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Sample records for borne therapeutic agents

  1. 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.

  2. Development of Class IIa Bacteriocins as Therapeutic Agents

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    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.

  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. 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 ...

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

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    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.

  6. 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.

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

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    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.

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

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    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.

  9. 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.

  10. 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

  11. 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.

  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. 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

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

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    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.

  15. 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

  16. 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.

  17. 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.

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

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    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.

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

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    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.

  20. 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.

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

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    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.

  2. 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.

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

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    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.

  4. 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.

  5. 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.

  6. 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

  7. 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

  8. 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.

  9. 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)

  10. 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

  11. 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.

  12. [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.

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. 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.

  18. 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.

  19. 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.

  20. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  2. 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...

  3. 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.

  4. 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.

  5. 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...

  6. 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.

  7. 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.

  8. 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...

  9. 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.

  10. 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.

  11. 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.

  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. 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

  14. 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)

  15. [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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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...

  1. 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.

  2. 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.

  3. 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.

  4. 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...

  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. 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.

  7. 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.

  8. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  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. 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.

  12. 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 ...

  13. 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.

  14. 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. 

  15. [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.

  16. 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

  17. 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...

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. 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.

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

    Directory of Open Access Journals (Sweden)

    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

  7. 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....

  8. 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

  9. 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.

  10. 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

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. 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...

  16. 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...

  17. 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...

  18. 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...

  19. 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.

  20. 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

  1. 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.

  2. 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

  3. 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.

  4. 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...

  5. 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.

  6. 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

  7. 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....

  8. 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

  9. 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...

  10. 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

  11. 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

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. 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 ...

  18. 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

  19. 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...

  20. 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...

  1. Targeted Anticancer Immunotoxins and Cytotoxic Agents with Direct Killing Moieties

    Directory of Open Access Journals (Sweden)

    Koji Kawakami

    2006-01-01

    Full Text Available Despite the progress of the bioinformatics approach to characterize cell-surface antigens and receptors on tumor cells, it remains difficult to generate novel cancer vaccines or neutralizing monoclonal antibody therapeutics. Among targeted cancer therapeutics, biologicals with targetable antibodies or ligands conjugated or fused to toxins or chemicals for direct cell-killing ability have been developed over the last 2 decades. These conjugated or fused chimeric proteins are termed immunotoxins or cytotoxic agents. Two agents, DAB389IL-2 (ONTAKTM targeting the interleukin-2 receptor and CD33-calicheamicin (Mylotarg®, have been approved by the FDA for cutaneous T-cell lymphoma (CTCL and relapsed acute myeloid leukemia (AML, respectively. Such targetable agents, including RFB4(dsFv-PE38 (BL22, IL13-PE38QQR, and Tf-CRM107, are being tested in clinical trials. Several agents using unique technology such as a cleavable adapter or immunoliposomes with antibodies are also in the preclinical stage. This review summarizes the generation, mechanism, and development of these agents. In addition, possible future directions of this therapeutic approach are discussed.

  2. 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.

  3. 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.

  4. 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.

  5. 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...

  6. 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.

  7. 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.

  8. 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

  9. 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.

  10. 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.

  11. Topical Botanical Agents for the Treatment of Psoriasis: A Systematic Review.

    Science.gov (United States)

    Farahnik, Benjamin; Sharma, Divya; Alban, Joseph; Sivamani, Raja K

    2017-08-01

    Patients with psoriasis often enquire about the use of numerous botanical therapeutics. It is important for dermatologists to be aware of the current evidence regarding these agents. We conducted a systematic literature search using the PubMed, MEDLINE, and EMBASE databases for controlled and uncontrolled clinical trials that assessed the use of topical botanical therapeutics for psoriasis. The search included the following keywords: 'psoriasis' and 'plant' or 'herbal' or 'botanical'. We also reviewed citations within articles to identify additional relevant sources. We then further refined the results by route of administration and the topical botanical agents are reviewed herein. A total of 27 controlled and uncontrolled clinical trials addressing the use of topical botanical agents for psoriasis were assessed in this review. We found that the most highly studied and most efficacious topical botanical therapeutics were Mahonia aquifolium, indigo naturalis, aloe vera, and, to a lesser degree, capsaicin. The most commonly reported adverse effects were local skin irritation, erythema, pruritus, burning, and pain. However, the overall evidence for these therapeutics remains limited in quantity and quality. The literature addresses a large number of studies in regard to botanicals for the treatment of psoriasis. While most agents appear to be safe, further research is necessary before topical botanical agents can be consistently recommended to patients.

  12. [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.

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. 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)

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. [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.

  3. 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

  4. 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.

  5. 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.

  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

    2013-01-01

    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

  7. 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.

  8. 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.

  9. Impacts of the Human Gut Microbiome on Therapeutics.

    Science.gov (United States)

    Vázquez-Baeza, Yoshiki; Callewaert, Chris; Debelius, Justine; Hyde, Embriette; Marotz, Clarisse; Morton, James T; Swafford, Austin; Vrbanac, Alison; Dorrestein, Pieter C; Knight, Rob

    2018-01-06

    The human microbiome contains a vast source of genetic and biochemical variation, and its impacts on therapeutic responses are just beginning to be understood. This expanded understanding is especially important because the human microbiome differs far more among different people than does the human genome, and it is also dramatically easier to change. Here, we describe some of the major factors driving differences in the human microbiome among individuals and populations. We then describe some of the many ways in which gut microbes modify the action of specific chemotherapeutic agents, including nonsteroidal anti-inflammatory drugs and cardiac glycosides, and outline the potential of fecal microbiota transplant as a therapeutic. Intriguingly, microbes also alter how hosts respond to therapeutic agents through various pathways acting at distal sites. Finally, we discuss some of the computational and practical issues surrounding use of the microbiome to stratify individuals for drug response, and we envision a future where the microbiome will be modified to increase everyone's potential to benefit from therapy.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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...

  15. 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.

  16. 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.

  17. 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

  18. 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

  19. Canine babesiosis in northern Portugal and molecular characterization of vector-borne co-infections

    Science.gov (United States)

    2010-01-01

    Background Protozoa and bacteria transmitted by arthropods, including ticks and phlebotomine sand flies, may cause a wide range of canine vector-borne diseases. Dogs can be simultaneously or sequentially infected with multiple pathogens. Canine babesiosis caused by Babesia canis canis and Babesia canis vogeli is known to occur in Portugal. This study assessed, by means of blood smear examination, PCR and DNA nucleotide sequencing, the presence of Babesia spp. and co-infecting agents Leishmania, Anaplasma/Ehrlichia and Hepatozoon in 45 dogs from northern Portugal clinically suspected of babesiosis. Results Forty-four dogs (98%) had infection with B. canis canis and one with B. canis vogeli. Co-infections were detected in nine animals (20%). Eight dogs were found infected with two vector-borne agents: six with B. canis canis and Leishmania infantum; one with B. canis canis and Ehrlichia canis; and one with B. canis canis and Hepatozoon canis. Another dog was infected with three vector-borne pathogens: B. canis vogeli, E. canis and L. infantum. Overall, L. infantum was found in seven (16%), E. canis in two (4%), and H. canis in one (2%) out of the 45 dogs with babesiosis. Almost 90% of the 45 cases of canine babesiosis were diagnosed in the colder months of October (18%), November (27%), December (20%), February (13%) and March (9%). Co-infections were detected in February, March, April, May, October and November. Twenty-two (50%) out of 44 dogs infected with B. canis were found infested by ticks including Dermacentor spp., Ixodes spp. and Rhipicephalus sanguineus. Mortality (9%) included two co-infected dogs that died spontaneously and two with single infections that were euthanized. Conclusions Babesia canis canis is the main etiological agent of canine babesiosis in northern Portugal. A higher sensitivity of Babesia spp. detection was obtained with PCR assays, compared to the observation of blood smears. Twenty percent of the dogs were co-infected with L. infantum

  20. Canine babesiosis in northern Portugal and molecular characterization of vector-borne co-infections

    Directory of Open Access Journals (Sweden)

    Machado João

    2010-04-01

    Full Text Available Abstract Background Protozoa and bacteria transmitted by arthropods, including ticks and phlebotomine sand flies, may cause a wide range of canine vector-borne diseases. Dogs can be simultaneously or sequentially infected with multiple pathogens. Canine babesiosis caused by Babesia canis canis and Babesia canis vogeli is known to occur in Portugal. This study assessed, by means of blood smear examination, PCR and DNA nucleotide sequencing, the presence of Babesia spp. and co-infecting agents Leishmania, Anaplasma/Ehrlichia and Hepatozoon in 45 dogs from northern Portugal clinically suspected of babesiosis. Results Forty-four dogs (98% had infection with B. canis canis and one with B. canis vogeli. Co-infections were detected in nine animals (20%. Eight dogs were found infected with two vector-borne agents: six with B. canis canis and Leishmania infantum; one with B. canis canis and Ehrlichia canis; and one with B. canis canis and Hepatozoon canis. Another dog was infected with three vector-borne pathogens: B. canis vogeli, E. canis and L. infantum. Overall, L. infantum was found in seven (16%, E. canis in two (4%, and H. canis in one (2% out of the 45 dogs with babesiosis. Almost 90% of the 45 cases of canine babesiosis were diagnosed in the colder months of October (18%, November (27%, December (20%, February (13% and March (9%. Co-infections were detected in February, March, April, May, October and November. Twenty-two (50% out of 44 dogs infected with B. canis were found infested by ticks including Dermacentor spp., Ixodes spp. and Rhipicephalus sanguineus. Mortality (9% included two co-infected dogs that died spontaneously and two with single infections that were euthanized. Conclusions Babesia canis canis is the main etiological agent of canine babesiosis in northern Portugal. A higher sensitivity of Babesia spp. detection was obtained with PCR assays, compared to the observation of blood smears. Twenty percent of the dogs were co

  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. {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. 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.

  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. 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...

  6. 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.

  7. 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.

  8. A comparative study on the cost of new antibiotics and drugs of other therapeutic categories.

    Science.gov (United States)

    Falagas, Matthew E; Fragoulis, Konstantinos N; Karydis, Ioannis

    2006-12-20

    Drug treatment is becoming more expensive due to the increased cost for the introduction of new drugs, and there seems to be an uneven distribution of medication cost for different therapeutic categories. We hypothesized that the cost of new antimicrobial agents may differ from that of other therapeutic categories and this may play a role in the stagnation of development of new antibiotics. We performed a pharmaco-economical comparative analysis of the drug cost of treatment for new agents introduced in the United States drug market in various therapeutic categories. We calculated the drug cost (in US dollars) of a ten-day treatment of all new drugs approved by the FDA during the period between January 1997 and July 2003, according to the 2004 Red Book Pharmacy's Fundamental Reference. New anti-neoplastic agents were found to be the most expensive drugs in comparison to all other therapeutic categories, with a median ten-day drug-treatment cost of US$848 compared to the median ten-day drug-treatment costs of all other categories ranging from US$29 to US$301. On the other hand, new antimicrobial drugs were found to be much less expensive, with a median ten-day drug-treatment cost of US$137 and $US85 for all anti-microbial agents and for anti-microbial agents excluding anti-HIV medications, respectively. The drug-treatment cost of new medications varies considerably by different therapeutic categories. This fact may influence industry decisions regarding the development of new drugs and may play a role in the shortage of new antimicrobial agents in the fight against the serious problem of antimicrobial resistance.

  9. Microbial glycolipoprotein-capped silver nanoparticles as emerging antibacterial agents against cholera.

    Science.gov (United States)

    Gahlawat, Geeta; Shikha, Sristy; Chaddha, Baldev Singh; Chaudhuri, Saumya Ray; Mayilraj, Shanmugam; Choudhury, Anirban Roy

    2016-02-01

    With the increased number of cholera outbreaks and emergence of multidrug resistance in Vibrio cholerae strains it has become necessary for the scientific community to devise and develop novel therapeutic approaches against cholera. Recent studies have indicated plausibility of therapeutic application of metal nano-materials. Among these, silver nanoparticles (AgNPs) have emerged as a potential antimicrobial agent to combat infectious diseases. At present nanoparticles are mostly produced using physical or chemical techniques which are toxic and hazardous. Thus exploitation of microbial systems could be a green eco-friendly approach for the synthesis of nanoparticles having similar or even better antimicrobial activity and biocompatibility. Hence, it would be worth to explore the possibility of utilization of microbial silver nanoparticles and their conjugates as potential novel therapeutic agent against infectious diseases like cholera. The present study attempted utilization of Ochrobactrum rhizosphaerae for the production of AgNPs and focused on investigating their role as antimicrobial agents against cholera. Later the exopolymer, purified from the culture supernatant, was used for the synthesis of spherical shaped AgNPs of around 10 nm size. Further the exopolymer was characterized as glycolipoprotein (GLP). Antibacterial activity of the novel GLP-AgNPs conjugate was evaluated by minimum inhibitory concentration, XTT reduction assay, scanning electron microscopy (SEM) and growth curve analysis. SEM studies revealed that AgNPs treatment resulted in intracellular contents leakage and cell lysis. The potential of microbially synthesized nanoparticles, as novel therapeutic agents, is still relatively less explored. In fact, the present study first time demonstrated that a glycolipoprotein secreted by the O. rhizosphaerae strain can be exploited for production of AgNPs which can further be employed to treat infectious diseases. Although this type of polymer has

  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. 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.

  12. The future of antibody therapeutics: ADCs bi-specifics and RIT

    International Nuclear Information System (INIS)

    Reichert, J.

    2015-01-01

    Full text of publication follows. Antibodies are widely accepted as remarkably versatile therapeutic agents. As evidence of this, the ∼ 30 antibody products marketed worldwide had total global sales of more than 50 billion dollars in 2012, and the commercial clinical pipeline currently comprises over 350 antibody-based product candidates. In a testament to scientific ingenuity, the investigational molecules (clinical and preclinical) are notably diverse in their composition of matter and include antibodies conjugated to a variety of agents (drugs, radioisotopes), bi-specific antibodies, and fragments or domains of antibodies. The concepts that form the basis of these agents were established decades ago, but advances in technology are now allowing new opportunities for their development. In this presentation, future directions in antibody therapeutics development will be discussed, with a focus on antibody-drug conjugates, bi-specific antibodies and radioimmunotherapy. (author)

  13. 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.

  14. 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.

  15. 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.

  16. [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.

  17. 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...

  18. 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.

  19. 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.

  20. Multiwalled carbon nanotube hybrids as MRI contrast agents

    Directory of Open Access Journals (Sweden)

    Nikodem Kuźnik

    2016-07-01

    Full Text Available Magnetic resonance imaging (MRI is one of the most commonly used tomography techniques in medical diagnosis due to the non-invasive character, the high spatial resolution and the possibility of soft tissue imaging. Contrast agents, such as gadolinium complexes and superparamagnetic iron oxides, are administered to spotlight certain organs and their pathologies. Many new models have been proposed that reduce side effects and required doses of these already clinically approved contrast agents. These new candidates often possess additional functionalities, e.g., the possibility of bioactivation upon action of particular stimuli, thus serving as smart molecular probes, or the coupling with therapeutic agents and therefore combining both a diagnostic and therapeutic role. Nanomaterials have been found to be an excellent scaffold for contrast agents, among which carbon nanotubes offer vast possibilities. The morphology of multiwalled carbon nanotubes (MWCNTs, their magnetic and electronic properties, the possibility of different functionalization and the potential to penetrate cell membranes result in a unique and very attractive candidate for a new MRI contrast agent. In this review we describe the different issues connected with MWCNT hybrids designed for MRI contrast agents, i.e., their synthesis and magnetic and dispersion properties, as well as both in vitro and in vivo behavior, which is important for diagnostic purposes. An introduction to MRI contrast agent theory is elaborated here in order to point to the specific expectations regarding nanomaterials. Finally, we propose a promising, general model of MWCNTs as MRI contrast agent candidates based on the studies presented here and supported by appropriate theories.

  1. 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, ...

  2. 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.

  3. 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

  4. Novel Ehrlichia and Hepatozoon agents infecting the crab-eating fox (Cerdocyon thous) in southeastern Brazil.

    Science.gov (United States)

    Almeida, Aliny P; Souza, Tayse D; Marcili, Arlei; Labruna, Marcelo B

    2013-05-01

    This study evaluated infection by vector-borne agents in 58 crab-eating fox (Cerdocyon thous L.) that were road-killed in an Atlantic rainforest reserve in the state of Espírito Santo, southeastern Brazil. Spleen, lung, or blood samples collected from the foxes were tested in the laboratory by a battery of polymerase chain reaction (PCR) assays targeting bacteria of the genera Rickettsia, Borrelia, Coxiella, Anaplasma, and Ehrlichia; and protozoa of the genera Babesia, Hepatozoon, and Leishmania. Of the targeted organisms, evidence of infection in the foxes was detected for Ehrlichia and Hepatozoon organisms only. Overall, six (10.3%) foxes were infected by an ehrlichial agent closely related to an ehrlichial agent recently detected in free-ranging Jaguars [(Panthera onca (L.)] in central-western Brazil, and to Ehrlichia ruminantium. For Hepatozoon, 28 (48.3%) foxes were infected by an agent closely related to Hepatozoon sp. Curupira 2 and H. americanum; and one (1.7%) fox was infected by an organism closely related to reptile-associated Hepatozoon agents. Finally, 11 (19.0%) foxes were found infested by Amblyomma cajennense (F.) nymphs, which were all PCR negative for the range of vector-borne agents cited above. Because the haplotypes found in free-ranging foxes are genetically closely related to pathogens of great veterinary importance, namely E. ruminantium and H. americanum, it is highly desirable to know if these novel organisms have any important role as agents of diseases in domestic animals and wildlife in Brazil.

  5. 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

  6. 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 ...

  7. 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

  8. [Public health pests. Arthropods and rodents as causative disease agents as well as reservoirs and vectors of pathogens].

    Science.gov (United States)

    Faulde, M; Freise, J

    2014-05-01

    Globally, infectious diseases pose the most important cause of death. Among known human pathogenic diseases, approximately 50 % are zoonoses. When considering emerging infectious diseases separately 73 % currently belong to the group of zoonoses. In Central Europe, hard ticks show by far the biggest potential as vectors of agents of human disease. Lyme borreliosis, showing an estimated annual incidence between 60,000 and 214,000 cases is by far the most frequent tick-borne disease in Germany. Continually, formerly unknown disease agents could be discovered in endemic vector species. Additionally, introduction of new arthropod vectors and/or agents of disease occur constantly. Recently, five mosquito species of the genus Aedes have been newly introduced to Europe where they are currently spreading in different regions. Uncommon autochthonous transmission of dengue and chikungunya fever viruses in Southern Europe could be directly linked to these vector species and of these Ae. albopictus and Ae. japonicus are currently reported to occur in Germany. The German Protection against Infection Act only covers the control of public health pests which are either active hematophagous vectors or mechanical transmitters of agents of diseases. Use of officially recommended biocidal products aiming to interrupt transmission cycles of vector-borne diseases, is confined to infested buildings only, including sewage systems in the case of Norway rat control. Outdoor vectors, such as hard ticks and mosquitoes, are currently not taken into consideration. Additionally, adjustments of national public health regulations, detailed arthropod vector and rodent reservoir mapping, including surveillance of vector-borne disease agents, are necessary in order to mitigate future disease risks.

  9. 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.

  10. 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...

  11. Imaging findings and therapeutic alternatives for peripheral vascular malformations

    International Nuclear Information System (INIS)

    Monsignore, Lucas Moretti; Nakiri, Guilherme Seizem; Santos, Daniela dos; Abud, Thiago Giansante; Abud, Daniel Giansante

    2010-01-01

    Peripheral vascular malformations represent a spectrum of lesions that appear through the lifetime and can be found in the whole body. Such lesions are uncommon and are frequently confounded with infantile hemangioma, a common benign neoplastic lesion. In the presence of such lesions, the correlation between the clinical and radiological findings is extremely important to achieve a correct diagnosis, which will guide the best therapeutic approach. The most recent classifications for peripheral vascular malformations are based on the blood flow (low or high) and on the main vascular components (arterial, capillary, lymphatic or venous). Peripheral vascular malformations represent a diagnostic and therapeutic challenge, and complementary methods such as computed tomography, Doppler ultrasonography and magnetic resonance imaging, in association with clinical findings can provide information regarding blood flow characteristics and lesions extent. Arteriography and venography confirm the diagnosis, evaluate the lesions extent and guide the therapeutic decision making. Generally, low flow vascular malformations are percutaneously treated with sclerosing agents injection, while in high flow lesions the approach is endovascular, with permanent liquid or solid embolization agents. (author)

  12. 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.

  13. 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.

  14. 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.

  15. 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

  16. 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

  17. 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.

  18. Meeting Report: High-Throughput Technologies for In Vivo Imaging Agents

    Directory of Open Access Journals (Sweden)

    Robert J. Gillies

    2005-04-01

    Full Text Available Combinatorial chemistry and high-throughput screening have become standard tools for discovering new drug candidates with suitable pharmacological properties. Now, those same technologies are starting to be applied to the problem of discovering novel in vivo imaging agents. Important differences in the biological and pharmacological properties needed for imaging agents, compared to those for a therapeutic agent, require new screening methods that emphasize those characteristics, such as optimized residence time and tissue specificity, that make for a good imaging agent candidate.

  19. 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.

  20. 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.

  1. 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.

  2. Zika Virus: Recent Advances towards the Development of Vaccines and Therapeutics.

    Science.gov (United States)

    McArthur, Monica A

    2017-06-13

    Zika is a rapidly emerging public health threat. Although clinical infection is frequently mild, significant neurological manifestations have been demonstrated in infants born to Zika virus (ZIKV) infected mothers. Due to the substantial ramifications of intrauterine infection, effective counter-measures are urgently needed. In order to develop effective anti-ZIKV vaccines and therapeutics, improved animal models and a better understanding of immunological correlates of protection against ZIKV are required. This review will summarize what is currently known about ZIKV, the clinical manifestations and epidemiology of Zika as well as, the development of animal models to study ZIKV infection, host immune responses against ZIKV, and the current state of development of vaccines and therapeutics against ZIKV.

  3. 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.

  4. 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...

  5. 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.

  6. 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

  7. Tofacitinib Suppresses Antibody Responses to Protein Therapeutics in Murine Hosts1

    Science.gov (United States)

    Onda, Masanori; Ghoreschi, Kamran; Steward-Tharp, Scott; Thomas, Craig; O’Shea, John J.; Pastan, Ira H.; FitzGerald, David J.

    2014-01-01

    Immunogenicity remains the ‘Achilles’ heel’ of protein-based therapeutics. Anti-drug antibodies produced in response to protein therapeutics can severely limit both the safety and efficacy of this expanding class of agent. Here we report that monotherapy of mice with tofacitinib (the Janus kinase inhibitor) quells antibody responses to an immunotoxin derived from the bacterial protein, Pseudomonas exotoxin A, as well as to the model antigen, keyhole limpet hemocyanin. Thousandfold reductions in IgG1 titers to both antigens were observed 21 days post-immunization. In fact, suppression was evident for all IgG isotypes and IgM. A reduction in IgG3 production was also noted with a thymus-independent type II antigen. Mechanistic investigations revealed that tofacitinib treatment led to reduced numbers of CD127+ pro-B cells. Furthermore, we observed fewer germinal center B cells and the impaired formation of germinal centers of mice treated with tofacitinib. Since normal immunoglobulin levels were still present during the tofacitinib treatment, this agent specifically reduced anti-drug antibodies, thus preserving the potential efficacy of biological therapeutics, including those that are used as cancer therapeutics. PMID:24890727

  8. Targeted Therapeutic Nanoparticles: An Immense Promise to Fight against Cancer

    Directory of Open Access Journals (Sweden)

    Sheikh Tasnim Jahan

    2017-01-01

    Full Text Available In nanomedicine, targeted therapeutic nanoparticle (NP is a virtual outcome of nanotechnology taking the advantage of cancer propagation pattern. Tying up all elements such as therapeutic or imaging agent, targeting ligand, and cross-linking agent with the NPs is the key concept to deliver the payload selectively where it intends to reach. The microenvironment of tumor tissues in lymphatic vessels can also help targeted NPs to achieve their anticipated accumulation depending on the formulation objectives. This review accumulates the application of poly(lactic-co-glycolic acid (PLGA and polyethylene glycol (PEG based NP systems, with a specific perspective in cancer. Nowadays, PLGA, PEG, or their combinations are the mostly used polymers to serve the purpose of targeted therapeutic NPs. Their unique physicochemical properties along with their biological activities are also discussed. Depending on the biological effects from parameters associated with existing NPs, several advantages and limitations have been explored in teaming up all the essential facts to give birth to targeted therapeutic NPs. Therefore, the current article will provide a comprehensive review of various approaches to fabricate a targeted system to achieve appropriate physicochemical properties. Based on such findings, researchers can realize the benefits and challenges for the next generation of delivery systems.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. Punica granatum and its therapeutic implications on breast carcinogenesis: A review.

