relied on surgery, radiation therapy, and chemotherapy. In recent years, these interventions have become increasingly replaced or complemented by more targeted approaches that are informed by a deeper understanding of the underlying biology. Still, the implementation of fully rational patient-specific drug design appears to be years away. Here, we present a vision of rational drug design for cancer that is defined by two major components: modularity and image guidance. We suggest that modularity can be achieved by combining a nanocarrier and an oligonucleotide component into the therapeutic. Image guidance can be incorporated into the nanocarrier component by labeling with a specific imaging reporter, such as a radionuclide or contrast agent for magnetic resonance imaging. While limited by the need for additional technological advancement in the areas of cancer biology, nanotechnology, and imaging, this vision for the future of cancer therapy can be used as a guide to future research endeavors.

  12. Epidemiology and control of malaria and other arthropod born diseases

    Directory of Open Access Journals (Sweden)

    F. J. López-Antuñano

    1992-01-01

    Full Text Available Malaria and other arthropod born diseases remain a serious public health problem affecting the lives and health of certain social groups when the two basic strategies to control fail due to : (1 the lack of effective chemoprophylaxis/chemotherapy or the rapid development of drug resistance of the infectious agents and (2 the ineffectiveness of pesticides or the arthropod vectors develop resistance to them. These situations enhances the need for the design and implementation of other alternatives for sustainable health programmes. The application of the epidemiological methods is essential not only for analyzing the relevant data for the understanding of the biological characteristics of the infectious agents, their reservoirs and vectors and the methods for their control, but also for the assessment of the human behaviour, the environmental, social and economic factors involved in disease transmission and the capacity of the health systems to implement interventions for both changes in human behaviour and environmental management to purpose guaranteed prevention and control of malaria and other arthropod born diseases with efficiency, efficacy and equity. This paper discuss the evolution of the malaria arthropod diseases programmes in the American Region and the perspectives for their integration into health promotion programs and emphasis is made in the need to establish solid basis in the decision-making process for the selection of intervention strategies to remove the risk factors determining the probability to get sick or die from ABDs. The implications of the general planning and the polices to be adopted in an area should be analyzed in the light of programme feasibility at the local level, in the multisectoral context specific social groups and taking in consideration the principles of stratification and equity

  13. Behavioural responses of two-spotted spider mites induced by predator-borne and prey-borne cues.

    Science.gov (United States)

    Gyuris, Enikő; Szép, Erna; Kontschán, Jenő; Hettyey, Attila; Tóth, Zoltán

    2017-11-01

    Applying predatory mites as biological control agents is a well established method against spider mites which are major pests worldwide. Although antipredator responses can influence the outcome of predator-prey interactions, we have limited information about what cues spider mites use to adjust their behavioural antipredator responses. We experimentally exposed two-spotted spider mites (Tetranychus urticae) to different predator-borne cues (using a specialist predator, Phytoseiulus persimilis, or a generalist predator, Amblyseius swirskii), conspecific prey-borne cues, or both, and measured locomotion and egg-laying activity. The reactions to predator species compared to each other manifested in reversed tendencies: spider mites increased their locomotion activity in the presence of P. persimilis, whereas they decreased it when exposed to A. swirskii. The strongest response was triggered by the presence of a killed conspecific: focal spider mites decreased their locomotion activity compared to the control group. Oviposition activity was not affected by either treatment. Our results point out that spider mites may change their behaviour in response to predators, and also to the presence of killed conspecifics, but these effects were not enhanced when both types of cues were present. The effect of social contacts among prey conspecifics on predator-induced behavioural defences is discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Wavefield separation by energy norm Born scattering

    KAUST Repository

    Sun, Bingbing

    2017-08-17

    In Reflection Based Waveform Inversion, the gradient is computed by cross-correlating the direct and Born scattered wavefield with their adjoints applied to the data residuals. In this case, the transmitted part of the Born scattered wavefield produces high wavenumber artifacts, which would harm the convergence of the inversion process. We propose an efficient Energy Norm Born Scattering (ENBS) to attenuate the transmission components of the Born modeling, and allow it to produce only reflections. ENBS is derived from the adjoint of the Energy Norm (inverse scattering) imaging condition and in order to get deeper insights of how this method works, we show analytically that given an image, in which reflectivity is represented by a Dirac delta function, ENBS attenuates transmission energy perfectly. We use numerical examples to demonstrate that ENBS works in both the time and the frequency domain. We also show that in reflection waveform inversion (RWI) the wave path constructed by ENBS would be cleaner and free of high wavenumber artifacts associated with conventional Born scattering.

  15. Wavefield separation by energy norm Born scattering

    KAUST Repository

    Sun, Bingbing; Alkhalifah, Tariq Ali

    2017-01-01

    In Reflection Based Waveform Inversion, the gradient is computed by cross-correlating the direct and Born scattered wavefield with their adjoints applied to the data residuals. In this case, the transmitted part of the Born scattered wavefield produces high wavenumber artifacts, which would harm the convergence of the inversion process. We propose an efficient Energy Norm Born Scattering (ENBS) to attenuate the transmission components of the Born modeling, and allow it to produce only reflections. ENBS is derived from the adjoint of the Energy Norm (inverse scattering) imaging condition and in order to get deeper insights of how this method works, we show analytically that given an image, in which reflectivity is represented by a Dirac delta function, ENBS attenuates transmission energy perfectly. We use numerical examples to demonstrate that ENBS works in both the time and the frequency domain. We also show that in reflection waveform inversion (RWI) the wave path constructed by ENBS would be cleaner and free of high wavenumber artifacts associated with conventional Born scattering.

  16. Therapeutic strategies to improve control of hypertension.

    Science.gov (United States)

    Armario, Pedro; Waeber, Bernard

    2013-03-01

    Blood pressure is poorly controlled in most European countries and the control rate is even lower in high-risk patients such as patients with chronic kidney disease, diabetic patients or previous coronary heart disease. Several factors have been associated with poor control, some of which involve the characteristic of the patients themselves, such as socioeconomic factors, or unsuitable life-styles, other factors related to hypertension or to associated comorbidity, but there are also factors directly associated with antihypertensive therapy, mainly involving adherence problems, therapeutic inertia and therapeutic strategies unsuited to difficult-to-control hypertensive patients. It is common knowledge that only 30% of hypertensive patients can be controlled using monotherapy; all the rest require a combination of two or more antihypertensive drugs, and this can be a barrier to good adherence and log-term persistence in patients who also often need to use other drugs, such as antidiabetic agents, statins or antiplatelet agents. The fixed combinations of three antihypertensive agents currently available can facilitate long-term control of these patients in clinical practice. If well tolerated, a long-term therapeutic regimen that includes a diuretic, an ACE inhibitor or an angiotensin receptor blocker, and a calcium channel blocker is the recommended optimal triple therapy.

  17. Botanical polysaccharides: macrophage immunomodulation and therapeutic potential.

    Science.gov (United States)

    Schepetkin, Igor A; Quinn, Mark T

    2006-03-01

    Botanical polysaccharides exhibit a number of beneficial therapeutic properties, and it is thought that the mechanisms involved in these effects are due to the modulation of innate immunity and, more specifically, macrophage function. In this review, we summarize our current state of understanding of the macrophage modulatory effects of botanical polysaccharides isolated from a wide array of different species of flora, including higher plants, mushrooms, lichens and algae. Overall, the primary effect of botanical polysaccharides is to enhance and/or activate macrophage immune responses, leading to immunomodulation, anti-tumor activity, wound-healing and other therapeutic effects. Furthermore, botanical and microbial polysaccharides bind to common surface receptors and induce similar immunomodulatory responses in macrophages, suggesting that evolutionarily conserved polysaccharide structural features are shared between these organisms. Thus, the evaluation of botanical polysaccharides provides a unique opportunity for the discovery of novel therapeutic agents and adjuvants that exhibit beneficial immunomodulatory properties.

  18. Therapeutic embolization in pulmonary hemorrhage

    International Nuclear Information System (INIS)

    Gasparini, D.

    1989-01-01

    The author's purpose was to evaluate the efficacy of therapeutic embolization in pulmonary hemorrage performed with fibrin foam (Spongostan) suspended in sclerosing agents (hidroxy-poliethoxy-dodecano 3%, or natrium morruate 5%), and electrocoagulation (Bitrol, spa) as an alternative to surgery. Twenty patients were embolized: 17 with fibrin foam and sclerosing agents only, 2 with the addition of electrocoagulation and a Gianturco coil respectively, and 1 with electrocoagulation alone. The follow-up ranges from 3 to 42 months (average 22). A patient affected by aspergilloma died a few days after hemoptysis. The patient treated by electrocoagulation alone suffers from periodical hematic expectoration (spitting). The remaining 18 patients have not shown any pathological findings. In 2 cases the arterial occlusion was confirmed by angiography, while in 1 case partial arterial recanalization was observed. Such a finding was due to the vessel dimensions and to hyperflux values. In similar cases, obstruction must be completed different techniques (e.g. Gianturco coils, electrocoagulation, detachable balloons, etc.). The absence of flux resulting from embolization improves electrocoagulation efficiency, which should be considered as the technique of choice. Even though additional trials are needed, the techniques have proven quite reliable and suitable to replace surgery in low-aggression lesions

  19. Tornado-borne missile speeds. Final report

    International Nuclear Information System (INIS)

    Simiu, E.; Cordes, M.

    1976-04-01

    An investigation of the question of tornado-borne missile speeds was carried out, with a view to identify pertinent areas of uncertainty and to estimate credible tornado-borne missile speeds - within the limitations inherent in the present state of the art. The investigation consists of two parts: (1) a study in which a rational model for the missile motion is proposed, and numerical experiments are carried out corresponding to various assumptions on the initial conditions of the missile motion, the structure of the tornado flow, and the aerodynamic properties of the missile; (2) a theoretical and experimental study of tornado-borne missile aerodynamics, conducted by Colorado State Univ. (CSU) to be covered in a separate report by CSU. In the present report, the factors affecting missile motion and their influence upon such motion are examined

  20. Dual symmetry in Born-Infeld theory

    International Nuclear Information System (INIS)

    Khademi, S; Ayoubi, A

    2008-01-01

    Born-Infeld theory is a non-linear formalism which has many applications in string and electromagnetic theories. Although, the existence of magnetic monopoles and dyons are suggested by Born-Infeld theory, but this theory is not invariant under the dual transformations. In this theory electric fields for point charged particles are not singular at origin (r = 0), but magnetic fields and vector potentials are still singular. In this paper we show that the vanishing of dual symmetry is responsible for these singularities. Furthermore, we present the dual symmetric Born-Infeld theory, by a symmetric definition of electromagnetic fields in terms of new scalar and vector potentials, as well as the ordinary ones. All singularities of vector potential and magnetic field are removed as an immediate consequence of this symmetry.

  1. On transparent potentials: a Born approximation study

    International Nuclear Information System (INIS)

    Coudray, C.

    1980-01-01

    In the frame of the scattering inverse problem at fixed energy, a class of potentials transparent in Born approximation is obtained. All these potentials are spherically symmetric and are oscillating functions of the reduced radial variable. Amongst them, the Born approximation of the transparent potential of the Newton-Sabatier method is found. In the same class, quasi-transparent potentials are exhibited. Very general features of potentials transparent in Born approximation are then stated. And bounds are given for the exact scattering amplitudes corresponding to most of the potentials previously exhibited. These bounds, obtained at fixed energy, and for large values of the angular momentum, are found to be independent on the energy

  2. Interacting agents in finance

    NARCIS (Netherlands)

    Hommes, C.; Durlauf, S.N.; Blume, L.E.

    2008-01-01

    Interacting agents in finance represent a behavioural, agent-based approach in which financial markets are viewed as complex adaptive systems consisting of many boundedly rational agents interacting through simple heterogeneous investment strategies, constantly adapting their behaviour in response

  3. Riot Control Agents

    Science.gov (United States)

    ... Submit What's this? Submit Button Facts About Riot Control Agents Interim document Recommend on Facebook Tweet Share Compartir What riot control agents are Riot control agents (sometimes referred to ...

  4. Molecular survey on zoonotic tick-borne bacteria and chlamydiae in feral pigeons (Columba livia domestica).

    Science.gov (United States)

    Ebani, Valentina Virginia; Bertelloni, Fabrizio; Mani, Paolo

    2016-04-01

    To determine the presence of zoonotic tick-borne bacteria in feral pigeons (Columba livia domestica) from urban areas. Spleen samples from 84 feral pigeons, found dead with traumatic injuries in urban areas, were examined by PCR to detect DNA of Anaplasma phagocytophilum, Bartonella spp., Borrelia burgdorferi sensu lato, Coxiella burnetii, Rickettsia spp., and Chlamydophila spp. Twenty (23.8%) pigeons were infected by tick-borne agents, in particular 2 (2.38%) animals resulted positive for Bartonella spp., 5 (5.95%) for C. burnetii, 5 (5.95%) for Rickettsia spp., 13 (15.47%) for B. burgdorferi sensu lato. All birds scored negative for A. phagocytophilum. Moreover, 17 (20.23%) pigeons were positive for Chlamydophila spp. and among them 10 (11.9%) for Chlamydophila psittaci. Mixed infections by two or three agents were detected in 8 (9.52%) animals. Feral pigeons living in urban and periurban areas are a hazard for the human health as source of several pathogens. The obtained results confirm pigeons as reservoirs of chlamydial agents and suggest that they may be involved in the epidemiology of zoonotic tick-borne infections too. Copyright © 2016 Hainan Medical College. Production and hosting by Elsevier B.V. All rights reserved.

  5. [Conflicts and vector-borne diseases

    DEFF Research Database (Denmark)

    Bygbjerg, Ib Christian

    2010-01-01

    Based on literature and personal experiences, vector-borne diseases and conflicts are reviewed. Simple rapid diagnostic tests for three important parasitoses are available. Resort is often made to case definitions and to presumptive treatment. Resistance is an emerging problem. Vaccines are still...... not available for most diseases. Promising preventive methods, including long-lasting impregnated bed-nets and tents, are available. War has been an impetus for disclosing life-cycles of vector-borne diseases and for control methods; peace, reconciliation and poverty reduction are required to achieve lasting...

  6. Pap Tests and Foreign-Born Women

    Centers for Disease Control (CDC) Podcasts

    2007-11-26

    Foreign-born women living in the U.S. are less likely to have Pap tests to detect cervical cancer than women born in this country. The problem is worse for women from certain countries or regions. Find out why this is a disturbing trend, who these women are and why they are less likely to get a Pap test, and what CDC is doing about it.  Created: 11/26/2007 by National Breast and Cervical Cancer Early Detection Program.   Date Released: 12/7/2007.

  7. Probabilities from entanglement, Born's rule from envariance

    International Nuclear Information System (INIS)

    Zurek, W.

    2005-01-01

    Full text: I shall discuss consequences of envariance (environment - assisted invariance) symmetry exhibited by entangled quantum states. I shall focus on the implications of envariance for the understanding of the origins and nature of ignorance, and, hence, for the origin of probabilities in physics. While the derivation of the Born's rule for probabilities (pk IykI2) is the principal accomplishment of this research, I shall explore the possibility that several other symptoms of the quantum - classical transition that are a consequence of decoherence can be justified directly by envariance -- i.e., without invoking Born's rule. (author)

  8. Born's reciprocity principle in stochastic phase space

    International Nuclear Information System (INIS)

    Prugovecki, E.

    1981-01-01

    It is shown that the application of Born's reciprocity principle to relativistic quantum mechanics in stochastic phase space (by the requirement that the proper wave functions of extended particles satisfy the Born-Lande as well as the Klein-Gordon equation) leads to the unique determination of these functions for any given value of their rms radius. The resulting particle propagators display not only Lorentz but also reciprocal invariance. This feature remains true even in the case of mass-zero particles, such as photons, when their localization is achieved by means of extended test particles whose proper wave functions obey the reciprocity principle. (author)

  9. Therapeutic strategies in the treatment of periodontitis

    Directory of Open Access Journals (Sweden)

    Liljana Bogdanovska

    2012-04-01

    Full Text Available Periodontitis is a chronic inflammatory process which affects the tooth - supporting structures of the teeth. The disease is initiated by subgingival periopathogenic bacteria in susceptible periodontal sites. The host immune response towards periodontal pathogens helps to sustain periodontal disease and eventual alveolar bone loss. Although scaling and root planing is the standard treatment modality for periodontitis, it suffers from several drawbacks such as the inability to reach the base of deep pockets and doesn’t arrest migration of periodontal pathogens from other sites in the oral cavity. In order to overcome the limitations of scaling and root planning, adjunctive chemotherapeutics and host modulatory agents to the treatment are used. These therapeutic agents show substantial beneficial effects when compared to scaling and root planning alone. This review will cover an update on chemotherapeutic and past and future host immune modulatory agents used adjunctively to treat and manage periodontal diseases.

  10. Injectable agents affecting subcutaneous fats.

    Science.gov (United States)

    Chen, David Lk; Cohen, Joel L; Green, Jeremy B

    2015-09-01

    Mesotherapy is an intradermal or subcutaneous injection of therapeutic agents to induce local effects, and was pioneered in Europe during the 1950s. For the past 2 decades, there has been significant interest in the use of mesotherapy for minimally invasive local fat contouring. Based on the theorized lipolytic effects of the agent phosphatidylcholine, initial attempts involved its injection into subcutaneous tissue. With further studies, however, it became apparent that the activity attributed to phosphatidylcholine mesotherapy was due to the adipolytic effects of deoxycholate, a detergent used to solubilize phosphatidylcholine. Since then, clinical trials have surfaced that demonstrate the efficacy of a proprietary formulation of deoxycholate for local fat contouring. Current trials on mesotherapy with salmeterol, a b-adrenergic agonist and lipolysis stimulator, are underway-with promising preliminary results as well. ©2015 Frontline Medical Communications.

  11. Rickettsial and other tick-borne infections.

    Science.gov (United States)

    Flicek, Barbara Fouts

    2007-03-01

    Tick bites are best prevented by people avoiding tick-infested areas. When this is not possible, tick bites may be prevented by the wearing of long trousers that are tucked into boots. The best method to avoid tick bites is twofold: application of a topical deet (N,N-diethyl-m-toluamide) repellent to exposed skin, and treatment of clothing with permethrin. This system is currently used by the US Army to protect soldiers. Ticks can crawl underneath clothing and bite untreated portions of the body; therefore, treating clothing is imperative. Permethrin is nontoxic to humans, and can be used in any age group. Permethrin is commercially available. Checking clothing regularly while in tick-infested areas is highly recommended to back up the few hours of protection provided by the insect repellents. It is also recommended that the entire body be carefully screened for ticks and other parasites by campers and hunters while they are staying in and after leaving infested areas. Any tick found should be removed immediately. Removing ticks may not be easy. It is best to use blunt, rounded forceps, and a magnifying glass to remove ticks, especially when immature ticks are found. The forceps are used to grasp the mouthparts of the tick as close as possible to the skin, and then the tick is pulled upward, perpendicular to the skin, with a continuous and steady action. Usually any mouth parts of the tick retained in the skin are eliminated uneventfully by the body. Other methods of removing ticks, such as using fingers, lighted cigarettes, petroleum jelly, or suntan oil, should be avoided. Killing the tick in situ may increase the risk of regurgitation by the tick and the transmission of infectious agents. Most stick bites are uncomplicated, and result only in benign cutaneous inflammatory reactions that may be pruritic for a few days. As a result of mouthparts being retained at the feeding site, a granuloma may rarely develop. There are no data to indicate that antimicrobial

  12. [Conflicts and vector-borne diseases

    DEFF Research Database (Denmark)

    Bygbjerg, Ib Christian

    2010-01-01

    Based on literature and personal experiences, vector-borne diseases and conflicts are reviewed. Simple rapid diagnostic tests for three important parasitoses are available. Resort is often made to case definitions and to presumptive treatment. Resistance is an emerging problem. Vaccines are still...

  13. Scientific Discoveries the Year I Was Born

    Science.gov (United States)

    Cherif, Abour

    2012-01-01

    The author has successfully used a learning activity titled "The Year I Was Born" to motivate students to conduct historical research and present key scientific discoveries from their birth year. The activity promotes writing, helps students enhance their scientific literacy, and also improves their attitude toward the learning of science. As one…

  14. Testing Born-Infeld Electrodynamics in Waveguides

    International Nuclear Information System (INIS)

    Ferraro, Rafael

    2007-01-01

    Waveguides can be employed to test nonlinear effects in electrodynamics. We solve Born-Infeld equations for TE waves in a rectangular waveguide. We show that the energy velocity acquires a dependence on the amplitude, and harmonic components appear as a consequence of the nonlinear behavior

  15. Born with Protection against Whooping Cough

    Centers for Disease Control (CDC) Podcasts

    This podcast provides information about whooping cough, a disease that can be deadly for babies, and CDC’s recommendation that all women receive the Tdap vaccine during the third trimester of every pregnancy so their babies can be born with protection from this serious disease.