    Science.gov (United States)

    Vini, Ravindran; Sreeja, Sreeharshan

    2015-01-01

    Punica granatum has a recorded history of pharmacological properties which can be attributed to its rich reservoir of phytochemicals. Investigations in recent years have established its tremendous potential as an antitumorogenic agent against various cancers including breast cancer, which is the second leading cause of cancer-related deaths in women. The plausible role of Punica as a therapeutic agent, as an adjuvant in chemotherapy, and its dietary implications as chemopreventive agent in breast cancer have been explored. Mechanistic studies have revealed that Punica extracts and its components, individually or in combination, can modulate and target key proteins and genes involved in breast cancer. Our earlier finding also demonstrated the role of methanolic extract of pomegranate pericarp in reducing proliferation in breast cancer by binding to estrogen receptor at the same time not affecting uterine weight unlike estradiol or tamoxifen. This review analyses other plausible mechanisms of Punica in preventing the progression of breast cancer and how it can possibly be a therapeutic agent by acting at various steps of carcinogenesis including proliferation, invasion, migration, metastasis, angiogenesis, and inflammation via various molecular mechanisms. © 2015 International Union of Biochemistry and Molecular Biology.

  14. Stigma, discrimination, or symptomatology differences in self-reported mental health between US-born and Somalia-born Black Americans.

    Science.gov (United States)

    Henning-Smith, Carrie; Shippee, Tetyana P; McAlpine, Donna; Hardeman, Rachel; Farah, Farhiya

    2013-05-01

    We examined differences in self-reported mental health (SRMH) between US-born and Somalia-born Black Americans compared with White Americans. We tested how SRMH was affected by stigma toward seeing a mental health provider, discrimination in the health care setting, or symptoms of depression. Data were from a 2008 survey of adults in Minnesota and were limited to US-born and Somalia-born Black and White Americans (n = 938). Somalia-born adults were more likely to report better SRMH than either US-born Black or White Americans. They also reported lower levels of discrimination (18.6%) than US-born Black Americans (33.4%), higher levels of stigma (23.6% vs 4.7%), and lower levels of depressive symptoms (9.1% vs 31.6%). Controlling for stigma, discrimination, and symptomatology, Somalia-born Black Americans reported better SRMH than White and Black Americans (odds ratio = 4.76). Mental health programming and health care providers who focus on Black Americans' mental health might be missing important sources of heterogeneity. It is essential to consider the role of race and ethnicity, but also of nativity, in mental health policy and programming.

  15. 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.

  16. [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.

  17. 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.

  18. 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.

  19. Anti-herpesvirus agents: a patent and literature review (2003 to present).

    Science.gov (United States)

    Skoreński, Marcin; Sieńczyk, Marcin

    2014-08-01

    The standard therapy used to treat herpesvirus infections is based on the application of DNA polymerase inhibitors such as ganciclovir or aciclovir. Unfortunately, all of these compounds exhibit relatively high toxicity and the mutation of herpesviruses results in the appearance of new drug-resistant strains. Consequently, there is a great need for the development of new, effective and safe anti-herpesvirus agents that employ different patterns of therapeutic action at various stages of the virus life cycle. Patents and patent applications concerning the development of anti-herpesvirus agents displaying different mechanisms of action that have been published since 2003 are reviewed. In addition, major discoveries in this field that have been published in academic papers have also been included. Among all the anti-herpesvirus agents described in this article, the inhibitors of viral serine protease seem to present one of the most effective/promising therapeutics. Unfortunately, the practical application of these antiviral agents has not yet been proven in any clinical trials. Nevertheless, the dynamic and extensive work on this subject gives hope that a new class of anti-herpesvirus agents aimed at the enzymatic activity of herpesvirus serine protease may be developed.

  20. 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

  1. 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

  2. Guilt about being born and debt concerning the gift of life.

    Science.gov (United States)

    Lotterman, Andrew C

    2003-01-01

    A very powerful form of preoedipal guilt stems from a sense of having damaged the life-giving parent with one's most basic needs. A related phenomenon is the child's sense that another subjectivity has deliberately chosen to give and sustain the child's life. This experience gives rise to a compelling mixture of awe, reverence, and obligation, a sense of guilt about being born, of debt concerning the gift of life. This sense of guilt and debt are part of every child's development. Depending on how conflicts surrounding them are negotiated, the child can come to feel either an appetite for living or a crushing sense of selfishness and unworthiness. Such forms of guilt and debt may lead not only to masochism generally, but to a particularly pernicious form of negative therapeutic reaction that can sabotage psychoanalytic work. A patient may feel, for instance, that a successful psychoanalysis is a selfish indulgence and an immoral betrayal of a sacred duty to rescue his or her parents from their misery. Guilt about being born and the sense of debt concerning the gift of life are linked to various developmental, psychodynamic, interpersonal, and cultural phenomena.

  3. 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.

  4. Study on coinfecting vector-borne pathogens in dogs and ticks in Rio Grande do Norte, Brazil

    Directory of Open Access Journals (Sweden)

    Luiz Ricardo Gonçalves

    Full Text Available Since dogs presenting several vector borne diseases can show none or nonspecific clinical signs depending on the phase of infection, the assessment of the particular agents involved is mandatory. The present study aimed to investigate the presence of Babesia spp., Ehrlichia spp., Anaplasma spp., Hepatozoon spp. and Leishmania spp. in blood samples and ticks, collected from two dogs from Rio Grande do Norte showing suggestive tick-borne disease by using molecular techniques. DNA of E. canis, H. canis and L. infantum were detected in blood samples and R. sanguineus ticks collected from dogs. Among all samples analyzed, two showed the presence of multiple infections with E. canis, H. canis and L. infantum chagasi. Here we highlighted the need for molecular differential diagnosis in dogs showing nonspecific clinical signs.

  5. 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...

  6. 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

  7. 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.

  8. 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

  9. 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.

  10. 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...

  11. 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'.

  12. 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.

  13. 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

  14. [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...

  15. 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:…

  16. 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.

  17. 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

  18. Bifunctional chelating agent for the design and development of site specific radiopharmaceuticals and biomolecule conjugation strategy

    Science.gov (United States)

    Katti, Kattesh V.; Prabhu, Kandikere R.; Gali, Hariprasad; Pillarsetty, Nagavara Kishore; Volkert, Wynn A.

    2003-10-21

    There is provided a method of labeling a biomolecule with a transition metal or radiometal in a site specific manner to produce a diagnostic or therapeutic pharmaceutical compound by synthesizing a P.sub.2 N.sub.2 -bifunctional chelating agent intermediate, complexing the intermediate with a radio metal or a transition metal, and covalently linking the resulting metal-complexed bifunctional chelating agent with a biomolecule in a site specific manner. Also provided is a method of synthesizing the --PR.sub.2 containing biomolecules by synthesizing a P.sub.2 N.sub.2 -bifunctional chelating agent intermediate, complexing the intermediate with a radiometal or a transition metal, and covalently linking the resulting radio metal-complexed bifunctional chelating agent with a biomolecule in a site specific manner. There is provided a therapeutic or diagnostic agent comprising a --PR.sub.2 containing biomolecule.

  19. 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.

  20. MicroRNAs in cancer therapeutics: "from the bench to the bedside".

    Science.gov (United States)

    Monroig-Bosque, Paloma del C; Rivera, Carlos A; Calin, George A

    2015-01-01

    MicroRNAs (miRNAs) are non-coding RNA transcripts that regulate physiological processes by targeting proteins directly. Their involvement in research has been robust, and evidence of their regulative functions has granted them the title: master regulators of the human genome. In cancer, they are considered important therapeutic agents, due to the fact that their aberrant expression contributes to disease development, progression, metastasis, therapeutic response and patient overall survival. This has endeavored fields of biomedical sciences to invest in developing and exploiting miRNA-based therapeutics thoroughly. Herein we highlight relevant ongoing/open clinical trials involving miRNAs and cancer.

  1. Offending Behavior, Drug Use, and Mental Health Among Foreign-Born versus U.S. Born Latino Criminal Justice Clients.

    Science.gov (United States)

    Ibañez, Gladys E; Agudo, Michelle; Martin, Steve S; O'Connell, Daniel J; Auf, Rehab; Sheehan, Diana M

    2017-06-01

    Little is known about the offending behavior and recidivism factors of Latinos by nativity (U.S. born, foreign-born). The present study focused on Latinos in community corrections (n = 201) in Miami, Florida, and examined differences in criminal activity, drug use, and mental health by nativity. Data were collected utilizing convenience sampling between June 2014 and December 2015. The research question was: what are the offending, drug use, and mental health histories of Latinos involved in community corrections? Participants were mostly male (n = 120; 59.7%), White (n = 105; 52.2%), and Cuban (n = 97; 48.3%). U.S. born community corrections clients (n = 141) were more likely to report more lifetime and recent criminal activity; and more likely to report lifetime and recent drug use behavior than foreign-born Latinos (n = 60). No differences were found in recent mental health. Correctional healthcare should tailor services such as substance abuse treatment differently toward U.S. born and foreign-born Latinos.

  2. EphB4 as a therapeutic target in mesothelioma

    International Nuclear Information System (INIS)

    Liu, Ren; Ferguson, Benjamin D; Zhou, Yue; Naga, Kranthi; Salgia, Ravi; Gill, Parkash S; Krasnoperov, Valery

    2013-01-01

    Malignant pleural mesothelioma (MPM) often develops decades following exposure to asbestos. Current best therapy produces a response in only half of patients, and the median survival with this therapy remains under a year. A search for novel targets and therapeutics is underway, and recently identified targets include VEGF, Notch, and EphB4-Ephrin-B2. Each of these targets has dual activity, promoting tumor cell growth as well as tumor angiogenesis. We investigated EphB4 expression in 39 human mesothelioma tissues by immunohistochemistry. Xenograft tumors established with human mesothelioma cells were treated with an EphB4 inhibitor (monomeric soluble EphB4 fused to human serum albumin, or sEphB4-HSA). The combinatorial effect of sEphB4-HSA and biologic agent was also studied. EphB4 was overexpressed in 72% of mesothelioma tissues evaluated, with 85% of epithelioid and 38% of sarcomatoid subtypes demonstrating overexpression. The EphB4 inhibitor sEphB4-HSA was highly active as a single agent to inhibit tumor growth, accompanied by tumor cell apoptosis and inhibition of PI3K and Src signaling. Combination of sEphB4-HSA and the anti-VEGF antibody (Bevacizumab) was superior to each agent alone and led to complete tumor regression. EphB4 is a potential therapeutic target in mesothelioma. Clinical investigation of sEphB4-HSA as a single agent and in combination with VEGF inhibitors is warranted

  3. 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.

  4. 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.

  5. Green synthesized nanoparticles in the fight against mosquito-borne diseases and cancer-a brief review.

    Science.gov (United States)

    Benelli, Giovanni

    2016-12-01

    Nanobiomedicine and parasitology are facing a number of key challenges, which mostly deal with the paucity of effective preventive and curative tools against mosquito-borne diseases and cancer. In this scenario, the employ of botanical and invertebrate extracts as reducing, stabilizing and capping agents for the synthesis of nanoparticles is advantageous over chemical and physical methods, since it is one-pot, cheap, and does not require high pressure, energy, temperature, or the use of highly toxic chemicals. Considering the overlooked connection between mosquito vector activity and the spread of cancer in USA, this review focused on the current knowledge available about green synthesized nanoparticles with efficacy against mosquito-borne diseases and cancer. Green fabricated metal nanoparticles showed antiplasmodial activity that often encompasses the efficacy of currently marked drugs for malaria treatment. They have been also reported as growth inhibitors against dengue virus (serotype DEN-2), with moderate cytotoxicity on mammalian cells. However, this feature is strongly dependent to the botanical agents employed during nanosynthesis. In addition, green nanoparticles have been successfully used to reduce mosquito young instar populations in the field. The final section focuses on some issues for future research, with special reference to the chemical standardization of the botanical extracts used for nanosynthesis and the potential effects on green fabricated nanoparticles on non-target organisms. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Systemic use of tumor necrosis factor alpha as an anticancer agent

    Science.gov (United States)

    Roberts, Nicholas J.; Zhou, Shibin; Diaz, Luis A.; Holdhoff, Matthias

    2011-01-01

    Tumor necrosis factor-α (TNF-α) has been discussed as a potential anticancer agent for many years, however initial enthusiasm about its clinical use as a systemic agent was curbed due to significant toxicities and lack of efficacy. Combination of TNF-α with chemotherapy in the setting of hyperthermic isolated limb perfusion (ILP), has provided new insights into a potential therapeutic role of this agent. The therapeutic benefit from TNF-α in ILP is thought to be not only due to its direct anti-proliferative effect, but also due to its ability to increase penetration of the chemotherapeutic agents into the tumor tissue. New concepts for the use of TNF-α as a facilitator rather than as a direct actor are currently being explored with the goal to exploit the ability of this agent to increase drug delivery and to simultaneously reduce systemic toxicity. This review article provides a comprehensive overview on the published previous experience with systemic TNF-α. Data from 18 phase I and 10 phase II single agent as well as 18 combination therapy studies illustrate previously used treatment and dose schedules, response data as well as the most prominently observed adverse effects. Also discussed, based on recent preclinical data, is a potential future role of systemic TNF-α in combination with liposomal chemotherapy to facilitate increased drug uptake into tumors. PMID:22036896

  7. 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

  8. 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)

  9. 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.

  10. 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.

  11. [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...

  12. Engineered Polymer-Based Nanomaterials for Diagnostic, Therapeutic and Theranostic Applications.

    Science.gov (United States)

    Parisi, Ortensia Ilaria; Scrivano, Luca; Sinicropi, Maria Stefania; Picci, Nevio; Puoci, Francesco

    2016-01-01

    Nanomedicine can be defined as the medical application of molecular nanotechnology and it plays a key role and pharmaceutical research and development, especially related to cancer prevention, monitoring, diagnosis and treatment. In this context, nanomaterials are attracting significant research interest due to their abilities to stay in the blood for long time, accumulate in pathological sites including tumors or inflammatory areas via the enhanced permeability and retention (EPR) effect, and facilitate targeted delivery of specific therapeutic agents. In the last decades, considerable attention was attracted by the development of nano-sized carriers, based on natural or synthetic polymers, able to provide the controlled release of anticancer drugs in the aim to overcome the drawbacks associated to the conventional chemotherapy. Furthermore, when loaded with imaging agents, this kind of systems offers the opportunity to exploit optical or magnetic resonance imaging (MRI) in cancer diagnosis. Polymeric materials are characterized by several functionalities where both therapeutic and imaging components, and also targeting moieties, can be attached for simultaneous targeted therapy and imaging providing innovative platforms defined as theranostic agents with a great potential in monitoring and treatment of cancer.

  13. 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.

  14. Modelling soil borne fungal pathogens of arable crops under climate change.

    Science.gov (United States)

    Manici, L M; Bregaglio, S; Fumagalli, D; Donatelli, M

    2014-12-01

    Soil-borne fungal plant pathogens, agents of crown and root rot, are seldom considered in studies on climate change and agriculture due both to the complexity of the soil system and to the incomplete knowledge of their response to environmental drivers. A controlled chamber set of experiments was carried out to quantify the response of six soil-borne fungi to temperature, and a species-generic model to simulate their response was developed. The model was linked to a soil temperature model inclusive of components able to simulate soil water content also as resulting from crop water uptake. Pathogen relative growth was simulated over Europe using the IPCC A1B emission scenario derived from the Hadley-CM3 global climate model. Climate scenarios of soil temperature in 2020 and 2030 were compared to the baseline centred in the year 2000. The general trend of the response of soil-borne pathogens shows increasing growth in the coldest areas of Europe; however, a larger rate of increase is shown from 2020 to 2030 compared to that of 2000 to 2020. Projections of pathogens of winter cereals indicate a marked increase of growth rate in the soils of northern European and Baltic states. Fungal pathogens of spring sowing crops show unchanged conditions for their growth in soils of the Mediterranean countries, whereas an increase of suitable conditions was estimated for the areals of central Europe which represent the coldest limit areas where the host crops are currently grown. Differences across fungal species are shown, indicating that crop-specific analyses should be ran.

  15. Essential oils as natural food antimicrobial agents: a review.

    Science.gov (United States)

    Vergis, Jess; Gokulakrishnan, P; Agarwal, R K; Kumar, Ashok

    2015-01-01

    Food-borne illnesses pose a real scourge in the present scenario as the consumerism of packaged food has increased to a great extend. Pathogens entering the packaged foods may survive longer, which needs a check. Antimicrobial agents either alone or in combination are added to the food or packaging materials for this purpose. Exploiting the antimicrobial property, essential oils are considered as a "natural" remedy to this problem other than its flavoring property instead of using synthetic agents. The essential oils are well known for its antibacterial, antiviral, antimycotic, antiparasitic, and antioxidant properties due to the presence of phenolic functional group. Gram-positive organisms are found more susceptible to the action of the essential oils. Essential oils improve the shelf-life of packaged products, control the microbial growth, and unriddle the consumer concerns regarding the use of chemical preservatives. This review is intended to provide an overview of the essential oils and their role as natural antimicrobial agents in the food industry.

  16. Immunotherapeutics in Pediatric Autoimmune Central Nervous System Disease: Agents and Mechanisms.

    Science.gov (United States)

    Nosadini, Margherita; Sartori, Stefano; Sharma, Suvasini; Dale, Russell C

    2017-08-01

    Beyond the major advances produced by careful clinical-radiological phenotyping and biomarker development in autoimmune central nervous system disorders, a comprehensive knowledge of the range of available immune therapies and a deeper understanding of their action should benefit therapeutic decision-making. This review discusses the agents used in neuroimmunology and their mechanisms of action. First-line treatments typically include corticosteroids, intravenous immunoglobulin, and plasmapheresis, while for severe disease second-line "induction" agents such as rituximab or cyclophosphamide are used. Steroid-sparing agents such as mycophenolate, azathioprine, or methotrexate are often used in potentially relapsing or corticosteroid-dependent diseases. Lessons from adult neuroimmunology and rheumatology could be translated into pediatric autoimmune central nervous system disease in the future, including the potential utility of monoclonal antibodies targeting lymphocytes, adhesion molecules for lymphocytic migration, cytokines or their receptors, or complement. Finally, many agents used in other fields have multiple mechanisms of action, including immunomodulation, with potential usefulness in neuroimmunology, such as antibiotics, psychotropic drugs, probiotics, gut health, and ketogenic diet. All currently accepted and future potential agents have adverse effects, which can be severe; therefore, a "risk-versus-benefit" determination should guide therapeutic decision-making. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. 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...

  18. 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....

  19. Superparamagnetic Bifunctional Bisphosphonates Nanoparticles: A Potential MRI Contrast Agent for Osteoporosis Therapy and Diagnostic

    Directory of Open Access Journals (Sweden)

    Y. Lalatonne

    2010-01-01

    Full Text Available A bone targeting nanosystem is reported here which combined magnetic contrast agent for Magnetic Resonance Imaging (MRI and a therapeutic agent (bisphosphonates into one drug delivery system. This new targeting nanoplatform consists of superparamagnetic γFe2O3 nanoparticles conjugated to 1,5-dihydroxy-1,5,5-tris-phosphono-pentyl-phosphonic acid (di-HMBPs molecules with a bisphosphonate function at the outer of the nanoparticle surface for bone targeting. The as-synthesized nanoparticles were evaluated as a specific MRI contrast agent by adsorption study onto hydroxyapatite and MRI measurment. The strong adsorption of the bisphosphonates nanoparticles to hydroxyapatite and their use as MRI T2∗ contrast agent were demonstrated. Cellular tests performed on human osteosarcoma cells (MG63 show that γFe2O3@di-HMBP hybrid nanomaterial has no citoxity effect in cell viability and may act as a diagnostic and therapeutic system.

  20. 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.

  1. 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.

  2. Therapeutic peptides for cancer therapy. Part I - peptide inhibitors of signal transduction cascades.

    Science.gov (United States)

    Bidwell, Gene L; Raucher, Drazen

    2009-10-01

    Therapeutic peptides have great potential as anticancer agents owing to their ease of rational design and target specificity. However, their utility in vivo is limited by low stability and poor tumor penetration. The authors review the development of peptide inhibitors with potential for cancer therapy. Peptides that inhibit signal transduction cascades are discussed. The authors searched Medline for articles concerning the development of therapeutic peptides and their delivery. Given our current knowledge of protein sequences, structures and interaction interfaces, therapeutic peptides that inhibit interactions of interest are easily designed. These peptides are advantageous because they are highly specific for the interaction of interest, and they are much more easily developed than small molecule inhibitors of the same interactions. The main hurdle to application of peptides for cancer therapy is their poor pharmacokinetic and biodistribution parameters. Therefore, successful development of peptide delivery vectors could potentially make possible the use of this new and very promising class of anticancer agents.

  3. 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.

  4. 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

  5. Sphingosine 1-phosphate (S1P) signalling: Role in bone biology and potential therapeutic target for bone repair.

    Science.gov (United States)

    Sartawi, Ziad; Schipani, Ernestina; Ryan, Katie B; Waeber, Christian

    2017-11-01

    The lipid mediator sphingosine 1-phosphate (S1P) affects cellular functions in most systems. Interest in its therapeutic potential has increased following the discovery of its G protein-coupled receptors and the recent availability of agents that can be safely administered in humans. Although the role of S1P in bone biology has been the focus of much less research than its role in the nervous, cardiovascular and immune systems, it is becoming clear that this lipid influences many of the functions, pathways and cell types that play a key role in bone maintenance and repair. Indeed, S1P is implicated in many osteogenesis-related processes including stem cell recruitment and subsequent differentiation, differentiation and survival of osteoblasts, and coupling of the latter cell type with osteoclasts. In addition, S1P's role in promoting angiogenesis is well-established. The pleiotropic effects of S1P on bone and blood vessels have significant potential therapeutic implications, as current therapeutic approaches for critical bone defects show significant limitations. Because of the complex effects of S1P on bone, the pharmacology of S1P-like agents and their physico-chemical properties, it is likely that therapeutic delivery of S1P agents will offer significant advantages compared to larger molecular weight factors. Hence, it is important to explore novel methods of utilizing S1P agents therapeutically, and improve our understanding of how S1P and its receptors modulate bone physiology and repair. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Star-Shaped Polypeptides: Synthesis and Opportunities for Delivery of Therapeutics.

    Science.gov (United States)

    Byrne, Mark; Murphy, Robert; Kapetanakis, Antonios; Ramsey, Joanne; Cryan, Sally-Ann; Heise, Andreas

    2015-09-17

    Significant advances in the synthesis of polypeptides by N-carboxyanhydride (NCA) polymerisation over the last decade have enabled the design of advanced polypeptide architectures such as star-shaped polypeptides. These materials combine the functionality offered by amino acids with the flexibility of creating stable nanoparticles with adjustable cargo space for therapeutic delivery. This review highlights recent advances in the synthesis of star polypeptides by NCA polymerisation followed by a critical review of the applications of this class of polymer in the delivery of therapeutic agents. This includes examples of traditional small-molecule drugs as well as the emerging class of biologics such as genetic therapeutics (gene delivery). © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. ACCOUNTING INFORMATION SYSTEMS: AN APPROACH FOCUSED ON OBJECTS WITH INTELLIGENT AGENTS

    Directory of Open Access Journals (Sweden)

    Marcelo Botelho da Costa Moraes

    2010-01-01

    Full Text Available Accounting aims at the treatment of information related to economic events within organizations. In order to do so, the double entry method is used (debt and credit accounting, which only considers monetary variations. With the development of information technologies, accounting information systems are born. In the 1980’s, the REA model (economic Resources, economic Events and economic Agents is created, which focuses on accounting information records, based on the association of economic resources, economic events and economic agents. The objective of this work is to demonstrate an object-oriented modeling with intelligent agents use, for information development and analysis focused on users. The proposed model is also analyzed according to accounting information quality, necessary for accounting information users, capable to comply with the needs of different user groups, with advantages in applications.

  8. Work Disability Among Native-born and Foreign-born Americans: On Origins, Health, and Social Safety Nets.

    Science.gov (United States)

    Engelman, Michal; Kestenbaum, Bert M; Zuelsdorff, Megan L; Mehta, Neil K; Lauderdale, Diane S

    2017-12-01

    Public debates about both immigration policy and social safety net programs are increasingly contentious. However, little research has explored differences in health within America's diverse population of foreign-born workers, and the effect of these workers on public benefit programs is not well understood. We investigate differences in work disability by nativity and origins and describe the mix of health problems associated with receiving Social Security Disability Insurance benefits. Our analysis draws on two large national data sources-the American Community Survey and comprehensive administrative records from the Social Security Administration-to determine the prevalence and incidence of work disability between 2001 and 2010. In sharp contrast to prior research, we find that foreign-born adults are substantially less likely than native-born Americans to report work disability, to be insured for work disability benefits, and to apply for those benefits. Overall and across origins, the foreign-born also have a lower incidence of disability benefit award. Persons from Africa, Northern Europe, Canada, and parts of Asia have the lowest work disability benefit prevalence rates among the foreign-born; persons from Southern Europe, Western Europe, the former Soviet Union, and the Caribbean have the highest rates.

  9. 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

  10. 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.