  16. Joint Laxity in Preschool Children Born Preterm.

    Science.gov (United States)

    Romeo, Domenico M; Velli, Chiara; Lucibello, Simona; Ferrantini, Gloria; Leo, Giuseppina; Brogna, Claudia; Cota, Francesco; Ricci, Daniela; Gallini, Francesca; Romagnoli, Costantino; Vento, Giovanni; Mercuri, Eugenio

    2018-06-01

    To evaluate the prevalence of joint laxity in children born preterm assessed in the first 2 years, the relationship between joint laxity and motor performance at preschool age, and possible changes over time in a subgroup of children followed longitudinally. The revised scale of Beighton Score was used to evaluate joint laxity in a population of 132 preschool children born preterm between 24 and 32 weeks of gestational age. All were assessed for joint laxity between 12 and 24 months of age. Children also performed the Movement Assessment Battery for Children-Second Edition between the age of 3 years and 6 months and 4 years; the age at onset of independent walking also was recorded. The total Beighton Score ranged between 0 and 8. Twenty percent of the cohort showed joint laxity. No differences related to sex or gestational age were observed. Children born preterm with joint laxity achieved later independent walking and achieved lower scores on Movement Assessment Battery for Children-Second Edition than those without joint laxity. In 76 children born preterm, an assessment for joint laxity was repeated once between 25 and 36 months and again after >36 months. No statistically significant difference was observed between the 3 assessments. The Beighton Score can be used to assess generalized joint laxity in children born preterm. As the presence of joint laxity influenced motor competences, the possibility to early identify these infants in the first 2 years is of interest to benefit from early intervention and potentially improve gross motor skills and coordination. Copyright © 2018 Elsevier Inc. All rights reserved.

  17. Therapeutic Vaccination for HPV Induced Cervical Cancers

    Directory of Open Access Journals (Sweden)

    Joeli A. Brinkman

    2007-01-01

    Full Text Available Cervical Cancer is the second leading cause of cancer–related deaths in women worldwide and is associated with Human Papillomavirus (HPV infection, creating a unique opportunity to treat cervical cancer through anti-viral vaccination. Although a prophylactic vaccine may be available within a year, millions of women, already infected, will continue to suffer from HPV-related disease, emphasizing the need to develop therapeutic vaccination strategies. A majority of clinical trials examining therapeutic vaccination have shown limited efficacy due to examining patients with more advanced-stage cancer who tend to have decreased immune function. Current trends in clinical trials with therapeutic agents examine patients with pre-invasive lesions in order to prevent invasive cervical cancer. However, longer follow-up is necessary to correlate immune responses to lesion regression. Meanwhile, preclinical studies in this field include further exploration of peptide or protein vaccination, and the delivery of HPV antigens in DNA-based vaccines or in viral vectors. As long as pre-clinical studies continue to advance, the prospect of therapeutic vaccination to treat existing lesions seem good in the near future. Positive consequences of therapeutic vaccination would include less disfiguring treatment options and fewer instances of recurrent or progressive lesions leading to a reduction in cervical cancer incidence.

  18. Reasoning about emotional agents

    OpenAIRE

    Meyer, J.-J.

    2004-01-01

    In this paper we discuss the role of emotions in artificial agent design, and the use of logic in reasoning about the emotional or affective states an agent can reside in. We do so by extending the KARO framework for reasoning about rational agents appropriately. In particular we formalize in this framework how emotions are related to the action monitoring capabilities of an agent.

  19. Chemotherapeutic agent and tracer composition and use thereof

    International Nuclear Information System (INIS)

    Babb, A. L.

    1985-01-01

    A therapeutic composition suitable for extracorporeal treatment of whole blood comprises a dialyzable chemotherapeutic agent and a dialyzable fluorescable tracer means. The removal rate of the fluorescable tracer compound from treated blood during hemodialysis is a function of the removal rate of unreacted chemotherapeutic agent present. The residual chemotherapeutic agent concentration after hemodialysis is ascertained by measuring the concentration of the fluorescable tracer compound in a dialysate using fluorometric techniques

  20. Therapeutic HIV Peptide Vaccine

    DEFF Research Database (Denmark)

    Fomsgaard, Anders

    2015-01-01

    Therapeutic vaccines aim to control chronic HIV infection and eliminate the need for lifelong antiretroviral therapy (ART). Therapeutic HIV vaccine is being pursued as part of a functional cure for HIV/AIDS. We have outlined a basic protocol for inducing new T cell immunity during chronic HIV-1...... infection directed to subdominant conserved HIV-1 epitopes restricted to frequent HLA supertypes. The rationale for selecting HIV peptides and adjuvants are provided. Peptide subunit vaccines are regarded as safe due to the simplicity, quality, purity, and low toxicity. The caveat is reduced immunogenicity...

  1. Differences in the self-reported racism experiences of US-born and foreign-born Black pregnant women

    OpenAIRE

    Dominguez, Tyan Parker; Strong, Emily Ficklin; Krieger, Nancy; Gillman, Matthew W.; Rich-Edwards, Janet W.

    2009-01-01

    Differential exposure to minority status stressors may help explain differences in United States (US)-born and foreign-born Black women’s birth outcomes. We explored self-reports of racism recorded in a survey of 185 US-born and 114 foreign-born Black pregnant women enrolled in Project Viva, a prospective cohort study of pregnant women in Boston, Massachusetts, USA. Self-reported prevalence of personal racism and group racism was significantly higher among US-born than foreign-born Black preg...

  2. Contrast Agent in Magnetic Resonance Imaging

    DEFF Research Database (Denmark)

    Vu-Quang, Hieu

    2015-01-01

    Nanoparticles have been employed as contrast agent in magnetic resonance imaging (MRI) in order to improve sensitivity and accuracy in diagnosis. In addition, these contrast agents are potentially combined with other therapeutic compounds or near infrared bio-imaging (NIR) fluorophores to obtain...... theranostic or dual imaging purposes, respectively. There were two main types of MRI contrast agent that were synthesized during this PhD project including fluorine containing nanoparticles and magnetic nanoparticles. In regard of fluorine containing nanoparticles, there were two types contrast agent...... cancer cells for cancer diagnosis in MRI. F127-Folate coated SPION were stable in various types of suspension medium for over six months. They could specifically target folate receptor of cancer cells in vitro and in vivo thus enhancing the contrast in MRI T2/T2* weighted images. These are preliminary...

  3. Chemical warfare agents.

    Science.gov (United States)

    Kuca, Kamil; Pohanka, Miroslav

    2010-01-01

    Chemical warfare agents are compounds of different chemical structures. Simple molecules such as chlorine as well as complex structures such as ricin belong to this group. Nerve agents, vesicants, incapacitating agents, blood agents, lung-damaging agents, riot-control agents and several toxins are among chemical warfare agents. Although the use of these compounds is strictly prohibited, the possible misuse by terrorist groups is a reality nowadays. Owing to this fact, knowledge of the basic properties of these substances is of a high importance. This chapter briefly introduces the separate groups of chemical warfare agents together with their members and the potential therapy that should be applied in case someone is intoxicated by these agents.

  4. Approximated solutions to Born-Infeld dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Ferraro, Rafael [Instituto de Astronomía y Física del Espacio (IAFE, CONICET-UBA),Casilla de Correo 67, Sucursal 28, 1428 Buenos Aires (Argentina); Departamento de Física, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires,Ciudad Universitaria, Pabellón I, 1428 Buenos Aires (Argentina); Nigro, Mauro [Departamento de Física, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires,Ciudad Universitaria, Pabellón I, 1428 Buenos Aires (Argentina)

    2016-02-01

    The Born-Infeld equation in the plane is usefully captured in complex language. The general exact solution can be written as a combination of holomorphic and anti-holomorphic functions. However, this solution only expresses the potential in an implicit way. We rework the formulation to obtain the complex potential in an explicit way, by means of a perturbative procedure. We take care of the secular behavior common to this kind of approach, by resorting to a symmetry the equation has at the considered order of approximation. We apply the method to build approximated solutions to Born-Infeld electrodynamics. We solve for BI electromagnetic waves traveling in opposite directions. We study the propagation at interfaces, with the aim of searching for effects susceptible to experimental detection. In particular, we show that a reflected wave is produced when a wave is incident on a semi-space containing a magnetostatic field.

  5. Scalar geons in Born-Infeld gravity

    Energy Technology Data Exchange (ETDEWEB)

    Afonso, V.I. [Unidade Acadêmica de Física, Universidade Federal de Campina Grande, 58109-970 Campina Grande, PB (Brazil); Olmo, Gonzalo J. [Departamento de Física Teórica and IFIC, Centro Mixto Universidad de Valencia—CSIC, Universidad de Valencia, Burjassot-46100, Valencia (Spain); Rubiera-Garcia, D., E-mail: viafonso@df.ufcg.edu.br, E-mail: gonzalo.olmo@uv.es, E-mail: drgarcia@fc.ul.pt [Instituto de Astrofísica e Ciências do Espaço, Faculdade de Ciências da Universidade de Lisboa, Edifício C8, Campo Grande, P-1749-016 Lisbon (Portugal)

    2017-08-01

    The existence of static, spherically symmetric, self-gravitating scalar field solutions in the context of Born-Infeld gravity is explored. Upon a combination of analytical approximations and numerical methods, the equations for a free scalar field (without a potential term) are solved, verifying that the solutions recover the predictions of General Relativity far from the center but finding important new effects in the central regions. We find two classes of objects depending on the ratio between the Schwarzschild radius and a length scale associated to the Born-Infeld theory: massive solutions have a wormhole structure, with their throat at r ≈ 2 M , while for the lighter configurations the topology is Euclidean. The total energy density of these solutions exhibits a solitonic profile with a maximum peaked away from the center, and located at the throat whenever a wormhole exists. The geodesic structure and curvature invariants are analyzed for the various configurations considered.

  6. Approximated solutions to Born-Infeld dynamics

    International Nuclear Information System (INIS)

    Ferraro, Rafael; Nigro, Mauro

    2016-01-01

    The Born-Infeld equation in the plane is usefully captured in complex language. The general exact solution can be written as a combination of holomorphic and anti-holomorphic functions. However, this solution only expresses the potential in an implicit way. We rework the formulation to obtain the complex potential in an explicit way, by means of a perturbative procedure. We take care of the secular behavior common to this kind of approach, by resorting to a symmetry the equation has at the considered order of approximation. We apply the method to build approximated solutions to Born-Infeld electrodynamics. We solve for BI electromagnetic waves traveling in opposite directions. We study the propagation at interfaces, with the aim of searching for effects susceptible to experimental detection. In particular, we show that a reflected wave is produced when a wave is incident on a semi-space containing a magnetostatic field.

  7. On generalized Born-Infeld electrodynamics

    International Nuclear Information System (INIS)

    Kruglov, S I

    2010-01-01

    The generalized Born-Infeld electrodynamics with two parameters is investigated. In this model the propagation of a linearly polarized laser beam in the external transverse magnetic field is considered. It was shown that there is the effect of vacuum birefringence, and we evaluate induced ellipticity. The upper bounds on the combination of parameters introduced from the experimental data of BRST and PVLAS Collaborations were obtained. When two parameters are equal to each other, we arrive at Born-Infeld electrodynamics and the effect of vacuum birefringence vanishes. We find the canonical and symmetrical Belinfante energy-momentum tensors. The trace of the energy-momentum tensor is not zero and the dilatation symmetry is broken. The four-divergence of the dilatation current is equal to the trace of the Belinfante energy-momentum tensor and is proportional to the parameter (with the dimension of the field strength) of the model. The dual symmetry is also broken in the model considered.

  8. Generalized Born Models of Macromolecular Solvation Effects

    Science.gov (United States)

    Bashford, Donald; Case, David A.

    2000-10-01

    It would often be useful in computer simulations to use a simple description of solvation effects, instead of explicitly representing the individual solvent molecules. Continuum dielectric models often work well in describing the thermodynamic aspects of aqueous solvation, and approximations to such models that avoid the need to solve the Poisson equation are attractive because of their computational efficiency. Here we give an overview of one such approximation, the generalized Born model, which is simple and fast enough to be used for molecular dynamics simulations of proteins and nucleic acids. We discuss its strengths and weaknesses, both for its fidelity to the underlying continuum model and for its ability to replace explicit consideration of solvent molecules in macromolecular simulations. We focus particularly on versions of the generalized Born model that have a pair-wise analytical form, and therefore fit most naturally into conventional molecular mechanics calculations.

  9. Geometrical dynamics of Born-Infeld objects

    Energy Technology Data Exchange (ETDEWEB)

    Cordero, Ruben [Departamento de Fisica, Escuela Superior de Fisica y Matematicas del I.P.N., Unidad Adolfo Lopez Mateos, Edificio 9, 07738 Mexico, D.F. (Mexico); Molgado, Alberto [Facultad de Ciencias, Universidad de Colima, Bernal DIaz del Castillo 340, Col. Villas San Sebastian, Colima (Mexico); Rojas, Efrain [Facultad de Fisica e Inteligencia Artificial, Universidad Veracruzana, 91000 Xalapa, Veracruz (Mexico)

    2007-03-21

    We present a geometrically inspired study of the dynamics of Dp-branes. We focus on the usual non-polynomial Dirac-Born-Infeld action for the worldvolume swept out by the brane in its evolution in general background spacetimes. We emphasize the form of the resulting equations of motion which are quite simple and resemble Newton's second law, complemented with a conservation law for a worldvolume bicurrent. We take a closer look at the classical Hamiltonian analysis which is supported by the ADM framework of general relativity. The constraints and their algebra are identified as well as the geometrical role they play in phase space. In order to illustrate our results, we review the dynamics of a D1-brane immersed in a AdS{sub 3} x S{sup 3} background spacetime. We exhibit the mechanical properties of Born-Infeld objects paving the way to a consistent quantum formulation.

  10. Geometrical dynamics of Born-Infeld objects

    International Nuclear Information System (INIS)

    Cordero, Ruben; Molgado, Alberto; Rojas, Efrain

    2007-01-01

    We present a geometrically inspired study of the dynamics of Dp-branes. We focus on the usual non-polynomial Dirac-Born-Infeld action for the worldvolume swept out by the brane in its evolution in general background spacetimes. We emphasize the form of the resulting equations of motion which are quite simple and resemble Newton's second law, complemented with a conservation law for a worldvolume bicurrent. We take a closer look at the classical Hamiltonian analysis which is supported by the ADM framework of general relativity. The constraints and their algebra are identified as well as the geometrical role they play in phase space. In order to illustrate our results, we review the dynamics of a D1-brane immersed in a AdS 3 x S 3 background spacetime. We exhibit the mechanical properties of Born-Infeld objects paving the way to a consistent quantum formulation

  11. serological detection of seed borne viruses in cowpea regenerated

    African Journals Online (AJOL)

    Administrator

    out to detect the presence of seed borne viruses in fourteen cowpea accessions ... were serologically indexed to detect any seed-borne viruses after acclimatisation to screen house conditions. The .... showed external virus-like symptoms were.

  12. Born-Infeld gravity in Weitzenboeck spacetime

    International Nuclear Information System (INIS)

    Ferraro, Rafael; Fiorini, Franco

    2008-01-01

    Using the teleparallel equivalent of general relativity formulated in Weitzenboeck spacetime, we thoroughly explore a kind of Born-Infeld regular gravity leading to second order field equations for the vielbein components. We explicitly solve the equations of motion for two examples: the extended Banados-Teitelboim-Zanelli black hole, which exists even if the cosmological constant is positive, and a cosmological model with matter, where the scale factor is well behaved, thus giving a singularity-free solution.

  13. Mosquito-borne viruses in Europe

    Czech Academy of Sciences Publication Activity Database

    Hubálek, Zdeněk

    2008-01-01

    Roč. 103, Suppl. 1 (2008), S29-S43 ISSN 0932-0113. [Vector-borne diseases: impact of climate change on vectors and rodent reservoirs. Berlin, 27.09.2007-28.09.2007] R&D Projects: GA AV ČR IAA600930611 Institutional research plan: CEZ:AV0Z60930519 Keywords : moboviruses * epidemiology Subject RIV: EE - Microbiology, Virology Impact factor: 1.473, year: 2008

  14. Leak detection using structure-borne noise

    Science.gov (United States)

    Holland, Stephen D. (Inventor); Chimenti, Dale E. (Inventor); Roberts, Ronald A. (Inventor)

    2010-01-01

    A method for detection and location of air leaks in a pressure vessel, such as a spacecraft, includes sensing structure-borne ultrasound waveforms associated with turbulence caused by a leak from a plurality of sensors and cross correlating the waveforms to determine existence and location of the leak. Different configurations of sensors and corresponding methods can be used. An apparatus for performing the methods is also provided.

  15. Dynamics of Born-Infeld membranes

    Energy Technology Data Exchange (ETDEWEB)

    Cordero, R [Departamento de Fisica, Escuela Superior de Fisica y Matematicas del I.P.N., Unidad Adolfo Lopez Mateos, Edificio 9, 07738 Mexico, D.F. (Mexico); Molgado, A [Facultad de Ciencias, Universidad de Colima, Bernal DIaz del Castillo 340, Col. Villas San Sebastian, Colima (Mexico); Rojas, E [Facultad de Fisica e Inteligencia Artificial, Universidad Veracruzana, 91000 Xalapa, Veracruz (Mexico)

    2007-11-15

    We present a geometrical inspired study of the dynamics of Dp-branes. We focus on the usual nonpolynomial Dirac-Born-Infeld action for the worldvolume swept out by the brane in its evolution in general background spacetimes. We emphasize the form of the resulting equations of motion which are quite simple and resemble Newton's second law, complemented with a conservation law for a worldvolume bicurrent.

  16. Dynamics of Born-Infeld membranes

    International Nuclear Information System (INIS)

    Cordero, R; Molgado, A; Rojas, E

    2007-01-01

    We present a geometrical inspired study of the dynamics of Dp-branes. We focus on the usual nonpolynomial Dirac-Born-Infeld action for the worldvolume swept out by the brane in its evolution in general background spacetimes. We emphasize the form of the resulting equations of motion which are quite simple and resemble Newton's second law, complemented with a conservation law for a worldvolume bicurrent

  17. Therapeutic apheresis for severe hypertriglyceridemia in pregnancy.

    Science.gov (United States)

    Basar, Rafet; Uzum, Ayse Kubat; Canbaz, Bulent; Dogansen, Sema Ciftci; Kalayoglu-Besisik, Sevgi; Altay-Dadin, Senem; Aral, Ferihan; Ozbey, Nese Colak

    2013-05-01

    During pregnancy, a progressive increase in serum triglyceride (TG) and cholesterol levels is observed whereas TG levels mostly remain hypertriglyceridemia, pregnancy may cause extremely elevated TG levels leading to potentially life-threatening pancreatitis attacks and chylomicronemia syndrome. The only safe medical treatment option during pregnancy is ω-3 fatty acids, which have moderate TG lowering effects. Therapeutic apheresis could be used as primary treatment approach during pregnancy. We reported the effect of double filtration apheresis in one pregnant women with severe hypertriglyceridemia, therapeutic plasmapheresis and double filtration methods in the other severe hypertriglyceridemic pregnant woman; a 32-year-old pregnant woman (patient 1) with a history of hypertriglyceridemia-induced acute pancreatitis during pregnancy and a 30-year-old pregnant woman with extremely high TG levels (12,000 mg/dl) leading to chylomicronemia syndrome (patient 2). Medical nutrition therapy and ω-3 fatty acids were also provided. Double filtration apheresis (patient 1) and plasmapheresis + double filtration apheresis (patient 2) were used. When we calculated the TG levels before and after therapeutic apheresis, maximum decrease achieved with double filtration apheresis was 46.3 % for patient 1 and 37.3 % for patient 2. However, with plasmapheresis TG level declined by 72 % in patient 2. Plasmapheresis seemed to be more efficient to decrease TG levels. Iron deficiency anemia was the main complication apart from technical difficulties by lipemic obstruction of tubing system. Healthy babies were born. Delivery led to decreases in TG levels. It is concluded that during pregnancy therapeutic apheresis is an effective method to decrease extremely high TG levels and risks of its potentially life-threatening complications.

  18. Marketing therapeutic recreation services.

    Science.gov (United States)

    Thorn, B E

    1984-01-01

    The use of marketing strategies can enhance the delivery of therapeutic recreation services. This article discusses how agencies can adapt marketing techniques and use them to identify potential markets, improve image, evaluate external pressures, and maximize internal strengths. Four variables that can be controlled and manipulated in a proposed marketing plan are product, price, place and promotion.

  19. Therapeutic Recombinant Monoclonal Antibodies

    Science.gov (United States)

    Bakhtiar, Ray

    2012-01-01

    During the last two decades, the rapid growth of biotechnology-derived techniques has led to a myriad of therapeutic recombinant monoclonal antibodies with significant clinical benefits. Recombinant monoclonal antibodies can be obtained from a number of natural sources such as animal cell cultures using recombinant DNA engineering. In contrast to…

  20. Therapeutic applications of radiopharmaceuticals

    International Nuclear Information System (INIS)

    Baker, W.J.; Datz, F.L.; Beightol, R.W.

    1987-01-01

    Whether a radiopharmaceutical has diagnostic or therapeutic application depends on both the isotope and pharmaceutical used. For diagnostic applications, the isotope should undergo only γ-decay, since usually only γ-radiation is detected by nuclear medicine cameras. The half-life should be just long enough to allow the procedure to be performed. In contrast, the isotope needed for therapeutic purposes should have particulate radiation, such as a β-particle (electron), since these are locally absorbed an increase the local radiation dose. γ-Radiation, which penetrates the tissues, produces less radiation dose than do Β-particles. Several references dealing with radioactive decay, particulate interactions, and diagnostic and therapeutic applications of radiopharmaceuticals are available. Radiopharmaceuticals can legally be used only by physicians who are qualified by specific training in the safe handling of radionuclides. The experience and training of these physicians must be approved by the Nuclear Regulatory Commission or Agreement State Agency authorized to license the use of radiopharmaceuticals. A list of all byproduct material and procedures is available in the Code of Federal Regulations. Of the many radiopharmaceuticals available for diagnostic and therapeutic use, only those commonly used are discussed in this chapter

  1. Spectrophotometric determination of substrate-borne polyacrylamide.

    Science.gov (United States)

    Lu, Jianhang; Wu, Laosheng

    2002-08-28

    Polyacrylamides (PAMs) have wide application in many industries and in agriculture. Scientific research and industrial applications manifested a need for a method that can quantify substrate-borne PAM. The N-bromination method (a PAM analytical technique based on N-bromination of amide groups and spectrophotometric determination of the formed starch-triiodide complex), which was originally developed for determining PAM in aqueous solutions, was modified to quantify substrate-borne PAM. In the modified method, the quantity of substrate-borne PAM was converted to a concentration of starch-triiodide complex in aqueous solution that was then measured by spectrophotometry. The method sensitivity varied with substrates due to sorption of reagents and reaction intermediates on the substrates. Therefore, separate calibration for each substrate was required. Results from PAM samples in sand, cellulose, organic matter burnt soils, and clay minerals showed that this method had good accuracy and reproducibility. The PAM recoveries ranged from 95.8% to 103.7%, and the relative standard deviations (n = 4) were application and facilitating PAM-related research.

  2. Zoonotic aspects of vector-borne infections.

    Science.gov (United States)

    Failloux, A-B; Moutailler, S

    2015-04-01

    Vector-borne diseases are principally zoonotic diseases transmitted to humans by animals. Pathogens such as bacteria, parasites and viruses are primarily maintained within an enzootic cycle between populations of non-human primates or other mammals and largely non-anthropophilic vectors. This 'wild' cycle sometimes spills over in the form of occasional infections of humans and domestic animals. Lifestyle changes, incursions by humans into natural habitats and changes in agropastoral practices create opportunities that make the borders between wildlife and humans more permeable. Some vector-borne diseases have dispensed with the need for amplification in wild or domestic animals and they can now be directly transmitted to humans. This applies to some viruses (dengue and chikungunya) that have caused major epidemics. Bacteria of the genus Bartonella have reduced their transmission cycle to the minimum, with humans acting as reservoir, amplifier and disseminator. The design of control strategies for vector-borne diseases should be guided by research into emergence mechanisms in order to understand how a wild cycle can produce a pathogen that goes on to cause devastating urban epidemics.

  3. Review of the trends and causes of food borne outbreaks in Malaysia from 1988 to 1997.

    Science.gov (United States)

    Meftahuddin, T

    2002-03-01

    This paper examines the trend and possible contributing factors for the occurrence of the food borne diseases outbreaks in Malaysia. These diseases mainly are cholera, typhoid fever, hepatitis A, dysentery and food poisoning. The outbreaks still occur sporadically in certain high risk areas throughout the country. The incidence rate of all the other three major food borne diseases steadily declined from the year 1988 to 1997 except for food poisoning and cholera. Statistic of food poisoning from the year 1996 to 1997 showed that 66.5% of the outbreak occurred in schools whereas only 0.4% originated from the contaminated food sold at various public food outlets. The school age group is always more affected than the general population. Amongst the contributing factors identified are related to unhygienic food handling practices followed by inadequate safe water supply and poor environmental sanitation. A multisectoral approach between Ministry of Health and other government agencies or private agents needs to be undertaken in the management of the food borne diseases in order to curb the incidences of food borne diseases in Malaysia.

  4. Tick-borne pathogen – Reversed and conventional discovery of disease

    Directory of Open Access Journals (Sweden)

    Ellen eTijsse Klasen

    2014-07-01

    Full Text Available Molecular methods have increased the number of known microorganisms associated with ticks significantly. Some of these newly identified microorganisms are readily linked to human disease while others are yet unknown to cause human disease. The face of tick-borne disease discovery has changed with more diseases now being discovered in a ‘reversed way’, detecting disease cases only years after the tick-borne microorganism was first discovered. Compared to the conventional discovery of infectious diseases, this order of discoveries presents researchers with new challenges. Especially estimating public health risks of such agents is challenging, as case definitions and diagnostic procedures may initially be missing. We discuss the advantages and shortcomings of molecular methods, serology, epidemiological studies that might be used to study some fundamental questions regarding newly identified tick-borne diseases. With increased tick-exposure and improved detection methods, more tick-borne microorganisms will be added to the list of pathogens causing disease in humans in future.

  5. The wild life of tick-borne pathogens

    OpenAIRE

    Hofmeester, Tim R.

    2016-01-01

    Diseases that are transmitted by arthropod vectors from animal hosts to humans – so called zoonotic vector-borne diseases – have increased in incidence in the last decades. In North America and Europe, tick-borne pathogens cause the majority of vector-borne diseases, including Lyme borreliosis and tick-borne encephalitis. The pathogens causing these diseases are transmitted by tick species within the Ixodes ricinus complex. These are generalist ticks that have a multi-year lifecycle with thre...

  6. Dysconnectivity of neurocognitive networks at rest in very-preterm born adults

    Directory of Open Access Journals (Sweden)

    Thomas P. White

    2014-01-01

    directed coherence. Together these findings show that resting-state functional connectivity of preterm-born individuals remains compromised in adulthood; and present consistent evidence that the striatal salience network is preferentially affected. Therapeutic practices directed at strengthening within-network cohesion and fine-tuning between-network inter-relations may have the potential to mitigate the cognitive, behavioural and psychiatric repercussions of preterm birth.

  7. The wild life of tick-borne pathogens

    NARCIS (Netherlands)

    Hofmeester, Tim R.

    2016-01-01

    Diseases that are transmitted by arthropod vectors from animal hosts to humans – so called zoonotic vector-borne diseases – have increased in incidence in the last decades. In North America and Europe, tick-borne pathogens cause the majority of vector-borne diseases, including Lyme borreliosis

  8. MijnBorne2030: evaluatie van een democratisch experiment

    NARCIS (Netherlands)

    Denters, Sebastianus A.H.; Klok, Pieter J.

    2015-01-01

    This article is about one of the experiments in local democratic renewal: MyBorne2030 (in Dutch ‘MijnBorne2030’). The aim of the project was to develop a communal vision for Borne (a relatively small suburban municipality of 20.000 inhabitants in the East of the Netherlands) for the year 2030. A

  9. Louse-Borne Relapsing Fever with Meningeal Involvement in an Immigrant from Somalia to Italy, October 2015.

    Science.gov (United States)

    Zammarchi, Lorenzo; Antonelli, Alberto; Bartolini, Laura; Pecile, Patrizia; Trotta, Michele; Rogasi, Pier Giorgio; Santini, Maria Grazia; Dilaghi, Beatrice; Grifoni, Stefano; Rossolini, Gian Maria; Bartoloni, Alessandro

    2016-05-01

    Borrelia recurrentis, transmitted by Pediculus humanus humanus, is the etiological agent of louse-borne relapsing fever (LBRF). Currently the main focus of endemicity of LBRF is localized in East African countries. From July 2015 to October 2015, 36 cases of LBRF have been diagnosed in Europe in immigrants from the Horn of Africa. Here we report a case of LBRF with meningitis diagnosed in Florence, Italy, in an immigrant arrived from Somalia. In October 2015, a 19-year-old Somali male presented to the emergency department of the Azienda Ospedaliero Universitaria Careggi, Florence, Italy, with a 3-day history of high fever. The patient had disembarked in Sicily 10 days before admission after a long migration trip from his country of origin. On clinical examination, neck stiffness was found. Main laboratory findings were thrombocytopenia, increased procalcitonin, and increased polymorphonucleates in the cerebrospinal fluid. Suspecting a possible meningitis, the patient was treated with ceftriaxone, pending results of laboratory testing for malaria, and developed severe hypotension that was treated with fluid resuscitation and hydrocortisone. Hemoscopic testing revealed the presence of spirochetes and no malaria parasites. The patient rapidly improved with doxycycline for 7 days and ceftriaxone for 11 days, then was lost to follow-up. Total DNA from blood was extracted, and amplification and sequencing with universal 16S rDNA primers D88 and E94 revealed a 100% identity with B. recurrentis A1. LBRF is a rare but emerging infectious disease among vulnerable displaced immigrants from the Horn of Africa. Since immigrants from endemic areas can carry the vector with them, the infection should be suspected even in subjects with compatible clinical features living in the same place where new arrival immigrants are hosted. Healthcare providers should be aware of this condition to implement adequate diagnostic, therapeutic, and public health measures.

  10. Therapeutic targets in liver fibrosis.

    Science.gov (United States)

    Fallowfield, Jonathan A

    2011-05-01

    Detailed analysis of the cellular and molecular mechanisms that mediate liver fibrosis has provided a framework for therapeutic approaches to prevent, slow down, or even reverse fibrosis and cirrhosis. A pivotal event in the development of liver fibrosis is the activation of quiescent hepatic stellate cells (HSCs) to scar-forming myofibroblast-like cells. Consequently, HSCs and the factors that regulate HSC activation, proliferation, and function represent important antifibrotic targets. Drugs currently licensed in the US and Europe for other indications target HSC-related components of the fibrotic cascade. Their deployment in the near future looks likely. Ultimately, treatment strategies for liver fibrosis may vary on an individual basis according to etiology, risk of fibrosis progression, and the prevailing pathogenic milieu, meaning that a multiagent approach could be required. The field continues to develop rapidly and starts to identify exciting potential targets in proof-of-concept preclinical studies. Despite this, no antifibrotics are currently licensed for use in humans. With epidemiological predictions for the future prevalence of viral, obesity-related, and alcohol-related cirrhosis painting an increasingly gloomy picture, and a shortfall in donors for liver transplantation, the clinical urgency for new therapies is high. There is growing interest from stakeholders keen to exploit the market potential for antifibrotics. However, the design of future trials for agents in the developmental pipeline will depend on strategies that enable equal patient stratification, techniques to reliably monitor changes in fibrosis over time, and the definition of clinically meaningful end points.

  11. Therapeutic drug monitoring of antimicrobials

    Science.gov (United States)

    Roberts, Jason A; Norris, Ross; Paterson, David L; Martin, Jennifer H

    2012-01-01

    Optimizing the prescription of antimicrobials is required to improve clinical outcome from infections and to reduce the development of antimicrobial resistance. One such method to improve antimicrobial dosing in individual patients is through application of therapeutic drug monitoring (TDM). The aim of this manuscript is to review the place of TDM in the dosing of antimicrobial agents, specifically the importance of pharmacokinetics (PK) and pharmacodynamics (PD) to define the antimicrobial exposures necessary for maximizing killing or inhibition of bacterial growth. In this context, there are robust data for some antimicrobials, including the ratio of a PK parameter (e.g. peak concentration) to the minimal inhibitory concentration of the bacteria associated with maximal antimicrobial effect. Blood sampling of an individual patient can then further define the relevant PK parameter value in that patient and, if necessary, antimicrobial dosing can be adjusted to enable achievement of the target PK/PD ratio. To date, the clinical outcome benefits of a systematic TDM programme for antimicrobials have only been demonstrated for aminoglycosides, although the decreasing susceptibility of bacteria to available antimicrobials and the increasing costs of pharmaceuticals, as well as emerging data on pharmacokinetic variability, suggest that benefits are likely. PMID:21831196

  12. Prospects for therapeutic mitochondrial transplantation.

    Science.gov (United States)

    Gollihue, Jenna L; Rabchevsky, Alexander G

    2017-07-01

    Mitochondrial dysfunction has been implicated in a multitude of diseases and pathological conditions- the organelles that are essential for life can also be major players in contributing to cell death and disease. Because mitochondria are so well established in our existence, being present in all cell types except for red blood cells and having the responsibility of providing most of our energy needs for survival, then dysfunctional mitochondria can elicit devastating cellular pathologies that can be widespread across the entire organism. As such, the field of "mitochondrial medicine" is emerging in which disease states are being targeted therapeutically at the level of the mitochondrion, including specific antioxidants, bioenergetic substrate additions, and membrane uncoupling agents. New and compelling research investigating novel techniques for mitochondrial transplantation to replace damaged or dysfunctional mitochondria with exogenous healthy mitochondria has shown promising results, including tissue sparing accompanied by increased energy production and decreased oxidative damage. Various experimental techniques have been attempted and each has been challenged to accomplish successful transplantation. The purpose of this review is to present the history of mitochondrial transplantation, the different techniques used for both in vitro and in vivo delivery, along with caveats and pitfalls that have been discovered along the way. Results from such pioneering studies are promising and could be the next big wave of "mitochondrial medicine" once technical hurdles are overcome. Copyright © 2017 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

  13. Radiopharmaceutical scanning agents

    International Nuclear Information System (INIS)

    1976-01-01

    This invention is directed to dispersions useful in preparing radiopharmaceutical scanning agents, to technetium labelled dispersions, to methods for preparing such dispersions and to their use as scanning agents

  14. Taskable Reactive Agent Communities

    National Research Council Canada - National Science Library

    Myers, Karen

    2002-01-01

    The focus of Taskable Reactive Agent Communities (TRAC) project was to develop mixed-initiative technology to enable humans to supervise and manage teams of agents as they perform tasks in dynamic environments...

  15. Prostate Cancer Prognostic Factors Among Asian Patients Born in the US Compared to Those Born Abroad.

    Science.gov (United States)

    Xu, Junjun; Goodman, Michael; Jemal, Ahemdin; Fedewa, Stacey A

    2015-06-01

    US surveillance data indicate that incidence of prostate cancer differs by place of birth among Asian men. However, it is less clear if the prognostic factors for prostate cancer also differ by place of birth. The study included 7,824 Asian prostate cancer patients diagnosed between 2004 and 2009 and reported to the Surveillance Epidemiology and End Results (SEER) program. Logistic regression models were used to evaluate the relation of place of birth (foreign born vs. US born) to three outcomes: prostate specific antigen (PSA) level, Gleason score, and T classification, adjusting for age, marital status, Rural-Urban Continuum Code, and SEER registry. All outcome variables were binary using different cutoffs: ≥ 4, ≥ 10 and ≥ 20 ng/ml for PSA; ≥ 7 and ≥ 8 for Gleason score; and ≥ T2 and ≥ T3 for T classification. Elevated PSA was more common among foreign born Asian men regardless of the cut point used. In the analysis comparing foreign born versus US born patients by ethnic group, the association with PSA was most pronounced at cut point of ≥ 20 ng/ml for Chinese men (OR 1.68, 95% CI 1.02-2.75), and at cut point of ≥ 4 ng/ml for Japanese men (OR 2.73, 95% CI 1.20-6.21). A statistically significant association with Gleason score was only found for Japanese men and only for the cutoff ≥ 7 (OR 1.71, 95% CI 1.12-2.61). There was no difference in clinical T classification between foreign-born and US-born Asian men. Inclusion of cases with missing place of birth or restriction of data to those who underwent radical prostatectomy did not substantially change the results. The data suggest that foreign-born Asian prostate cancer patients may have moderately elevated PSA levels at diagnosis compared with their US born counterparts. For the other prognostic markers, the associations were less consistent and did not form a discernible pattern.

  16. Neurosteroids in Schizophrenia: Pathogenic and Therapeutic Implications

    Directory of Open Access Journals (Sweden)

    HuaLin Cai

    2018-03-01

    Full Text Available Neurosteroids are a group of important endogenous molecules affecting many neural functions in the brain. Increasing evidence suggests a possible role of these neurosteroids in the pathology and symptomatology of schizophrenia (SZ and other mental disorders. The aim of this review is to summarize the current knowledge about the neural functions of neurosteroids in the brain, and to evaluate the role of the key neurosteroids as candidate modulators in the etiology and therapeutics of SZ. The present paper provides a brief introduction of neurosteroid metabolism and distribution, followed by a discussion of the mechanisms underlying neurosteroid actions in the brain. The content regarding the modulation of the GABAA receptor is elaborated, given the considerable knowledge of its interactions with other neurotransmitter and neuroprotective systems, as well as its ameliorating effects on stress that may play a role in the SZ pathophysiology. In addition, several preclinical and clinical studies suggested a therapeutic benefit of neurosteroids in SZ patients, even though the presence of altered neurosteroid pathways in the circulating blood and/or brain remains debatable. Following treatment of antipsychotic drugs in SZ, therapeutic benefits have also been linked to the regulation of neurosteroid signaling. Specifically, the neurosteroids such as pregnenolone and dehydroepiandrosterone affect a broad spectrum of behavioral functions through their unique molecular characteristics and may represent innovative therapeutic targets for SZ. Future investigations in larger cohorts with long-term follow-ups will be required to ascertain the neuropsychopharmacological role of this yet unexploited class of neurosteroid agents.

  17. Imaging enabled platforms for development of therapeutics

    Science.gov (United States)

    Celli, Jonathan; Rizvi, Imran; Blanden, Adam R.; Evans, Conor L.; Abu-Yousif, Adnan O.; Spring, Bryan Q.; Muzikansky, Alona; Pogue, Brian W.; Finkelstein, Dianne M.; Hasan, Tayyaba

    2011-03-01

    Advances in imaging and spectroscopic technologies have enabled the optimization of many therapeutic modalities in cancer and noncancer pathologies either by earlier disease detection or by allowing therapy monitoring. Amongst the therapeutic options benefiting from developments in imaging technologies, photodynamic therapy (PDT) is exceptional. PDT is a photochemistry-based therapeutic approach where a light-sensitive molecule (photosensitizer) is activated with light of appropriate energy (wavelength) to produce reactive molecular species such as free radicals and singlet oxygen. These molecular entities then react with biological targets such as DNA, membranes and other cellular components to impair their function and lead to eventual cell and tissue death. Development of PDT-based imaging also provides a platform for rapid screening of new therapeutics in novel in vitro models prior to expensive and labor-intensive animal studies. In this study we demonstrate how an imaging platform can be used for strategizing a novel combination treatment strategy for multifocal ovarian cancer. Using an in vitro 3D model for micrometastatic ovarian cancer in conjunction with quantitative imaging we examine dose and scheduling strategies for PDT in combination with carboplatin, a chemotherapeutic agent presently in clinical use for management of this deadly form of cancer.

  18. Dendrimer-based Macromolecular MRI Contrast Agents: Characteristics and Application

    Directory of Open Access Journals (Sweden)

    Hisataka Kobayashi

    2003-01-01

    Full Text Available Numerous macromolecular MRI contrast agents prepared employing relatively simple chemistry may be readily available that can provide sufficient enhancement for multiple applications. These agents operate using a ~100-fold lower concentration of gadolinium ions in comparison to the necessary concentration of iodine employed in CT imaging. Herein, we describe some of the general potential directions of macromolecular MRI contrast agents using our recently reported families of dendrimer-based agents as examples. Changes in molecular size altered the route of excretion. Smaller-sized contrast agents less than 60 kDa molecular weight were excreted through the kidney resulting in these agents being potentially suitable as functional renal contrast agents. Hydrophilic and larger-sized contrast agents were found better suited for use as blood pool contrast agents. Hydrophobic variants formed with polypropylenimine diaminobutane dendrimer cores created liver contrast agents. Larger hydrophilic agents are useful for lymphatic imaging. Finally, contrast agents conjugated with either monoclonal antibodies or with avidin are able to function as tumor-specific contrast agents, which also might be employed as therapeutic drugs for either gadolinium neutron capture therapy or in conjunction with radioimmunotherapy.

  19. Users, Bystanders and Agents

    DEFF Research Database (Denmark)

    Krummheuer, Antonia Lina

    2015-01-01

    Human-agent interaction (HAI), especially in the field of embodied conversational agents (ECA), is mainly construed as dyadic communication between a human user and a virtual agent. This is despite the fact that many application scenarios for future ECAs involve the presence of others. This paper...

  20. Asymptotically Optimal Agents

    OpenAIRE

    Lattimore, Tor; Hutter, Marcus

    2011-01-01

    Artificial general intelligence aims to create agents capable of learning to solve arbitrary interesting problems. We define two versions of asymptotic optimality and prove that no agent can satisfy the strong version while in some cases, depending on discounting, there does exist a non-computable weak asymptotically optimal agent.

  1. Reasoning about emotional agents

    NARCIS (Netherlands)

    Meyer, J.-J.

    In this paper we discuss the role of emotions in artificial agent design, and the use of logic in reasoning about the emotional or affective states an agent can reside in. We do so by extending the KARO framework for reasoning about rational agents appropriately. In particular we formalize in

  2. Therapeutic Symptomatic Strategies in the Parasomnias.

    Science.gov (United States)

    Manni, Raffaele; Toscano, Gianpaolo; Terzaghi, Michele

    2018-06-05

    The purpose of this review was to discuss the currently available pharmacologic and non-pharmacologic treatment options for parasomnias. Recent pathophysiological findings about sleep structure in parasomnias helped understanding several drug mechanisms of action. Serotoninergic theory accounts for the effect of serotoninergic drugs. Study about spectral analysis of sleep showed the effect of clonazepam on spectral bands. Cannabinoids proved to be effective in some of parasomnias, as in many other neurological disorders. A series of therapeutic strategies were analyzed and compared. Benzodiazepines, antidepressant drugs, and L-5-hydroxytryptophan may be beneficial in DOA. SSRI and topiramate are effective in SRED. RBD responds to clonazepam, melatonin, and to a lesser extent to dopaminergic and anticholinergic agents. Prazosin and cannabinoids are effective in nightmare disorder. Sleep paralysis may respond to antidepressant agents. Tricyclic antidepressant may be effective in sleep-related hallucinations and exploding head syndrome. Sleep enuresis may be successfully treated with desmopressin, anticholinergic drugs, and imipramine.