  11. 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

  12. Effects of treatment with antimicrobial agents on the human colonic microflora

    OpenAIRE

    Rafii, Fatemeh

    2008-01-01

    Fatemeh Rafii, John B Sutherland, Carl E CernigliaDivision of Microbiology, National Center for Toxicological Research, FDA, Jefferson, AR, USAAbstract: Antimicrobial agents are the most valuable means available for treating bacterial infections. However, the administration of therapeutic doses of antimicrobial agents to patients is a leading cause of disturbance of the normal gastrointestinal microflora. This disturbance results in diminishing the natural defense mechanisms provided by the c...

  13. 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.

  14. Speciation in Metal Toxicity and Metal-Based Therapeutics

    Directory of Open Access Journals (Sweden)

    Douglas M. Templeton

    2015-04-01

    Full Text Available Metallic elements, ions and compounds produce varying degrees of toxicity in organisms with which they come into contact. Metal speciation is critical to understanding these adverse effects; the adjectives “heavy” and “toxic” are not helpful in describing the biological properties of individual elements, but detailed chemical structures are. As a broad generalization, the metallic form of an element is inert, and the ionic salts are the species that show more significant bioavailability. Yet the salts and other chelates of a metal ion can give rise to quite different toxicities, as exemplified by a range of carcinogenic potential for various nickel species. Another important distinction comes when a metallic element is organified, increasing its lipophilicity and hence its ability to penetrate the blood brain barrier, as is seen, for example, with organic mercury and tin species. Some metallic elements, such as gold and platinum, are themselves useful therapeutic agents in some forms, while other species of the same element can be toxic, thus focusing attention on species interconversions in evaluating metal-based drugs. The therapeutic use of metal-chelating agents introduces new species of the target metal in vivo, and this can affect not only its desired detoxification, but also introduce a potential for further mechanisms of toxicity. Examples of therapeutic iron chelator species are discussed in this context, as well as the more recent aspects of development of chelation therapy for uranium exposure.

  15. Near Infrared Fluorescence Imaging in Nano-Therapeutics and Photo-Thermal Evaluation

    Science.gov (United States)

    Vats, Mukti; Mishra, Sumit Kumar; Baghini, Mahdieh Shojaei; Chauhan, Deepak S.; Srivastava, Rohit; De, Abhijit

    2017-01-01

    The unresolved and paramount challenge in bio-imaging and targeted therapy is to clearly define and demarcate the physical margins of tumor tissue. The ability to outline the healthy vital tissues to be carefully navigated with transection while an intraoperative surgery procedure is performed sets up a necessary and under-researched goal. To achieve the aforementioned objectives, there is a need to optimize design considerations in order to not only obtain an effective imaging agent but to also achieve attributes like favorable water solubility, biocompatibility, high molecular brightness, and a tissue specific targeting approach. The emergence of near infra-red fluorescence (NIRF) light for tissue scale imaging owes to the provision of highly specific images of the target organ. The special characteristics of near infra-red window such as minimal auto-fluorescence, low light scattering, and absorption of biomolecules in tissue converge to form an attractive modality for cancer imaging. Imparting molecular fluorescence as an exogenous contrast agent is the most beneficial attribute of NIRF light as a clinical imaging technology. Additionally, many such agents also display therapeutic potentials as photo-thermal agents, thus meeting the dual purpose of imaging and therapy. Here, we primarily discuss molecular imaging and therapeutic potentials of two such classes of materials, i.e., inorganic NIR dyes and metallic gold nanoparticle based materials. PMID:28452928

  16. 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.

  17. 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.

  18. 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.

  19. Development of new therapeutic methods of lung cancer through team approach study

    International Nuclear Information System (INIS)

    Park, Jong Ho; Zo, Jae Ill; Baek, Hee Jong; Jung, Jin Haeng; Lee, Jae Cheol; Ryoo, Baek Yeol; Kim, Mi Sook; Choi, Du Hwan; Park, Sun Young; Lee, Hae Young

    2000-12-01

    The aims of this study were to make the lung cancer clinics in Korea Cancer Center Hospital, and to establish new therapeutic methods of lung cancer for increasing the cure rate and survival rate of patients. Also another purpose of this study was to establish a common treatment method in our hospital. All patients who were operated in Korea Cancer Center Hospital from 1987 due to lung cancer were followed up and evaluated. And we have been studied the effect of postoperative adjuvant therapy in stage I, II, IIIA non-small cell lung cancer patients from 1989 with the phase three study form. Follow-up examinations were scheduled in these patients and interim analysis was made. Also we have been studied the effect of chemo-therapeutic agents in small cell lung cancer patients from 1997 with the phase two study form. We evaluated the results of this study. Some important results of this study were as follows. 1. The new therapeutic method (surgery + MVP chemotherapy) was superior to the standard therapeutic one in stage I Non-small cell lung cancer patients. So, we have to change the standard method of treatment in stage I NSCLC. 2. Also, this new therapeutic method made a good result in stage II NSCLC patients. And this result was reported in The Annals of Thoracic Surgery. 3. However, this new therapeutic method was not superior to the standard treatment method (surgery only) in stage IIIA NSCLC patients. So, we must develop new chemo-therapeutic agents in the future for advanced NSCLC patients. 4. In the results of the randomized phase II studies about small cell lung cancer, there was no difference in survival between Etoposide + Carboplatin + Ifosfamide + Cisplatin group and Etoposide + Carboplatin + Ifosfamide + Cisplatin + Tamoxifen group in both the limited and extended types of small cell lung cancer patients

  20. 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

  1. 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.

  2. Trends in GPCR drug discovery: new agents, targets and indications

    DEFF Research Database (Denmark)

    Hauser, Alexander Sebastian; Gloriam, David E.; Attwood, Misty M.

    2017-01-01

    current trends across molecule types, drug targets and therapeutic indications, including showing that 475 drugs (~34% of all drugs approved by the US Food and Drug Administration (FDA)) act at 108 unique GPCRs. Approximately 321 agents are currently in clinical trials, of which ~20% target 66 potentially...... are also highly represented. The 224 (56%) non-olfactory GPCRs that have not yet been explored in clinical trials have broad untapped therapeutic potential, particularly in genetic and immune system disorders. Finally, we provide an interactive online resource to analyse and infer trends in GPCR drug......G protein-coupled receptors (GPCRs) are the most intensively studied drug targets, mostly due to their substantial involvement in human pathophysiology and their pharmacological tractability. Here, we report an up-to-date analysis of all GPCR drugs and agents in clinical trials, which reveals...

  3. Therapeutic applications of histone deacetylase inhibitors in sarcoma.

    Science.gov (United States)

    Tang, Fan; Choy, Edwin; Tu, Chongqi; Hornicek, Francis; Duan, Zhenfeng

    2017-09-01

    Sarcomas are a rare group of malignant tumors originating from mesenchymal stem cells. Surgery, radiation and chemotherapy are currently the only standard treatments for sarcoma. However, their response rates to chemotherapy are quite low. Toxic side effects and multi-drug chemoresistance make treatment even more challenging. Therefore, better drugs to treat sarcomas are needed. Histone deacetylase inhibitors (HDAC inhibitors, HDACi, HDIs) are epigenetic modifying agents that can inhibit sarcoma growth in vitro and in vivo through a variety of pathways, including inducing tumor cell apoptosis, causing cell cycle arrest, impairing tumor invasion and preventing metastasis. Importantly, preclinical studies have revealed that HDIs can not only sensitize sarcomas to chemotherapy and radiotherapy, but also increase treatment responses when combined with other chemotherapeutic drugs. Several phase I and II clinical trials have been conducted to assess the efficacy of HDIs either as monotherapy or in combination with standard chemotherapeutic agents or targeted therapeutic drugs for sarcomas. Combination regimen for sarcomas appear to be more promising than monotherapy when using HDIs. This review summarizes our current understanding and therapeutic applications of HDIs in sarcomas. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Peroxisome Proliferator-Activated Receptor Ligands and Their Role in Chronic Myeloid Leukemia: Therapeutic Strategies.

    Science.gov (United States)

    Yousefi, Bahman; Samadi, Nasser; Baradaran, Behzad; Shafiei-Irannejad, Vahid; Zarghami, Nosratollah

    2016-07-01

    Imatinib therapy remains the gold standard for treatment of chronic myeloid leukemia; however, the acquired resistance to this therapeutic agent in patients has urged the scientists to devise modalities for overcoming this chemoresistance. For this purpose, initially therapeutic agents with higher tyrosine kinase activity were introduced, which had the potential for inhibiting even mutant forms of Bcr-Abl. Furthermore, coupling imatinib with peroxisome proliferator-activated receptor ligands also showed beneficial effects in chronic myeloid leukemia cell proliferation. These combination protocols inhibited cell growth and induced apoptosis as well as differentiation in chronic myeloid leukemia cell lines. In addition, peroxisome proliferator-activated receptors ligands increased imatinib uptake by upregulating the expression of human organic cation transporter 1. Taken together, peroxisome proliferator-activated receptors ligands are currently being considered as novel promising therapeutic candidates for chronic myeloid leukemia treatment, because they can synergistically enhance the efficacy of imatinib. In this article, we reviewed the potential of peroxisome proliferator-activated receptors ligands for use in chronic myeloid leukemia treatment. The mechanism of action of these therapeutics modalities are also presented in detail. © 2016 John Wiley & Sons A/S.

  5. Curcumin as a potential therapeutic candidate for Helicobacter pylori associated diseases

    Science.gov (United States)

    Sarkar, Avijit; De, Ronita; Mukhopadhyay, Asish K

    2016-01-01

    Curcumin, a yellow pigment and principal polyphenolic Curcuminoid obtained from the turmeric rhizome Curcuma longa, is commonly used as a food-coloring agent. Studies suggest that curcumin has a wide range of beneficial properties e.g., anti-inflammatory, anti-oxidant, anti-cancer, anti-proliferative, anti-fungal and anti-microbial. These pleiotropic activities prompted several research groups to elucidate the role of curcumin in Helicobacter pylori (H. pylori) infection. This is the first review with this heading where we discussed regarding the role of curcumin as an anti-H. pylori agent along with its potential in other gastrointestinal diseases. Based on several in vitro, early cell culture, animal research and few pre-clinical trials, curcumin projected as a potential therapeutic candidate against H. pylori mediated gastric pathogenesis. This review sheds light on the anti-H. pylori effects of curcumin in different models with meticulous emphasis on its anti-oxidant, anti-inflammatory and anti-carcinogenic effects as well as some critical signaling and effecter molecules. Remarkably, non-toxic molecule curcumin fulfills the characteristics for an ideal chemopreventive agent against H. pylori mediated gastric carcinogenesis but the foremost challenge is to obtain the optimum therapeutic levels of curcumin, due to its low solubility and poor bioavailability. Further, we have discussed about the possibilities for improving its efficacy and bioavailability. Lastly, we concluded with the anticipation that in near future curcumin may be used to develop a therapeutic drug against H. pylori mediated gastric ailments through improved formulation or delivery systems, facilitating its enhanced absorption and cellular uptake. PMID:26973412

  6. 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.

  7. Acinetobacter pneumonia: Is the outcome different from the pneumonias caused by other agents

    Directory of Open Access Journals (Sweden)

    Edis Ebru

    2010-01-01

    Full Text Available Background : The principal aim of the present study was to determine whether Acinetobacter spp. pneumonia differs from hospital-acquired pneumonias (HAPs caused by other agents with respect to therapeutic success and survival rate. METHODS : This study includes 140 adult patients diagnosed with HAPs caused by identified etiologic agents between March 2005 and February 2006. These patients were divided into two groups according to the agent responsible for their infection (Acinetobacter spp. [n = 63] or non-Acinetobacter spp. [n = 77]. The groups were compared in terms of risk factors, therapeutic success and six-week survival rates. Results : Previous antibiotic use and the risk of aspiration were independent factors responsible for the development of Acinetobacter spp. pneumonia. Hypoalbuminemia, steroid use and the use of a mechanical ventilator were determined to be mortality-associated independent risk factors for Acinetobacter spp. pneumonia. The clinical success rate at the end of therapy was 41.6% and, at the sixth week, the survival rate was 35% among patients in whom Acinetobacter spp. was the causative agent. Conversely, in the control group, these values were 43 and 32%, respectively ( P > 0.05. We found that the use of the appropriate antibiotics for the treatment of Acinetobacter spp. pneumonia was an important factor in survival ( P < 0.001. Conclusion : The outcomes of Acinetobacter spp. pneumonia do not differ from HAPs associated with non-Acinetobacter spp. in terms of therapeutic success and survival rates.

  8. Emerging protein targets for metal-based pharmaceutical agents : An update

    NARCIS (Netherlands)

    de Almeida, Andreia; Oliveira, Bruno L.; Correia, Joao D. G.; Soveral, Graca; Casini, Angela

    2013-01-01

    The peculiar chemical properties of metal-based drugs impart innovative pharmacological profiles to this class of therapeutic and diagnostic agents, most likely in relation to novel molecular mechanisms still poorly understood. However, inorganic drugs have been scarcely considered for medicinal

  9. Future prospects of therapeutic clinical trials in acute myeloid leukemia

    Science.gov (United States)

    Khan, Maliha; Mansoor, Armaghan-e-Rehman; Kadia, Tapan M

    2017-01-01

    Acute myeloid leukemia (AML) is a markedly heterogeneous hematological malignancy that is most commonly seen in elderly adults. The response to current therapies to AML is quite variable, and very few new drugs have been recently approved for use in AML. This review aims to discuss the issues with current trial design for AML therapies, including trial end points, patient enrollment, cost of drug discovery and patient heterogeneity. We also discuss the future directions in AML therapeutics, including intensification of conventional therapy and new drug delivery mechanisms; targeted agents, including epigenetic therapies, cell cycle regulators, hypomethylating agents and chimeric antigen receptor T-cell therapy; and detail of the possible agents that may be incorporated into the treatment of AML in the future. PMID:27771959

  10. 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

  11. Let the sun shine in: mechanisms and potential for therapeutics in skin photodamage.

    Science.gov (United States)

    Wondrak, Georg T

    2007-05-01

    Photoaging and photocarcinogenesis are the two Janus faces of skin photodamage. Reactivity-based design of prototype agents that antagonize, modulate and reverse the chemistry of skin photodamage holds promise in delivering unprecedented therapeutic benefit. In contrast to structure-based approaches that use selective ligands to target macromolecules, reactivity-based drug discovery uses chemical reagents as therapeutics to target reactive chemical species as key mediators of skin photo-oxidative stress. The following classes of reactivity-based agents for skin photoprotection can be distinguished based on their mechanism of action: direct antagonists of photo-oxidative stress (sunscreens, quenchers of photo-excited states, antioxidants, redox modulators and glycation inhibitors) and skin photo-adaptation inducers (nuclear factor erythroid 2-related factor 2 [Nrf2] activators, heat-shock response inducers and metallothionein inducers).

  12. Challenges in the development of magnetic particles for therapeutic applications.

    Science.gov (United States)

    Barry, Stephen E

    2008-09-01

    Certain iron-based particle formulations have useful magnetic properties that, when combined with low toxicity and desirable pharmacokinetics, encourage their development for therapeutic applications. This mini-review begins with background information on magnetic particle use as MRI contrast agents and the influence of material size on pharmacokinetics and tissue penetration. Therapeutic investigations, including (1) the loading of bioactive materials, (2) the use of stationary, high-gradient (HG) magnetic fields to concentrate magnetic particles in tissues or to separate material bound to the particles from the body, and (3) the application of high power alternating magnetic fields (AMF) to generate heat in magnetic particles for hyperthermic therapeutic applications are then surveyed. Attention is directed mainly to cancer treatment, as selective distribution to tumors is well-suited to particulate approaches and has been a focus of most development efforts. While magnetic particles have been explored for several decades, their use in therapeutic products remains minimal; a discussion of future directions and potential ways to better leverage magnetic properties and to integrate their use into therapeutic regimens is discussed.

  13. Mortality differences between the foreign-born and locally-born population in France (2004-2007).

    Science.gov (United States)

    Boulogne, Roxane; Jougla, Eric; Breem, Yves; Kunst, Anton E; Rey, Grégoire

    2012-04-01

    In contrast to the situation in many European countries, the mortality of immigrants in France has been little studied. The main reasons for the lack of studies are based on ethical and ideological considerations. The objective of this study is to explore mortality by country of birth in Metropolitan (i.e. 'mainland') France. Complete mortality data were used to study the relative risks of mortality of the foreign- and locally-born populations by gender, age and cause of death for the period 2004-2007 in Metropolitan France. Analyses were conducted by countries of birth grouped into geographic areas and by the Human Development Index (HDI). The differentials in mortality between foreign-born and locally-born populations were not homogeneous. The figures varied by age (higher foreign-born mortality for the young; lower mortality for migrants aged 15-64 years), gender (female migrants more frequently had higher relative mortality than men migrants), country of birth (Eastern European-born migrants had higher mortality, while those born in Morocco, Central Asia, 'other Asian countries' and America had lower mortality) and cause of death (migrant mortality was higher overall for deaths caused by infectious diseases and diabetes, and lower for violent death and neoplasm). Moreover, mortality relative risks for male, violent deaths and cancer were positively associated with country-of-birth HDI, while female mortality and infectious disease mortality were negatively associated with country-of-birth HDI. Some important caveats have to be considered because the study did not control for individuals socioeconomic position in France, or length of residence in the host country. A strong healthy migrant effect was suggested and its intensity varies with age and gender (which may reflect different reasons for migration). For some specific causes of death, a lifestyle effect seems to explain mortality differentials. The associations between HDI and mortality show that mortality

  14. 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.

  15. 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...

  16. Air travel and vector-borne disease movement.

    Science.gov (United States)

    Tatem, A J; Huang, Z; Das, A; Qi, Q; Roth, J; Qiu, Y

    2012-12-01

    Recent decades have seen substantial expansions in the global air travel network and rapid increases in traffic volumes. The effects of this are well studied in terms of the spread of directly transmitted infections, but the role of air travel in the movement of vector-borne diseases is less well understood. Increasingly however, wider reaching surveillance for vector-borne diseases and our improving abilities to map the distributions of vectors and the diseases they carry, are providing opportunities to better our understanding of the impact of increasing air travel. Here we examine global trends in the continued expansion of air transport and its impact upon epidemiology. Novel malaria and chikungunya examples are presented, detailing how geospatial data in combination with information on air traffic can be used to predict the risks of vector-borne disease importation and establishment. Finally, we describe the development of an online tool, the Vector-Borne Disease Airline Importation Risk (VBD-Air) tool, which brings together spatial data on air traffic and vector-borne disease distributions to quantify the seasonally changing risks for importation to non-endemic regions. Such a framework provides the first steps towards an ultimate goal of adaptive management based on near real time flight data and vector-borne disease surveillance.

  17. BET inhibitors in metastatic prostate cancer: therapeutic implications and rational drug combinations.

    Science.gov (United States)

    Markowski, Mark C; De Marzo, Angelo M; Antonarakis, Emmanuel S

    2017-12-01

    The bromodomain and extra-terminal (BET) family of proteins are epigenetic readers of acetylated histones regulating a vast network of protein expression across many different cancers. Therapeutic targeting of BET is an attractive area of clinical development for metastatic castration-resistant prostate cancer (mCRPC), particularly due to its putative effect on c-MYC expression and its interaction with the androgen receptor (AR). Areas covered: We speculate that a combination approach using inhibitors of BET proteins (BETi) with other targeted therapies may be required to improve the therapeutic index of BET inhibition in the management of prostate cancer. Preclinical data has identified several molecular targets that may enhance the effect of BET inhibition in the clinic. This review will summarize the known preclinical data implicating BET as an important therapeutic target in advanced prostate cancer, highlight the ongoing clinical trials targeting this protein family, and speculate on rationale combination strategies using BETi together with other agents in prostate cancer. A literature search using Pubmed was performed for this review. Expert opinion: Use of BETi in the treatment of mCRPC patients may require the addition of a second novel agent.

  18. Preparation, Surface Properties, and Therapeutic Applications of Gold Nanoparticles in Biomedicine.

    Science.gov (United States)

    Panahi, Yunes; Mohammadhosseini, Majid; Nejati-Koshki, Kazem; Abadi, Azam Jafari Najaf; Moafi, Hadi Fallah; Akbarzadeh, Abolfazl; Farshbaf, Masoud

    2017-02-01

    Gold nanoparticles (AuNPs) due to their unique properties and manifold surface functionalities have been applied in bio-nanotechnology. The application of GNPs in recent medical and biological research is very extensive. Especially it involves applications such as detection and photothermalysis of microorganisms and cancer stem cells, biosensors; optical bio-imaging and observing of cells and these nanostructures also serve as practical platforms for therapeutic agents. In this review we studied all therapeutic applications of gold nanoparticles in biomedicine, synthesis methods, and surface properties. © Georg Thieme Verlag KG Stuttgart · New York.

  19. Molecular Targets in Alzheimer’s Disease: From Pathogenesis to Therapeutics

    Directory of Open Access Journals (Sweden)

    Xuan Cheng

    2015-01-01

    Full Text Available Alzheimer’s disease (AD is characterized by progressive cognitive decline usually beginning with impairment in the ability to form recent memories. Nonavailability of definitive therapeutic strategy urges developing pharmacological targets based on cell signaling pathways. A great revival of interest in nutraceuticals and adjuvant therapy has been put forward. Tea polyphenols for their multiple health benefits have also attracted the attention of researchers. Tea catechins showed enough potentiality to be used in future as therapeutic targets to provide neuroprotection against AD. This review attempts to present a concise map of different receptor signaling pathways associated with AD with an insight into drug designing based on the proposed signaling pathways, molecular mechanistic details of AD pathogenesis, and a scientific rationale for using tea polyphenols as proposed therapeutic agents in AD.

  20. Decorporation of metal ions by chelating agents

    International Nuclear Information System (INIS)

    Koenig, T.

    1978-01-01

    Simple model designs to simulate the effect of therapeutical chelating agents on the behaviour of metals in mammal organisms with and without excretion have been derived and analytical solutions given for the corresponding differential equations. The possibilities of these models in the short-term description of plasma kinetics of various metals, the competition of the therapeutical ligands with proteins for the metal and of the metabolism of chelating agents were tested and the properties applying extreme conceivable parameters were analyzed. The simple models were successsively expanded in logical sequence, so that it was possible to qualitatively well describe over a long period of time, the metallic kinetics in plasma, organs and urine, the retention of the ligands and their effect on the metal excretion. Two suggestions were given to describe the so-called after-effect, an increased excretion of the metal at times when the ligand is almost completely excreted and their different behaviour after injecting the metal chelate is given. Calculations on the therapy with several ligand data as well as on dose fractionation are described resting on the ratios in the plutonium-239 chosen model parameters and the determining mechanisms analyzed. (orig./MG) [de

  1. Molecular Characterization of Gastric Carcinoma: Therapeutic Implications for Biomarkers and Targets

    Directory of Open Access Journals (Sweden)

    Lionel Kankeu Fonkoua

    2018-03-01

    Full Text Available Palliative chemotherapy is the mainstay of treatment of advanced gastric carcinoma (GC. Monoclonal antibodies including trastuzumab, ramucirumab, and pembrolizumab have been shown to provide additional benefits. However, the clinical outcomes are often unpredictable and they can vary widely among patients. Currently, no biomarker is available for predicting treatment response in the individual patient except human epidermal growth factor receptor 2 (HER2 amplification and programmed death-ligand 1 (PD-L1 expression for effectiveness of trastuzumab and pembrolizumab, respectively. Multi-platform molecular analysis of cancer, including GC, may help identify predictive biomarkers to guide selection of therapeutic agents. Molecular classification of GC by The Cancer Genome Atlas Research Network and the Asian Cancer Research Group is expected to identify therapeutic targets and predictive biomarkers. Complementary to molecular characterization of GC is molecular profiling by expression analysis and genomic sequencing of tumor DNA. Initial analysis of patients with gastroesophageal carcinoma demonstrates that the ratio of progression-free survival (PFS on molecular profile (MP-based treatment to PFS on treatment prior to molecular profiling exceeds 1.3, suggesting the potential value of MP in guiding selection of individualized therapy. Future strategies aiming to integrate molecular classification and profiling of tumors with therapeutic agents for achieving the goal of personalized treatment of GC are indicated.

  2. Molecular Characterization of Gastric Carcinoma: Therapeutic Implications for Biomarkers and Targets.

    Science.gov (United States)

    Kankeu Fonkoua, Lionel; Yee, Nelson S

    2018-03-09

    Palliative chemotherapy is the mainstay of treatment of advanced gastric carcinoma (GC). Monoclonal antibodies including trastuzumab, ramucirumab, and pembrolizumab have been shown to provide additional benefits. However, the clinical outcomes are often unpredictable and they can vary widely among patients. Currently, no biomarker is available for predicting treatment response in the individual patient except human epidermal growth factor receptor 2 (HER2) amplification and programmed death-ligand 1 (PD-L1) expression for effectiveness of trastuzumab and pembrolizumab, respectively. Multi-platform molecular analysis of cancer, including GC, may help identify predictive biomarkers to guide selection of therapeutic agents. Molecular classification of GC by The Cancer Genome Atlas Research Network and the Asian Cancer Research Group is expected to identify therapeutic targets and predictive biomarkers. Complementary to molecular characterization of GC is molecular profiling by expression analysis and genomic sequencing of tumor DNA. Initial analysis of patients with gastroesophageal carcinoma demonstrates that the ratio of progression-free survival (PFS) on molecular profile (MP)-based treatment to PFS on treatment prior to molecular profiling exceeds 1.3, suggesting the potential value of MP in guiding selection of individualized therapy. Future strategies aiming to integrate molecular classification and profiling of tumors with therapeutic agents for achieving the goal of personalized treatment of GC are indicated.