  3. One-stage tooth-borne distraction versus two stage bone-borne distraction in surgically assisted maxillary expansion (SARME).

    Science.gov (United States)

    Seeberger, Robin; Abe-Nickler, Dorothee; Hoffmann, Jürgen; Kunzmann, Kevin; Zingler, Sebastian

    2015-12-01

    To evaluate and compare the effects of tooth-borne and bone-borne distraction devices in surgically assisted maxillary expansion (SARME) on dental and skeletal structures. A sample of 33 skeletally mature patients with transverse maxillary deficiencies was examined with cone beam computed tomography (CBCT) before and 3 months after surgery. Fourteen patients were treated with tooth-borne devices and 19 patients with bone-borne devices. Dental crown expansion in the first premolars did not differ significantly between the two groups, and median expansion was 5.55 mm (interquartile range [IQR] 5.23) in the tooth-borne device group and 4.6 mm (IQR 3.4) in the bone-borne device group. In the first molars, crown expansion and lateral tipping were significantly greater in the tooth-borne device group (P ≤ .02). The median skeletal nasal isthmus increase was significantly more in the bone-borne device group at 3.0 mm than in the tooth-borne device group at 0.98 mm (P ≤ .02). Both tooth-borne and bone-borne devices are effective treatment modalities to correct maxillary transverse deficiencies. Bone-borne devices produced greater widening of the skeletal nasal floor and fewer dental side effects in the first molars. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Supramolecular Nanoparticles for Molecular Diagnostics and Therapeutics

    Science.gov (United States)

    Chen, Kuan-Ju

    Over the past decades, significant efforts have been devoted to explore the use of various nanoparticle-based systems in the field of nanomedicine, including molecular imaging and therapy. Supramolecular synthetic approaches have attracted lots of attention due to their flexibility, convenience, and modularity for producing nanoparticles. In this dissertation, the developmental story of our size-controllable supramolecular nanoparticles (SNPs) will be discussed, as well as their use in specific biomedical applications. To achieve the self-assembly of SNPs, the well-characterized molecular recognition system (i.e., cyclodextrin/adamantane recognition) was employed. The resulting SNPs, which were assembled from three molecular building blocks, possess incredible stability in various physiological conditions, reversible size-controllability and dynamic disassembly that were exploited for various in vitro and in vivo applications. An advantage of using the supramolecular approach is that it enables the convenient incorporation of functional ligands onto SNP surface that confers functionality ( e.g., targeting, cell penetration) to SNPs. We utilized SNPs for molecular imaging such as magnetic resonance imaging (MRI) and positron emission tomography (PET) by introducing reporter systems (i.e., radio-isotopes, MR contrast agents, and fluorophores) into SNPs. On the other hand, the incorporation of various payloads, including drugs, genes and proteins, into SNPs showed improved delivery performance and enhanced therapeutic efficacy for these therapeutic agents. Leveraging the powers of (i) a combinatorial synthetic approach based on supramolecular assembly and (ii) a digital microreactor, a rapid developmental pathway was developed that is capable of screening SNP candidates for the ideal structural and functional properties that deliver optimal performance. Moreover, SNP-based theranostic delivery systems that combine reporter systems and therapeutic payloads into a

  5. Therapeutic advancement of chronic lymphocytic leukemia

    Directory of Open Access Journals (Sweden)

    Lu Kang

    2012-09-01

    Full Text Available Abstract Despite the combinations of chemotherapy with monoclonal antibodies have further improved response rates, chronic lymphocytic leukemia (CLL remains an incurable disease with an extremely variable course. This article reviews the ongoing clinical advances in the treatment of CLL in both previously untreated and relapsed disease and focuses on the benefit of different therapeutic strategies, the most effective therapy combinations and the potential activity of novel agents. Novel agents and combination therapies have been investigated by several studies in both the upfront and relapsed setting, particularly for patients with 17p deletion, TP53 mutation and fludarabine-refractory CLL. While these agents and combination therapies have improved initial response rates, ongoing studies are continued to determine and improve the efficacy and safety. Despite advancements in the treatment of CLL have led to high response rates, allogeneic hematopoietic stem cell transplantation (allo-HSCT remains the only curative option and reduced-intensity conditioning (RIC allo-HSCT must be strongly considered whenever feasible. As such, ongoing studies of these agents and other novel approaches in clinical development are needed to expand and improve treatment options for CLL patients.

  6. Tumor angiogenesis--a new therapeutic target in gliomas

    DEFF Research Database (Denmark)

    Lund, E L; Spang-Thomsen, M; Skovgaard-Poulsen, H

    1998-01-01

    significant angiogenic activity primarily by the expression of the angiogenic factor VEGF Anti-angiogenic therapy represents a new promising therapeutic modality in solid tumors. Several agents are currently under evaluation in clinical trials. The present review describes the principal inducers...

  7. Radiographic scanning agent

    International Nuclear Information System (INIS)

    Bevan, J.A.

    1983-01-01

    This invention relates to radiodiagnostic agents and more particularly to a composition and method for preparing a highly effective technetium-99m-based bone scanning agent. One deficiency of x-ray examination is the inability of that technique to detect skeletal metastases in their incipient stages. It has been discovered that the methanehydroxydiphosphonate bone mineral-seeking agent is unique in that it provides the dual benefits of sharp radiographic imaging and excellent lesion detection when used with technetium-99m. This agent can also be used with technetium-99m for detecting soft tissue calcification in the manner of the inorganic phosphate radiodiagnostic agents

  8. Agente adaptable y aprendizaje

    Directory of Open Access Journals (Sweden)

    Arturo Angel Lara Rivero

    2013-05-01

    Full Text Available En este trabajo se contrasta el concepto de agente programado con el de agente complejo adaptable, se presenta una nueva visión ligada al aprendizaje y la estructura del agente. La imagen del agente se analiza considerando los modelos internos, la práctica, el concepto de rutina y la influencia en su comportamiento, y la importancia del aprendizaje ex ante y ex post. Por último se muestra que la resolución de problemas está sujeta a restricciones del agente y se describen las formas de explorar el espacio de soluciones mediante tres tipos de exploración: exhaustiva, aleatoria y selectiva.

  9. OUTCOMES OF TICK-BORNE ENCEPHALITIS IN THE TOMSK REGION

    Directory of Open Access Journals (Sweden)

    T. S. Pinegina

    2013-01-01

    Full Text Available The results of the study outcomes of tick-borne encephalitis in adults in the Tomsk Region. Patients conducted a comprehensive clinical and laboratory examination. Revealed the prevalence of autonomic disorders in individuals who have had at different periods of tick-borne encephalitis, which is regarded as the effects of tick-borne infection. Residual effects of tick-borne encephalitis occurs mainly in the form of light paresis after suffering a focal forms. Among the chronic (progredient forms of tick-borne encephalitis often formed hyperkinetic options. Most of the study revealed the presence of precipitating factors that could have an influence on the outcome. Fundamental diffe rences in all-clinical and immunological analyses at patients with various outcomes of tick-borne encephalitis it wasn't noted. KEY WORDS: tick-borne encephalitis, Tomsk Region, the outcomes.

  10. Born too soon: preterm birth matters.

    Science.gov (United States)

    Howson, Christopher P; Kinney, Mary V; McDougall, Lori; Lawn, Joy E

    2013-01-01

    Urgent action is needed to address preterm birth given that the fi rst country-level estimates show that globally 15 million babies are born too soon and rates are increasing in most countries with reliable time trend data. As the fi rst in a supplement entitled “Born Too Soon”, this paper focuses on the global policy context. Preterm birth is critical for progress on Millennium Development Goal 4 (MDG) for child survival by 2015 and beyond, and gives added value to maternal health (MDG 5) investments also linking to non-communicable diseases. For preterm babies who survive, the additional burden of prematurity-related disability may aff ect families and health systems. Prematurity is an explicit priority in many high-income settings; however, more attention is needed especially in low- and middle-income countries where the invisibility of preterm birth as well as its myths and misconceptions have slowed action on prevention and care. Recent global attention to preterm birth hit a tipping point in 2012, with the May 2 publication of Born Too Soon: The Global Action Report on Preterm Birth and with the 2nd annual World Prematurity Day on November 17 which mobilised the actions of partners in many countries to address preterm birth and newborn health. Interventions to strengthen preterm birth prevention and care span the continuum of care for reproductive, maternal, newborn and child health. Both prevention of preterm birth and implementation of care of premature babies require more research, as well as more policy attention and programmatic investment.

  11. Convergence of the Distorted Wave Born series

    International Nuclear Information System (INIS)

    MacMillan, D.S.

    1981-01-01

    The aim of this thesis is to begin to understand the idea of reaction mechanisms in nonrelativistic scattering systems. If we have a complete reaction theory of a particular scattering system, then we claim that the theory itself must contain information about important reaction mechanisms in the system. This information can be used to decide what reaction mechanisms should be included in an approximate calculation. To investigate this claim, we studied several solvable models. The primary concept employed in studying our models is the convergence of the multistep series generated by iterating the corresponding scattering integral equation. We known that the eigenvalues of the kernel of the Lippmann-Schwinger equation for potential scattering determine the rate of convergence of the Born series. The Born series will converge only if these eigenvalues all life within the unit circle. We extend these results to a study of the distorted wave Born series for inelastic scattering. The convergence criterion tells us when approximations are valid. We learn how the convergence of the distorted wave series depends upon energy, coupling constants, angular momentum, and angular momentum transfer. In one of our models, we look at several possible distorting potentials to see which one gives the best convergence. We have also applied our results to several actual DWBA or coupled channel calculations in the literature. In addition to the study of models of two-body scattering systems, we have considered the case of rearrangement scattering. We have discussed the formulation of (N greater than or equal to 3)-body distorted wave equations in which the interior dynamics have been redistributed by introducing compact N-body distortion potentials

  12. Characterization of tick-borne encephalitis virus from Latvia.

    Science.gov (United States)

    Mavtchoutko, V; Vene, S; Haglund, M; Forsgren, M; Duks, A; Kalnina, V; Hörling, J; Lundkvist, A

    2000-02-01

    Viruses of the tick-borne encephalitis (TBE) antigenic complex, within the family Flaviviridae, cause a variety of diseases including uncomplicated febrile illness, encephalitis, meningo-encephalitis, hemorrhagic fever and chronic disease in humans, domesticated animals or wildlife species. TBE is a serious problem in Latvia with up to a 1,000 patients confirmed serologically annually 1994-1995. No previous data had been reported on the causative agent of TBE in Latvia. In the present study, a virus was isolated from serum of a patient with clinical symptoms of an acute TBE infection. Nucleotide sequence information obtained by direct reverse transcription-polymerase chain reaction (RT-PCR) and the serological characteristics of the isolated virus strain, designated TBE-Latvia-1-96, indicated a closer relationship to the Vasilchenko strain, isolated in Novosibirsk (Siberia, Russia), as compared to the western European or far eastern subtypes of TBE viruses. In a mouse neurovirulence assay, a significant difference in survival rates (days) was shown between Latvia-1-96 and the western European TBE virus subtype. Copyright 2000 Wiley-Liss, Inc.

  13. Notes on Born-Infeld-type electrodynamics

    Science.gov (United States)

    Kruglov, S. I.

    2017-11-01

    We propose a new model of nonlinear electrodynamics (NLED) with three parameters. Born-Infeld (BI) electrodynamics and exponential electrodynamics are particular cases of this model. The phenomenon of vacuum birefringence in the external magnetic field is studied. We show that there is no singularity of the electric field at the origin of point-like charged particles. The corrections to Coulomb’s law at r →∞ are obtained. We calculate the total electrostatic energy of charges, for different parameters of the model, which is finite.

  14. Wormholes in Einstein-Born-Infeld Gravity

    Directory of Open Access Journals (Sweden)

    Kim Jin Young

    2018-01-01

    Full Text Available We introduce a new approach to construct wormholes without introducing exotic matters in Einstein-Born-Infeld gravity with a cosmological constant. Contary to the conventional approach, the throat is located at the place where the solutions can be joined smoothly. The metric and its derivatives are continuous so that the exotic matters are not needed there. The exoticity of the energy-momentum tensor is not essential to sustain the wormhole. We also present a method to check the stability of wormholes in the new approach.

  15. Born with Protection against Whooping Cough

    Centers for Disease Control (CDC) Podcasts

    2015-01-22

    This podcast provides information about whooping cough, a disease that can be deadly for babies, and CDC’s recommendation that all women receive the Tdap vaccine during the third trimester of every pregnancy so their babies can be born with protection from this serious disease.  Created: 1/22/2015 by National Center for Immunization and Respiratory Diseases (NCIRD), Division of Bacterial Diseases (DBD), Meningitis and Vaccine Preventable Diseases Branch (MVPDB).   Date Released: 1/22/2015.

  16. [Tick borne encephalitis and enviromental changes].

    Science.gov (United States)

    Zajkowska, Joanna; Malzahn, Elzbieta; Kondrusik, Maciej; Grygorczuk, Sambor; Pancewicz, Sławomir S; Kuśmierczyk, Justyna; Czupryna, Piotr; Hermanowska-Szpakowicz, Teresa

    2006-01-01

    Currently observed markedly increased incidence of various tick borne diseases in many parts of Europe is due to documented climatic changes as well anthropogenic influence on habitat structure. One of the analyzed factors is tendency to increase of the spring temperatures, especially in the third decade of the April. Such conditions (spring temperatures above 7-10 degrees C) let the nymphs and larvae of Ixodes ricinus to feed simultaneously on rodents. This increases the risk of infection of Ixodes ricinus with TBE virus, so dangerous for humans.

  17. MRI in tick-borne encephalitis

    International Nuclear Information System (INIS)

    Alkadhi, H.; Kollias, S.S.

    2000-01-01

    The tick-borne encephalitis (TBE) virus gives rise to epidemic encephalitis. Mild forms usually manifest as influenza-like episodes or are clinically silent. MRI is usually normal in TBE. We describe severe TBE in a patient who presented with fever and altered mental status after a tick bite and a specific antibody response to TBE. MRI revealed pronounced signal abnormalities in the basal ganglia and thalamus, without contrast enhancement. These findings coincide well with neuropathological studies of severe nerve cell degeneration with inflammatory cell infiltrates, neuronophagia and reactive astrocytosis in the deep grey matter. We review the literature and discuss the relevant differential diagnosis. (orig.)

  18. Potential Therapeutic Uses of p19ARF Mimics in Mammary Tumorigenesis

    National Research Council Canada - National Science Library

    Hann, Stephen R

    2005-01-01

    Since many breast tumors have deregulated c-Myc we hypothesize that an ARF mimic would be a valuable therapeutic agent for breast cancer to inhibit c-Myc-induced transformation/tumorigenesis without...

  19. Biocontrol and Rapid Detection of Food-borne Pathogens Using Bacteriophages and Endolysins

    Directory of Open Access Journals (Sweden)

    Jaewoo eBai

    2016-04-01

    Full Text Available Bacteriophages have been suggested as natural food preservatives as well as rapid detection materials for food-borne pathogens in various foods. Since Listeria monocytogenes-targeting phage cocktail (ListShield was approved for applications in foods, numerous phages have been screened and experimentally characterized for phage applications in foods. A single phage and phage cocktail treatments to various foods contaminated with food-borne pathogens including E. coli O157:H7, Salmonella enterica, Campylobacter jejuni, Listeria monocytogenes, Staphylococcus aureus, Cronobacter sakazakii, and Vibrio spp. revealed that they have great potential to control various food-borne pathogens and may be alternative for conventional food preservatives. In addition, phage-derived endolysins with high host specificity and host lysis activities may be preferred to food applications rather than phages. For rapid detection of food-borne pathogens, cell-wall binding domains (CBDs from endolysins have been suggested due to their high host-specific binding. Fluorescence-tagged CBDs have been successfully evaluated and suggested to be alternative materials of expensive antibodies for various detection applications. Most recently, reporter phage systems have been developed and tested to confirm their usability and accuracy for specific detection. These systems revealed some advantages like rapid detection of only viable pathogenic cells without interference by food components in a very short reaction time, suggesting that these systems may be suitable for monitoring of pathogens in foods. Consequently, phage is the next-generation biocontrol agent as well as rapid detection tool to confirm and even identify the food-borne pathogens present in various foods.

  20. Tick-Borne Diseases in Turkey: A Review Based on One Health Perspective.

    Directory of Open Access Journals (Sweden)

    Abdullah Inci

    2016-12-01

    Full Text Available The importance of tick-borne diseases is increasing all over the world, including Turkey. Global warming, environmental and ecological changes and the existence of suitable habitats increase the impact of ticks and result in frequent emergence or re-emergence of tick-borne diseases (TBDs with zoonotic characteristics. In Turkey, almost 19 TBDs have been reported in animals and men, involving four protozoa (babesiosis, theileriosis, cytauxzoonosis, hepatozoonosis, one filarial nematode (acanthocheilonemasis, ten bacterial agents (anaplasmosis, ehrlichiosis, aegyptianellosis, tick-borne typhus, Candidatus Rickettsia vini, Lyme borreliosis, tick-borne relapsing fever [TBRF], tularaemia, bartonellosis, and hemoplasmosis, and four viral infections (tick-borne encephalitis [TBE], Crimean-Congo Haemorrhagic Fever [CCHF], louping-ill [LI], and lumpy skin disease [LSD]. The growing number of TBD cases, in particular the fatal viral epidemics in humans, have led to increased public awareness and concern against TBDs in recent years. The World Health Organization (WHO has developed a new political concept, called the "One Health" initiative, which is especially relevant for developing strategies against tick infestations and TBD control in humans and animals. It would be beneficial for Turkey to adopt this new strategy and establish specific research and control programs in coordination with international organizations like WHO, the World Organization for Animal Health (OIE, the Food and Agriculture Organization (FAO, the Centers for Disease Control and Prevention (CDC, and the European Center for Disease Prevention and Control (ECDC to combat TBDs based on the "One Health Initiative" concept. In this article, we review the occurrence of primary TBDs in man and animals in Turkey in light of the "One Health" perspective.

  1. Dendrimers as Potential Therapeutic Tools in HIV Inhibition

    Directory of Open Access Journals (Sweden)

    Xiangbo Li

    2013-07-01

    Full Text Available The present treatments for HIV transfection include chemical agents and gene therapies. Although many chemical drugs, peptides and genes have been developed for HIV inhibition, a variety of non-ignorable drawbacks limited the efficiency of these materials. In this review, we discuss the application of dendrimers as both therapeutic agents and non-viral vectors of chemical agents and genes for HIV treatment. On the one hand, dendrimers with functional end groups combine with the gp120 of HIV and CD4 molecule of host cell to suppress the attachment of HIV to the host cell. Some of the dendrimers are capable of intruding into the cell and interfere with the later stages of HIV replication as well. On the other hand, dendrimers are also able to transfer chemical drugs and genes into the host cells, which conspicuously increase the anti-HIV activity of these materials. Dendrimers as therapeutic tools provide a potential treatment for HIV infection.

  2. U.S.-born compared to non-U.S.-born abused women: analysis of baseline data.

    Science.gov (United States)

    Montalvo-Liendo, Nora; Koci, Anne; McFarlane, Judith; Gilroy, Heidi; Maddoux, John

    2013-01-01

    It is evident from recent studies that a woman's citizenship status does not exempt her from exposure to partner violence. The purpose of this article was to examine if social support, self-efficacy, and marginalization of abused women differ based on U.S. born compared to non-U.S. born with and without documentation. The findings suggest that women who were born in the United States had significantly higher self-efficacy scores compared to non-U.S.-born women without documents. There were no significant differences in social support among abused women who are U.S. born compared to non-U.S. born with and without documentation. In addition, women who were not born in the United States and did not have documents had higher marginalization.

  3. Characterization of a Francisella tularensis-Caenorhabditis elegans Pathosystem for the Evaluation of Therapeutic Compounds

    OpenAIRE

    Jayamani, Elamparithi; Tharmalingam, Nagendran; Rajamuthiah, Rajmohan; Coleman, Jeffrey J.; Kim, Wooseong; Okoli, Ikechukwu; Hernandez, Ana M.; Lee, Kiho; Nau, Gerard J.; Ausubel, Frederick M.; Mylonakis, Eleftherios

    2017-01-01

    Francisella tularensis is a highly infectious Gram-negative intracellular pathogen that causes tularemia. Because of its potential as a bioterrorism agent, there is a need for new therapeutic agents. We therefore developed a whole-animal Caenorhabditis elegans-F. tularensis pathosystem for high-throughput screening to identify and characterize potential therapeutic compounds. We found that the C. elegans p38 mitogen-activate protein (MAP) kinase cascade is involved in the immune response to F...

  4. Social Trust and Children Born of War

    Directory of Open Access Journals (Sweden)

    Voicu Bogdan

    2014-12-01

    Full Text Available This paper considers two assumptions commonly used in analyzing the formation of social trust. They stress the importance of early socialization, on one hand, and of life events, on the other. We consider birth as a major life event for anyone and focus on the situation of Children Born of War. This group, even if lesser visible in some societies, has the peculiar characteristic to be born and socialized in very specific conditions. Typically, these people are the offspring of foreign soldiers, and local women. They may bear stigma, might be marginalized in family, school and society, and might develop a low level of generalized trust even if they may have lived all life in a culture rich in social trust. We explore at theoretical level their case, bring in a few statistics, and suggest a research direction that may be fruitful in learning about both such hidden populations and about social trust. In the end, we argue upon the importance of the topic for post-conflict societies.

  5. Open bite in prematurely born children.

    Science.gov (United States)

    Harila, V; Heikkinen, T; Grön, M; Alvesalo, L

    2007-01-01

    The aims of this study were to: examine the expression of open bite in prematurely born children and discuss the etiological factors that may lead to bite it. The subjects were 328 prematurely born (cross-sectional study of the Collaborative Perinatal Project in the 1960s and 1970s. Dental documents, including casts and photographs, were taken once at the age of 6-12 years in the mixed dentition. The occlusion was recorded by examining and measuring the hard stone casts. Vertical open bite was recorded only for full erupted teeth. The statistical method used was chi-square analysis. Significant differences in the incidence of anterior open bite (from left to right canine) was found between the preterm and control groups and between gender and ethnic groups. The prevalence of anterior open bite was nearly 9% in the preterm group and almost 7% in the control group. African Americans (9%) had a significantly greater incidence of open bite than Caucasians (3%; Pbite than boys (8% vs 6%; Pbite was increased--especially in preterm African American boys compared to controls (11% vs 8%). The results show differences in the development of anterior open bite between ethnic and gender groups. Premature birth may also influence dental occlusal development. Of importance are the patient's: general health condition; respiratory infections; inadequate nasal- and mouth-breathing; oral habits; and other medical problems. Preterm children may be relatively more predisposed to etiological factors for the development of anterior open bite.

  6. Moral actor, selfish agent.

    Science.gov (United States)

    Frimer, Jeremy A; Schaefer, Nicola K; Oakes, Harrison

    2014-05-01

    People are motivated to behave selfishly while appearing moral. This tension gives rise to 2 divergently motivated selves. The actor-the watched self-tends to be moral; the agent-the self as executor-tends to be selfish. Three studies present direct evidence of the actor's and agent's distinct motives. To recruit the self-as-actor, we asked people to rate the importance of various goals. To recruit the self-as-agent, we asked people to describe their goals verbally. In Study 1, actors claimed their goals were equally about helping the self and others (viz., moral); agents claimed their goals were primarily about helping the self (viz., selfish). This disparity was evident in both individualist and collectivist cultures, attesting to the universality of the selfish agent. Study 2 compared actors' and agents' motives to those of people role-playing highly prosocial or selfish exemplars. In content (Study 2a) and in the impressions they made on an outside observer (Study 2b), actors' motives were similar to those of the prosocial role-players, whereas agents' motives were similar to those of the selfish role-players. Study 3 accounted for the difference between the actor and agent: Participants claimed that their agent's motives were the more realistic and that their actor's motives were the more idealistic. The selfish agent/moral actor duality may account for why implicit and explicit measures of the same construct diverge, and why feeling watched brings out the better angels of human nature.

  7. Stroke and Therapeutic Hypothermia

    Directory of Open Access Journals (Sweden)

    Ozlem Ozkan Kuscu

    2016-09-01

    Full Text Available Stroke is significant cause of morbidity and mortality caused by disruption of blood flow. Neural injury occurs with two stage; while primary neural injury occurs with disruption of blood flow, after days and hours with metabolic processes secondary injury develops in tissues which is non injured in the first stage. Therefore it is important to prevent and treat the secondary injury as much as preventing and treating the primary neural injury. In this article developing pathophysiological changes after stroke, mechanisms of therapeutic hypothermia, application methods, the factors that determine the effectiveness, side effects and complications were reviewed. [Archives Medical Review Journal 2016; 25(3.000: 351-368

  8. Food-borne zoonoses, the EU zoonosis legislation and the prospects for food safety and consumer protection during primary animal production.

    Science.gov (United States)

    Smulders, Frans J M; Vågsholm, Ivar; Korkeala, Hannu

    2008-01-01

    Zoonoses are diseases that are transmitted naturally between animals and humans. The control of food-borne zoonoses within the European Union is a prerequisite for assuring a functional internal market and consequently represents an important item on the political agenda. Unfortunately, until recently, gaining a clear view of the current incidence of food-borne zoonoses and the prevalence of its causative agents has been frustrated by the absence of reliable monitoring and reporting systems. Similarly, it has become clear that, Europe wide, one has witnessed only limited success with regard to the control of important food-borne agents such as Salmonella spp. The European Union has adopted legislation to remedy this situation and to control food-borne zoonoses in primary production. This contribution discusses the incentives for introducing EU Directive 2003/99/EC and EU Regulation No. 2160/2003, summarises their essentials and discusses major ramifications of both pieces of legislation for the prevention of food-borne zoonoses. It is concluded that there is reason for cautious optimism concerning human salmonellosis, while for other food-borne zoonoses there should be a call for action.

  9. Wildlife reservoirs for vector-borne canine, feline and zoonotic infections in Austria

    Directory of Open Access Journals (Sweden)

    Georg G. Duscher

    2015-04-01

    The role of wild ungulates, especially ruminants, as reservoirs for zoonotic disease on the other hand seems to be negligible, although the deer filaroid Onchocerca jakutensis has been described to infect humans. Deer may also harbour certain Anaplasma phagocytophilum strains with so far unclear potential to infect humans. The major role of deer as reservoirs is for ticks, mainly adults, thus maintaining the life cycle of these vectors and their distribution. Wild boar seem to be an exception among the ungulates as, in their interaction with the fox, they can introduce food-borne zoonotic agents such as Trichinella britovi and Alaria alata into the human food chain.

  10. The therapeutic journey of benzimidazoles: a review.

    Science.gov (United States)

    Bansal, Yogita; Silakari, Om

    2012-11-01

    Presence of benzimidazole nucleus in numerous categories of therapeutic agents such as antimicrobials, antivirals, antiparasites, anticancer, anti-inflammatory, antioxidants, proton pump inhibitors, antihypertensives, anticoagulants, immunomodulators, hormone modulators, CNS stimulants as well as depressants, lipid level modulators, antidiabetics, etc. has made it an indispensable anchor for development of new therapeutic agents. Varied substitutents around the benzimidazole nucleus have provided a wide spectrum of biological activities. Importance of this nucleus in some activities like, Angiotensin I (AT(1)) receptor antagonism and proton-pump inhibition is reviewed separately in literature. Even some very short reviews on biological importance of this nucleus are also known in literature. However, owing to fast development of new drugs possessing benzimidazole nucleus many research reports are generated in short span of time. So, there is a need to couple the latest information with the earlier information to understand the current status of benzimidazole nucleus in medicinal chemistry research. In the present review, various derivatives of benzimidazole with different pharmacological activities are described on the basis of substitution pattern around the nucleus with an aim to help medicinal chemists for developing an SAR on benzimidazole derived compounds for each activity. This discussion will further help in the development of novel benzimidazole compounds. Copyright © 2012 Elsevier Ltd. All rights reserved.

  11. Gray wolf exposure to emerging vector-borne diseases in Wisconsin with comparison to domestic dogs and humans

    Science.gov (United States)

    Jara, Rocio F.; Wydeven, Adrian P.; Samuel, Michael D.

    2016-01-01

    World-wide concern over emerging vector-borne diseases has increased in recent years for both animal and human health. In the United Sates, concern about vector-borne diseases in canines has focused on Lyme disease, anaplasmosis, ehrlichiosis, and heartworm which infect domestic and wild canids. Of these diseases, Lyme and anaplasmosis are also frequently diagnosed in humans. Gray wolves (Canis lupus) recolonized Wisconsin in the 1970s, and we evaluated their temporal and geographic patterns of exposure to these four vector-borne diseases in Wisconsin as the population expanded between 1985 and 2011. A high proportion of the Wisconsin wolves were exposed to the agents that cause Lyme (65.6%) and anaplasma (47.7%), and a smaller proportion to ehrlichiosis (5.7%) and infected with heartworm (9.2%). Wolf exposure to tick borne diseases was consistently higher in older animals. Wolf exposure was markedly higher than domestic dog (Canis familiaris) exposure for all 4 disease agents during 2001–2013. We found a cluster of wolf exposure to Borrelia burgdorferi in northwestern Wisconsin, which overlaps human and domestic dog clusters for the same pathogen. In addition, wolf exposure to Lyme disease in Wisconsin has increased, corresponding with the increasing human incidence of Lyme disease in a similar time period. Despite generally high prevalence of exposure none of these diseases appear to have slowed the growth of the Wisconsin wolf population.

  12. Gray Wolf Exposure to Emerging Vector-Borne Diseases in Wisconsin with Comparison to Domestic Dogs and Humans.

    Directory of Open Access Journals (Sweden)

    Rocio F Jara

    Full Text Available World-wide concern over emerging vector-borne diseases has increased in recent years for both animal and human health. In the United Sates, concern about vector-borne diseases in canines has focused on Lyme disease, anaplasmosis, ehrlichiosis, and heartworm which infect domestic and wild canids. Of these diseases, Lyme and anaplasmosis are also frequently diagnosed in humans. Gray wolves (Canis lupus recolonized Wisconsin in the 1970s, and we evaluated their temporal and geographic patterns of exposure to these four vector-borne diseases in Wisconsin as the population expanded between 1985 and 2011. A high proportion of the Wisconsin wolves were exposed to the agents that cause Lyme (65.6% and anaplasma (47.7%, and a smaller proportion to ehrlichiosis (5.7% and infected with heartworm (9.2%. Wolf exposure to tick borne diseases was consistently higher in older animals. Wolf exposure was markedly higher than domestic dog (Canis familiaris exposure for all 4 disease agents during 2001-2013. We found a cluster of wolf exposure to Borrelia burgdorferi in northwestern Wisconsin, which overlaps human and domestic dog clusters for the same pathogen. In addition, wolf exposure to Lyme disease in Wisconsin has increased, corresponding with the increasing human incidence of Lyme disease in a similar time period. Despite generally high prevalence of exposure none of these diseases appear to have slowed the growth of the Wisconsin wolf population.

  13. Chromosome analyses of nurses handling cytostatic agents

    International Nuclear Information System (INIS)

    Waksvik, H.; Klepp, O.; Brogger, A.

    1981-01-01

    A cytogenetic study of ten nurses handling cytostatic agents (average exposure, 2150 hours) and ten female hospital clerks revealed an increased frequency of chromosome gaps and a slight increase in sister chromatid exchange frequency among the nurses. The increase may be due to exposure to cytostatic drugs and points to these agents as a possible occupational health hazard. A second group of 11 nurses handling cytostatic agents for a shorter period of time (average exposure, 1078 hours), and three other groups (eight nurses engaged in therapeutic and diagnostic radiology, nine nurses engaged in anesthesiology, and seven nurses in postoperative ward) did not differ from the office personnel, except for an increased frequency of chromosome gaps in the radiology group

  14. Pharmacogenetics approach to therapeutics.

    Science.gov (United States)

    Koo, Seok Hwee; Lee, Edmund Jon Deoon

    2006-01-01

    1. Pharmacogenetics refers to the study of genetically controlled variations in drug response. Functional variants caused by single nucleotide polymorphisms (SNPs) in genes encoding drug-metabolising enzymes, transporters, ion channels and drug receptors have been known to be associated with interindividual and interethnic variation in drug response. Genetic variations in these genes play a role in influencing the efficacy and toxicity of medications. 2. Rapid, precise and cost-effective high-throughput technological platforms are essential for performing large-scale mutational analysis of genetic markers involved in the aetiology of variable responses to drug therapy. 3. The application of a pharmacogenetics approach to therapeutics in general clinical practice is still far from being achieved today owing to various constraints, such as limited accessibility of technology, inadequate knowledge, ambiguity of the role of variants and ethical concerns. 4. Drug actions are determined by the interplay of several genes encoding different proteins involved in various biochemical pathways. With rapidly emerging SNP discovery technological platforms and widespread knowledge on the role of SNPs in disease susceptibility and variability in drug response, the pharmacogenetics approach to therapeutics is anticipated to take off in the not-too-distant future. This will present profound clinical, economic and social implications for health care.

  15. Therapeutic nuclear medicine

    International Nuclear Information System (INIS)

    Baum, Richard P.

    2014-01-01

    Discusses all aspects of radionuclide therapy, including basic principles, newly available treatments, regulatory requirements, and future trends. Provides the knowledge required to administer radionuclide therapy safely and effectively in the individual patient. Explains the role of the therapeutic nuclear physician in effectively coordinating a diverse multidisciplinary team. Written by leading experts. The recent revolution in molecular biology offers exciting new opportunities for targeted radionuclide therapy. The selective irradiation of tumor cells through molecular biological mechanisms is now permitting the radiopharmaceutical control of tumors that are unresectable and unresponsive to either chemotherapy or conventional radiotherapy. In this up-to-date, comprehensive book, world-renowned experts discuss the basic principles of radionuclide therapy, explore in detail the available treatments, explain the regulatory requirements, and examine likely future developments. The full range of clinical applications is considered, including thyroid cancer, hematological malignancies, brain tumors, liver cancer, bone and joint disease, and neuroendocrine tumors. The combination of theoretical background and practical information will provide the reader with all the knowledge required to administer radionuclide therapy safely and effectively in the individual patient. Careful attention is also paid to the important role of the therapeutic nuclear physician in delivering the effective coordination of a diverse multidisciplinary team that is essential to the safe provision of treatment.

  16. Mechanisms of Plasma Therapeutics

    Science.gov (United States)

    Graves, David

    2015-09-01

    In this talk, I address research directed towards biomedical applications of atmospheric pressure plasma such as sterilization, surgery, wound healing and anti-cancer therapy. The field has seen remarkable growth in the last 3-5 years, but the mechanisms responsible for the biomedical effects have remained mysterious. It is known that plasmas readily create reactive oxygen species (ROS) and reactive nitrogen species (RNS). ROS and RNS (or RONS), in addition to a suite of other radical and non-radical reactive species, are essential actors in an important sub-field of aerobic biology termed ``redox'' (or oxidation-reduction) biology. It is postulated that cold atmospheric plasma (CAP) can trigger a therapeutic shielding response in tissue in part by creating a time- and space-localized, burst-like form of oxy-nitrosative stress on near-surface exposed cells through the flux of plasma-generated RONS. RONS-exposed surface layers of cells communicate to the deeper levels of tissue via a form of the ``bystander effect,'' similar to responses to other forms of cell stress. In this proposed model of CAP therapeutics, the plasma stimulates a cellular survival mechanism through which aerobic organisms shield themselves from infection and other challenges.

  17. Therapeutic nuclear medicine

    Energy Technology Data Exchange (ETDEWEB)

    Baum, Richard P. (ed.) [ENETS Center of Excellence, Bad Berka (Germany). THERANOSTICS Center for Molecular Radiotherapy and Molecular Imaging

    2014-07-01

    Discusses all aspects of radionuclide therapy, including basic principles, newly available treatments, regulatory requirements, and future trends. Provides the knowledge required to administer radionuclide therapy safely and effectively in the individual patient. Explains the role of the therapeutic nuclear physician in effectively coordinating a diverse multidisciplinary team. Written by leading experts. The recent revolution in molecular biology offers exciting new opportunities for targeted radionuclide therapy. The selective irradiation of tumor cells through molecular biological mechanisms is now permitting the radiopharmaceutical control of tumors that are unresectable and unresponsive to either chemotherapy or conventional radiotherapy. In this up-to-date, comprehensive book, world-renowned experts discuss the basic principles of radionuclide therapy, explore in detail the available treatments, explain the regulatory requirements, and examine likely future developments. The full range of clinical applications is considered, including thyroid cancer, hematological malignancies, brain tumors, liver cancer, bone and joint disease, and neuroendocrine tumors. The combination of theoretical background and practical information will provide the reader with all the knowledge required to administer radionuclide therapy safely and effectively in the individual patient. Careful attention is also paid to the important role of the therapeutic nuclear physician in delivering the effective coordination of a diverse multidisciplinary team that is essential to the safe provision of treatment.

  18. Agent Architectures for Compliance

    Science.gov (United States)

    Burgemeestre, Brigitte; Hulstijn, Joris; Tan, Yao-Hua

    A Normative Multi-Agent System consists of autonomous agents who must comply with social norms. Different kinds of norms make different assumptions about the cognitive architecture of the agents. For example, a principle-based norm assumes that agents can reflect upon the consequences of their actions; a rule-based formulation only assumes that agents can avoid violations. In this paper we present several cognitive agent architectures for self-monitoring and compliance. We show how different assumptions about the cognitive architecture lead to different information needs when assessing compliance. The approach is validated with a case study of horizontal monitoring, an approach to corporate tax auditing recently introduced by the Dutch Customs and Tax Authority.

  19. Stabilized radiographic scanning agents

    International Nuclear Information System (INIS)

    Fawzi, M.B.

    1982-01-01

    Stable compositions useful as technetium 99m-based scintigraphic agents comprise gentisic acid or a pharmaceutically-acceptable salt or ester thereof in combination with a pertechnetate reducing agent or dissolved in pertechnetate-99m (sup(99m)TcOsub(4)sup(-)) solution. The compositions are especially useful in combination with a phosphate or phosphonate material that carries the radionuclide to bone, thus providing a skeletal imaging agent

  20. Non-pet dogs as sentinels and potential synanthropic reservoirs of tick-borne and zoonotic bacteria

    OpenAIRE

    Hornok, Sandor; Denes, Bela; Meli, Marina L.; Tanczos, Balazs; Fekete, Lilla; Gyuranecz, Miklos; de la Fuente, Jose; Fernandez de Mera, Isabel G.; Farkas, Robert; Hofmann-Lehmann, Regina

    2013-01-01

    Blood samples were collected from 100 shepherd dogs, 12 hunting dogs and 14 stray dogs (apparently healthy) in southern Hungary to screen for the presence of emerging tick-borne pathogens. Based on real-time PCR results, 14 dogs (11%) had single or dual haemoplasma infection, and a same number of samples were positive for Anaplasma phagocytophilum. In one sample Coxiella burnetii was molecularly identified, and 20.3% of dogs seroconverted to the Q fever agent. Rickettsaemia (sensu stricto) wa...

  1. Contrast agents for MRI

    International Nuclear Information System (INIS)

    Bonnemain, B.

    1994-01-01

    Contrast agents MRI (Magnetic Resonance Imaging) have been developed to improve the diagnostic information obtained by this technic. They mainly interact on T1 and T2 parameters and increase consequently normal to abnormal tissues contrast. The paramagnetic agents which mainly act on longitudinal relaxation rate (T1) are gadolinium complexes for which stability is the main parameter to avoid any release of free gadolinium. The superparamagnetic agents that decrease signal intensity by an effect on transversal relaxation rate (T2) are developed for liver, digestive and lymph node imaging. Many area of research are now opened for optimal use of present and future contrast agents in MRI. (author). 28 refs., 4 tabs

  2. Decontamination Data - Blister Agents

    Data.gov (United States)

    U.S. Environmental Protection Agency — Decontamination efficacy data for blister agents on various building materials using various decontamination solutions. This dataset is associated with the following...

  3. Limited-Sampling Strategies for Therapeutic Drug Monitoring of Moxifloxacin in Patients With Tuberculosis

    NARCIS (Netherlands)

    Pranger, Arianna D.; Kosterink, Jos G. W.; van Altena, Richard; Aarnoutse, Rob E.; van der Werf, Tjip S.; Uges, Donald R. A.; Alffenaar, Jan-Willem C.

    Background: Moxifloxacin (MFX) is a potent drug for multidrug resistant tuberculosis(TB) treatment and is also useful if first-line agents are not tolerated. Therapeutic drug monitoring may help to prevent treatment failure. Obtaining a full concentration-time curve of MFX for therapeutic drug

  4. Limited-sampling strategies for therapeutic drug monitoring of moxifloxacin in patients with tuberculosis

    NARCIS (Netherlands)

    Pranger, A.D.; Kosterink, J.G.W.; Altena, R. van; Aarnoutse, R.E.; Werf, T.S. van der; Uges, D.R.A.; Alffenaar, J.W.C.

    2011-01-01

    BACKGROUND: Moxifloxacin (MFX) is a potent drug for multidrug resistant tuberculosis(TB) treatment and is also useful if first-line agents are not tolerated. Therapeutic drug monitoring may help to prevent treatment failure. Obtaining a full concentration-time curve of MFX for therapeutic drug

  5. Therapeutic touch: influence on vital signs of newborns

    Science.gov (United States)

    Ramada, Nadia Christina Oliveira; Almeida, Fabiane de Amorim; Cunha, Mariana Lucas da Rocha

    2013-01-01

    ABSTRACT Objective>: To compare vital signs before and after the therapeutic touch observed in hospitalized newborns in neonatal intensive care unit. Methods: This was a quasi-experimental study performed at a neonatal intensive care unit of a municipal hospital, in the city of São Paulo (SP), Brazil. The sample included 40 newborns submitted to the therapeutic touch after a painful procedure. We evaluated the vital signs, such as heart and respiratory rates, temperature and pain intensity, before and after the therapeutic touch. Results: The majority of newborns were male (n=28; 70%), pre-term (n=19; 52%) and born from vaginal delivery (n=27; 67%). Respiratory distress was the main reason for hospital admission (n=16; 40%). There was a drop in all vital signs after therapeutic touch, particularly in pain score, which had a considerable reduction in the mean values, from 3.37 (SD=1.31) to 0 (SD=0.0). All differences found were statistically significant by the Wilcoxon test (p<0.05). Conclusion: The results showed that therapeutic touch promotes relaxation of the baby, favoring reduction in vital signs and, consequently in the basal metabolism rate. PMID:24488378

  6. Canine vector-borne diseases in Brazil

    Science.gov (United States)

    Dantas-Torres, Filipe

    2008-01-01

    Canine vector-borne diseases (CVBDs) are highly prevalent in Brazil and represent a challenge to veterinarians and public health workers, since some diseases are of great zoonotic potential. Dogs are affected by many protozoa (e.g., Babesia vogeli, Leishmania infantum, and Trypanosoma cruzi), bacteria (e.g., Anaplasma platys and Ehrlichia canis), and helminths (e.g., Dirofilaria immitis and Dipylidium caninum) that are transmitted by a diverse range of arthropod vectors, including ticks, fleas, lice, triatomines, mosquitoes, tabanids, and phlebotomine sand flies. This article focuses on several aspects (etiology, transmission, distribution, prevalence, risk factors, diagnosis, control, prevention, and public health significance) of CVBDs in Brazil and discusses research gaps to be addressed in future studies. PMID:18691408

  7. Canine vector-borne diseases in Brazil

    Directory of Open Access Journals (Sweden)

    Dantas-Torres Filipe

    2008-08-01

    Full Text Available Abstract Canine vector-borne diseases (CVBDs are highly prevalent in Brazil and represent a challenge to veterinarians and public health workers, since some diseases are of great zoonotic potential. Dogs are affected by many protozoa (e.g., Babesia vogeli, Leishmania infantum, and Trypanosoma cruzi, bacteria (e.g., Anaplasma platys and Ehrlichia canis, and helminths (e.g., Dirofilaria immitis and Dipylidium caninum that are transmitted by a diverse range of arthropod vectors, including ticks, fleas, lice, triatomines, mosquitoes, tabanids, and phlebotomine sand flies. This article focuses on several aspects (etiology, transmission, distribution, prevalence, risk factors, diagnosis, control, prevention, and public health significance of CVBDs in Brazil and discusses research gaps to be addressed in future studies.