  3. [Knowledge of vector-borne diseases (dengue, rickettsiosis and Chagas disease) in physicians].

    Science.gov (United States)

    Lugo-Caballero, César I; Dzul-Rosado, Karla; Dzul-Tut, Irving; Balam-May, Ángel; Zavala-Castro, Jorge

    2017-01-01

    The ecological conditions of Yucatan made it a suitable region for the acquisition of vector-borne diseases such as dengue, rickettsiosis, and Chagas disease. As the epidemiological burden of these diseases shows an alarming increase of severe cases, the early establishment of diagnosis and therapeutics by first-contact physicians is a critical step that is not being fulfilled due to several reasons, including poor knowledge. To determine the level of knowledge related to dengue, Chagas disease, and rickettsiosis among rural first-contact physicians of Yucatan. A survey was applied to 90 first-contact physicians from rural clinics of Yucatan, which included 32 items related to the diagnosis, treatment, and prevention of dengue, rickettsiosis, and Chagas disease. Answers were analyzed by central tendency statistics. Differences were observed among every category, however; diagnosis and therapeutics showed the lower values. Globally, 62.5% of respondents showed moderate knowledge, 37.5% poor knowledge, and 0% adequate knowledge. Results suggest that a strong campaign for a continuous diffusion of knowledge regarding these diseases is needed. In regions with high prevalence of these kinds of diseases, like Yucatan, the impact of these results on the epidemiological burden of these diseases must be evaluated.

  4. Using geographical information systems to explore disparities in preterm birth rates among foreign-born and U.S.-born Black mothers.

    Science.gov (United States)

    Bloch, Joan Rosen

    2011-01-01

    To examine spatial patterns of neighborhood contextual factors of stress with preterm birth (PTB) and nativity (foreign-born and U.S.-born) among Black mothers. Descriptive geographic-spatial research. Births to Philadelphia residents during 2003-2005 in the context of Philadelphia residential neighborhoods (N = 350) were studied. All data were aggregated to neighborhood levels (census tracts). Maps were created to assess geographic-spatial patterns. A geographic information system (GIS) database was created that imported geo-coded data on births, crime (assaults with guns and domestic abuse), poverty, race, and nativity (foreign-born vs. U.S.-born). Clear visual patterns of "bad" neighborhoods emerged and were significantly associated with higher prevalence of PTB for foreign-born Black and U.S.-born Black mothers (p < .0001). This study demonstrated how GIS visually clarified important spatial patterns of adverse living conditions and PTB prevalence. Nurses can use GIS to better understand living environments of mothers and their families and to target interventions in geographical areas with the greatest service needs. Further research on individual and contextual factors is warranted to address the observed health disparities among the heterogeneous groups of foreign-born Black mothers. Despite limitations of aggregate data, it is clear that where mothers live matters. This has important implications for nursing practice and policy. © 2011 AWHONN, the Association of Women's Health, Obstetric and Neonatal Nurses.

  5. Using Geographical Information Systems to Explore Disparities in Preterm Birth Rates Among Foreign-born and U.S.-born Black Mothers

    Science.gov (United States)

    Bloch, Joan Rosen

    2012-01-01

    Objective To examine spatial patterns of neighborhood contextual factors of stress with preterm birth (PTB) and nativity (foreign-born and U.S.-born) among Black mothers. Design Descriptive geographic-spatial research. Setting & Participants Births to Philadelphia residents during 2003–2005 in the context of Philadelphia residential neighborhoods (N = 350) were studied. Methods All data were aggregated to neighborhood levels (census tracts). Maps were created to assess geographic-spatial patterns. A geographic information system (GIS) database was created that imported geo-coded data on births, crime (assaults with guns and domestic abuse), poverty, race, and nativity (foreign-born vs. U.S.-born). Results Clear visual patterns of “bad” neighborhoods emerged and were significantly associated with higher prevalence of PTB for foreign-born Black and U.S.-born Black mothers (p GIS visually clarified important spatial patterns of adverse living conditions and PTB prevalence. Nurses can use GIS to better understand living environments of mothers and their families and to target interventions in geographical areas with the greatest service needs. Further research on individual and contextual factors is warranted to address the observed health disparities among the heterogeneous groups of foreign-born Black mothers. Despite limitations of aggregate data, it is clear that where mothers live matters. This has important implications for nursing practice and policy. PMID:22273411

  6. Curcumin as potential therapeutic natural product: a nanobiotechnological perspective.

    Science.gov (United States)

    Shome, Soumitra; Talukdar, Anupam Das; Choudhury, Manabendra Dutta; Bhattacharya, Mrinal Kanti; Upadhyaya, Hrishikesh

    2016-12-01

    Nanotechnology-based drug delivery systems can resolve the poor bioavailability issue allied with curcumin. The therapeutic potential of curcumin can be enhanced by making nanocomposite preparation of curcumin with metal oxide nanoparticles, poly lactic-co-glycolic acid (PLGA) nanoparticles and solid lipid nanoparticles that increases its bioavailability in the tissue. Curcumin has manifold therapeutic effects which include antidiabetic, antihypertensive, anticancer, anti-inflammatory and antimicrobial properties. Curcumin can inhibit diabetes, heavy metal and stress-induced hypertension with its antioxidant, chelating and inhibitory effects on the pathways that lead to hypertension. Curcumin is an anticancer agent that can prevent abnormal cell proliferation. Nanocurcumin is an improved form of curcumin with enhanced therapeutic properties due to improved delivery to the diseased tissue, better internalization and reduced systemic elimination. Curcumin has multiple pharmacologic effects, but its poor bioavailability reduces its therapeutic effects. By conjugating curcumin to metal oxide nanoparticles or encapsulation in lipid nanoparticles, dendrimers, nanogels and polymeric nanoparticles, the water solubility and bioavailability of curcumin can be improved and thus increase its pharmacological effectiveness. © 2016 Royal Pharmaceutical Society.

  7. Tools for predicting the PK/PD of therapeutic proteins.

    Science.gov (United States)

    Diao, Lei; Meibohm, Bernd

    2015-07-01

    Assessments of the pharmacokinetic/pharmacodynamic (PK/PD) characteristics are an integral part in the development of novel therapeutic agents. Compared with traditional small molecule drugs, therapeutic proteins possess many distinct PK/PD features that necessitate the application of modified or separate approaches for assessing their PK/PD relationships. In this review, the authors discuss tools that are utilized to describe and predict the PK/PD features of therapeutic proteins and that are valuable additions in the armamentarium of drug development approaches to facilitate and accelerate their successful preclinical and clinical development. A variety of state-of-the-art PK/PD tools is currently being applied and has been adjusted to support the development of proteins as therapeutics, including allometric scaling approaches, target-mediated disposition models, first-in-man dose calculations, physiologically based PK models and empirical and semi-mechanistic PK/PD modeling. With the advent of the next generation of biologics including bioengineered antibody constructs being developed, these tools will need to be further refined and adapted to ensure their applicability and successful facilitation of the drug development process for these novel scaffolds.

  8. 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.

  9. 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

  10. Prevalence of acid-reducing agents (ARA) in cancer populations and ARA drug-drug interaction potential for molecular targeted agents in clinical development.

    Science.gov (United States)

    Smelick, Gillian S; Heffron, Timothy P; Chu, Laura; Dean, Brian; West, David A; Duvall, Scott L; Lum, Bert L; Budha, Nageshwar; Holden, Scott N; Benet, Leslie Z; Frymoyer, Adam; Dresser, Mark J; Ware, Joseph A

    2013-11-04

    Acid-reducing agents (ARAs) are the most commonly prescribed medications in North America and Western Europe. There are currently no data describing the prevalence of their use among cancer patients. However, this is a paramount question due to the potential for significant drug-drug interactions (DDIs) between ARAs, most commonly proton pump inhibitors (PPIs), and orally administered cancer therapeutics that display pH-dependent solubility, which may lead to decreased drug absorption and decreased therapeutic benefit. Of recently approved orally administered cancer therapeutics, >50% are characterized as having pH-dependent solubility, but there are currently no data describing the potential for this ARA-DDI liability among targeted agents currently in clinical development. The objectives of this study were to (1) determine the prevalence of ARA use among different cancer populations and (2) investigate the prevalence of orally administered cancer therapeutics currently in development that may be liable for an ARA-DDI. To address the question of ARA use among cancer patients, a retrospective cross-sectional analysis was performed using two large healthcare databases: Thomson Reuters MarketScan (N = 1,776,443) and the U.S. Department of Veterans Affairs (VA, N = 1,171,833). Among all cancer patients, the total prevalence proportion of ARA use (no. of cancer patients receiving an ARA/total no. of cancer patients) was 20% and 33% for the MarketScan and VA databases, respectively. PPIs were the most commonly prescribed agent, comprising 79% and 65% of all cancer patients receiving a prescription for an ARA (no. of cancer patients receiving a PPI /no. of cancer patients receiving an ARA) for the MarketScan and VA databases, respectively. To estimate the ARA-DDI liability of orally administered molecular targeted cancer therapeutics currently in development, two publicly available databases, (1) Kinase SARfari and (2) canSAR, were examined. For those orally administered

  11. Intestinal parasites and vector-borne pathogens in stray and free-roaming cats living in continental and insular Greece

    Science.gov (United States)

    Diakou, Anastasia; Di Cesare, Angela; Accettura, Paolo Matteo; Barros, Luciano; Iorio, Raffaella; Paoletti, Barbara; Frangipane di Regalbono, Antonio; Halos, Lénaïg; Beugnet, Frederic; Traversa, Donato

    2017-01-01

    This survey investigated the distribution of various intestinal parasites and vector-borne pathogens in stray and free-roaming cats living in four regions of Greece. A total number of one hundred and fifty cats living in three Islands (Crete, Mykonos and Skopelos) and in Athens municipality was established as a realistic aim to be accomplished in the study areas. All cats were examined with different microscopic, serological and molecular assays aiming at evaluating the occurrence of intestinal parasites, and exposure to or presence of vector-borne infections. A total of 135 cats (90%) was positive for one or more parasites and/or pathogens transmitted by ectoparasites. Forty-four (29.3%) cats were positive for one single infection, while 91 (60.7%) for more than one pathogen. A high number of (n. 53) multiple infections caused by feline intestinal and vector-borne agents including at least one zoonotic pathogen was detected. Among them, the most frequently recorded helminths were roundworms (Toxocara cati, 24%) and Dipylidium caninum (2%), while a high number of examined animals (58.8%) had seroreaction for Bartonella spp., followed by Rickettsia spp. (43.2%) and Leishmania infantum (6.1%). DNA-based assays revealed the zoonotic arthropod-borne organisms Bartonella henselae, Bartonella clarridgeiae, Rickettsia spp., and L. infantum. These results show that free-ranging cats living in areas of Greece under examination may be exposed to a plethora of internal parasites and vector-borne pathogens, some of them potentially able to infect humans. Therefore, epidemiological vigilance and appropriate control measures are crucial for the prevention and control of these infections and to minimize the risk of infection for people. PMID:28141857

  12. Intestinal parasites and vector-borne pathogens in stray and free-roaming cats living in continental and insular Greece.

    Directory of Open Access Journals (Sweden)

    Anastasia Diakou

    2017-01-01

    Full Text Available This survey investigated the distribution of various intestinal parasites and vector-borne pathogens in stray and free-roaming cats living in four regions of Greece. A total number of one hundred and fifty cats living in three Islands (Crete, Mykonos and Skopelos and in Athens municipality was established as a realistic aim to be accomplished in the study areas. All cats were examined with different microscopic, serological and molecular assays aiming at evaluating the occurrence of intestinal parasites, and exposure to or presence of vector-borne infections. A total of 135 cats (90% was positive for one or more parasites and/or pathogens transmitted by ectoparasites. Forty-four (29.3% cats were positive for one single infection, while 91 (60.7% for more than one pathogen. A high number of (n. 53 multiple infections caused by feline intestinal and vector-borne agents including at least one zoonotic pathogen was detected. Among them, the most frequently recorded helminths were roundworms (Toxocara cati, 24% and Dipylidium caninum (2%, while a high number of examined animals (58.8% had seroreaction for Bartonella spp., followed by Rickettsia spp. (43.2% and Leishmania infantum (6.1%. DNA-based assays revealed the zoonotic arthropod-borne organisms Bartonella henselae, Bartonella clarridgeiae, Rickettsia spp., and L. infantum. These results show that free-ranging cats living in areas of Greece under examination may be exposed to a plethora of internal parasites and vector-borne pathogens, some of them potentially able to infect humans. Therefore, epidemiological vigilance and appropriate control measures are crucial for the prevention and control of these infections and to minimize the risk of infection for people.

  13. Intestinal parasites and vector-borne pathogens in stray and free-roaming cats living in continental and insular Greece.

    Science.gov (United States)

    Diakou, Anastasia; Di Cesare, Angela; Accettura, Paolo Matteo; Barros, Luciano; Iorio, Raffaella; Paoletti, Barbara; Frangipane di Regalbono, Antonio; Halos, Lénaïg; Beugnet, Frederic; Traversa, Donato

    2017-01-01

    This survey investigated the distribution of various intestinal parasites and vector-borne pathogens in stray and free-roaming cats living in four regions of Greece. A total number of one hundred and fifty cats living in three Islands (Crete, Mykonos and Skopelos) and in Athens municipality was established as a realistic aim to be accomplished in the study areas. All cats were examined with different microscopic, serological and molecular assays aiming at evaluating the occurrence of intestinal parasites, and exposure to or presence of vector-borne infections. A total of 135 cats (90%) was positive for one or more parasites and/or pathogens transmitted by ectoparasites. Forty-four (29.3%) cats were positive for one single infection, while 91 (60.7%) for more than one pathogen. A high number of (n. 53) multiple infections caused by feline intestinal and vector-borne agents including at least one zoonotic pathogen was detected. Among them, the most frequently recorded helminths were roundworms (Toxocara cati, 24%) and Dipylidium caninum (2%), while a high number of examined animals (58.8%) had seroreaction for Bartonella spp., followed by Rickettsia spp. (43.2%) and Leishmania infantum (6.1%). DNA-based assays revealed the zoonotic arthropod-borne organisms Bartonella henselae, Bartonella clarridgeiae, Rickettsia spp., and L. infantum. These results show that free-ranging cats living in areas of Greece under examination may be exposed to a plethora of internal parasites and vector-borne pathogens, some of them potentially able to infect humans. Therefore, epidemiological vigilance and appropriate control measures are crucial for the prevention and control of these infections and to minimize the risk of infection for people.

  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. HIV and sexual health knowledge and sexual experience among Australian-born and overseas-born students in Sydney.

    Science.gov (United States)

    Song, Angela; Richters, Juliet; Crawford, June; Kippax, Sue

    2005-09-01

    To examine differences between Australian-born and Asian-born first-year university students in Sydney in their sexual behavior and knowledge about the prevention and transmission of human immunodeficiency virus (HIV) and other sexually transmissible infections (STIs). Students were recruited from a stall during the student Orientation Week in both 2002 and 2003 at the University of New South Wales. A short questionnaire was completed and returned anonymously. Data on age, gender, country of birth, sexual behavior, and sexual health knowledge were collected. A score was calculated based on the sum of the correct answers given to 12 HIV/STI transmission and prevention questions. The students were then divided into three groups according to their country of birth (Australia, Asia, and elsewhere) and their knowledge scores were compared. Students born in certain Asian countries were also asked their perception of the HIV epidemic in their home country compared with Australia. A total of 1185 first-year students completed the questionnaire. Although older on average, Asian-born students were less likely to have had sexual intercourse and had had fewer sexual partners. They also had consistently poorer HIV/STI knowledge scores than Australian-born students. Students born in China, Hong Kong, Indonesia, Malaysia, and Singapore but not Thailand underestimated the prevalence of HIV in their country of birth in comparison with Australia. The combination of poorer knowledge, apparent misconception of the extent of HIV epidemic in their home country (or Australia), and potential later frequent travel indicates a potential risk for later transmission of HIV/STIs. The university is an underused setting for prevention health education.

  17. Discriminating between absorption and scattering coefficients in optical characterisation measurements on gold nanoparticle based photoacoustic contrast agents

    NARCIS (Netherlands)

    Ungureanu, C.; Manohar, Srirang; van Leeuwen, Ton; Amelink, A.; Sterenborg, Henricus J.C.M.; Oraevsky, Alexander A.; Wang, Lihong V.

    2009-01-01

    Plasmon resonant nanoparticles such as gold nanoshells and gold nanorods can be tuned to possess sharp interaction peaks in the near-infrared wavelength regions. These have great importance as contrast agents in photoacoustic imaging and as photothermal agents for therapeutic applications due to

  18. 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

  19. 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-.

  20. Usefulness of radiatively obtained acrylamide polymers for production of drug forms with controlled release of the therapeutic component

    International Nuclear Information System (INIS)

    Mosiniak, T.; Switek, W.

    1988-01-01

    Using 60 Co gamma radiation as a factor initiating polymerization and cross-linking of polymers, polyacrylamide matrices were formed with the following therapeutic agents: aspirin, amidopyrin, sodium salicylate. Gamma radiation doses ranged from 3.5 to 22.5 kGy, dose rate was 0.138 Gy x s -1 . Kinetics of the therapeutic agent release from the matrix polymers was determined by measurement of per cent of the drug release in the course of time and calculations of release rate constants. The preparations containing slowly released drugs were obtained. 12 figs., 2 tabs., 11 refs. (author)

  1. Emerging Vector-Borne Diseases - Incidence through Vectors.

    Science.gov (United States)

    Savić, Sara; Vidić, Branka; Grgić, Zivoslav; Potkonjak, Aleksandar; Spasojevic, Ljubica

    2014-01-01

    Vector-borne diseases use to be a major public health concern only in tropical and subtropical areas, but today they are an emerging threat for the continental and developed countries also. Nowadays, in intercontinental countries, there is a struggle with emerging diseases, which have found their way to appear through vectors. Vector-borne zoonotic diseases occur when vectors, animal hosts, climate conditions, pathogens, and susceptible human population exist at the same time, at the same place. Global climate change is predicted to lead to an increase in vector-borne infectious diseases and disease outbreaks. It could affect the range and population of pathogens, host and vectors, transmission season, etc. Reliable surveillance for diseases that are most likely to emerge is required. Canine vector-borne diseases represent a complex group of diseases including anaplasmosis, babesiosis, bartonellosis, borreliosis, dirofilariosis, ehrlichiosis, and leishmaniosis. Some of these diseases cause serious clinical symptoms in dogs and some of them have a zoonotic potential with an effect to public health. It is expected from veterinarians in coordination with medical doctors to play a fundamental role at primarily prevention and then treatment of vector-borne diseases in dogs. The One Health concept has to be integrated into the struggle against emerging diseases. During a 4-year period, from 2009 to 2013, a total number of 551 dog samples were analyzed for vector-borne diseases (borreliosis, babesiosis, ehrlichiosis, anaplasmosis, dirofilariosis, and leishmaniasis) in routine laboratory work. The analysis was done by serological tests - ELISA for borreliosis, dirofilariosis, and leishmaniasis, modified Knott test for dirofilariosis, and blood smear for babesiosis, ehrlichiosis, and anaplasmosis. This number of samples represented 75% of total number of samples that were sent for analysis for different diseases in dogs. Annually, on average more then half of the samples

  2. HIV Transmission Dynamics Among Foreign-Born Persons in the United States.

    Science.gov (United States)

    Valverde, Eduardo E; Oster, Alexandra M; Xu, Songli; Wertheim, Joel O; Hernandez, Angela L

    2017-12-15

    In the United States (US), foreign-born persons are disproportionately affected by HIV and differ epidemiologically from US-born persons with diagnosed HIV infection. Understanding HIV transmission dynamics among foreign-born persons is important to guide HIV prevention efforts for these populations. We conducted molecular transmission network analysis to describe HIV transmission dynamics among foreign-born persons with diagnosed HIV. Using HIV-1 polymerase nucleotide sequences reported to the US National HIV Surveillance System for persons with diagnosed HIV infection during 2001-2013, we constructed a genetic distance-based transmission network using HIV-TRACE and examined the birth region of potential transmission partners in this network. Of 77,686 people, 12,064 (16%) were foreign born. Overall, 28% of foreign-born persons linked to at least one other person in the transmission network. Of potential transmission partners, 62% were born in the United States, 31% were born in the same region as the foreign-born person, and 7% were born in another region of the world. Most transmission partners of male foreign-born persons (63%) were born in the United States, whereas most transmission partners of female foreign-borns (57%) were born in their same world region. These finding suggests that a majority of HIV infections among foreign-born persons in our network occurred after immigrating to the United States. Efforts to prevent HIV infection among foreign-born persons in the United States should include information of the transmission networks in which these individuals acquire or transmit HIV to develop more targeted HIV prevention interventions.

  3. Antibody-Based Agents in the Management of Antibiotic-Resistant Staphylococcus aureus Diseases

    Science.gov (United States)

    Speziale, Pietro; Rindi, Simonetta

    2018-01-01

    Staphylococcus aureus is a human pathogen that can cause a wide spectrum of diseases, including sepsis, pneumonia, arthritis, and endocarditis. Ineffective treatment of a number of staphylococcal infections with antibiotics is due to the development and spread of antibiotic-resistant strains following decades of antibiotic usage. This has generated renewed interest within the scientific community in alternative therapeutic agents, such as anti-S. aureus antibodies. Although the role of antibodies in the management of S. aureus diseases is controversial, the success of this pathogen in neutralizing humoral immunity clearly indicates that antibodies offer the host extensive protection. In this review, we report an update on efforts to develop antibody-based agents, particularly monoclonal antibodies, and their therapeutic potential in the passive immunization approach to the treatment and prevention of S. aureus infections. PMID:29533985

  4. 3D culture of Her2+ breast cancer cells promotes AKT to MAPK switching and a loss of therapeutic response.

    Science.gov (United States)

    Gangadhara, Sharath; Smith, Chris; Barrett-Lee, Peter; Hiscox, Stephen

    2016-06-01

    The Her2 receptor is overexpressed in up to 25 % of breast cancers and is associated with a poor prognosis. Around half of Her2+ breast cancers also express the estrogen receptor and treatment for such tumours can involve both endocrine and Her2-targeted therapies. However, despite preclinical data supporting the effectiveness of these agents, responses can vary widely in the clinical setting. In light of the increasing evidence pointing to the interplay between the tumour and its extracellular microenvironment as a significant determinant of therapeutic sensitivity and response here we investigated the impact of 3D matrix culture of breast cancer cells on their therapeutic sensitivity. A 3D Matrigel-based culture system was established and optimized for the growth of ER+/Her2+ breast cancer cell models. Growth of cells in response to trastuzumab and endocrine agents in 3D culture versus routine monolayer culture were assessed using cell counting and Ki67 staining. Endogenous and trastuzumab-modulated signalling pathway activity in 2D and 3D cultures were assessed using Western blotting. Breast cancer cells in 3D culture displayed an attenuated response to both endocrine agents and trastuzumab compared with cells cultured in traditional 2D monolayers. Underlying this phenomenon was an apparent matrix-induced shift from AKT to MAPK signalling; consequently, suppression of MAPK in 3D cultures restores therapeutic response. These data suggest that breast cancer cells in 3D culture display a reduced sensitivity to therapeutic agents which may be mediated by internal MAPK-mediated signalling. Targeting of adaptive pathways that maintain growth in 3D culture may represent an effective strategy to improve therapeutic response clinically.

  5. 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.