  8. Other impacts of soil-borne radionuclides

    International Nuclear Information System (INIS)

    Sheppard, S.C.; Macdonald, C.R.

    1996-01-01

    Soils surround us daily, and humans and animals are exposed to soil in more ways than simply through ingestion of plants. Despite strict personal and food-industry hygiene, some soil will always be present in our diet. This often involves the very fine soil particles known to be especially effective in sorbing radionuclides. The soil we ingest may come through skin contact or through soil adhering to crop plants and other foods. Inhalation of soil particles by humans and other animals must also be considered. Throughout the consideration of the impacts of soil-borne radionuclides, there must be recognition of potential impacts on non-human biota, and of non-radiological impacts. The chemical toxicity of long-lived radionuclides may be just as important as their radiological impact for non-human biota. These issues and associated assessment modelling approaches are discussed, with examples and data drawn from our research programs. (J.P.N.)

  9. Human sparganosis, a neglected food borne zoonosis.

    Science.gov (United States)

    Liu, Quan; Li, Ming-Wei; Wang, Ze-Dong; Zhao, Guang-Hui; Zhu, Xing-Quan

    2015-10-01

    Human sparganosis is a food borne zoonosis caused by the plerocercoid larvae (spargana) of various diphyllobothroid tapeworms of the genus Spirometra. Human infections are acquired by ingesting the raw or undercooked meat of snakes or frogs, drinking untreated water, or using raw flesh in traditional poultices. More than 1600 cases of sparganosis have been documented worldwide, mostly in east and southeast Asia. Sporadic cases have been reported in South America, Europe, and Africa, and several cases have been described in travellers returning from endemic regions. Epidemiological data suggest that the increased effect of sparganosis on human health is because of greater consumption of raw meat of freshwater frogs and snakes. This Review provides information about the Spirometra parasites and their lifecycles, summarises clinical features, diagnosis, and treatment of human sparganosis, and describes geographical distribution and infection characteristics of Spirometra parasites in host animals. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Risk based surveillance for vector borne diseases

    DEFF Research Database (Denmark)

    Bødker, Rene

    of samples and hence early detection of outbreaks. Models for vector borne diseases in Denmark have demonstrated dramatic variation in outbreak risk during the season and between years. The Danish VetMap project aims to make these risk based surveillance estimates available on the veterinarians smart phones...... in Northern Europe. This model approach may be used as a basis for risk based surveillance. In risk based surveillance limited resources for surveillance are targeted at geographical areas most at risk and only when the risk is high. This makes risk based surveillance a cost effective alternative...... sample to a diagnostic laboratory. Risk based surveillance models may reduce this delay. An important feature of risk based surveillance models is their ability to continuously communicate the level of risk to veterinarians and hence increase awareness when risk is high. This is essential for submission...

  11. Antibody Engineering and Therapeutics

    Science.gov (United States)

    Almagro, Juan Carlos; Gilliland, Gary L; Breden, Felix; Scott, Jamie K; Sok, Devin; Pauthner, Matthias; Reichert, Janice M; Helguera, Gustavo; Andrabi, Raiees; Mabry, Robert; Bléry, Mathieu; Voss, James E; Laurén, Juha; Abuqayyas, Lubna; Barghorn, Stefan; Ben-Jacob, Eshel; Crowe, James E; Huston, James S; Johnston, Stephen Albert; Krauland, Eric; Lund-Johansen, Fridtjof; Marasco, Wayne A; Parren, Paul WHI; Xu, Kai Y

    2014-01-01

    The 24th Antibody Engineering & Therapeutics meeting brought together a broad range of participants who were updated on the latest advances in antibody research and development. Organized by IBC Life Sciences, the gathering is the annual meeting of The Antibody Society, which serves as the scientific sponsor. Preconference workshops on 3D modeling and delineation of clonal lineages were featured, and the conference included sessions on a wide variety of topics relevant to researchers, including systems biology; antibody deep sequencing and repertoires; the effects of antibody gene variation and usage on antibody response; directed evolution; knowledge-based design; antibodies in a complex environment; polyreactive antibodies and polyspecificity; the interface between antibody therapy and cellular immunity in cancer; antibodies in cardiometabolic medicine; antibody pharmacokinetics, distribution and off-target toxicity; optimizing antibody formats for immunotherapy; polyclonals, oligoclonals and bispecifics; antibody discovery platforms; and antibody-drug conjugates. PMID:24589717

  12. [Therapeutic education didactic techniques].

    Science.gov (United States)

    Valverde, Maite; Vidal, Mercè; Jansa, Margarida

    2012-10-01

    This article includes an introduction to the role of Therapeutic Education for Diabetes treatment according to the recommendations of the American Diabetes Association (ADA), the Diabetes Education Study Group (DESG) of the "European Association for Study of Diabetes (EASD) and the clinical Practice Guidelines (CPG) of the Spanish Ministry of Health. We analyze theoretical models and the differences between teaching vs. learning as well as current trends (including Internet), that can facilitate meaningful learning of people with diabetes and their families and relatives. We analyze the differences, similarities, advantages and disadvantages of individual and group education. Finally, we describe different educational techniques (metaplan, case method, brainstorming, role playing, games, seminars, autobiography, forums, chats,..) applicable to individual, group or virtual education and its application depending on the learning objective.

  13. Refractive index in generalized superconductors with Born-Infeld electrodynamics

    Science.gov (United States)

    Cheng, Jun; Pan, Qiyuan; Yu, Hongwei; Jing, Jiliang

    2018-03-01

    We investigate, in the probe limit, the negative refraction in the generalized superconductors with the Born-Infeld electrodynamics. We observe that the system has a negative Depine-Lakhtakia index in the superconducting phase at small frequencies and the greater the Born-Infeld corrections the larger the range of frequencies or the range of temperatures for which the negative refraction occurs. Furthermore, we find that the tunable Born-Infeld parameter can be used to improve the propagation of light in the holographic setup. Our analysis indicates that the Born-Infeld electrodynamics plays an important role in determining the optical properties of the boundary theory.

  14. Modelling spread of Bluetongue and other vector borne diseases in Denmark and evaluation of intervention strategies

    DEFF Research Database (Denmark)

    Græsbøll, Kaare

    that describes spread of disease using vectors or hosts as agents of the spread. The model is run with bluetongue as the primary case study, and it is demonstrated how an epidemic outbreak of bluetongue 8 in Denmark is sensitive to the use of pasture, climate, vaccination, vector abundance, and flying parameters......The main outcome of this PhD project is a generic model for non-contagious infectious vector-borne disease spread by one vector species between up to two species of hosts distributed on farms and pasture. The model features a within-herd model of disease, combined with a triple movement kernel....... In constructing a more process oriented agent-based approach to spread modeling new parameters describing vector behavior were introduced. When these vector flying parameters have been quantified by experiments, this model can be implemented on areas naïve to the modeled disease with a high predictive power...

  15. Racial/ethnic disparities in obesity among US-born and foreign-born adults by sex and education.

    Science.gov (United States)

    Barrington, Debbie S; Baquero, Maria C; Borrell, Luisa N; Crawford, Natalie D

    2010-02-01

    This study examines sex and education variations in obesity among US- and foreign-born whites, blacks, and Hispanics utilizing 1997-2005 data from the National Health Interview Survey on 267,585 adults aged > or =18 years. After adjusting for various demographic, health, and socioeconomic factors via logistic regression, foreign-born black men had the lowest odds for obesity relative to US-born white men. The largest racial/ethnic disparity in obesity was between US-born black and white women. High educational attainment diminished the US-born black-white and Hispanic-white disparities among women, increased these disparities among men, and had minimal effect on foreign-born Hispanic-white disparities among women and men. Comprehension of these relationships is vital for conducting effective obesity research and interventions within an increasingly diverse United States.

  16. Molecular investigation of tick-borne pathogens in dogs from Luanda, Angola.

    Science.gov (United States)

    Cardoso, Luís; Oliveira, Ana Cristina; Granada, Sara; Nachum-Biala, Yaarit; Gilad, Matan; Lopes, Ana Patrícia; Sousa, Sérgio Ramalho; Vilhena, Hugo; Baneth, Gad

    2016-05-10

    No molecular data have been available on tick-borne pathogens that infect dogs from Angola. The occurrence of agents from the genera Anaplasma, Babesia, Ehrlichia and Hepatozoon was assessed in 103 domestic dogs from Luanda, by means of the polymerase chain reaction (PCR) and DNA sequence analysis. Forty-six dogs (44.7 %) were positive for at least one pathogen. Twenty-one animals (20.4 %) were found infected with Anaplasma platys, 18 (17.5 %) with Hepatozoon canis, six (5.8 %) with Ehrlichia canis, six (5.8 %) with Babesia vogeli, one (1.0 %) with Babesia gibsoni and one (1.0 %) with an unnamed Babesia sp. The molecular frequency of single infections taken together was 37.9 % and that of co-infections with several combinations of two pathogens accounted for 6.8 % of the animals. This is the first report of A. platys, B. vogeli, B. gibsoni, E. canis and H. canis infections diagnosed by PCR in domestic dogs from Angola. The present study provides evidence that dogs in Luanda are widely exposed to, and at risk of becoming infected with, tick-borne pathogens. Further investigation is needed, including a larger number of animals, canine populations from other cities and provinces of the country, as well as potential vector ticks, aiming at better characterizing and controlling canine vector-borne diseases in Angola.

  17. Change Agent Survival Guide

    Science.gov (United States)

    Dunbar, Folwell L.

    2011-01-01

    Consulting is a rough racket. Only a tarantula hair above IRS agents, meter maids and used car sales people, the profession is a prickly burr for slings and arrows. Throw in education, focus on dysfunctional schools and call oneself a "change agent," and this bad rap all but disappears. Unfortunately, though, consulting/coaching/mentoring in…

  18. Teaching Tourism Change Agents

    DEFF Research Database (Denmark)

    Stilling Blichfeldt, Bodil; Kvistgaard, Hans-Peter; Hird, John

    2017-01-01

    course that is part of a Tourism Master’s program, where a major challenge is not only to teach students about change and change agents, but to teach them how change feels and ho w to become change agents. The c hange management course contains an experiment inspired by experiential teaching literature...... change in tourism in the future....

  19. Travel Agent Course Outline.

    Science.gov (United States)

    British Columbia Dept. of Education, Victoria.

    Written for college entry-level travel agent training courses, this course outline can also be used for inservice training programs offered by travel agencies. The outline provides information on the work of a travel agent and gives clear statements on what learners must be able to do by the end of their training. Material is divided into eight…

  20. Radiographic scintiscanning agent

    International Nuclear Information System (INIS)

    Bevan, J.A.

    1979-01-01

    A new technetium-based scintiscanning agent has been prepared comprising a water soluble sup(99m)Tc-methanehydroxydiphosphonate in combination with a reducing agent selected from stannous, ferrous, chromous and titanous salts. As an additional stabilizer salts and esters of gentisic or ascorbic acids have been used. (E.G.)

  1. Radiographic scanning agent

    International Nuclear Information System (INIS)

    Tofe, A.J.

    1976-01-01

    A stable radiographic scanning agent on a sup(99m)Tc basis has been developed. The substance contains a pertechnetate reduction agent, tin(II)-chloride, chromium(II)-chloride, or iron(II)-sulphate, as well as an organospecific carrier and ascorbic acid or a pharmacologically admissible salt or ester of ascorbic acid. (VJ) [de

  2. Stable radiographic scanning agents

    International Nuclear Information System (INIS)

    1976-01-01

    Stable compositions which are useful in the preparation of Technetium-99m-based scintigraphic agents are discussed. They are comprised of ascorbic acid or a pharmaceutically acceptable salt or ester thereof in combination with a pertechnetate reducing agent or dissolved in oxidized pertechnetate-99m (sup(99m)TcO 4 - ) solution

  3. Hyperthermia and chemotherapy agent

    International Nuclear Information System (INIS)

    Roizin-Towle, L.; Hall, E.J.

    1981-01-01

    The use of chemotherapeutic agents for the treatment of cancer dates back to the late 19th century, but the modern era of chemotherapy drugs was ushered in during the 1940's with the development of the polyfunctional alkylating agent. Since then, numerous classes of drugs have evolved and the combined use of antineoplastic agents with other treatment modalities such as radiation or heat, remains a large relatively unexplored area. This approach, combining local hyperthermia with chemotherapy agents affords a measure of targeting and selective toxicity not previously available for drugs. In this paper, the effects of adriamycin, bleomycin and cis-platinum are examined. The adjuvant use of heat may also reverse the resistance of hypoxic cells noted for some chemotherapy agents

  4. Differences in sleep habits, study time, and academic performance between US-born and foreign-born college students.

    Science.gov (United States)

    Eliasson, Arne H; Eliasson, Arn H; Lettieri, Christopher J

    2017-05-01

    To inform the design of a sleep improvement program for college students, we assessed academic performance, sleep habits, study hours, and extracurricular time, hypothesizing that there would be differences between US-born and foreign-born students. Questionnaires queried participants on bedtimes, wake times, nap frequency, differences in weekday and weekend sleep habits, study hours, grade point average, time spent at paid employment, and other extracurricular activities. Comparisons were made using chi square tests for categorical data and t tests for continuous data between US-born and foreign-born students. Of 120 participants (55 % women) with racial diversity (49 whites, 18 blacks, 26 Hispanics, 14 Asians, and 13 other), 49 (41 %) were foreign-born. Comparisons between US-born and foreign-born students showed no differences in average age or gender though US-born had more whites. There were no differences between US-born and foreign-born students for grade point averages, weekday bedtimes, wake times, or total sleep times. However, US-born students averaged 50 min less study time per day (p = 0.01), had almost 9 h less paid employment per week (14.5 vs 23.4 h per week, p = 0.001), and stayed up to socialize more frequently (63 vs 43 %, p = 0.03). Foreign-born students awakened an hour earlier and averaged 40 min less sleep per night on weekends. Cultural differences among college students have a profound effect on sleep habits, study hours, and extracurricular time. The design of a sleep improvement program targeting a population with diverse cultural backgrounds must factor in such behavioral variations in order to have relevance and impact.

  5. Prevalence of Hepatitis B Surface Antigen in US-Born and Foreign-Born Asian/Pacific Islander College Students

    Science.gov (United States)

    Quang, Yen N.; Vu, Joanne; Yuk, Jihey; Li, Chin-Shang; Chen, Moon; Bowlus, Christopher L.

    2010-01-01

    The prevalence of chronic hepatitis B (HBV) among college-age US-born Asian and Pacific Islanders (A/PI) is not well known. Objectives: To compare the prevalence of hepatitis B surface antigen (HBsAg) seropositivity in US-born to A/PI-born students at a public university. Participants: Undergraduate who self-identified themselves as A/PI. Results:…

  6. Young adult outcomes of children born to teen mothers: effects of being born during their teen or later years.

    Science.gov (United States)

    Lipman, Ellen L; Georgiades, Katholiki; Boyle, Michael H

    2011-03-01

    Children of teen mothers exhibit adverse outcomes through adolescence. It is unclear whether these adverse outcomes extend to adulthood and apply to all of her children, or only those born when she was a teen. We examine the associations between young adult functioning and being born to a teen mother aged ≤20 years at the time of birth (current teen), and being born to a teen mother later in her life (>21 years, prior teen). The 1983 Ontario Child Health Study (OCHS) and 2001 follow-up are used, including 2,355 participants 4 to 16 years old in 1983 with 2001 data. Using multilevel modeling we assessed the association between being born to a current versus prior teen mother, relative to a nonteen mother, and 2001 outcomes, controlling for individual and family level characteristics assessed in childhood. Being born to a teen mother (versus a nonteen mother) is associated with poorer educational achievement, life satisfaction, and personal income. Accounting for time of sample children's birth in teen mothers' lives, individuals born to current and prior teen mothers showed a ~0.8-year educational deficit, relative to individuals born to nonteen mothers in fully adjusted models. Individuals born to current teen mothers reported lower life satisfaction and personal income (-$7,262). There were no significant group differences at follow-up in mental or physical health between individuals born to nonteen mothers and those born to current or prior teen mothers. Although being born to a teen mother exerts a pervasive adverse effect on educational attainment, the adverse effects on life satisfaction and personal income appear to be selective for individuals born to a current teen mother. Further research is required to understand these differential effects. Copyright © 2011 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

  7. Ivacaftor: A Novel Gene-Based Therapeutic Approach for Cystic Fibrosis

    OpenAIRE

    Condren, Michelle E.; Bradshaw, Marquita D.

    2013-01-01

    Ivacaftor is a new therapeutic agent that acts at the cystic fibrosis transmembrane conductance regulator (CFTR) channel to alter activity. It is approved for use in patients 6 years and older with cystic fibrosis who have at least 1 G551D mutation in the CFTR gene. It is unlike any other current pharmacologic agent for cystic fibrosis in that it specifically targets the gene defect associated with cystic fibrosis as opposed to treating resulting symptomology. Mucoactive agents, antibiotics, ...

  8. Technological advancements for the detection of and protection against biological and chemical warfare agents.

    Science.gov (United States)

    Eubanks, Lisa M; Dickerson, Tobin J; Janda, Kim D

    2007-03-01

    There is a growing need for technological advancements to combat agents of chemical and biological warfare, particularly in the context of the deliberate use of a chemical and/or biological warfare agent by a terrorist organization. In this tutorial review, we describe methods that have been developed both for the specific detection of biological and chemical warfare agents in a field setting, as well as potential therapeutic approaches for treating exposure to these toxic species. In particular, nerve agents are described as a typical chemical warfare agent, and the two potent biothreat agents, anthrax and botulinum neurotoxin, are used as illustrative examples of potent weapons for which countermeasures are urgently needed.

  9. Wildlife reservoirs for vector-borne canine, feline and zoonotic infections in Austria

    Science.gov (United States)

    Duscher, Georg G.; Leschnik, Michael; Fuehrer, Hans-Peter; Joachim, Anja

    2014-01-01

    Austria's mammalian wildlife comprises a large variety of species, acting and interacting in different ways as reservoir and intermediate and definitive hosts for different pathogens that can be transmitted to pets and/or humans. Foxes and other wild canids are responsible for maintaining zoonotic agents, e.g. Echinococcus multilocularis, as well as pet-relevant pathogens, e.g. Hepatozoon canis. Together with the canids, and less commonly felids, rodents play a major role as intermediate and paratenic hosts. They carry viruses such as tick-borne encephalitis virus (TBEV), bacteria including Borrelia spp., protozoa such as Toxoplasma gondii, and helminths such as Toxocara canis. The role of wild ungulates, especially ruminants, as reservoirs for zoonotic disease on the other hand seems to be negligible, although the deer filaroid Onchocerca jakutensis has been described to infect humans. Deer may also harbour certain Anaplasma phagocytophilum strains with so far unclear potential to infect humans. The major role of deer as reservoirs is for ticks, mainly adults, thus maintaining the life cycle of these vectors and their distribution. Wild boar seem to be an exception among the ungulates as, in their interaction with the fox, they can introduce food-borne zoonotic agents such as Trichinella britovi and Alaria alata into the human food chain. PMID:25830102

  10. [Nuclear transfer and therapeutic cloning].

    Science.gov (United States)

    Xu, Xiao-Ming; Lei, An-Min; Hua, Jin-Lian; Dou, Zhong-Ying

    2005-03-01

    Nuclear transfer and therapeutic cloning have widespread and attractive prospects in animal agriculture and biomedical applications. We reviewed that the quality of oocytes and nuclear reprogramming of somatic donor cells were the main reasons of the common abnormalities in cloned animals and the low efficiency of cloning and showed the problems and outlets in therapeutic cloning, such as some basic problems in nuclear transfer affected clinical applications of therapeutic cloning. Study on isolation and culture of nuclear transfer embryonic stem (ntES) cells and specific differentiation of ntES cells into important functional cells should be emphasized and could enhance the efficiency. Adult stem cells could help to cure some great diseases, but could not replace therapeutic cloning. Ethics also impeded the development of therapeutic cloning. It is necessary to improve many techniques and reinforce the research of some basic theories, then somatic nuclear transfer and therapeutic cloning may apply to agriculture reproduction and benefit to human life better.