  6. Old and new challenges in Parkinson's disease therapeutics.

    Science.gov (United States)

    Pires, Ana O; Teixeira, F G; Mendes-Pinheiro, B; Serra, Sofia C; Sousa, Nuno; Salgado, António J

    2017-09-01

    Parkinson's disease (PD) is a neurodegenerative disorder characterized by the degeneration of dopaminergic neurons and/or loss od neuronal projections, in several dopaminergic networks. Current treatments for idiopathic PD rely mainly on the use of pharmacologic agents to improve motor symptomatology of PD patients. Nevertheless, so far PD remains an incurable disease. Therefore, it is of utmost importance to establish new therapeutic strategies for PD treatment. Over the last 20 years, several molecular, gene and cell/stem-cell therapeutic approaches have been developed with the aim of counteracting or retarding PD progression. The scope of this review is to provide an overview of PD related therapies and major breakthroughs achieved within this field. In order to do so, this review will start by focusing on PD characterization and current treatment options covering thereafter molecular, gene and cell/stem cell-based therapies that are currently being studied in animal models of PD or have recently been tested in clinical trials. Among stem cell-based therapies, those using MSCs as possible disease modifying agents for PD therapy and, specifically, the MSCs secretome contribution to meet the clinical challenge of counteracting or retarding PD progression, will be more deeply explored. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Interactions of radiation with novel chemotherapeutic agents: Taxanes and nucleoside analogs

    International Nuclear Information System (INIS)

    Milas, Luka

    1997-01-01

    The combination of chemotherapeutic agents and radiotherapy is an appealing approach to improving the results of cancer treatment. By their independent action or interactive action chemotherapeutic drugs reduce cell burden in tumors undergoing radiotherapy, thereby increasing the chances of tumor control. In addition, the drugs may spatially cooperate with radiotherapy through their systemic action on metastatic disease. Recently, a number of new chemotherapeutic agents have been introduced for cancer treatment, which in addition have high potential to increase therapeutic ratio of radiotherapy. These agents include taxanes (paclitaxel and docetaxel) and the nucleoside analogs fludarabine and gemcitabine. Paclitaxel is a natural product isolated from the bark of Taxus brevifolia and taxotere is a semisynthetic analogue of paclitaxel prepared from needle extracts of Taxus baccata. By binding to cellular tubulin structures, taxanes interfere with tubulin polymerization and promote microtubule assembly, resulting in accumulation of cells in the radiosensitive G2 and M phases of the cell cycle. In vivo studies have demonstrated two major mechanisms of tumor radioenhancement by taxanes: mitotic arrest and tumor reoxygenation. Fludarabine and gemcitabine inhibit DNA synthesis and the repair of radiation-induced chromosome breaks. The mechanism of their radioenhancing activity include inhibition of repair of radiation induced damage, apoptosis induction and cell cycle synchronization. Because both classes of these agents affect radioresponse of normal dose-limiting tissues much less than that of tumors, they can greatly increase therapeutic ratio of radiotherapy. The objective of this course is to overview the rationale for using these drugs as radioenhancing agents, the experimental findings in preclinical studies, the mechanisms of their interaction, and the clinical application of these agents

  8. Report on the Technical Meeting on Therapeutic Radiopharmaceuticals

    International Nuclear Information System (INIS)

    2009-01-01

    The purpose of the TM was to provide an experts' platform to facilitate exploring the current status and future directions on therapeutic radiopharmaceuticals. The invited talks and presentations in the TM were in the following topics: - Radionuclide Production; - Production and availability of alpha emitters and their radiopharmaceuticals; - Therapeutic radiopharmaceutical chemistry; - Targets and biological evaluation; - Medical physics and dosimetry; - Clinical applications including radioimmunotherapy and clinical needs; - Peptide receptor mediated therapy Panel discussions: - Radionuclide therapy using alpha emitters; - Regulatory challenges with therapeutic radiopharmaceuticals; - International activities in radionuclide therapy. he technical meeting generated a large interest among scientists and physicians working in the field of targeted therapy using radiopharmaceuticals. Participants from both developed and developing MS reported on recent developments on the research work and clinical studies going on in the field and provided their views on the future developments in this field. The unexpected high number of participants and the high number of presentations with exceptional quality underlines the great interest of scientists and professionals in therapeutic applications using radiolabelled drugs / biomolecules. The intensive discussions including panels specified the challenges in the future on developing novel agents and to finally use them for the benefit of patients. The IAEA can play as vital role in streamlining developments and to provide tools to overcome scientific, professional and regulatory challenges in the field of therapeutic radiopharmaceuticals

  9. Report on the Technical Meeting on Therapeutic Radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2009-07-01

    The purpose of the TM was to provide an experts' platform to facilitate exploring the current status and future directions on therapeutic radiopharmaceuticals. The invited talks and presentations in the TM were in the following topics: - Radionuclide Production; - Production and availability of alpha emitters and their radiopharmaceuticals; - Therapeutic radiopharmaceutical chemistry; - Targets and biological evaluation; - Medical physics and dosimetry; - Clinical applications including radioimmunotherapy and clinical needs; - Peptide receptor mediated therapy Panel discussions: - Radionuclide therapy using alpha emitters; - Regulatory challenges with therapeutic radiopharmaceuticals; - International activities in radionuclide therapy. he technical meeting generated a large interest among scientists and physicians working in the field of targeted therapy using radiopharmaceuticals. Participants from both developed and developing MS reported on recent developments on the research work and clinical studies going on in the field and provided their views on the future developments in this field. The unexpected high number of participants and the high number of presentations with exceptional quality underlines the great interest of scientists and professionals in therapeutic applications using radiolabelled drugs / biomolecules. The intensive discussions including panels specified the challenges in the future on developing novel agents and to finally use them for the benefit of patients. The IAEA can play as vital role in streamlining developments and to provide tools to overcome scientific, professional and regulatory challenges in the field of therapeutic radiopharmaceuticals

  10. Allostatic load in foreign-born and US-born blacks: evidence from the 2001-2010 National Health and Nutrition Examination Survey.

    Science.gov (United States)

    Doamekpor, Lauren A; Dinwiddie, Gniesha Y

    2015-03-01

    We tested whether the immigrant health advantage applies to non-Hispanic Black immigrants and examined whether nativity-based differences in allostatic load exist among non-Hispanic Blacks. We used pooled data from the 2001-2010 National Health and Nutrition Examination Survey to compare allostatic load scores for US-born (n = 2745) and foreign-born (n = 152) Black adults. We used multivariate logistic regression techniques to assess the association between nativity and high allostatic load scores, controlling for gender, age, health behaviors, and socioeconomic status. For foreign-born Blacks, length of stay and age were powerful predictors of allostatic load scores. For older US-born Blacks and those who were widowed, divorced, or separated, the risk of high allostatic load was greater. Foreign-born Blacks have a health advantage in allostatic load. Further research is needed that underscores a deeper understanding of the mechanisms driving this health differential to create programs that target these populations differently.

  11. Biomedicines—Moving Biologic Agents into Approved Treatment Options

    Directory of Open Access Journals (Sweden)

    Kenneth Cornetta

    2013-03-01

    Full Text Available The development of biologic agents for therapeutic purposes, or biomedicines, has seen an active area of research both at the bench and in clinical trials. There is mounting evidence that biologic products can provide effective therapy for diseases that have been unresponsive to traditional pharmacologic approaches. Monoclonal antibody therapy for cancer and rheumatologic diseases has become a well accepted part of disease treatment plans. Gene therapy products have been approved in China and Europe. Bioengineering of new agents capitalizing on microRNA biology, nanoparticle technology, stem cell biology, and an increasing understanding of immunology predict a rich future for product development. [...

  12. 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.

  13. Quercetin in Cancer Treatment, Alone or in Combination with Conventional Therapeutics?

    Science.gov (United States)

    Brito, Ana Filipa; Ribeiro, Marina; Abrantes, Ana Margarida; Pires, Ana Salomé; Teixo, Ricardo Jorge; Tralhão, José Guilherme; Botelho, Maria Filomena

    2015-01-01

    Cancer is a problem of global importance, since the incidence is increasing worldwide and therapeutic options are generally limited. Thus, it becomes imperative to find new therapeutic targets as well as new molecules with therapeutic potential for tumors. Flavonoids are polyphenolic compounds that may be potential therapeutic agents. Several studies have shown that these compounds have a higher anticancer potential. Among the flavonoids in the human diet, quercetin is one of the most important. In the last decades, several anticancer properties of quercetin have been described, such as cell signaling, pro-apoptotic, anti-proliferative and anti-oxidant effects, growth suppression. In fact, it is now well known that quercetin has diverse biological effects, inhibiting multiple enzymes involved in cell proliferation, as well as, in signal transduction pathways. On the other hand, there are also studies reporting potential synergistic effects when combined quercetin with chemotherapeutic agents or radiotherapy. In fact, several studies which aim to explore the anticancer potential of these combined treatments have already been published, the majority with promising results. Actually it is well known that quercetin can act on the chemosensitization and radiosensitization but also as chemoprotective and radioprotective, protecting normal cells of the side effects that results from chemotherapy and radiotherapy, which obviously provides notable advantages in their use in anticancer treatment. Thus, all these data indicate that quercetin may have a key role in anticancer treatment. In this context, this review is focused on the relationship between flavonoids and cancer, with special emphasis on the role of quercetin.

  14. Degradation product characterization of therapeutic oligonucleotides using liquid chromatography mass spectrometry.

    Science.gov (United States)

    Elzahar, N M; Magdy, N; El-Kosasy, Amira M; Bartlett, Michael G

    2018-05-01

    Synthetic antisense phosphorothioate oligonucleotides (PS) have undergone rapid development as novel therapeutic agents. The increasing significance of this class of drugs requires significant investment in the development of quality control methods. The determination of the many degradation pathways of such complex molecules presents a significant challenge. However, an understanding of the potential impurities that may arise is necessary to continue to advance these powerful new therapeutics. In this study, four different antisense oligonucleotides representing several generations of oligonucleotide therapeutic agents were evaluated under various stress conditions (pH, thermal, and oxidative stress) using ion-pairing reversed-phase liquid chromatography tandem mass spectrometry (IP-RPLC-MS/MS) to provide in-depth characterization and identification of the degradation products. The oligonucleotide samples were stressed under different pH values at 45 and 90 °C. The main degradation products were observed to be losses of nucleotide moieties from the 3'- and 5'-terminus, depurination, formation of terminal phosphorothioates, and production of ribose, ribophosphorothioates (Rp), and phosphoribophosphorothioates (pRp). Moreover, the effects of different concentrations of hydrogen peroxide were studied resulting in primarily extensive desulfurization and subsequent oxidation of the phosphorothioate linkage to produce the corresponding phosphodiester. The reaction kinetics for the degradation of the oligonucleotides under the different stress conditions were studied and were found to follow pseudo-first-order kinetics. Differences in rates exist even for oligonucleotides of similar length but consisting of different sequences. Graphical abstract Identification of degradation products across several generations of oligonucleotide therapeutics using LC-MS.

  15. Quality of Cancer Care Among Foreign-Born and US-Born Patients With Lung or Colorectal Cancer

    DEFF Research Database (Denmark)

    Nielsen, Signe Smith; He, Yulei; Ayanian, John Z.

    2010-01-01

      BACKGROUND: Disparities in care have been documented for foreign-born cancer patients in the United States. However, few data are available regarding patients with lung and colorectal cancer. In the current study, the authors assessed whether patient-reported quality and receipt of recommended...... from 2003 through 2005. Logistic regression was used to assess the association between nativity and patient-reported quality of care and receipt of recommended treatments (adjuvant chemotherapy for stage III colon cancer, adjuvant chemotherapy and radiotherapy for stage II/III rectal cancer......, and curative surgery for stage I/II non-small cell lung cancer). The authors also assessed whether language explained any differences in care by nativity. RESULTS: Overall, 46% of patients reported excellent care, but foreign-born patients were less likely than US-born patients to report excellent quality...

  16. Thermostating extended Lagrangian Born-Oppenheimer molecular dynamics.

    Science.gov (United States)

    Martínez, Enrique; Cawkwell, Marc J; Voter, Arthur F; Niklasson, Anders M N

    2015-04-21

    Extended Lagrangian Born-Oppenheimer molecular dynamics is developed and analyzed for applications in canonical (NVT) simulations. Three different approaches are considered: the Nosé and Andersen thermostats and Langevin dynamics. We have tested the temperature distribution under different conditions of self-consistent field (SCF) convergence and time step and compared the results to analytical predictions. We find that the simulations based on the extended Lagrangian Born-Oppenheimer framework provide accurate canonical distributions even under approximate SCF convergence, often requiring only a single diagonalization per time step, whereas regular Born-Oppenheimer formulations exhibit unphysical fluctuations unless a sufficiently high degree of convergence is reached at each time step. The thermostated extended Lagrangian framework thus offers an accurate approach to sample processes in the canonical ensemble at a fraction of the computational cost of regular Born-Oppenheimer molecular dynamics simulations.

  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. 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...

  19. Recent Perspectives on Genome, Transmission, Clinical Manifestation, Diagnosis, Therapeutic Strategies, Vaccine Developments, and Challenges of Zika Virus Research

    Directory of Open Access Journals (Sweden)

    Apoorva Shankar

    2017-09-01

    Full Text Available One of the potential threats to public health microbiology in 21st century is the increased mortality rate caused by Zika virus (ZIKV, a mosquito-borne flavivirus. The severity of ZIKV infection urged World Health Organization (WHO to declare this virus as a global concern. The limited knowledge on the structure, virulent factors, and replication mechanism of the virus posed as hindrance for vaccine development. Several vector and non-vector-borne mode of transmission are observed for spreading the disease. The similarities of the virus with other flaviviruses such as dengue and West Nile virus are worrisome; hence, there is high scope to undertake ZIKV research that probably provide insight for novel therapeutic intervention. Thus, this review focuses on the recent aspect of ZIKV research which includes the outbreak, genome structure, multiplication and propagation of the virus, current animal models, clinical manifestations, available treatment options (probable vaccines and therapeutics, and the recent advancements in computational drug discovery pipelines, challenges and limitation to undertake ZIKV research. The review suggests that the infection due to ZIKV became one of the universal concerns and an interdisciplinary environment of in vitro cellular assays, genomics, proteomics, and computational biology approaches probably contribute insights for screening of novel molecular targets for drug design. The review tried to provide cutting edge knowledge in ZIKV research with future insights required for the development of novel therapeutic remedies to curtail ZIKV infection.

  20. Glyoxylate as a reducing agent for manganese(III) in salen scaffold ...

    Indian Academy of Sciences (India)

    being the monohydrate gem-diol forms) followed by the slow electron transfer ... stress and implicated as possible therapeutic agents .... excess HGl at different pHs (1.8–2.5) were set aside ...... sion (UGC), New Delhi in terms of a Teacher Fel-.

  1. 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...

  2. Viral agents that cause infection through the consumption and handling of food

    International Nuclear Information System (INIS)

    Gomez Murillo, Ileana

    2014-01-01

    Viral agents: Norovirus, Rotavirus, Hepatitis A and E, Nipah virus, highly pathogenic avian influenza and coronavirus that cause the SARS are studied as protagonists in the production of food-borne infectious processes. The most common sources of pollution, viral characteristics that influence the control, routes, methods of detection and prevention of pathogens in food are analyzed. Methodological techniques are investigated to improve early detection of viral pathogens in food, control measures and prevention of food contamination [es

  3. 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.

  4. Challenges to oligonucleotides-based therapeutics for Duchenne muscular dystrophy

    Directory of Open Access Journals (Sweden)

    Goyenvalle Aurélie

    2011-02-01

    Full Text Available Abstract Antisense oligonucleotides are short nucleic acids designed to bind to specific messenger RNAs in order to modulate splicing patterns or inhibit protein translation. As such, they represent promising therapeutic tools for many disorders and have been actively developed for more than 20 years as a form of molecular medicine. Although significant progress has been made in developing these agents as drugs, they are yet not recognized as effective therapeutics and several hurdles remain to be overcome. Within the last few years, however, the prospect of successful oligonucleotides-based therapies has moved a step closer, in particular for Duchenne muscular dystrophy. Clinical trials have recently been conducted for this myopathy, where exon skipping is being used to achieve therapeutic outcomes. In this review, the recent developments and clinical trials using antisense oligonucleotides for Duchenne muscular dystrophy are discussed, with emphasis on the challenges ahead for this type of therapy, especially with regards to delivery and regulatory issues.

  5. 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.

  6. 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.

  7. Gelatin sponge particle used as an embolic agent in transcatheter arterial chemoembolization treatment for primary hepatocellular carcinoma: its current situation in research

    International Nuclear Information System (INIS)

    Ao Jin; Zhang Yuewei; Xu Ke

    2011-01-01

    Transcatheter arterial chemoembolization (TACE) is one of the most commonly used therapeutic procedures for primary hepatocellular carcinoma (HCC). As an important and easily-available embolic agent, gelatin sponge (Gelfoam) particles have been constantly and widely employed in clinical practice. Various types of embolic agents have been continuously developed and effectively used in TACE for liver cancers. For recent years, great progress has been made in the clinical use of gelatin sponge particles, as the most traditional embolic agent, in the interventional therapeutic field for HCC. This article aims to make a comprehensive review about gelatin sponge. (authors)

  8. [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...

  9. Terapia com agentes biológicos na criança e no adolescente Treatment with biologic agents in child and adolescent

    Directory of Open Access Journals (Sweden)

    Ricardo Maisse Suehiro

    2010-06-01

    Full Text Available OBJETIVO: Revisar os mecanismos fisiopatológicos e novos alvos terapêuticos, os agentes biológicos disponíveis, principais indicações e a evidência científica atual para o uso de terapias biológicas na população pediátrica. FONTES DE DADOS: Pesquisa na base de dados Medline e SciELO, nas línguas inglesa e portuguesa, entre 2000 e 2009. As palavras-chave usadas foram "agentes biológicos", "crianças" e "adolescentes". SÍNTESE DOS DADOS: Os agentes biológicos são uma importante opção terapêutica para tratar as doenças autoimunes refratárias às terapias convencionais na infância e na adolescência. Com exceção da artrite idiopática juvenil, a maioria dos estudos em outras doenças autoimunes não é controlada. CONCLUSÕES: Os agentes biológicos têm demonstrado eficácia no tratamento de doenças autoimunes pediátricas como artrite idiopática juvenil, miopatias idiopáticas inflamatórias, lúpus eritematoso juvenil, vasculites, uveítes crônicas, doenças inflamatórias intestinais e púrpura trombocitopênica imune crônica, assim como no linfoma não-Hodgkin. Considerando-se o custo elevado e os potenciais eventos adversos, o uso desses agentes deve ser individualizado e acompanhado por especialista.OBJECTIVE: To review the physiopathology and new therapeutical targets, the available biologic agents, the main indications and the current scientific evidence for the use of biological therapies in the pediatric population. DATA SOURCES: A bibliographical search was obtained from Medline and SciELO databases in English and Portuguese from 2000 to 2009. The key-words included were "biologic agent", "children" and "adolescent". DATA SYNTHESIS: Biologic agents are important therapeutic options to treat refractory autoimmune diseases to conventional therapies in childhood and adolescence. Excluding juvenile idiopathic arthritis, the majority of studies in other autoimmune diseases are uncontrolled trials. CONCLUSIONS

  10. Mechanisms of chemoresistance to alkylating agents in malignant glioma.

    Science.gov (United States)

    Sarkaria, Jann N; Kitange, Gaspar J; James, C David; Plummer, Ruth; Calvert, Hilary; Weller, Michael; Wick, Wolfgang

    2008-05-15

    Intrinsic or acquired chemoresistance to alkylating agents is a major cause of treatment failure in patients with malignant brain tumors. Alkylating agents, the mainstay of treatment for brain tumors, damage the DNA and induce apoptosis, but the cytotoxic activity of these agents is dependent on DNA repair pathways. For example, O6-methylguanine DNA adducts can cause double-strand breaks, but this is dependent on a functional mismatch repair pathway. Thus, tumor cell lines deficient in mismatch repair are resistant to alkylating agents. Perhaps the most important mechanism of resistance to alkylating agents is the DNA repair enzyme O6-methylguanine methyltransferase, which can eliminate the cytotoxic O6-methylguanine DNA adduct before it causes harm. Another mechanism of resistance to alkylating agents is the base excision repair (BER) pathway. Consequently, efforts are ongoing to develop effective inhibitors of BER. Poly(ADP-ribose)polymerase plays a pivotal role in BER and is an important therapeutic target. Developing effective strategies to overcome chemoresistance requires the identification of reliable preclinical models that recapitulate human disease and which can be used to facilitate drug development. This article describes the diverse mechanisms of chemoresistance operating in malignant glioma and efforts to develop reliable preclinical models and novel pharmacologic approaches to overcome resistance to alkylating agents.

  11. 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.

  12. 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...

  13. Hepatitis B core protein as a therapeutic target.

    Science.gov (United States)

    Mak, Lung-Yi; Wong, Danny Ka-Ho; Seto, Wai-Kay; Lai, Ching-Lung; Yuen, Man Fung

    2017-12-01

    Chronic hepatitis B virus (HBV) infection is difficult to cure, due to the presence of covalently-closed-circular DNA and virus-mediated blunting of host immune response. Existing therapies with nucleos(t)ide analogue or pegylated-interferon are not sufficient to achieve a high rate of HBV surface antigen seroclearance, a more desirable treatment outcome. Novel therapeutic agents targeting alternative viral replication steps are being developed. In this review, we will discuss the hepatitis B core antigen (HBcAg) as a therapeutic target. Areas covered: The basic structure and fundamental functions of HBcAg including nucleocapsid assembly, pre-genomic RNA encapsidation, reverse transcription, virion formation, cccDNA amplification, immune response regulation, and HBx protein interaction will be reviewed. Most of these are identified as therapeutic targets and tested in in vitro and in vivo studies, although clinical trials are scanty. Among the different components, the core protein allosteric modulators (CpAM) have been most widely investigated and appear promising in clinical trials. Expert opinion: The multiple and essential functions of HBcAg for HBV life cycle are important and attractive targets for HBV therapeutic interventions. Controlled trials involving CpAM are awaited. Apart from CpAM, drugs directed against different functions of HBcAg may be further explored to maximize the chance of cure.

  14. Efficacy of antidotes (midazolam, atropine and HI-6) on nerve agent induced molecular and neuropathological changes

    OpenAIRE

    RamaRao, Golime; Afley, Prachiti; Acharya, Jyothiranjan; Bhattacharya, Bijoy Krishna

    2014-01-01

    Background Recent alleged attacks with nerve agent sarin on civilians in Syria indicate their potential threat to both civilian and military population. Acute nerve agent exposure can cause rapid death or leads to multiple and long term neurological effects. The biochemical changes that occur following nerve agent exposure needs to be elucidated to understand the mechanisms behind their long term neurological effects and to design better therapeutic drugs to block their multiple neurotoxic ef...

  15. 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.

  16. Antimicrobials and therapeutic decision making: an historical perspective.

    Science.gov (United States)

    Quintiliani, R; Nightingale, C H

    1991-01-01

    In an effort to remedy inappropriate and excessive use of antimicrobials and to control costs, most hospitals have developed some type of antimicrobial management program. At Hartford Hospital, our most effective approaches have been those that reduce the chances for physician error, decrease the burden on ancillary services, and encourage short hospital stays. These include automatic correction of dose and dosing intervals of antimicrobials and, if possible, their conversion by pharmacy to cost-effective alternative agents; daily review of patients who are taking the drugs by an antimicrobial team; and replacement of parenteral with oral agents as soon as possible. Physician acceptance of these approaches will require significant changes in traditional prescribing styles and willingness to allow pharmacists to implement the recommendations of therapeutic and medical staff committees.

  17. Neurocognitive outcome in young adults born late-preterm.

    Science.gov (United States)

    Heinonen, Kati; Lahti, Jari; Sammallahti, Sara; Wolke, Dieter; Lano, Aulikki; Andersson, Sture; Pesonen, Anu-Katriina; Eriksson, Johan G; Kajantie, Eero; Raikkonen, Katri

    2018-03-01

    This study examined whether late-preterm birth (34+0 to 36+6wks+d gestational age) was associated with neurocognitive deficit in young adulthood, and whether small for gestational age (SGA) birth amplified any adversity. Participants derived from the prospective regional cohort study, the Arvo Ylppö Longitudinal Study (n=786; 398 females, 388 males) (mean age 25y 4mo, SD 8mo), born 1985 to 1986 late-preterm (n=119; 21 SGA, intelligence, executive functioning, attention, and memory, and reported their education. Those born late-preterm scored -3.71 (95% confidence interval [CI] -6.71 to -0.72) and -3.11 (95% CI -6.01 to -0.22) points lower on Full-scale and Verbal IQ than peers born at term. Compared with those born at term and appropriate for gestational age (≥-2 to increase the risk of poorer neurocognitive functioning in adulthood. But the double burden of being born late-preterm and SGA seems to increase this risk. Late-preterm birth did not increase the risk of poorer neurocognitive functioning in adulthood. But the double burden of being born late-preterm and being small for gestational age did increase this risk. © 2017 Mac Keith Press.

  18. 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.

  19. Development of (F-18)-Labeled Amyloid Imaging Agents for PET

    International Nuclear Information System (INIS)

    Mathis, C.A.

    2007-01-01

    The applicant proposes to design and synthesize a series of fluorine-18-labeled radiopharmaceuticals to be used as amyloid imaging agents for positron emission tomography (PET). The investigators will conduct comprehensive iterative in vitro and in vivo studies based upon well defined acceptance criteria in order to identify lead agents suitable for human studies. The long term goals are to apply the selected radiotracers as potential diagnostic agents of Alzheimer's disease (AD), as surrogate markers of amyloid in the brain to determine the efficacy of anti-amyloid therapeutic drugs, and as tools to help address basic scientific questions regarding the progression of the neuropathology of AD, such as testing the 'amyloid cascade hypothesis' which holds that amyloid accumulation is the primary cause of AD.

  20. 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.

  1. Therapeutic Approaches Using Riboflavin in Mitochondrial Energy Metabolism Disorders.

    Science.gov (United States)

    Henriques, Bárbara J; Lucas, Tânia G; Gomes, Cláudio M

    2016-01-01

    Riboflavin, or vitamin B2, plays an important role in the cell as biological precursor of FAD and FMN, two important flavin cofactors which are essential for the structure and function of flavoproteins. Riboflavin has been used in therapeutic approaches of various inborn errors of metabolism, notably in metabolic disorders resulting either from defects in proteins involved in riboflavin metabolism and transport or from defects in flavoenzymes. The scope of this review is to provide an updated perspective of clinical cases in which riboflavin was used as a potential therapeutic agent in disorders affecting mitochondrial energy metabolism. In particular, we discuss available mechanistic insights on the role of riboflavin as a pharmacological chaperone for the recovery of misfolded metabolic flavoenzymes.

  2. [Utilization of polymeric micelle magnetic resonance imaging (MRI) contrast agent for theranostic system].

    Science.gov (United States)

    Shiraishi, Kouichi

    2013-01-01

    We applied a polymeric micelle carrier system for the targeting of a magnetic resonance imaging (MRI) contrast agent. Prepared polymeric micelle MRI contrast agent exhibited a long circulation characteristic in blood, and considerable amount of the contrast agent was found to accumulate in colon 26 solid tumor by the EPR effect. The signal intensities of tumor area showed 2-folds increase in T1-weighted images at 24 h after i.v. injection. To observe enhancement of the EPR effect by Cderiv pretreatment on tumor targeting, we used the contrast agent for the evaluation by means of MRI. Cderiv pretreatment significantly enhanced tumor accumulation of the contrast agent. Interestingly, very high signal intensity in tumor region was found at 24 h after the contrast agent injection in Cderiv pretreated mice. The contrast agent visualized a microenvironmental change in tumor. These results indicate that the contrast agent exhibits potential use for tumor diagnostic agent. To combine with a polymeric micelle carrier system for therapeutic agent, the usage of the combination makes a new concept of "theranostic" for a better cancer treatment.

  3. 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

  4. 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.

  5. The development prospection of HDAC inhibitors as a potential therapeutic direction in Alzheimer?s disease

    OpenAIRE

    Yang, Shuang-shuang; Zhang, Rui; Wang, Gang; Zhang, Yong-fang

    2017-01-01

    Alzheimer?s disease (AD) is a chronic neurodegenerative disease, which is associated with learning and memory impairment in the elderly. Recent studies have found that treating AD in the way of chromatin remodeling via histone acetylation is a promising therapeutic regimen. In a number of recent studies, inhibitors of histone deacetylase (HDACs) have been found to be a novel promising therapeutic?agents for neurological disorders, particularly for AD and other neurodegenerative diseases. Alth...

  6. Impact of Neighborhood Environments on Health Consciousness, Information Seeking, and Attitudes among US-Born and Non-US-Born Free Clinic Patients.

    Science.gov (United States)

    Kamimura, Akiko; Ashby, Jeanie; Jess, Allison; Trinh, Ha Ngoc; Nourian, Maziar M; Finlayson, Sarah Yukie; Prudencio, Liana; Reel, Justine J

    2015-12-01

    This study examined the impact of neighborhood environments on health consciousness, information seeking, and attitudes among uninsured free clinic patients to better understand the specific needs of the population for health promotion and prevention efforts. US-born English-speaking, non-US-born English-speaking, and Spanish-speaking free clinic patients completed a self-administered survey using reliable measures in autumn 2014 (N = 769). The results of this study suggest that social cohesion is positively associated with health consciousness, information seeking, and attitudes. Lower levels of available healthy food in the community were associated with higher levels of health consciousness. Although Spanish speakers reported lower levels of the availability of healthy food, social cohesion, and access to the Internet or text messaging compared with US-born or non-US-born English speakers, they were more likely to be health conscious and have higher levels of health information seeking. Spanish speakers as well as non-US-born English speakers, were more likely to attend health education classes compared with US-born English speakers. Health education programs for free clinic patients should include strategies to increase social cohesion. Health education programs should consider the diverse needs of these individual populations to maximize the effectiveness of the programs for free clinic patients.

  7. Therapeutic Potential of Mesenchymal Stem Cell-Derived Exosomes in the Treatment of Eye Diseases.

    Science.gov (United States)

    Harrell, C Randall; Simovic Markovic, Bojana; Fellabaum, Crissy; Arsenijevic, Aleksandar; Djonov, Valentin; Arsenijevic, Nebojsa; Volarevic, Vladislav

    2018-05-18

    Mesenchymal stem cells (MSCs) were, due to their immunomodulatory and pro-angiogenic characteristics, extensively explored as new therapeutic agents in cell-based therapy of uveitis, glaucoma, retinal and ocular surface diseases.Since it was recently revealed that exosomes play an important role in biological functions of MSCs, herewith we summarized current knowledge about the morphology, structure, phenotype and functional characteristics of MSC-derived exosomes emphasizing their therapeutic potential in the treatment of eye diseases.MSC-derived exosomes were as efficient as transplanted MSCs in limiting the extent of eye injury and inflammation. Immediately after intravitreal injection, MSC-derived exosomes, due to nano-dimension, diffused rapidly throughout the retina and significantly attenuated retinal damage and inflammation. MSC-derived exosomes successfully delivered trophic and immunomodulatory factors to the inner retina and efficiently promoted survival and neuritogenesis of injured retinal ganglion cells. MSC-derived exosomes efficiently suppressed migration of inflammatory cells, attenuated detrimental Th1 and Th17 cell-driven immune response and ameliorated experimental autoimmune uveitis. MSC-derived exosomes were able to fuse with the lysosomes within corneal cells, enabling delivering of MSC-derived active β-glucuronidase and consequent catabolism of accumulated glycosaminoglycans, indicating their therapeutic potential in the treatment of Mucopolysaccharidosis VII (Sly Syndrome). Importantly, beneficent effects were noticed only in animals that received MSC-derived exosomes and were not seen after therapy with fibroblasts-derived exosomes confirming specific therapeutic potential of MSCs and their products in the treatment of eye diseases.In conclusion, MSC-derived exosomes represent potentially new therapeutic agents in the therapy of degenerative and inflammatory ocular diseases.

  8. Scaling adult doses of antifungal and antibacterial agents to children.

    Science.gov (United States)

    Dawson, Thomas H

    2012-06-01

    My general pharmacokinetic scaling theory is discussed for the important matter of determining pediatric dosing for existing and new therapeutic drugs when optimal, or near-optimal, dosing for adults is known. The basis for the scaling is the requirement of a time-scaled likeness of the free-drug concentration time histories of children and adults. Broad categories of single and periodic dosing are considered. The former involves the scaling of dosage, and the latter involves both the dosage and schedule. The validity of the scaling relations is demonstrated by using measurements from previously reported clinical trials with adults and children (with ages generally 1 year or older) for the relatively new antifungal agent caspofungin and for the relatively new antibacterial agent linezolid. Standard pharmacodynamic effectiveness criteria are shown to be satisfied for the scaled dosage and schedule for children to the same extent that they are for the referenced adult. Consideration of scaling from adults to children is discussed for the case of new agents where no pediatric data are available and needed parameters are determined from in vitro measurements and preclinical animal data. A connection is also made between the allometric representation of clearance data and the dosing formulas. Limitations of the scaling results for infants because of growth and maturational matters are discussed. The general conclusion from this work is that the scaling theory does indeed have application to pediatric dosing for children, for both confirmation and refinement of present practice and guidance in pediatric treatment with new therapeutic agents.

  9. Behavioural skills in 7 year old children born post-term

    DEFF Research Database (Denmark)

    Olesen, Annette Wind; Olsen, Jørn; Zhu, Jin Liang

    2014-01-01

    Abstract Objective: To study behavioural skills at the age of seven in a Danish population of children born post-term. Design: Cohort study. Setting: The Danish National Birth Cohort; children born from 1997 to 2003. Population: Data was obtained from a cohort of about 100,000 women...... and their children. All singletons born in gestational week 39-45 were identified, and then restricted to children whose mothers filled out a Strength and Difficulties Questionnaire (STQ) when they were seven years of age. The study population constituted 33842 singletons (21249 born at term and 12593 born post...

  10. 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.

  11. Atopic diseases in twins born after assisted reproduction.

    Science.gov (United States)

    Jäderberg, Ida; Thomsen, Simon F; Kyvik, Kirsten O; Skytthe, Axel; Backer, Vibeke

    2012-03-01

    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 = 0.773 respectively) compared with children born after spontaneous conception. Assisted reproduction did not modify the heritability of atopic diseases. This study does not support an association between assisted reproduction and development of atopic diseases. This result must be confirmed in subsequent studies, preferably of singleton populations. © 2011 Blackwell Publishing Ltd.

  12. Work Hours of Immigrant Versus U.S.-Born Female Workers.

    Science.gov (United States)

    Bae, Sung-Heui

    2017-10-01

    This study was a secondary analysis of cross-sectional data extracted from the 2011-2012 California Health Interview Survey. Data from 8,931 full-time (i.e., 21 hours or more per week) women workers aged 18 to 85 years were analyzed to examine the nature and prevalence of immigrant female workers' work hours, overtime, and related factors in the United States compared to U.S.-born female workers. Results showed that foreign-born female workers did not work longer hours than U.S.-born female workers. Foreign-born female workers who reported poor health worked longer hours than did their U.S.-born counterparts. Foreign-born female workers who were self-employed or worked in family businesses tended to work longer hours than did those women who worked for private companies or nonprofit organizations.

  13. Potential of Microbispora sp. V2 as biocontrol agent against Sclerotium rolfsii, the causative agent of southern blight of Zea mays L (Baby corn)--in vitro studies.

    Science.gov (United States)

    Patil, N N; Waghmode, M S; Gaikwad, P S; Gajbhiye, M H; Gunjal, A B; Nawani, N N; Kapadnis, B P

    2014-11-01

    The study was undertaken with the aim of exploring novel and beneficial agro activities of rare actinomycetes like Microbispora sp. V2. The antagonistic activity of Microbispora sp. V2 was evaluated as a biocontrol agents against Sclerotium rolfsii, a soil-borne fungal plant pathogen. The methodology performed for evaluation of biocontrol agent was in vitro evaluation assay which comprised of three tests viz., cellophane overlay technique, seed germination test and Thiram (fungicide) tolerance of Microbispora sp. V2. The isolate was found to inhibit the fungal pathogen Sclerotium rolfsii to 91.43% in cellophane assay. In seed germination assay, Microbispora sp. V2 treated seeds resulted in 25.75% increased germination efficiency, as compared to seeds infected by Sclerotium rolfsii. The isolate Microbispora sp. V2 could tolerate 1000 microg mL(-1) of Thiram (fungicide). The in vitro assay studies proved that Microbispora sp. V2 can be used as antifungal antagonist and thus posses' great potential as biocontrol agent against southern blight caused by Sclerotium rolfsii in Zea mays L (Baby corn) which causes large economical losses.

  14. Nitric oxide: cancer target or anticancer agent?

    Science.gov (United States)

    Mocellin, Simone

    2009-03-01

    Despite the improved understanding of nitric oxide (NO) biology and the large amount of preclinical experiments testing its role in cancer development and progression, it is still debated whether NO should be considered a potential anticancer agent or instead a carcinogen. The complexity of NO effects within a cell and the variability of the final biological outcome depending upon NO levels makes it highly challenging to determine the therapeutic value of interfering with the activity of this intriguing gaseous messenger. This uncertainty has so far halted the clinical implementation of NO-based therapeutics in the field of oncology. Accordingly, only an in depth knowledge of the mechanisms leading to experimental tumor regression or progression in response to NO will allow us to exploit this molecule to fight cancer.

  15. Manufacturing of Human Extracellular Vesicle-Based Therapeutics for Clinical Use

    Directory of Open Access Journals (Sweden)

    Mario Gimona

    2017-06-01

    Full Text Available Extracellular vesicles (EVs derived from stem and progenitor cells may have therapeutic effects comparable to their parental cells and are considered promising agents for the treatment of a variety of diseases. To this end, strategies must be designed to successfully translate EV research and to develop safe and efficacious therapies, whilst taking into account the applicable regulations. Here, we discuss the requirements for manufacturing, safety, and efficacy testing of EVs along their path from the laboratory to the patient. Development of EV-therapeutics is influenced by the source cell types and the target diseases. In this article, we express our view based on our experience in manufacturing biological therapeutics for routine use or clinical testing, and focus on strategies for advancing mesenchymal stromal cell (MSC-derived EV-based therapies. We also discuss the rationale for testing MSC-EVs in selected diseases with an unmet clinical need such as critical size bone defects, epidermolysis bullosa and spinal cord injury. While the scientific community, pharmaceutical companies and clinicians are at the point of entering into clinical trials for testing the therapeutic potential of various EV-based products, the identification of the mode of action underlying the suggested potency in each therapeutic approach remains a major challenge to the translational path.

  16. Transport of nanoparticles through the blood-brain barrier for imaging and therapeutic applications

    Science.gov (United States)

    Shilo, Malka; Motiei, Menachem; Hana, Panet; Popovtzer, Rachela

    2014-01-01

    A critical problem in the treatment of neurodegenerative disorders and diseases, such as Alzheimer's and Parkinson's, is the incapability to overcome the restrictive mechanism of the blood-brain barrier (BBB) and to deliver important therapeutic agents to the brain. During the last decade, nanoparticles have gained attention as promising drug delivery agents that can transport across the BBB and increase the uptake of appropriate drugs in the brain. In this study we have developed insulin-targeted gold nanoparticles (INS-GNPs) and investigated quantitatively the amount of INS-GNPs that cross the BBB by the receptor-mediated endocytosis process. For this purpose, INS-GNPs and control GNPs were injected into the tail vein of male BALB/c mice. Major organs were then extracted and a blood sample was taken from the mice, and thereafter analyzed for gold content by flame atomic absorption spectroscopy. Results show that two hours post-intravenous injection, the amount of INS-GNPs found in mouse brains is over 5 times greater than that of the control, untargeted GNPs. Results of further experimentation on a rat model show that INS-GNPs can also serve as CT contrast agents to highlight specific brain regions in which they accumulate. Due to the fact that they can overcome the restrictive mechanism of the BBB, this approach could be a potentially valuable tool, helping to confront the great challenge of delivering important imaging and therapeutic agents to the brain for detection and treatment of neurodegenerative disorders and diseases.

  17. 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.

  18. 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.

  19. 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

  20. Novel therapeutic uses and formulations of botulinum neurotoxins: a patent review (2012 - 2014).

    Science.gov (United States)

    Kane, Christopher D; Nuss, Jonathan E; Bavari, Sina

    2015-06-01

    Botulinum neurotoxins (BoNTs) are among the most toxic of known biological molecules and function as acetylcholine release inhibitors and neuromuscular blocking agents. Paradoxically, these properties also make them valuable therapeutic agents for the treatment of movement disorders, urological conditions and hypersecretory disorders. Greater understanding of their molecular mechanism of action and advances in protein engineering has led to significant efforts to improve and expand their function with a view towards broadening their therapeutic potential. Searches of Espacenet and Google Patent have revealed a number of patents related to BoNTs. This review will focus on novel therapeutic uses and formulations disclosed during 2012 - 2014. The seven patents discussed will include nanoformulations of FDA-approved BoNTs, additional BoNT subtypes and novel BoNT variants and chimeras created through protein engineering. Supporting patents and related publications are also briefly discussed. The clinical and commercial success of BoNTs has prompted investigation into novel BoNTs or BoNT-mediated chimeras with promising in vitro results. Distinct strategies including the use of nanoformulations and targeted delivery have been implemented to identify new indication and improved functionality. Greater understanding of their systemic exposure, efficacy and safety profiles will be required for further development.

  1. Recent advances in (therapeutic protein drug development [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    H.A. Daniel Lagassé

    2017-02-01

    Full Text Available Therapeutic protein drugs are an important class of medicines serving patients most in need of novel therapies. Recently approved recombinant protein therapeutics have been developed to treat a wide variety of clinical indications, including cancers, autoimmunity/inflammation, exposure to infectious agents, and genetic disorders. The latest advances in protein-engineering technologies have allowed drug developers and manufacturers to fine-tune and exploit desirable functional characteristics of proteins of interest while maintaining (and in some cases enhancing product safety or efficacy or both. In this review, we highlight the emerging trends and approaches in protein drug development by using examples of therapeutic proteins approved by the U.S. Food and Drug Administration over the previous five years (2011–2016, namely January 1, 2011, through August 31, 2016.

  2. 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.

  3. Internalized racism and mental health among African-Americans, US-born Caribbean Blacks, and foreign-born Caribbean Blacks.

    Science.gov (United States)

    Mouzon, Dawne M; McLean, Jamila S

    2017-02-01

    The tripartite model of racism includes personally mediated racism, institutionalized racism, and the less-oft studied internalized racism. Internalized racism - or negative beliefs about one's racial group - results from cultural racism that is endemic in American society. In this project, we studied whether these negative stereotypes are associated with mental health among African-Americans and Caribbean Blacks. Using secondary data from the National Survey of American Life, we investigated the association between internalized racism and mental health (measured by depressive symptoms and serious psychological distress (SPD)) among these two groups. We also explored whether ethnicity/nativity and mastery moderate the association between internalized racism and mental health among African-Americans and Caribbean Blacks. Internalized racism was positively associated with depressive symptoms and SPD among all Black subgroups. However, internalized racism was a weaker predictor of SPD among foreign-born Caribbean Blacks than US-born Caribbean Blacks and US-born African-Americans. Additionally, higher mastery was protective against distress associated with internalized racism. Internalized racism is an important yet understudied determinant of mental health among Blacks. Future studies should take into account additional heterogeneity within the Black population (e.g. African-born individuals) and other potential protective mechanisms in addition to mastery (e.g. self-esteem and racial identity).

  4. Trends in GPCR drug discovery: new agents, targets and indications.

    Science.gov (United States)

    Hauser, Alexander S; Attwood, Misty M; Rask-Andersen, Mathias; Schiöth, Helgi B; Gloriam, David E

    2017-12-01

    G protein-coupled receptors (GPCRs) are the most intensively studied drug targets, mostly due to their substantial involvement in human pathophysiology and their pharmacological tractability. Here, we report an up-to-date analysis of all GPCR drugs and agents in clinical trials, which reveals current trends across molecule types, drug targets and therapeutic indications, including showing that 475 drugs (~34% of all drugs approved by the US Food and Drug Administration (FDA)) act at 108 unique GPCRs. Approximately 321 agents are currently in clinical trials, of which ~20% target 66 potentially novel GPCR targets without an approved drug, and the number of biological drugs, allosteric modulators and biased agonists has increased. The major disease indications for GPCR modulators show a shift towards diabetes, obesity and Alzheimer disease, although several central nervous system disorders are also highly represented. The 224 (56%) non-olfactory GPCRs that have not yet been explored in clinical trials have broad untapped therapeutic potential, particularly in genetic and immune system disorders. Finally, we provide an interactive online resource to analyse and infer trends in GPCR drug discovery.

  5. Therapeutic options to treat sulfur mustard poisoning--the road ahead.

    Science.gov (United States)

    Smith, William J

    2009-09-01

    For the past 15 years the international research community has conducted a basic and applied research program aimed at identifying a medical countermeasure against chemical threat vesicant, or blistering, agents. The primary emphasis of this program has been the development of therapeutic protection against sulfur mustard and its cutaneous pathology-blister formation. In addition to the work on a medical countermeasures, significant research has been conducted on the development of topical skin protectants and medical strategies for wound healing. This review will focus on the pharmacological strategies investigated, novel therapeutic targets currently under investigation and therapeutic approaches being considered for transition to advanced development. Additionally, we will review the expansion of our understanding of the pathophysiological mechanisms of mustard injury that has come from this research. While great strides have been made through these investigations, the complexity of the mustard insult demands that further studies extend the inroads made and point the way toward better understanding of cellular and tissue disruptions caused by sulfur mustard.

  6. Human Health Consequences of Use of Antimicrobial Agents in Aquaculture

    DEFF Research Database (Denmark)

    Heuer, Ole Eske; Kruse, H.; Grave, K.

    2009-01-01

    industry in many regions of the world and the widespread, intensive, and often unregulated use of antimicrobial agents in this area of animal production, efforts are needed to prevent development and spread of antimicrobial resistance in aquaculture to reduce the risk to human health....... in aquaculture, several are classified by the World Health Organisation as critically important for use in humans. Occurrence of resistance to these antimicrobial agents in human pathogens severely limits the therapeutic options in human infections. Considering the rapid growth and importance of aquaculture...... gene transfer and reach human pathogens, or drug-resistant pathogens from the aquatic environment may reach humans directly. Horizontal gene transfer may occur in the aquaculture environment, in the food chain, or in the human intestinal tract. Among the antimicrobial agents commonly used...

  7. Therapeutic Strategies to Enhance the Anticancer Efficacy of Histone Deacetylase Inhibitors

    Directory of Open Access Journals (Sweden)

    Claudia P. Miller

    2011-01-01

    Full Text Available Histone acetylation is a posttranslational modification that plays a role in regulating gene expression. More recently, other nonhistone proteins have been identified to be acetylated which can regulate their function, stability, localization, or interaction with other molecules. Modulating acetylation with histone deacetylase inhibitors (HDACi has been validated to have anticancer effects in preclinical and clinical cancer models. This has led to development and approval of the first HDACi, vorinostat, for the treatment of cutaneous T cell lymphoma. However, to date, targeting acetylation with HDACi as a monotherapy has shown modest activity against other cancers. To improve their efficacy, HDACi have been paired with other antitumor agents. Here, we discuss several combination therapies, highlighting various epigenetic drugs, ROS-generating agents, proteasome inhibitors, and DNA-damaging compounds that together may provide a therapeutic advantage over single-agent strategies.

  8. Silencing urease: A key evolutionary step that facilitated the adaptation of Yersinia pestis to the flea-borne transmission route

    Science.gov (United States)

    Chouikha, Iman; Hinnebusch, B. Joseph

    2014-01-01

    The arthropod-borne transmission route of Yersinia pestis, the bacterial agent of plague, is a recent evolutionary adaptation. Yersinia pseudotuberculosis, the closely related food-and water-borne enteric species from which Y. pestis diverged less than 6,400 y ago, exhibits significant oral toxicity to the flea vectors of plague, whereas Y. pestis does not. In this study, we identify the Yersinia urease enzyme as the responsible oral toxin. All Y. pestis strains, including those phylogenetically closest to the Y. pseudotuberculosis progenitor, contain a mutated ureD allele that eliminated urease activity. Restoration of a functional ureD was sufficient to make Y. pestis orally toxic to fleas. Conversely, deletion of the urease operon in Y. pseudotuberculosis rendered it nontoxic. Enzymatic activity was required for toxicity. Because urease-related mortality eliminates 30–40% of infective flea vectors, ureD mutation early in the evolution of Y. pestis was likely subject to strong positive selection because it significantly increased transmission potential. PMID:25453069

  9. Silencing urease: a key evolutionary step that facilitated the adaptation of Yersinia pestis to the flea-borne transmission route.

    Science.gov (United States)

    Chouikha, Iman; Hinnebusch, B Joseph

    2014-12-30

    The arthropod-borne transmission route of Yersinia pestis, the bacterial agent of plague, is a recent evolutionary adaptation. Yersinia pseudotuberculosis, the closely related food-and water-borne enteric species from which Y. pestis diverged less than 6,400 y ago, exhibits significant oral toxicity to the flea vectors of plague, whereas Y. pestis does not. In this study, we identify the Yersinia urease enzyme as the responsible oral toxin. All Y. pestis strains, including those phylogenetically closest to the Y. pseudotuberculosis progenitor, contain a mutated ureD allele that eliminated urease activity. Restoration of a functional ureD was sufficient to make Y. pestis orally toxic to fleas. Conversely, deletion of the urease operon in Y. pseudotuberculosis rendered it nontoxic. Enzymatic activity was required for toxicity. Because urease-related mortality eliminates 30-40% of infective flea vectors, ureD mutation early in the evolution of Y. pestis was likely subject to strong positive selection because it significantly increased transmission potential.