  11. Agent Programming Languages and Logics in Agent-Based Simulation

    DEFF Research Database (Denmark)

    Larsen, John

    2018-01-01

    and social behavior, and work on verification. Agent-based simulation is an approach for simulation that also uses the notion of agents. Although agent programming languages and logics are much less used in agent-based simulation, there are successful examples with agents designed according to the BDI...

  12. Biological warfare agents

    Directory of Open Access Journals (Sweden)

    Duraipandian Thavaselvam

    2010-01-01

    Full Text Available The recent bioterrorist attacks using anthrax spores have emphasized the need to detect and decontaminate critical facilities in the shortest possible time. There has been a remarkable progress in the detection, protection and decontamination of biological warfare agents as many instrumentation platforms and detection methodologies are developed and commissioned. Even then the threat of biological warfare agents and their use in bioterrorist attacks still remain a leading cause of global concern. Furthermore in the past decade there have been threats due to the emerging new diseases and also the re-emergence of old diseases and development of antimicrobial resistance and spread to new geographical regions. The preparedness against these agents need complete knowledge about the disease, better research and training facilities, diagnostic facilities and improved public health system. This review on the biological warfare agents will provide information on the biological warfare agents, their mode of transmission and spread and also the detection systems available to detect them. In addition the current information on the availability of commercially available and developing technologies against biological warfare agents has also been discussed. The risk that arise due to the use of these agents in warfare or bioterrorism related scenario can be mitigated with the availability of improved detection technologies.

  13. Biological warfare agents

    Science.gov (United States)

    Thavaselvam, Duraipandian; Vijayaraghavan, Rajagopalan

    2010-01-01

    The recent bioterrorist attacks using anthrax spores have emphasized the need to detect and decontaminate critical facilities in the shortest possible time. There has been a remarkable progress in the detection, protection and decontamination of biological warfare agents as many instrumentation platforms and detection methodologies are developed and commissioned. Even then the threat of biological warfare agents and their use in bioterrorist attacks still remain a leading cause of global concern. Furthermore in the past decade there have been threats due to the emerging new diseases and also the re-emergence of old diseases and development of antimicrobial resistance and spread to new geographical regions. The preparedness against these agents need complete knowledge about the disease, better research and training facilities, diagnostic facilities and improved public health system. This review on the biological warfare agents will provide information on the biological warfare agents, their mode of transmission and spread and also the detection systems available to detect them. In addition the current information on the availability of commercially available and developing technologies against biological warfare agents has also been discussed. The risk that arise due to the use of these agents in warfare or bioterrorism related scenario can be mitigated with the availability of improved detection technologies. PMID:21829313

  14. Multimodal nanoparticle imaging agents: design and applications

    Science.gov (United States)

    Burke, Benjamin P.; Cawthorne, Christopher; Archibald, Stephen J.

    2017-10-01

    Molecular imaging, where the location of molecules or nanoscale constructs can be tracked in the body to report on disease or biochemical processes, is rapidly expanding to include combined modality or multimodal imaging. No single imaging technique can offer the optimum combination of properties (e.g. resolution, sensitivity, cost, availability). The rapid technological advances in hardware to scan patients, and software to process and fuse images, are pushing the boundaries of novel medical imaging approaches, and hand-in-hand with this is the requirement for advanced and specific multimodal imaging agents. These agents can be detected using a selection from radioisotope, magnetic resonance and optical imaging, among others. Nanoparticles offer great scope in this area as they lend themselves, via facile modification procedures, to act as multifunctional constructs. They have relevance as therapeutics and drug delivery agents that can be tracked by molecular imaging techniques with the particular development of applications in optically guided surgery and as radiosensitizers. There has been a huge amount of research work to produce nanoconstructs for imaging, and the parameters for successful clinical translation and validation of therapeutic applications are now becoming much better understood. It is an exciting time of progress for these agents as their potential is closer to being realized with translation into the clinic. The coming 5-10 years will be critical, as we will see if the predicted improvement in clinical outcomes becomes a reality. Some of the latest advances in combination modality agents are selected and the progression pathway to clinical trials analysed. This article is part of the themed issue 'Challenges for chemistry in molecular imaging'.

  15. Drone-borne GPR design: Propagation issues

    Science.gov (United States)

    Chandra, Madhu; Tanzi, Tullio Joseph

    2018-01-01

    In this paper, we shall address the electromagnetic wave propagation issues that are critical to determining the feasibility of a drone-borne ground-penetrating radar sensor for humanitarian applications, particularly in the context of disaster management. Frequency- and polarization-dependent scattering, attenuation and dispersion of radar signals penetrating into the sub-surface region will determine the applicability of a drone-mounted radar sensor capable of registering radar echoes for observing and monitoring sub-surface features. The functionality of the radar will thus be assessed depending on key radar parameters that include the central radar frequency, the modulation depth, and the mode of radar operation (pulsed FM, FM-CW), the antenna type, the available power-budget. In the analysis to be presented, the radar equation, together with the aforementioned propagation effects, will be used to simulate the signal strength of radar echoes under different conditions arising from the chosen key-radar parameters and the assumed physical properties of the sub-surface earth medium. The analysis to be presented will indicate whether or not the drone-borne ground-penetrating radar is a feasible system and if it could be constructed with the technologies available today. Taking into account the strict constraints involved to design drone applications for Public Protection and Disaster Relief (PPDR), the ideas developed hereafter are both prospective and exploratory. The objective is to see if a solution can be found in the near future. xml:lang="fr" Dans l'analyse présentée, l'équation radar, ainsi que les effets de propagation susmentionnés, serviront à simuler la puissance du signal des échos radar sous différentes conditions découlant des paramètres clés choisis et les propriétés physiques du milieu sous la surface. L'étude a pour objectif de démontrer si le système est réalisable et s'il peut être construit avec les technologies disponibles

  16. Chronic health conditions in Jewish Holocaust survivors born during World War II.

    Science.gov (United States)

    Keinan-Boker, Lital; Shasha-Lavsky, Hadas; Eilat-Zanani, Sofia; Edri-Shur, Adi; Shasha, Shaul M

    2015-04-01

    Findings of studies addressing outcomes of war-related famine in non-Jewish populations in Europe during the Second World War (WWII) confirmed an association between prenatal/early life exposure to hunger and adult obesity, diabetes, hypertension, cardiovascular disease and the metabolic syndrome. Fetal programming was suggested as the explanatory mechanism. To study the association between being born during WWII in Europe and physical long-term outcomes in child Holocaust survivors. We conducted a cross-sectional study on all Jewish Clalit Health Services (CHS) North District members born in 1940-1945 in Europe ('exposed', n = 653) or in Israel to Europe-born parents ('non-exposed', n = 433). Data on sociodemographic variables, medical diagnoses, medication procurement, laboratory tests and health services utilization were derived from the CHS computerized database and compared between the groups. The exposed were significantly more likely than the non-exposed to present with dyslipidemia (81% vs. 72%, respectively), hypertension (67% vs. 53%), diabetes mellitus (41% vs. 28%), vascular disease (18% vs. 9%) and the metabolic syndrome (17% vs. 9%). The exposed also made lower use of health services but used anti-depressive agents more often compared to the non-exposed. In multivariate analyses, being born during WWII remained an independent risk marker for hypertension (OR = 1.52), diabetes mellitus (OR = 1.60), vascular disease (OR = 1.99) and the metabolic syndrome (OR = 2.14). The results of this cross-sectional study based on highly validated data identify a high risk group for chronic morbidity. A question regarding potential trans-generational effects that may impact the 'second generation' is also raised.

  17. Recent Progress in Functional Micellar Carriers with Intrinsic Therapeutic Activities for Anticancer Drug Delivery.

    Science.gov (United States)

    Qu, Ying; Chu, BingYang; Shi, Kun; Peng, JinRong; Qian, ZhiYong

    2017-12-01

    Polymeric micelles have presented superior delivery properties for poorly water-soluble chemotherapeutic agents. However, it remains discouraging that there may be some additional short or long-term toxicities caused by the metabolites of high quantities of carriers. If carriers had simultaneous therapeutic effects with the drug, these issues would not be a concern. For this, carriers not only simply act as drug carriers, but also exert an intrinsic therapeutic effect as a therapeutic agent. The functional micellar carriers would be beneficial to maximize the anticancer effect, overcome the drug resistance and reduce the systemic toxicity. In this review, we aim to summarize the recent progress on the development of functional micellar carriers with intrinsic anticancer activities for the delivery of anticancer drugs. This review focuses on the design strategies, properties of carriers and the drug loading behavior. In addition, the combinational therapeutic effects between carriers and chemotherapeutic agents are also discussed.

  18. Molecularly targeted therapeutic radiopharmaceuticals

    International Nuclear Information System (INIS)

    Saw, M.M.

    2007-01-01

    Full text: It is generally agreed that current focus of nuclear medicine development should be on molecular imaging and therapy. Though, the widespread use of the terminology 'molecular imaging' is quite recent, nuclear medicine has used molecular imaging techniques for more than 20 years ago. A variety of radiopharmaceuticals have been introduced for the internal therapy of malignant and inflammatory lesions in nuclear medicine. In the field of bio/medical imaging, nuclear medicine is one of the disciplines which has the privilege of organized and well developed chemistry/ pharmacy section; radio-chemistry/radiopharmacy. Fundamental principles have been developed more than 40 years ago and advanced research is going well into postgenomic era. The genomic revolution and dramatically increased insight in the molecular mechanisms underlying pathology have led to paradigm shift in drug development. Likewise does in the nuclear medicine. Here, the author will present current clinical and pre-clinical therapeutic radiopharmaceuticals based on molecular targets such as membrane-bound receptors, enzymes, nucleic acids, sodium iodide symporter, etc, in correlation with fundamentals of radiopharmacy. (author)

  19. Functional outcome at school age of children born with gastroschisis

    NARCIS (Netherlands)

    Lap, Chiara C M M; Bolhuis, Sandra W; Van Braeckel, Koenraad J. A.; Reijneveld, Sijmen A.; Manten, Gwendolyn T. R.; Bos, Arend F.; Hulscher, Jan

    Objective: We aimed to determine motor, cognitive and behavioural outcomes of school aged children born with gastroschisis compared to matched controls. Study design: We compared outcomes of 16 children born with gastroschisis treated at the University Medical Center Groningen, the Netherlands,

  20. Tick-borne encephalitis: Pathogenesis and clinical implications

    Czech Academy of Sciences Publication Activity Database

    Růžek, Daniel; Dobler, G.; Mantke, O. D.

    2010-01-01

    Roč. 8, č. 4 (2010), s. 223-232 ISSN 1477-8939 R&D Projects: GA ČR GPP302/10/P438; GA MŠk(CZ) LC06009 Institutional research plan: CEZ:AV0Z60220518 Keywords : Tick-borne encephalitis * Tick-borne encephalitis virus * Pathogenesis * Clinical data Subject RIV: EE - Microbiology, Virology

  1. An investigation into the prevalence of water borne diseases in ...

    African Journals Online (AJOL)

    Water-borne diseases are the most prevalent infectious diseases in the developing countries especially in new settlements along the river. The present investigation was carried out to assess the prevalence rate of water-borne diseases among people residing near the left bank of River Ravi. This study has a descriptive ...

  2. Perinatal outcomes in 375 children born after oocyte donation

    DEFF Research Database (Denmark)

    Malchau, Sara S; Loft, Anne; Larsen, Elisabeth C

    2013-01-01

    To describe perinatal outcomes in children born after oocyte donation (OD) compared with in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), and spontaneous conception (SC).......To describe perinatal outcomes in children born after oocyte donation (OD) compared with in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), and spontaneous conception (SC)....

  3. Type specimens of Pectinidae (Bivalvia) described by Ignaz von Born

    NARCIS (Netherlands)

    Dijkstra, H.H.

    2009-01-01

    Born described in two publications (1778, 1780) the molluscs in the collection of Empress Maria Theresa (1717-1780), now in the Natural History Museum at Vienna. In this paper the Pectinidae type material is described. Ten new species were introduced of which Argopecten nucleus (Born, 1778) and

  4. Human to human transmission of arthropod-borne pathogens

    NARCIS (Netherlands)

    Martina, Byron E.; Barzon, Luisa; Pijlman, Gorben P.; Fuente, de la José; Rizzoli, Annapaola; Wammes, Linda J.; Takken, Willem; Rij, van Ronald P.; Papa, Anna

    2017-01-01

    Human-to-human (H2H) transmitted arthropod-borne pathogens are a growing burden worldwide, with malaria and dengue being the most common mosquito-borne H2H transmitted diseases. The ability of vectors to get infected by humans during a blood meal to further propel an epidemic depends on complex

  5. Human to human transmission of arthropod-borne pathogens

    NARCIS (Netherlands)

    Martina, B.E.; Barzon, L.; Pijlman, G.P.; Fuente, J. de la; Rizzoli, A.; Wammes, L.J.; Takken, W.; Rij, R.P. van; Papa, A.

    2017-01-01

    Human-to-human (H2H) transmitted arthropod-borne pathogens are a growing burden worldwide, with malaria and dengue being the most common mosquito-borne H2H transmitted diseases. The ability of vectors to get infected by humans during a blood meal to further propel an epidemic depends on complex

  6. Survey of spatial distribution of vector-borne disease in ...

    African Journals Online (AJOL)

    Neighborhood dogs may act as reservoirs and disseminators of vector-borne diseases in urban areas. Accordingly, the aim of this study was to ascertain the health status and the vector-borne pathogens infecting dogs living in public areas with high levels of human movement in the city of Curitiba, southern Brazil.

  7. Rethinking Therapeutic Misconception in Biobanking

    DEFF Research Database (Denmark)

    Tupasela, Aaro; Snell, Karoliina; Cañada, Jose

    2017-01-01

    Some authors have noted that in biobank research participants may be guided by what is called therapeutic misconception, whereby participants attribute therapeutic intent to research procedures.This article argues that the notion of therapeutic misconception is increasingly less justified when...... underpinnings for the need to separate research and treatment, and thus the notion of therapeutic misconception in the fi rst place. We call this tension between research and treatment ambivalent research advancement to highlight the difficulties that various actors have in managing such shifts within...

  8. Therapeutic cloning: The ethical limits

    International Nuclear Information System (INIS)

    Whittaker, Peter A.

    2005-01-01

    A brief outline of stem cells, stem cell therapy and therapeutic cloning is given. The position of therapeutic cloning with regard to other embryonic manipulations - IVF-based reproduction, embryonic stem formation from IVF embryos and reproductive cloning - is indicated. The main ethically challenging stages in therapeutic cloning are considered to be the nuclear transfer process including the source of eggs for this and the destruction of an embryo to provide stem cells for therapeutic use. The extremely polarised nature of the debate regarding the status of an early human embryo is noted, and some potential alternative strategies for preparing immunocompatible pluripotent stem cells are indicated

  9. Therapeutic cloning in the mouse

    Science.gov (United States)

    Mombaerts, Peter

    2003-01-01

    Nuclear transfer technology can be applied to produce autologous differentiated cells for therapeutic purposes, a concept termed therapeutic cloning. Countless articles have been published on the ethics and politics of human therapeutic cloning, reflecting the high expectations from this new opportunity for rejuvenation of the aging or diseased body. Yet the research literature on therapeutic cloning, strictly speaking, is comprised of only four articles, all in the mouse. The efficiency of derivation of embryonic stem cell lines via nuclear transfer is remarkably consistent among these reports. However, the efficiency is so low that, in its present form, the concept is unlikely to become widespread in clinical practice. PMID:12949262

  10. Molecular Therapeutic Approaches for Pediatric Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Sarah K Tasian

    2014-03-01

    Full Text Available Approximately two thirds of children with acute myeloid leukemia (AML are cured with intensive multi-agent chemotherapy. However, primary chemorefractory and relapsed AML remains a significant source of childhood cancer mortality, highlighting the need for new therapies. Further therapy intensification with traditional cytotoxic agents is not feasible given the potential for significant toxicity to normal tissues with conventional chemotherapy and the risk for long-term end-organ dysfunction. Significant emphasis has been placed upon the development of molecularly targeted therapeutic approaches for adults and children with high-risk subtypes of AML with the goal of improving remission induction and minimizing relapse. Several promising agents are currently in clinical testing or late preclinical development for AML, including monoclonal antibodies against leukemia cell surface proteins, kinase inhibitors, proteasome inhibitors, epigenetic agents, and chimeric antigen receptor engineered T cell immunotherapies. Many of these therapies have been specifically tested in children with relapsed/refractory AML via phase 1 and 2 trials with a smaller number of new agents under phase 3 evaluation for children with de novo AML. Although successful identification and implementation of new drugs for children with AML remains a formidable challenge, enthusiasm for novel molecular therapeutic approaches is great given the potential for significant clinical benefit for children who will otherwise fail standard therapy.

  11. Culturally Aware Agent Communication

    DEFF Research Database (Denmark)

    Rehm, Matthias; Nakano, Yukiko; Koda, Tomoko

    2012-01-01

    Agent based interaction in the form of Embodied Conversational Agents (ECAs) has matured over the last decade and agents have become more and more sophisticated in terms of their verbal and nonverbal behavior like facial expressions or gestures. Having such “natural” communication channels...... available for expressing not only task-relevant but also socially and psychologically relevant information makes it necessary to take influences into account that are not readily implemented like emotions or cultural heuristics. These influences have a huge impact on the success of an interaction...

  12. Agent-Based Optimization

    CERN Document Server

    Jędrzejowicz, Piotr; Kacprzyk, Janusz

    2013-01-01

    This volume presents a collection of original research works by leading specialists focusing on novel and promising approaches in which the multi-agent system paradigm is used to support, enhance or replace traditional approaches to solving difficult optimization problems. The editors have invited several well-known specialists to present their solutions, tools, and models falling under the common denominator of the agent-based optimization. The book consists of eight chapters covering examples of application of the multi-agent paradigm and respective customized tools to solve  difficult optimization problems arising in different areas such as machine learning, scheduling, transportation and, more generally, distributed and cooperative problem solving.

  13. Promising biocidal activity of thymol loaded chitosan silver nanoparticles (T-C@AgNPs) as anti-infective agents against perilous pathogens.

    Science.gov (United States)

    Manukumar, H M; Umesha, S; Kumar, H N Naveen

    2017-09-01

    The advent of biodegradable polymer-encapsulated drug nanoparticles has made an exciting area of drug delivery research. The present study investigated novel and simple route for synthesis of thymol loaded chitosan silver nanoparticles (T-C@AgNPs) using chitosan and thymol as reducing, capping agent respectively to understand the therapeutic efficacy. The UV-vis spectroscopy, DLS, FT-IR, SEM, EDS, XRD used for characterization and radical scavenging activity, anti-microbial and biocompatibility was taken to ascertain an efficacy of novel T-C@AgNPs. The T-C@AgNPs intense peak at 490nm indicates the formation of nanoparticles and had average particle size of 28.94nm with spherical shape, monodisperse state in water, also exhibited excellent biocompatibility of cubic shaped pure silver element containing T-C@AgNPs. The antibacterial activity was studied for gram positive and gram negative food-borne pathogens and effective inhibition at 100μgmL -1 to S. aureus, S. epidermidis, S. haemolyticus (10.08, 10.00, 11.23mm) and S. typhimurium, P. aeruginosa and S. flexneri (9.28, 9.33, 12.03mm) compared to antibiotic Streptomycin. This study revealed the efficacy against multiple food-borne pathogens and therapeutic efficacy of T-C@AgNPs offers a valuable contribution in the area of nanotechnology. This proved to be a first-class novel antimicrobial material for the first time in this study. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Atopic diseases in twins born after assisted reproduction

    DEFF Research Database (Denmark)

    Jäderberg, Ida; Thomsen, Simon F; Kyvik, Kirsten Ohm

    2012-01-01

    Jäderberg I, Thomsen SF, Kyvik KO, Skytthe A, Backer V. Atopic diseases in twins born after assisted reproduction. Paediatric and Perinatal Epidemiology 2012; 26: 140-145. We examined the risk of atopic diseases in twins born after assisted reproduction. Data on atopic diseases and assisted...... reproduction in 9694 twin pairs, 3-20 years of age, from the Danish Twin Registry were collected via multidisciplinary questionnaires. The risk of atopic diseases in twins born after assisted reproduction was compared with the risk in twins born after spontaneous conception using logistic regression...... and variance components analysis. Children born after assisted reproduction did not have a different risk of atopic outcomes (adjusted odds ratios [95% confidence intervals] for asthma: 0.95 [0.85, 1.07], P = 0.403; hay fever: 1.01 [0.86, 1.18], P = 0.918; and atopic dermatitis: 1.02 [0.81, 1.11], P = 0...

  15. Newer Vaccines against Mosquito-borne Diseases.

    Science.gov (United States)

    Aggarwal, Anju; Garg, Neha

    2018-02-01

    Mosquitos are responsible for a number of protozoal and viral diseases. Malaria, dengue, Japanese encephalitis (JE) and chikungunya epidemics occur commonly all over the world, leading to marked mortality and morbidity in children. Zika, Yellow fever and West Nile fever are others requiring prevention. Environmental control and mosquito bite prevention are useful in decreasing the burden of disease but vaccination has been found to be most cost-effective and is the need of the hour. RTS,S/AS01 vaccine is the first malaria vaccine being licensed for use against P. falciparum malaria. Dengvaxia (CYD-TDV) against dengue was licensed first in Mexico in 2015. A Vero-cell derived, inactivated and alum-adjuvanted JE vaccine based on the SA14-14-2 strain was approved in 2009 in North America, Australia and various European countries. It can be used from 2 mo of age. In India, immunization is carried out in endemic regions at 1 y of age. Another inactivated Vero-cell culture derived Kolar strain, 821564XY, JE vaccine is being used in India. Candidate vaccines against dengue, chikungunya and West Nile fever are been discussed. A continued research and development of new vaccines are required for controlling these mosquito-borne diseases.