  10. Chemical Composition and Antimicrobial Activities of Essential Oils from Nepeta cataria L. against Common Causes of Food-Borne Infections

    Science.gov (United States)

    Zomorodian, Kamiar; Saharkhiz, Mohammad Jamal; Shariati, Samaneh; Pakshir, Keyvan; Rahimi, Mohammad Javad; Khashei, Reza

    2012-01-01

    Nepeta cataria L. is traditionally consumed as a food additive. The effects of three different harvest stages of N. cataria essential oils (EOs) against most common causes of food-borne infections were evaluated by broth microdilution method as recommended by the Clinical and Laboratory Standards Institute (CLSI). The chemical composition of the EOs from N. cataria has been analyzed by gas chromatography/mass spectrometry (GC/MS). The analysis of the EOs indicated that 4a-α,7-α,7a-β-nepetalactone (55–58%) and 4a-α,7-β,7a-α-nepetalactone (30–31.2%) were the major compounds of the EOs at all developmental stages. The results showed that the tested EOs exhibited antimicrobial activities against the food-borne pathogens at concentrations of 0.125–2 μL/mL. Based on these results, the EO of N. cataria can possibly be used in food products as a natural preservative agent. PMID:22779012

  11. Genetic Characterization of the Tick-Borne Orbiviruses

    Directory of Open Access Journals (Sweden)

    Manjunatha N. Belaganahalli

    2015-04-01

    Full Text Available The International Committee for Taxonomy of Viruses (ICTV recognizes four species of tick-borne orbiviruses (TBOs: Chenuda virus, Chobar Gorge virus, Wad Medani virus and Great Island virus (genus Orbivirus, family Reoviridae. Nucleotide (nt and amino acid (aa sequence comparisons provide a basis for orbivirus detection and classification, however full genome sequence data were only available for the Great Island virus species. We report representative genome-sequences for the three other TBO species (virus isolates: Chenuda virus (CNUV; Chobar Gorge virus (CGV and Wad Medani virus (WMV. Phylogenetic comparisons show that TBOs cluster separately from insect-borne orbiviruses (IBOs. CNUV, CGV, WMV and GIV share low level aa/nt identities with other orbiviruses, in ‘conserved’ Pol, T2 and T13 proteins/genes, identifying them as four distinct virus-species. The TBO genome segment encoding cell attachment, outer capsid protein 1 (OC1, is approximately half the size of the equivalent segment from insect-borne orbiviruses, helping to explain why tick-borne orbiviruses have a ~1 kb smaller genome.

  12. 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

  13. 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.

  14. The Prognostic, Diagnostic, and Therapeutic Potential of Tumor Antigens

    DEFF Research Database (Denmark)

    Olsen, Lars Rønn

    or abundance in cancer cells is often unique and their roles and functions in tumorigenesis are, in many cases, studied extensively. They, therefore, have the potential to be highly specific biomarkers as well as therapeutic targets, but complex analysis combining basic science, high-throughput methods...... of genomics and proteomics, and clinical studies need to be combined. These analyses produce large amounts of data that require advanced bioinformatics methods for collection, management, integration and interpretation. In this thesis, I have explored the potential of tumor antigens as biomarkers...... and therapeutic agents, by developing and implementing several computational tools and databases for immunotherapy target discovery, and have analyzed the potential of tumor antigens as proteogenomic biomarkers in invasive ductal carcinomas. In this analysis I have shown that the combination of proteomics...

  15. Mechanical and dynamic characteristics of encapsulated microbubbles coupled by magnetic nanoparticles as multifunctional imaging and drug delivery agents

    Science.gov (United States)

    Guo, Gepu; Lu, Lu; Yin, Leilei; Tu, Juan; Guo, Xiasheng; Wu, Junru; Xu, Di; Zhang, Dong

    2014-11-01

    Development of magnetic encapsulated microbubble agents that can integrate multiple diagnostic and therapeutic functions is a key focus in both biomedical engineering and nanotechnology and one which will have far-reaching impact on medical diagnosis and therapies. However, properly designing multifunctional agents that can satisfy particular diagnostic/therapeutic requirements has been recognized as rather challenging, because there is a lack of comprehensive understanding of how the integration of magnetic nanoparticles to microbubble encapsulating shells affects their mechanical properties and dynamic performance in ultrasound imaging and drug delivery. Here, a multifunctional imaging contrast and in-situ gene/drug delivery agent was synthesized by coupling super paramagnetic iron oxide nanoparticles (SPIOs) into albumin-shelled microbubbles. Systematical studies were performed to investigate the SPIO-concentration-dependence of microbubble mechanical properties, acoustic scattering response, inertial cavitation activity and ultrasound-facilitated gene transfection effect. These demonstrated that, with the increasing SPIO concentration, the microbubble mean diameter and shell stiffness increased and ultrasound scattering response and inertial cavitation activity could be significantly enhanced. However, an optimized ultrasound-facilitated vascular endothelial growth factor transfection outcome would be achieved by adopting magnetic albumin-shelled microbubbles with an appropriate SPIO concentration of 114.7 µg ml-1. The current results would provide helpful guidance for future development of multifunctional agents and further optimization of their diagnostic/therapeutic performance in clinic.

  16. Mechanical and dynamic characteristics of encapsulated microbubbles coupled by magnetic nanoparticles as multifunctional imaging and drug delivery agents

    International Nuclear Information System (INIS)

    Guo, Gepu; Lu, Lu; Tu, Juan; Guo, Xiasheng; Zhang, Dong; Yin, Leilei; Wu, Junru; Xu, Di

    2014-01-01

    Development of magnetic encapsulated microbubble agents that can integrate multiple diagnostic and therapeutic functions is a key focus in both biomedical engineering and nanotechnology and one which will have far-reaching impact on medical diagnosis and therapies. However, properly designing multifunctional agents that can satisfy particular diagnostic/therapeutic requirements has been recognized as rather challenging, because there is a lack of comprehensive understanding of how the integration of magnetic nanoparticles to microbubble encapsulating shells affects their mechanical properties and dynamic performance in ultrasound imaging and drug delivery. Here, a multifunctional imaging contrast and in-situ gene/drug delivery agent was synthesized by coupling super paramagnetic iron oxide nanoparticles (SPIOs) into albumin-shelled microbubbles. Systematical studies were performed to investigate the SPIO-concentration-dependence of microbubble mechanical properties, acoustic scattering response, inertial cavitation activity and ultrasound-facilitated gene transfection effect. These demonstrated that, with the increasing SPIO concentration, the microbubble mean diameter and shell stiffness increased and ultrasound scattering response and inertial cavitation activity could be significantly enhanced. However, an optimized ultrasound-facilitated vascular endothelial growth factor transfection outcome would be achieved by adopting magnetic albumin-shelled microbubbles with an appropriate SPIO concentration of 114.7 µg ml −1 . The current results would provide helpful guidance for future development of multifunctional agents and further optimization of their diagnostic/therapeutic performance in clinic. (paper)

  17. Molecular Detection and Characterization of Tick-borne Pathogens in Dogs and Ticks from Nigeria

    Science.gov (United States)

    Kamani, Joshua; Baneth, Gad; Mumcuoglu, Kosta Y.; Waziri, Ndadilnasiya E.; Eyal, Osnat; Guthmann, Yifat; Harrus, Shimon

    2013-01-01

    Background Only limited information is currently available on the prevalence of vector borne and zoonotic pathogens in dogs and ticks in Nigeria. The aim of this study was to use molecular techniques to detect and characterize vector borne pathogens in dogs and ticks from Nigeria. Methodology/Principal Findings Blood samples and ticks (Rhipicephalus sanguineus, Rhipicephalus turanicus and Heamaphysalis leachi) collected from 181 dogs from Nigeria were molecularly screened for human and animal vector-borne pathogens by PCR and sequencing. DNA of Hepatozoon canis (41.4%), Ehrlichia canis (12.7%), Rickettsia spp. (8.8%), Babesia rossi (6.6%), Anaplasma platys (6.6%), Babesia vogeli (0.6%) and Theileria sp. (0.6%) was detected in the blood samples. DNA of E. canis (23.7%), H. canis (21.1%), Rickettsia spp. (10.5%), Candidatus Neoehrlichia mikurensis (5.3%) and A. platys (1.9%) was detected in 258 ticks collected from 42 of the 181 dogs. Co- infections with two pathogens were present in 37% of the dogs examined and one dog was co-infected with 3 pathogens. DNA of Rickettsia conorii israelensis was detected in one dog and Rhipicephalus sanguineus tick. DNA of another human pathogen, Candidatus N. mikurensis was detected in Rhipicephalus sanguineus and Heamaphysalis leachi ticks, and is the first description of Candidatus N. mikurensis in Africa. The Theileria sp. DNA detected in a local dog in this study had 98% sequence identity to Theileria ovis from sheep. Conclusions/Significance The results of this study indicate that human and animal pathogens are abundant in dogs and their ticks in Nigeria and portray the potential high risk of human exposure to infection with these agents. PMID:23505591

  18. Molecular detection and characterization of tick-borne pathogens in dogs and ticks from Nigeria.

    Directory of Open Access Journals (Sweden)

    Joshua Kamani

    Full Text Available BACKGROUND: Only limited information is currently available on the prevalence of vector borne and zoonotic pathogens in dogs and ticks in Nigeria. The aim of this study was to use molecular techniques to detect and characterize vector borne pathogens in dogs and ticks from Nigeria. METHODOLOGY/PRINCIPAL FINDINGS: Blood samples and ticks (Rhipicephalus sanguineus, Rhipicephalus turanicus and Heamaphysalis leachi collected from 181 dogs from Nigeria were molecularly screened for human and animal vector-borne pathogens by PCR and sequencing. DNA of Hepatozoon canis (41.4%, Ehrlichia canis (12.7%, Rickettsia spp. (8.8%, Babesia rossi (6.6%, Anaplasma platys (6.6%, Babesia vogeli (0.6% and Theileria sp. (0.6% was detected in the blood samples. DNA of E. canis (23.7%, H. canis (21.1%, Rickettsia spp. (10.5%, Candidatus Neoehrlichia mikurensis (5.3% and A. platys (1.9% was detected in 258 ticks collected from 42 of the 181 dogs. Co- infections with two pathogens were present in 37% of the dogs examined and one dog was co-infected with 3 pathogens. DNA of Rickettsia conorii israelensis was detected in one dog and Rhipicephalus sanguineus tick. DNA of another human pathogen, Candidatus N. mikurensis was detected in Rhipicephalus sanguineus and Heamaphysalis leachi ticks, and is the first description of Candidatus N. mikurensis in Africa. The Theileria sp. DNA detected in a local dog in this study had 98% sequence identity to Theileria ovis from sheep. CONCLUSIONS/SIGNIFICANCE: The results of this study indicate that human and animal pathogens are abundant in dogs and their ticks in Nigeria and portray the potential high risk of human exposure to infection with these agents.

  19. 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 ...

  20. Cancer chemopreventive and therapeutic effects of diosgenin, a food saponin.

    Science.gov (United States)

    Raju, Jayadev; Mehta, Rekha

    2009-01-01

    Cancer chemoprevention is a strategy taken to retard, regress, or resist the multistep process of carcinogenesis, including the blockage of its vital morphogenetic milestones viz. normal-preneoplasia-neoplasia-metastasis. For several reasons, including safety, minimal (or no) toxicity and side-effects, and better availability, alternatives such as naturally occurring phytochemicals that are found in foods are becoming increasingly popular over synthetic drugs. Food saponins have been used in complimentary and traditional medicine against a variety of diseases including several cancers. Diosgenin, a naturally occurring steroid saponin found abundantly in legumes and yams, is a well-known precursor of various synthetic steroidal drugs that are extensively used in the pharmaceutical industry. Over the past decade, a series of preclinical and mechanistic studies have been conducted to understand the role of diosgenin as a chemopreventive/therapeutic agent against several cancers. This review highlights the biological activity of diosgenin that contributes to cancer chemoprevention and control. The anticancer mode of action of diosgenin has been demonstrated via modulation of multiple cell signaling events involving critical molecular candidates associated with growth, differentiation, apoptosis, and oncogenesis. Altogether, these preclinical and mechanistic findings strongly implicate the use of diosgenin as a novel, multitarget-based chemopreventive or therapeutic agent against several cancer types. Future research in this field will help to establish not only whether diosgenin is safe and efficacious as a chemopreventive agent against several human cancers, but also to develop and evaluate standards of evidence for health claims for diosgenin-containing foods as they become increasingly popular and enter the marketplace labeled as functional foods and nutraceuticals.

  1. Obesity Among U.S.- and Foreign-Born Blacks by Region of Birth.

    Science.gov (United States)

    Mehta, Neil K; Elo, Irma T; Ford, Nicole D; Siegel, Karen R

    2015-08-01

    Large, recent migration streams from the non-Hispanic Caribbean islands and Africa have increased the share of U.S. blacks born outside of the U.S. Little is known about health patterns in these foreign-born populations. The purpose of this study is to compare obesity levels among self-identified U.S. blacks across birth regions and examine potential explanations for subgroup differences. Data were from the 2000-2013 National Health Interview Surveys. Three birthplace subgroups were examined: individuals born in the U.S., Caribbean/South America, and Africa, aged 25-59 years. Data were analyzed in 2013-2014. Compared to U.S.-born participants, foreign-born participants had significantly lower obesity (BMI ≥30) odds. The AORs were 0.51 (Caribbean/South American-born, 95% CI=0.44, 0.58) and 0.41 (African-born, 95% CI=0.34, 0.50) with reference to U.S.-born individuals. Education, income, and cigarette smoking did not explain the favorable weight pattern of the foreign born. Among the foreign born, those residing in the U.S. for ≥15 years had 51% (95% CI=10%, 108%) higher obesity odds compared with those residing for <5 years. No statistically significant differences in obesity odds between those born in the Caribbean/South America and Africa were detected. Foreign-born blacks generally had lower obesity levels compared to their U.S.-born counterparts, which was not explained by SES or smoking behaviors. Despite this advantage, obesity prevalence among foreign-born black women was around 30%, suggesting that obesity poses a significant health risk this population. Copyright © 2015 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

  2. Nucleotide excision repair is a potential therapeutic target in multiple myeloma

    Science.gov (United States)

    Szalat, R; Samur, M K; Fulciniti, M; Lopez, M; Nanjappa, P; Cleynen, A; Wen, K; Kumar, S; Perini, T; Calkins, A S; Reznichenko, E; Chauhan, D; Tai, Y-T; Shammas, M A; Anderson, K C; Fermand, J-P; Arnulf, B; Avet-Loiseau, H; Lazaro, J-B; Munshi, N C

    2018-01-01

    Despite the development of novel drugs, alkylating agents remain an important component of therapy in multiple myeloma (MM). DNA repair processes contribute towards sensitivity to alkylating agents and therefore we here evaluate the role of nucleotide excision repair (NER), which is involved in the removal of bulky adducts and DNA crosslinks in MM. We first evaluated NER activity using a novel functional assay and observed a heterogeneous NER efficiency in MM cell lines and patient samples. Using next-generation sequencing data, we identified that expression of the canonical NER gene, excision repair cross-complementation group 3 (ERCC3), significantly impacted the outcome in newly diagnosed MM patients treated with alkylating agents. Next, using small RNA interference, stable knockdown and overexpression, and small-molecule inhibitors targeting xeroderma pigmentosum complementation group B (XPB), the DNA helicase encoded by ERCC3, we demonstrate that NER inhibition significantly increases sensitivity and overcomes resistance to alkylating agents in MM. Moreover, inhibiting XPB leads to the dual inhibition of NER and transcription and is particularly efficient in myeloma cells. Altogether, we show that NER impacts alkylating agents sensitivity in myeloma cells and identify ERCC3 as a potential therapeutic target in MM. PMID:28588253

  3. Typing and virulence factors of food-borne Candida spp. isolates.

    Science.gov (United States)

    Rajkowska, Katarzyna; Kunicka-Styczyńska, Alina

    2018-08-20

    Food-borne yeasts, excluding yeasts used as starter cultures, are commonly considered as food spoilage microorganisms. However, the incidence of non-C. albicans Candida (NCAC) infections has increased considerably over the past two decades. Although 15 Candida species are frequently identified as pathogens, a threat to human from food-borne Candida is poorly recognized. In the present study food-borne NCAC were characterized for the virulence factors, known to be associated with yeast pathogenicity. All food-borne strains in planktonic forms and 89% in biofilm structures represented biotypes established for C. albicans, and 61% demonstrated hemolytic activity. 56-94% of food-borne isolates formed biofilms on glass and biomaterials at a level comparable to clinical C. albicans. Nine out of eighteen tested food-borne NCAC strains (C. krusei, C. lusitaniae, C. famata, C. colliculosa, C. parapsilosis, C. tropicalis) showed similarity to clinical C. albicans in terms of their biotypes and the tested virulence factors, allocating them in a group of risk of potential pathogens. However, their capacity to grow at 37 °C seems to be the preliminary criterion in the study of potential virulence of food-borne yeasts. Copyright © 2018 Elsevier B.V. All rights reserved.

  4. 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)

  5. Myocardial Energetics and Heart Failure: a Review of Recent Therapeutic Trials.

    Science.gov (United States)

    Bhatt, Kunal N; Butler, Javed

    2018-06-01

    Several novel therapeutics being tested in patients with heart failure are based on myocardial energetics. This review will provide a summary of the recent trials in this area, including therapeutic options targeting various aspects of cellular and mitochondrial metabolism. Agents that improve the energetic balance in myocardial cells have the potential to improve clinical heart failure status. The most promising therapies currently under investigation in this arena include (1) elamipretide, a cardiolipin stabilizer; (2) repletion of iron deficiency with intravenous ferrous carboxymaltose; (3) coenzyme Q10; and (4) the partial adenosine receptor antagonists capadenoson and neladenosone. Myocardial energetics-based therapeutics are groundbreaking in that they utilize novel mechanisms of action to improve heart failure symptoms, without causing the adverse neurohormonal side effects associated with current guideline-based therapies. The drugs appear likely to be added to the heart failure therapy armamentarium as adjuncts to current regimens in the near future.

  6. Antiangiogenic agents in the treatment of recurrent or newly diagnosed glioblastoma: Analysis of single-agent and combined modality approaches

    International Nuclear Information System (INIS)

    Beal, Kathryn; Abrey, Lauren E; Gutin, Philip H

    2011-01-01

    Surgical resection followed by radiotherapy and temozolomide in newly diagnosed glioblastoma can prolong survival, but it is not curative. For patients with disease progression after frontline therapy, there is no standard of care, although further surgery, chemotherapy, and radiotherapy may be used. Antiangiogenic therapies may be appropriate for treating glioblastomas because angiogenesis is critical to tumor growth. In a large, noncomparative phase II trial, bevacizumab was evaluated alone and with irinotecan in patients with recurrent glioblastoma; combination treatment was associated with an estimated 6-month progression-free survival (PFS) rate of 50.3%, a median overall survival of 8.9 months, and a response rate of 37.8%. Single-agent bevacizumab also exceeded the predetermined threshold of activity for salvage chemotherapy (6-month PFS rate, 15%), achieving a 6-month PFS rate of 42.6% (p < 0.0001). On the basis of these results and those from another phase II trial, the US Food and Drug Administration granted accelerated approval of single-agent bevacizumab for the treatment of glioblastoma that has progressed following prior therapy. Potential antiangiogenic agents-such as cilengitide and XL184-also show evidence of single-agent activity in recurrent glioblastoma. Moreover, the use of antiangiogenic agents with radiation at disease progression may improve the therapeutic ratio of single-modality approaches. Overall, these agents appear to be well tolerated, with adverse event profiles similar to those reported in studies of other solid tumors. Further research is needed to determine the role of antiangiogenic therapy in frontline treatment and to identify the optimal schedule and partnering agents for use in combination therapy

  7. 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…

  8. Hypoxia-Inducible Factors: Mediators of Cancer Progression; Prognostic and Therapeutic Targets in Soft Tissue Sarcomas

    International Nuclear Information System (INIS)

    Sadri, Navid; Zhang, Paul J.

    2013-01-01

    Soft-tissue sarcomas remain aggressive tumors that result in death in greater than a third of patients due to either loco-regional recurrence or distant metastasis. Surgical resection remains the main choice of treatment for soft tissue sarcomas with pre- and/or post-operational radiation and neoadjuvant chemotherapy employed in more advanced stage disease. However, in recent decades, there has been little progress in the average five-year survival for the majority of patients with high-grade soft tissue sarcomas, highlighting the need for improved targeted therapeutic agents. Clinical and preclinical studies demonstrate that tumor hypoxia and up-regulation of hypoxia-inducible factors (HIFs) is associated with decreased survival, increased metastasis, and resistance to therapy in soft tissue sarcomas. HIF-mediated gene expression regulates many critical aspects of tumor biology, including cell survival, metabolic programming, angiogenesis, metastasis, and therapy resistance. In this review, we discuss HIFs and HIF-mediated genes as potential prognostic markers and therapeutic targets in sarcomas. Many pharmacological agents targeting hypoxia-related pathways are in development that may hold therapeutic potential for treating both primary and metastatic sarcomas that demonstrate increased HIF expression

  9. Biologic agents in rheumatology: unmet issues after 200 trials and $200 billion sales.

    Science.gov (United States)

    Ioannidis, John P A; Karassa, Fotini B; Druyts, Eric; Thorlund, Kristian; Mills, Edward J

    2013-11-01

    Anti-TNF agents and other biologic therapies are widely prescribed for a variety of indications, with total sales that exceed $200 billion to date. In rheumatic diseases, biologic agents have now been studied in more than 200 randomized clinical trials and over 100 subsequent meta-analyses; however, the information obtained does not always meet the needs of patients and clinicians. In this Review, we discuss the current issues concerning the evidence derived from such studies: potential biases favouring positive results; a paucity of head-to-head comparisons between biologically active agents; overwhelming involvement of manufacturer sponsors in trials and in the synthesis of the evidence; the preference for trials with limited follow-up; and the potential for spurious findings on adverse events, leading to endless debates about malignancy risk. We debate the responsibilities of regulatory authorities, the pharmaceutical industry and academia in attempting to solve these shortcomings and challenges. We propose that improvements in the evidence regarding biologic treatments that are continually being added to the therapeutic armamentarium for rheumatic diseases might require revisiting the design and conduct of studies. For example, trials with long-term follow-up that are independent of the pharmaceutical industry, head-to-head comparisons of therapeutic agents and the use of rigorous clinical outcomes should be considered, and public availability of raw data endorsed.

  10. Obstetric and psychosocial risk factors for Australian-born and non-Australian born women and associated pregnancy and birth outcomes: a population based cohort study.

    Science.gov (United States)

    Dahlen, Hannah Grace; Barnett, Bryanne; Kohlhoff, Jane; Drum, Maya Elizabeth; Munoz, Ana Maria; Thornton, Charlene

    2015-11-09

    One in four Australians is born overseas and 47% are either born overseas or have a parent who was. Obstetric and psychosocial risk factors for these women may differ. Data from one Sydney hospital (2012-2013) of all births recorded in the ObstetriX database were analysed (n = 3,092). Demographics, obstetric and psychosocial risk profile, obstetric interventions and complications and selected maternal and neonatal outcomes were examined for women born in Australia and overseas. Women born in Australia were younger, more likely to be primiparous (28.6 v 27.5%), be obese (32.0% v 21.4%), smoke (19.7 % v 3.0%), have an epidural (26.2% v 20.2%) and were less likely to have gestational diabetes mellitus (GDM) (6.8% v 13.7% when compared to non-Australian born women. The highest rates of GDM, Gestational Hypertension (GH) and maternal anaemia were seen in women born in China, the Philippines and Pakistan respectively. Differences were also seen in psychosocial screening between Australian and non-Australian women with Australian-born women more likely to smoke and report a mental health disorder. There was an association between having an Edinburgh Postnatal Depression Scale (EPDS) ≥ 13 and other psychosocial issues, such as thoughts of self-harm, domestic violence, childhood abuse etc. These women were also less likely to breastfeed. Women with an EPDS ≥ 13 at booking compared to women with EPDS ≤12 had a higher chance of being diagnosed with GDM (AOR 1.85 95% CI 1.14-3.0). There are significant differences in obstetric and psychosocial risk profiles and maternal and neonatal outcomes between Australian-born and non-Australian born women. In particular there appears to be an association between an EPDS of ≥13 and developing GDM, which warrants further investigation.

  11. Augmentation of therapeutic potential of curcumin using nanotechnology: current perspectives.

    Science.gov (United States)

    Sivasami, Pulavendran; Hemalatha, Thiagarajan

    2018-02-28

    Curcumin, an active principle of Curcuma longa, is extracted from the rhizome. Its therapeutic efficiency has been proved using various in vitro and in vivo models. Inflammatory, neoplastic and preneoplastic diseases are the major targets using curcumin as therapeutic agent. Feasible clinical formulations could not be obtained because of its lack of solubility, stability and higher degradation rate. Recently, many techniques have been evolved to improve the physicochemical properties of pharmacological compounds, thereby increasing their biological activity. Curcumin has been developed using various techniques, particularly micro and nanotechnology to improve its stability and bioavailability. This review focuses on the studies pertaining to the delivery of curcumin in the form of micro and nanosize formulations for the treatment of a variety of diseases.

  12. Helping Oxytocin Deliver: Considerations in the Development of Oxytocin-Based Therapeutics for Brain Disorders.

    Directory of Open Access Journals (Sweden)

    Kai eMacdonald

    2013-03-01

    Full Text Available Concerns regarding a drought in psychopharmacology have risen from many quarters. From one perspective, the wellspring of bedrock medications for anxiety disorders, depression, and schizophrenia was serendipitously discovered over thirty year ago, the swell of pharmaceutical investment in drug discovery has receded, and the pipeline’s flow of medications with unique mechanisms of action (i.e. glutamatergic agents, CRF antagonists has slowed to a trickle. Might oxytocin (OT-based therapeutics be an oasis? Though a large basic science literature and a slowly increasing number of studies in human diseases support this hope, the bulk of extant OT studies in humans are single-dose studies on normals, and do not directly relate to improvements in human brain-based diseases. Instead, these studies have left us with a field pregnant with therapeutic possibilities, but barren of definitive treatments. In this clinically-oriented review, we discuss the extant OT literature with an eye toward helping OT deliver on its promise as a therapeutic agent. To this end, we identify ten key questions that we believe future OT research should address. From this overview, several conclusions are clear: 1 the OT system represents an extremely promising target for novel CNS drug development; 2 there is a pressing need for rigorous, randomized controlled clinical trials targeting actual patients; and 3 in order to inform the design and execution of these vital trials, we need further translational studies addressing the questions posed in this review. Looking forward, we extend a cautious hope that the next decade of OT research will birth oxytocin-targetted therapeutics that can truly deliver on this system’s therapeutic potential.