  16. The neonate was born with holoprosencephaly

    Directory of Open Access Journals (Sweden)

    reza saeidi

    2014-12-01

    Full Text Available holoprosencephaly is a rare congenital brain malformation resulting from failure of diverticulation and cleavage of primitive prosencephalon which occurs at 4 - 8th week of gestation and is usually associated with multiple midline facial anomalies. it is the most common forebrain developmental anomaly in humans with prevalence of 1/16,000 in live borns, an incidence as high as 1:250 in conceptuses, and a worldwide distribution6. The etiology of HPE is very heterogeneous. First, this pathology can be caused by environmental or metabolic factors. The only formally recognized environmental factors are insulin-dependent diabetes mellitus (1% risk of HPE and maternal alcoholism with a risk that cumulates with smoking . Clinical expression is variable, extending in unbroken sequence from a small brain with a single cerebral ventricle and cyclopia to clinically unaffected carriers in familial holoprosencephaly. Here. we report a boy 39 weeks neonatal case of holoprosencephaly with Antenatal ultrasonographic diagnosis, with microcephaly, hypotelorism, flat nose, a single nostril, a midline cleft lip and palate microcephaly.

  17. BAT-BORNE RABIES IN LATIN AMERICA

    Directory of Open Access Journals (Sweden)

    Luis E. Escobar

    2015-02-01

    Full Text Available The situation of rabies in America is complex: rabies in dogs has decreased dramatically, but bats are increasingly recognized as natural reservoirs of other rabies variants. Here, bat species known to be rabies-positive with different antigenic variants, are summarized in relation to bat conservation status across Latin America. Rabies virus is widespread in Latin American bat species, 22.5%75 of bat species have been confirmed as rabies-positive. Most bat species found rabies positive are classified by the International Union for Conservation of Nature as “Least Concern”. According to diet type, insectivorous bats had the most species known as rabies reservoirs, while in proportion hematophagous bats were the most important. Research at coarse spatial scales must strive to understand rabies ecology; basic information on distribution and population dynamics of many Latin American and Caribbean bat species is needed; and detailed information on effects of landscape change in driving bat-borne rabies outbreaks remains unassessed. Finally, integrated approaches including public health, ecology, and conservation biology are needed to understand and prevent emergent diseases in bats.

  18. Born Pupils? Natural Pedagogy and Cultural Pedagogy.

    Science.gov (United States)

    Heyes, Cecilia

    2016-03-01

    The theory of natural pedagogy is an important focus of research on the evolution and development of cultural learning. It proposes that we are born pupils; that human children genetically inherit a package of psychological adaptations that make them receptive to teaching. In this article, I first examine the components of the package-eye contact, contingencies, infant-directed speech, gaze cuing, and rational imitation-asking in each case whether current evidence indicates that the component is a reliable feature of infant behavior and a genetic adaptation for teaching. I then discuss three fundamental insights embodied in the theory: Imitation is not enough for cumulative cultural inheritance, the extra comes from blind trust, and tweaking is a powerful source of cognitive change. Combining the results of the empirical review with these insights, I argue that human receptivity to teaching is founded on nonspecific genetic adaptations for social bonding and social learning and acquires its species- and functionally specific features through the operation of domain-general processes of learning in sociocultural contexts. We engage, not in natural pedagogy, but in cultural pedagogy. © The Author(s) 2016.

  19. Born-Kothari Condensation for Fermions

    Directory of Open Access Journals (Sweden)

    Arnab Ghosh

    2017-09-01

    Full Text Available In the spirit of Bose–Einstein condensation, we present a detailed account of the statistical description of the condensation phenomena for a Fermi–Dirac gas following the works of Born and Kothari. For bosons, while the condensed phase below a certain critical temperature, permits macroscopic occupation at the lowest energy single particle state, for fermions, due to Pauli exclusion principle, the condensed phase occurs only in the form of a single occupancy dense modes at the highest energy state. In spite of these rudimentary differences, our recent findings [Ghosh and Ray, 2017] identify the foregoing phenomenon as condensation-like coherence among fermions in an analogous way to Bose–Einstein condensate which is collectively described by a coherent matter wave. To reach the above conclusion, we employ the close relationship between the statistical methods of bosonic and fermionic fields pioneered by Cahill and Glauber. In addition to our previous results, we described in this mini-review that the highest momentum (energy for individual fermions, prerequisite for the condensation process, can be specified in terms of the natural length and energy scales of the problem. The existence of such condensed phases, which are of obvious significance in the context of elementary particles, have also been scrutinized.

  20. Mobile Agent Data Integrity Using Multi-Agent Architecture

    National Research Council Canada - National Science Library

    McDonald, Jeffrey

    2004-01-01

    .... Security issues for mobile agents continue to produce research interest, particularly in developing mechanisms that guarantee protection of agent data and agent computations in the presence of malicious hosts...

  1. Ventilatory Efficiency in Children and Adolescents Born Extremely Preterm

    Directory of Open Access Journals (Sweden)

    Julie Hestnes

    2017-07-01

    Full Text Available Purpose: Children and adolescents born extremely preterm (EP have lower dynamic lung volumes and gas transfer capacity than subjects born at term. Most studies also report lower aerobic capacity. We hypothesized that ventilatory efficiency was poorer and that breathing patterns differed in EP−born compared to term−born individuals.Methods: Two area−based cohorts of participants born with gestational age ≤28 weeks or birth weight ≤1000 g in 1982−85 (n = 46 and 1991–92 (n = 35 were compared with individually matched controls born at term. Mean ages were 18 and 10 years, respectively. The participants performed an incremental treadmill exercise test to peak oxygen uptake with data averaged over 20 s intervals. For each participant, the relationship between exhaled minute ventilation (V˙E and carbon dioxide output (V˙CO2 was described by a linear model, and the relationship between tidal volume (VT and V˙E by a quadratic model. Multivariate regression analyses were done with curve parameters as dependent variables, and the categories EP vs. term−born, sex, age, height, weight and forced expiratory volume in 1 s (FEV1 as independent variables.Results: In adjusted analyses, the slope of the V˙E−V˙CO2 relationship was significantly steeper in the EP than the term-born group, whereas no group difference was observed for the breathing pattern, which was related to FEV1 only.Conclusion: EP-born participants breathed with higher V˙E for any given CO2 output, indicating lower ventilatory efficiency, possibly contributing to lower aerobic capacity. The breathing patterns did not differ between the EP and term−born groups when adjusted for FEV1.

  2. DNA molecules and human therapeutics

    African Journals Online (AJOL)

    PRECIOUS

    2009-12-29

    Dec 29, 2009 ... vectors, display non-toxicity and are simpler to develop. This review ... technology as well as a staged delivery mechanism for the introduction of plasmid-borne gene to target cells via the ... pathogen's gene to provide immunity against diseases by ... human cytomegalovirus, simian virus, human elongation.

  3. Delta agent (Hepatitis D)

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000216.htm Hepatitis D (Delta agent) To use the sharing features on this page, please enable JavaScript. Hepatitis D is a viral infection caused by the ...

  4. Escape of Tick-Borne Flavivirus from 2'-C-Methylated Nucleoside Antivirals Is Mediated by a Single Conservative Mutation in NS5 That Has a Dramatic Effect on Viral Fitness

    Czech Academy of Sciences Publication Activity Database

    Eyer, Luděk; Kondo, H.; Zouharová, D.; Hirano, M.; Valdés, James J.; Muto, M.; Kastl, T.; Kobayashi, S.; Haviernik, J.; Igarashi, K.; Kariwa, H.; Vaculovicova, M.; Černý, Jiří; Kizek, R.; Kroeger, A.; Lienenklaus, S.; Dejmek, Milan; Nencka, Radim; Palus, Martin; Salát, J.; De Clercq, E.; Yoshii, K.; Růžek, Daniel

    2017-01-01

    Roč. 91, č. 21 (2017), č. článku e01028-17. ISSN 0022-538X R&D Projects: GA MZd(CZ) NV16-34238A Institutional support: RVO:60077344 ; RVO:61388963 Keywords : antiviral agents * antiviral therapy * escape mutant * tick-borne * encephalitis virus * tick-borne pathogens Subject RIV: EE - Microbiology, Virology OBOR OECD: Virology Impact factor: 4.663, year: 2016

  5. Therapeutical aspect of trichomoniasis

    Directory of Open Access Journals (Sweden)

    Vukićević Jelica

    2003-01-01

    Full Text Available Trichomoniasis is frequent, parasitic and sexually transmitted infection of genitourinary tract. It is treated by metronidazole (5-nitroimidazole according to protocol recommended by Center for Disease Control (CDC formerly called: Communicable Disease Center [19]. The resistance of Trichomonas vaginalis (TV strains to metronidazole (MND was described in USA in 1960, and later on in many European countries [8, 9, 10, 11, 12, 13]. In these cases, due to persistent trichomonas infection, it is necessary to repeat MND treatment with moderate modification of dose and/or length of its application. Nevertheless, oncogenic and toxic effects of MND have to be taken into consideration. OBJECT The aim of this study was to investigate and analyze the incidence of TV in STD and lower susceptibility of certain TV strains to MND were analyzed. MATERIAL AND METHODS In three-year period (1999-2001 612 patients (244 females and 368 males suspected of STD were examined clinically and microbiologically at the Institute of Dermatovenereology in Belgrade. The patients detected for TV were treated according to CDC protocol. The affected were considered cured if there was no manifest clinical infection, and no TV verified by microbiological test. Results TV was isolated in 216 patients (35.29 % of all subjects. Trichomonas infection was found in 90 (36.88 % out of 244 tested females and in 126 (32.34 % of 368 males. Clinically manifested infection, with extensive urethral and vaginal secretion, was recorded in 161 patients, while the asymptomatic form was found in 55 subjects. This result indicates the predominance of manifested trichomonas infections (75.54 % of cases. The difference of distribution of clinical forms of trichomoniasis, in relation to sex, was not statistically significant (c2=0.854; p>0.05. The patients with verified trichomonas infection were treated by metronidazole according to CDC protocol. The recommended therapeutical scheme consisted of three

  6. Therapeutic touch: influence on vital signs of newborns.

    Science.gov (United States)

    Ramada, Nadia Christina Oliveira; Almeida, Fabiane de Amorim; Cunha, Mariana Lucas da Rocha

    2013-12-01

    To compare vital signs before and after the therapeutic touch observed in hospitalized newborns in neonatal intensive care unit. This was a quasi-experimental study performed at a neonatal intensive care unit of a municipal hospital, in the city of São Paulo (SP), Brazil. The sample included 40 newborns submitted to the therapeutic touch after a painful procedure. We evaluated the vital signs, such as heart and respiratory rates, temperature and pain intensity, before and after the therapeutic touch. The majority of newborns were male (n=28; 70%), pre-term (n=19; 52%) and born from vaginal delivery (n=27; 67%). Respiratory distress was the main reason for hospital admission (n=16; 40%). There was a drop in all vital signs after therapeutic touch, particularly in pain score, which had a considerable reduction in the mean values, from 3.37 (SD=1.31) to 0 (SD=0.0). All differences found were statistically significant by the Wilcoxon test (ptouch promotes relaxation of the baby, favoring reduction in vital signs and, consequently in the basal metabolism rate.

  7. Therapeutic antibodies as a treatment option for dengue fever.

    Science.gov (United States)

    Chan, Kuan Rong; Ong, Eugenia Z; Ooi, Eng Eong

    2013-11-01

    Dengue fever is the most prevalent mosquito-borne viral disease globally with about 100 million cases of acute dengue annually. Severe dengue infection can result in a life-threatening illness. In the absence of either a licensed vaccine or antiviral drug against dengue, therapeutic antibodies that neutralize dengue virus (DENV) may serve as an effective medical countermeasure against severe dengue. However, therapeutic antibodies would need to effectively neutralize all four DENV serotypes. It must not induce antibody-dependent enhancement of DENV infection in monocytes/macrophages through Fc gamma receptor (FcγR)-mediated phagocytosis, which is hypothesized to increase the risk of severe dengue. Here, we review the strategies and technologies that can be adopted to develop antibodies for therapeutic applications. We also discuss the mechanism of antibody neutralization in the cells targeted by DENV that express Fc gamma receptor. These studies have provided significant insight toward the use of therapeutic antibodies as a potentially promising bulwark against dengue.

  8. Agents Within our Midst

    Science.gov (United States)

    2012-03-14

    agents; and the development of bio -monitoring protocols for civilian and service personnel during a chemical attack. These efforts have resulted in greater...produced by staphylococcal bacteria that is and is classified as a CDC select agent which has the potential to be used as a biological weapon .1...NMR chemical shift perturbation titrations with Fab (fragment, antigen binding regions) domains of 20B1, 14G8, and 6D3 using deuterated (2H) SEB

  9. Adrenal imaging agents

    International Nuclear Information System (INIS)

    Davis, M.A.; Hanson, R.N.; Holman, B.L.

    1980-01-01

    The goals of this proposal are the development of selenium-containing analogs of the aromatic amino acids as imaging agents for the pancreas and of the adrenal cortex enzyme inhibitors as imaging agents for adrenal pathology. The objects for this year include (a) the synthesis of methylseleno derivatives of phenylalanine and tryptophan, and (b) the preparation and evaluation of radiolabeled iodobenzoyl derivatives of the selenazole and thiazole analogs of metyrapone and SU-9055

  10. Three-dimensional prospective evaluation of tooth-borne and bone-borne surgically assisted rapid maxillary expansion

    NARCIS (Netherlands)

    Nada, R.M.; Fudalej, P.S.; Maal, T.J.J.; Berge, S.J.; Mostafa, Y.A.; Kuijpers-Jagtman, A.M.

    2012-01-01

    AIM: To three-dimensionally (3D) assess the long-term effects of tooth-borne and bone-borne surgically assisted rapid maxillary expansion (SARME). SUBJECTS AND METHODS: This prospective cohort study comprised 45 consecutive skeletally mature non-syndromic patients with transverse maxillary

  11. Young Adult Outcomes of Children Born to Teen Mothers: Effects of Being Born during Their Teen or Later Years

    Science.gov (United States)

    Lipman, Ellen L.; Georgiades, Katholiki; Boyle, Michael H.

    2011-01-01

    Objective: Children of teen mothers exhibit adverse outcomes through adolescence. It is unclear whether these adverse outcomes extend to adulthood and apply to all of her children, or only those born when she was a teen. We examine the associations between young adult functioning and being born to a teen mother aged less than or equal to 20 years…

  12. Effect of Extracts and Bacteria from Korean Fermented Foods on the Control of Sesame Seed-Borne Fungal Diseases

    Directory of Open Access Journals (Sweden)

    Yong-Ki Kim

    2015-12-01

    isolated from the extract can be used as bio-control agents for suppressing sesame seed-borne diseases based on above described results.

  13. Therapeutic drug monitoring of atypical antipsychotic drugs

    Directory of Open Access Journals (Sweden)

    Grundmann Milan

    2014-12-01

    Full Text Available Schizophrenia is a severe psychiatric disorder often associated with cognitive impairment and affective, mainly depressive, symptoms. Antipsychotic medication is the primary intervention for stabilization of acute psychotic episodes and prevention of recurrences and relapses in patients with schizophrenia. Typical antipsychotics, the older class of antipsychotic agents, are currently used much less frequently than newer atypical antipsychotics. Therapeutic drug monitoring (TDM of antipsychotic drugs is the specific method of clinical pharmacology, which involves measurement of drug serum concentrations followed by interpretation and good cooperation with the clinician. TDM is a powerful tool that allows tailor-made treatment for the specific needs of individual patients. It can help in monitoring adherence, dose adjustment, minimizing the risk of toxicity and in cost-effectiveness in the treatment of psychiatric disorders. The review provides complex knowledge indispensable to clinical pharmacologists, pharmacists and clinicians for interpretation of TDM results.

  14. Comparison outcomes of sick babies born to teenage mothers with those born to adult mothers.

    Science.gov (United States)

    Chotigeat, Uraiwan; Sawasdiworn, Siraporn

    2011-08-01

    Adolescent period is the transitional stage of physical and mental development from childhood to adulthood. Pregnancy in teenage girls is generally classified to have a higher risk than those in adults. In many previous studies reported only the outcome of teenage mothers but no comparative outcome between sick babies born to teen mothers and adult mothers, so the authors conducted the present study. To compare the outcomes of sick infants born to teenage mothers with those born to adult mothers (age > or = 20 years). This prospective study was carried out from October 1st, 2006 to September 30th, 2009. The study group consisted of sick babies born to teenage mothers and admitted at Queen Sirikit National Institute of Child Health (QSNICH). These babies were compared to sick babies (control group) born to adult mothers during the same period. The demographic data of mothers and sick babies in both groups were recorded in the designed case record forms. Developmental assessment was done until two years of age. A total of 6,342 deliveries took place in Rajavithi Hospital during the study period of which 697 babies were born to teenage mothers. The incidence of teenage pregnancy was 10.99%. The number of sick babies from teenage mothers and adult mothers were 78 and 147 cases, respectively. There was a significantly higher mortality in the study group (7 cases, 9%) than the control group (4 cases, 2.7%). There was statistically significant difference in most of the demographic characteristics between the teenage and adult mothers except anemia, PROM and MSAF (meconium stain amniotic fluid). Although there was a trend of more cases of anemia and MSAF in teenage mothers than in adult mothers, there was no statistically significant difference. There was a shorter interval time from marriage to pregnancy in teen mothers than in adult mothers and a lower number of antenatal care visits with late antenatal care among the teenage mothers too. On comparing the data in infants

  15. Photoactivatable Lipid-based Nanoparticles as a Vehicle for Dual Agent Delivery | NCI Technology Transfer Center | TTC

    Science.gov (United States)

    Researchers at the National Cancer Institute (NCI) RNA Biology Laboratory have developed nanoparticles that can deliver an agent (i.e., therapeutic or imaging) and release the agent upon targeted photoactivation allowing for controlled temporal and localized release of the agent.

  16. Plants as sources of antiviral agents | Abonyi | African Journal of ...

    African Journals Online (AJOL)

    Antivirals are substances other than a virus or virus containing vaccine or specific antibody which can produce either a protective or therapeutic effect to the clear detectable advantage of the virus infected host. The search for antiviral agents began in earnest in the 1950s but this was directed mainly by chance, with little or ...

  17. Will biofilm disassembly agents make it to market?

    Science.gov (United States)

    Romero, Diego; Kolter, Roberto

    2011-07-01

    Nearly 12 years after promising results suggested that antibiofilm agents might be developed into novel therapeutics, there are no such products on the market. In our opinion, the reasons for this have been predominantly economic. Recent developments, however, suggest that there could still be emerging opportunities for the developments of such products. Copyright © 2011 Elsevier Ltd. All rights reserved.

  18. An update on anti-TNF agents in ulcerative colitis

    NARCIS (Netherlands)

    Samaan, Mark A.; Bagi, Preet; Vande Casteele, Niels; D'Haens, Geert R.; Levesque, Barrett G.

    2014-01-01

    Anti-tumor necrosis factor-α agents are key therapeutic options for the treatment of ulcerative colitis. Their efficacy and safety have been shown in large randomized controlled trials. The key evidence gained from these trials of infliximab, adalimumab, and golimumab is reviewed along with their

  19. The Promise of Neuroprotective Agents in Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Judith ePotashkin

    2011-11-01

    Full Text Available Parkinson’s Disease is characterized by loss of dopamine neurons in the substantia nigra of the brain. Since there are limited treatment options for PD, neuroprotective agents are currently being tested as a means to slow disease progression. Agents targeting oxidative stress, mitochondrial dysfunction and inflammation are prime candidates for neuroprotection. This review identifies Rasagiline, Minocycline and creatine, as the most promising neuroprotective agents for PD, and they are all currently in phase III trials. Other agents possessing protective characteristics in delaying PD include stimulants, vitamins, supplements, and other drugs. Additionally, combination therapies also show benefits in slowing PD progression. The identification of neuroprotective agents for PD provides us with therapeutic opportunities for modifying the course of disease progression and, perhaps, reducing the risk of onset when preclinical biomarkers become available.

  20. Therapeutic Inertia and Treatment Intensification.

    Science.gov (United States)

    Josiah Willock, Robina; Miller, Joseph B; Mohyi, Michelle; Abuzaanona, Ahmed; Muminovic, Meri; Levy, Phillip D

    2018-01-29

    This review aims to emphasize how therapeutic inertia, the failure of clinicians to intensify treatment when blood pressure rises or remains above therapeutic goals, contributes to suboptimal blood pressure control in hypertensive populations. Studies reveal that the therapeutic inertia is quite common and contributes to suboptimal blood pressure control. Quality improvement programs and standardized approaches to support antihypertensive treatment intensification are ways to combat therapeutic inertia. Furthermore, programs that utilize non-physician medical professionals such as pharmacists and nurses demonstrate promise in mitigating the effects of this important problem. Therapeutic inertia impedes antihypertensive management and requires a broad effort to reduce its effects. There is an ongoing need for renewed focus and research in this area to improve hypertension control.