  13. Firms' degree of born-globalness, international entrepreneurial orientation and export performance

    DEFF Research Database (Denmark)

    Servais, Per; Kuivalainen, Olli; Sundqvist, Sanna

    2007-01-01

    Despite the recent increase in 'born-global' studies, there has been little research on how the scale and scope of being a born-global firm affects performance: most of the earlier research takes no account either the number of or the distances between the countries on firm or export performance...... born-global pathways. The results of our empirical study on 185 Finnish exporting firms show that those that qualified as true born-globals had better export performance. Furthermore, depending on the degree of born-globalness, different dimensions of EO were of importance....

  14. Suboptimal care and maternal mortality among foreign-born women in Sweden

    DEFF Research Database (Denmark)

    Esscher, Annika; Binder-Finnema, Pauline; Bødker, Birgit

    2014-01-01

    that occurred in Sweden from 1988-2010. METHODS: A subset of maternal death records (n = 75) among foreign-born women from low- and middle-income countries and Swedish-born women were audited using structured implicit review. One case of foreign-born maternal death was matched with two native born Swedish cases...... language and suboptimal interpreter system or usage. Inadequate care occurred more often among the foreign-born (p = 0.04), whereas delays in consultation/referral and miscommunication between health care providers where equally common between the two groups. CONCLUSIONS: Suboptimal care factors, major...

  15. 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

  16. Phenotypic Plasticity Determines Cancer Stem Cell Therapeutic Resistance in Oral Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Adrian Biddle

    2016-02-01

    Full Text Available Cancer stem cells (CSCs drive tumour spread and therapeutic resistance, and can undergo epithelial-to-mesenchymal transition (EMT and mesenchymal-to-epithelial transition (MET to switch between epithelial and post-EMT sub-populations. Examining oral squamous cell carcinoma (OSCC, we now show that increased phenotypic plasticity, the ability to undergo EMT/MET, underlies increased CSC therapeutic resistance within both the epithelial and post-EMT sub-populations. The post-EMT CSCs that possess plasticity exhibit particularly enhanced therapeutic resistance and are defined by a CD44highEpCAMlow/−CD24+ cell surface marker profile. Treatment with TGFβ and retinoic acid (RA enabled enrichment of this sub-population for therapeutic testing, through which the endoplasmic reticulum (ER stressor and autophagy inhibitor Thapsigargin was shown to selectively target these cells. Demonstration of the link between phenotypic plasticity and therapeutic resistance, and development of an in vitro method for enrichment of a highly resistant CSC sub-population, provides an opportunity for the development of improved chemotherapeutic agents that can eliminate CSCs.

  17. Phenotypic Plasticity Determines Cancer Stem Cell Therapeutic Resistance in Oral Squamous Cell Carcinoma.

    Science.gov (United States)

    Biddle, Adrian; Gammon, Luke; Liang, Xiao; Costea, Daniela Elena; Mackenzie, Ian C

    2016-02-01

    Cancer stem cells (CSCs) drive tumour spread and therapeutic resistance, and can undergo epithelial-to-mesenchymal transition (EMT) and mesenchymal-to-epithelial transition (MET) to switch between epithelial and post-EMT sub-populations. Examining oral squamous cell carcinoma (OSCC), we now show that increased phenotypic plasticity, the ability to undergo EMT/MET, underlies increased CSC therapeutic resistance within both the epithelial and post-EMT sub-populations. The post-EMT CSCs that possess plasticity exhibit particularly enhanced therapeutic resistance and are defined by a CD44(high)EpCAM(low/-) CD24(+) cell surface marker profile. Treatment with TGFβ and retinoic acid (RA) enabled enrichment of this sub-population for therapeutic testing, through which the endoplasmic reticulum (ER) stressor and autophagy inhibitor Thapsigargin was shown to selectively target these cells. Demonstration of the link between phenotypic plasticity and therapeutic resistance, and development of an in vitro method for enrichment of a highly resistant CSC sub-population, provides an opportunity for the development of improved chemotherapeutic agents that can eliminate CSCs.

  18. Widening and Elaboration of Consecutive Research into Therapeutic Antioxidant Enzyme Derivatives

    Directory of Open Access Journals (Sweden)

    Alexander V. Maksimenko

    2016-01-01

    Full Text Available Undiminishing actuality of enzyme modification for therapeutic purposes has been confirmed by application of modified enzymes in clinical practice and numerous research data on them. Intravenous injection of the superoxide dismutase-chondroitin sulfate-catalase (SOD-CHS-CAT conjugate in preventive and medicative regimes in rats with endotoxin shock induced with a lipopolysaccharide bolus has demonstrated that antioxidant agents not only effectively prevent damage caused by oxidative stress (as believed previously but also can be used for antioxidative stress therapy. The results obtained emphasize the importance of investigation into the pathogenesis of vascular damage and the role of oxidative stress in it. The effects of intravenous medicative injection of SOD-CHS-CAT in a rat model of endotoxin shock have demonstrated a variety in the activity of this conjugate in addition to prevention of NO conversion in peroxynitrite upon interaction with O2∙- superoxide radical. Together with the literature data, these findings offer a prospect for the study of NO-independent therapeutic effects of SOD-CHS-CAT, implying the importance of a better insight into the mechanisms of the conjugate activity in modeled cardiovascular damage involving vasoactive agents other than NO.

  19. Biomedicines?Moving Biologic Agents into Approved Treatment Options

    OpenAIRE

    Cornetta, Kenneth

    2013-01-01

    The development of biologic agents for therapeutic purposes, or biomedicines, has seen an active area of research both at the bench and in clinical trials. There is mounting evidence that biologic products can provide effective therapy for diseases that have been unresponsive to traditional pharmacologic approaches. Monoclonal antibody therapy for cancer and rheumatologic diseases has become a well accepted part of disease treatment plans. Gene therapy products have been approved in China and...

  20. Preschool abilities of children born preterm and low weight

    Directory of Open Access Journals (Sweden)

    Sasha A. Martínez-Espiet

    2018-10-01

    Full Text Available The purpose of this study was to evaluate the development among a group of pre-school children born premature and with low weight. We evaluated a group of four years old children; 20 children born prematurely and 20 children born after a full gestation and desired weight, using the Beery-Buktenica visual-motor integration test. We also administered the Ages and Stages Questionnaire (ASQ-3 development test to all 40 mothers. Statistical analysis was performed using student t test for independent groups. The group of children born prematurely scored significantly lower on tests measuring visual perception skills (µ1 83.65 ; µ2 93.7 (p = 0.0001, visual-motor integration (µ1 93.6 ; µ2 104.8 (p = 0.001 and fine motor (µ1 36.00 ; µ2 44.25 (p=0.033 (p = 0.033, when compared to the group of children born after a full term. This study suggests that premature low weight born children have lower performance in the sensory-motor development during the preschool years. These disadvantages go unnoticed and may represent future delays on school tasks that require these skills. It is important to promote an early assessment and environmental stimulation among this population even in the absence of risk indicators.

  1. A readily applicable strategy to convert peptides to peptoid-based therapeutics.

    Directory of Open Access Journals (Sweden)

    Minyoung Park

    Full Text Available Incorporation of unnatural amino acids and peptidomimetic residues into therapeutic peptides is highly efficacious and commonly employed, but generally requires laborious trial-and-error approaches. Previously, we demonstrated that C20 peptide has the potential to be a potential antiviral agent. Herein we report our attempt to improve the biological properties of this peptide by introducing peptidomimetics. Through combined alanine, proline, and sarcosine scans coupled with a competitive fluorescence polarization assay developed for identifying antiviral peptides, we enabled to pinpoint peptoid-tolerant peptide residues within C20 peptide. The synergistic benefits of combining these (and other commonly employed methods could lead to a easily applicable strategy for designing and refining therapeutically-attractive peptidomimetics.

  2. 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

  3. Solid lipid nanoparticles as attractive drug vehicles: Composition, properties and therapeutic strategies.

    Science.gov (United States)

    Geszke-Moritz, Małgorzata; Moritz, Michał

    2016-11-01

    This work briefly reviews up-to-date developments in solid lipid nanoparticles (SLNs) as effective nanocolloidal system for drug delivery. It summarizes SLNs in terms of their preparation, surface modification and properties. The application of SLNs as a carrier system enables to improve the therapeutic efficacy of drugs from various therapeutic groups. Present uses of SLNs include cancer therapy, dermatology, bacterial infections, brain targeting and eye disorders among others. The usage of SLNs provides enhanced pharmacokinetic properties and modulated release of drugs. SLN ubiquitous application results from their specific features such as possibility of surface modification, increased permeation through biological barriers, resistance to chemical degradation, possibility of co-delivery of various therapeutic agents or stimuli-responsiveness. This paper will be useful to the scientists working in the domain of SLN-based drug delivery systems. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Therapeutic Targeting of CPT-11 Induced Diarrhea: A Case for Prophylaxis

    Science.gov (United States)

    Swami, Umang; Goel, Sanjay; Mani, Sridhar

    2014-01-01

    CPT-11 (irinotecan), a DNA topoisomerase I inhibitor is one of the main treatments for colorectal cancer. The main dose limiting toxicities are neutropenia and late onset diarrhea. Though neutropenia is manageable, CPT-11 induced diarrhea is frequently severe, resulting in hospitalizations, dose reductions or omissions leading to ineffective treatment administration. Many potential agents have been tested in preclinical and clinical studies to prevent or ameliorate CPT-11 induced late onset diarrhea. It is predicted that prophylaxis of CPT-11 induced diarrhea will reduce sub-therapeutic dosing as well as hospitalizations and will eventually lead to dose escalations resulting in better response rates. This article reviews various experimental agents and strategies employed to prevent this debilitating toxicity. Covered topics include schedule/dose modification, intestinal alkalization, structural/chemical modification, genetic testing, anti-diarrheal therapies, transporter (ABCB1, ABCC2, BCRP2) inhibitors, enzyme (β-glucuronidase, UGT1A1, CYP3A4, carboxylesterase, COX-2) inducers and inhibitors, probiotics, antibiotics, adsorbing agents, cytokine and growth factor activators and inhibitors and other miscellaneous agents. PMID:23597015

  5. Increased risk of peanut allergy in infants of Asian-born parents compared to those of Australian-born parents.

    Science.gov (United States)

    Koplin, J J; Peters, R L; Ponsonby, A-L; Gurrin, L C; Hill, D; Tang, M L K; Dharmage, S C; Allen, K J

    2014-12-01

    Asian infants appear to be over-represented among patients with clinical food allergy in Australia, but this has not been formally examined at the population level. Any difference in prevalence according to parental country of birth may be secondary to modifiable lifestyle factors. We aimed to quantify (i) differences in the prevalence of peanut allergy by parental country of birth and (ii) contribution of measured environmental exposures to these differences. The population-based HealthNuts study in Melbourne, Australia, screened 5276 infants (74% participation) with skin prick tests and sensitized infants underwent food challenge. Of these, 535 had a parent born in East Asia and 574 in UK/Europe. Associations between parents' country of birth and offspring peanut allergy were examined using multiple logistic regression. Compared to infants with two Australian-born parents, peanut allergy was more common among infants with parent/s born in East Asia (OR 3.4, 95% CI 2.2-5.1) but not those with parent/s born in the UK/Europe (OR 0.8, 95% CI 0.4-1.5). Paradoxically rates of allergic disease were lower among Asian parents. A higher prevalence of eczema among infants of Asian parents explained around 30% of the increase in peanut allergy, while differences in dog ownership explained around 18%. The high peanut allergy prevalence among infants of Asian-born parents appears to have occurred in a single generation and was not present among infants with parents migrating from other countries, suggesting gene-environment interactions are important. The role of eczema and microbial exposure in food allergy prevention warrants exploration. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Therapeutic potential of the SARMs: revisiting the androgen receptor for drug discovery.

    Science.gov (United States)

    Segal, Scott; Narayanan, Ramesh; Dalton, James T

    2006-04-01

    Selective androgen receptor modulators (SARMS) bind to the androgen receptor and demonstrate anabolic activity in a variety of tissues; however, unlike testosterone and other anabolic steroids, these nonsteroidal agents are able to induce bone and muscle growth, as well as shrinking the prostate. The potential of SARMS is to maximise the positive attributes of steroidal androgens as well as minimising negative effects, thus providing therapeutic opportunities in a variety of diseases, including muscle wasting associated with burns, cancer, end-stage renal disease, osteoporosis, frailty and hypogonadism. This review summarises androgen physiology, the current status of the R&D of SARMS and potential therapeutic indications for this emerging class of drugs.

  7. 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.

  8. Renal candidiasis in newborn: the ultrasonography as diagnostic and therapeutic method

    International Nuclear Information System (INIS)

    Lopez Pino, M.A.; Serrano Hernandez, C.; Alba Romero, C.; Aransay Bramtot, A.; Paul Diaz, L.

    1995-01-01

    We present a case of systemic candidiasis in a low-weight newborn. Renal involvement presented as unilateral hydronephrosis secondary to the fungal construction. Ultrasound served not only as a diagnostic tool, but as a guide for the performance of performance of percutaneous nephrostomy which was included in the therapeutic approach to decompress the excretory pathway and allow local installation of anti fungal agents. (Author) 16 refs

  9. 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.

  10. Volumetric changes of the nose and nasal airway 2 years after tooth-borne and bone-borne surgically assisted rapid maxillary expansion

    NARCIS (Netherlands)

    Nada, R.M.; Loon, B. van; Schols, J.G.J.H.; Maal, T.J.J.; Koning, M.J.J. de; Mostafa, Y.A.; Kuijpers-Jagtman, A.M.

    2013-01-01

    This study aimed to assess the effects of bone-borne and tooth-borne surgically assisted rapid maxillary expansion on the volumes of the nose and nasal airway 2 yr after maxillary expansion. This prospective cohort study included 32 patients with transverse maxillary hypoplasia. Expansion was

  11. Advances in Molecular Imaging of Locally Delivered Targeted Therapeutics for Central Nervous System Tumors

    Directory of Open Access Journals (Sweden)

    Umberto Tosi

    2017-02-01

    Full Text Available Thanks to the recent advances in the development of chemotherapeutics, the morbidity and mortality of many cancers has decreased significantly. However, compared to oncology in general, the field of neuro-oncology has lagged behind. While new molecularly targeted chemotherapeutics have emerged, the impermeability of the blood–brain barrier (BBB renders systemic delivery of these clinical agents suboptimal. To circumvent the BBB, novel routes of administration are being applied in the clinic, ranging from intra-arterial infusion and direct infusion into the target tissue (convection enhanced delivery (CED to the use of focused ultrasound to temporarily disrupt the BBB. However, the current system depends on a “wait-and-see” approach, whereby drug delivery is deemed successful only when a specific clinical outcome is observed. The shortcomings of this approach are evident, as a failed delivery that needs immediate refinement cannot be observed and corrected. In response to this problem, new theranostic agents, compounds with both imaging and therapeutic potential, are being developed, paving the way for improved and monitored delivery to central nervous system (CNS malignancies. In this review, we focus on the advances and the challenges to improve early cancer detection, selection of targeted therapy, and evaluation of therapeutic efficacy, brought forth by the development of these new agents.

  12. Advances in Molecular Imaging of Locally Delivered Targeted Therapeutics for Central Nervous System Tumors

    Science.gov (United States)

    Tosi, Umberto; Marnell, Christopher S.; Chang, Raymond; Cho, William C.; Ting, Richard; Maachani, Uday B.; Souweidane, Mark M.

    2017-01-01

    Thanks to the recent advances in the development of chemotherapeutics, the morbidity and mortality of many cancers has decreased significantly. However, compared to oncology in general, the field of neuro-oncology has lagged behind. While new molecularly targeted chemotherapeutics have emerged, the impermeability of the blood–brain barrier (BBB) renders systemic delivery of these clinical agents suboptimal. To circumvent the BBB, novel routes of administration are being applied in the clinic, ranging from intra-arterial infusion and direct infusion into the target tissue (convection enhanced delivery (CED)) to the use of focused ultrasound to temporarily disrupt the BBB. However, the current system depends on a “wait-and-see” approach, whereby drug delivery is deemed successful only when a specific clinical outcome is observed. The shortcomings of this approach are evident, as a failed delivery that needs immediate refinement cannot be observed and corrected. In response to this problem, new theranostic agents, compounds with both imaging and therapeutic potential, are being developed, paving the way for improved and monitored delivery to central nervous system (CNS) malignancies. In this review, we focus on the advances and the challenges to improve early cancer detection, selection of targeted therapy, and evaluation of therapeutic efficacy, brought forth by the development of these new agents. PMID:28208698

  13. The antioxidant paradox: what are antioxidants and how should they be used in a therapeutic context for cancer.

    Science.gov (United States)

    Bonner, Michael Y; Arbiser, Jack L

    2014-01-01

    So-called antioxidants have yet to make a clinical impact on the treatment of human cancer. The reasons for this failure are several. First, many agents that are called antioxidants are truly antioxidants at a given dose, but this dose may not have been given in clinical trials. Second, many agents are not antioxidants at all. Third, not all tumors use reactive oxygen as a signaling mechanism. Finally, reactive oxygen inhibition is often insufficient to kill or regress a tumor cell by itself, but requires sequential introduction of a therapeutic agent for maximal effect. We hope to provide a framework for the logical use of these agents in cancer.

  14. Bacterial food-borne pathogens in Indian food

    International Nuclear Information System (INIS)

    Bandekar, J.R.

    2015-01-01

    Food technology and food processing techniques have made tremendous advances in preservation of food and ensuring safety of food by killing food-borne pathogens. In addition to old techniques such as pasteurization, canning, dehydration, fermentation and salting, a number of new techniques such as radiation processing, high pressure technology and pulsed electric field technology are being applied for preservation of food and to ensure food safety. Total Quality Management (TQM) concepts have been developed to take care of food safety from farm to table. Hazard Analysis at Critical Control Points (HACCP) is being applied for mass scale production of food to make food free from pathogens. Despite these advances, food-borne diseases have become one of the most widespread public health problems in the world. About two thirds of all the outbreaks are traced to microbial contaminated food. According to World Health Organization (WHO) estimates, food-borne and waterborne diarrhoeal diseases kill an estimated 2 million people annually, including many children. Food safety is a major concern not only for developing countries but also for the developed countries. A number of factors such as emergence of new food-borne pathogens, development of drug resistance in pathogens, changing life style, globalization of the food supply etc. are responsible for the continuous persistence of food-borne diseases. The food-borne disease outbreaks due to E. coli O157:H7, Listeria monocytogenes, Salmonella and Campylobacter, are responsible for recall of many foods resulting in heavy losses to food industry. Due to consumer demand, a number of Ready-To-Eat (RTE) minimally processed foods are increasingly marketed; however, there is increased risk of foodborne diseases with these products. Food Technology Division of Bhabha Atomic Research Centre, Mumbai, has been working on food-borne bacterial pathogens particularly Salmonella, Campylobacter, Listeria monocytogenes, Vibrio and Aeromonasf

  15. A Prokinetic Agent with a Dual Effect – Itopride – In the Treatment of Dysmotility

    OpenAIRE

    Petr Dite; Martin Rydlo; Milan Dockal; Arnost Martinek

    2014-01-01

    A wide range of dyspeptic symptoms in clinical practice reflect the high prevalence of functional disorders of the gastrointestinal (GI) tract. Prokinetic agents are the current mainstay in the therapy of functional dyspepsia. One of these drugs is itopride. We evaluated therapeutic efficacy of itopride according to the literature review. The therapeutic potential of itopride is connected with a dual effect: influencing of enzyme acetylcholinesterase activity and blocking dopamine D2 receptor...

  16. Magic moment? Maternal marriage for children born out of wedlock.

    Science.gov (United States)

    Gibson-Davis, Christina

    2014-08-01

    To test the existence of the "magic moment" for parental marriage immediately post-birth and to inform policies that preferentially encourage biological over step parent marriage, this study estimates the incidence and stability of maternal marriage for children born out of wedlock. Data came from the National Survey of Family Growth on 5,255 children born non maritally. By age 15, 29 % of children born non maritally experienced a biological-father marriage, and 36 % experienced a stepfather marriage. Stepfather marriages occurred much later in a child's life-one-half occurred after the child turned age 7-and had one-third higher odds of dissolution. Children born to black mothers had qualitatively different maternal marriage experiences than children born to white or Hispanic mothers, with less biological-parent marriage and higher incidences of divorce. Findings support the existence of the magic moment and demonstrate that biological marriages were more enduring than stepfather marriages. Yet relatively few children born out of wedlock experienced stable, biological-parent marriages as envisioned by marriage promotion programs.

  17. Oral (Systemic) Botanical Agents for the Treatment of Psoriasis: A Review.

    Science.gov (United States)

    Farahnik, Benjamin; Sharma, Divya; Alban, Joseph; Sivamani, Raja

    2017-06-01

    Patients with psoriasis often use botanical therapies as part of their treatment. It is important for clinicians to be aware of the current evidence regarding these agents as they treat patients. A systematic literature search was conducted using the PubMed, MEDLINE, and EMBASE database for randomized clinical trials assessing the use of botanical therapeutics for psoriasis. The search included the following keywords: "psoriasis" and "plant" or "herbal" or "botanical." Citations within articles were also reviewed to identify relevant sources. The results were then further refined by route of administration, and the oral (systemic) botanical agents are reviewed herein. A total of 12 controlled and uncontrolled clinical trials addressing the use of oral, systemic botanical agents for psoriasis were assessed in this review. While overall evidence is limited in quantity and quality, HESA-A, curcumin, neem extract, and, to a lesser degree, Traditional Chinese Medicine seem to be the most efficacious agents. The literature addresses a large amount of studies in regards to botanicals for the treatment of psoriasis. While most agents appear to be safe, further research is necessary for evidence-based recommendation of oral botanical agents to psoriasis patients.

  18. Acquired hemophilia A: a review of recent data and new therapeutic options.

    Science.gov (United States)

    Franchini, Massimo; Vaglio, Stefania; Marano, Giuseppe; Mengoli, Carlo; Gentili, Sara; Pupella, Simonetta; Liumbruno, Giancarlo Maria

    2017-10-01

    Acquired hemophilia A (AHA) is a rare, but potentially life-threatening, bleeding disorder caused by an autoantibody against factor VIII that interferes with its coagulant function. We performed a narrative review focusing on the diagnostic aspects of AHA and on the current treatment strategies with particular regard to new data and therapeutic developments. The management of this severe hemorrhagic disorder is based on the control of bleeding with the use of bypassing agents and on the utilization of a variety of immunosuppressant agents with the goal of eliminating the autoantibody permanently. The optimal management of AHA should be multidisciplinary and requires a close collaboration between physicians from various specialties.

  19. Gynecologic cancer treatment: risk factors for therapeutically induced neoplasia

    International Nuclear Information System (INIS)

    Messerschmidt, G.L.; Hoover, R.; Young, R.C.

    1980-01-01

    Therapeutic intervention in a course of illness, while producing the desired result, also may have some adverse long-term effects on the patient. Second malignancies are one of the known complications of therapy. The treatments of gynecologic cancers by surgery, irradiation and chemotherapy have been associated with subsequent neoplasms. The use of normal skin from the thigh to fabricate an artificial vagina has resulted in more squamous cell carcinomas than expected. Alkylating agents used in the treatment of ovarian cancer and other diseases have been shown to lead to an increased risk of leukemia. The incidence of lymphoma and uterine, urinary bladder and colon carcinomas has been associated with prior irradiation for gynecologic disease. The literature regarding the therapeutically induced risk factors in gynecologic therapy is reviewed and areas of our knowledge that require more investigation are identified

  20. Assessing the Diversity of Rodent-Borne Viruses: Exploring of High-Throughput Sequencing and Classical Amplification/Sequencing Approaches.

    Science.gov (United States)

    Drewes, Stephan; Straková, Petra; Drexler, Jan F; Jacob, Jens; Ulrich, Rainer G

    2017-01-01

    Rodents are distributed throughout the world and interact with humans in many ways. They provide vital ecosystem services, some species are useful models in biomedical research and some are held as pet animals. However, many rodent species can have adverse effects such as damage to crops and stored produce, and they are of health concern because of the transmission of pathogens to humans and livestock. The first rodent viruses were discovered by isolation approaches and resulted in break-through knowledge in immunology, molecular and cell biology, and cancer research. In addition to rodent-specific viruses, rodent-borne viruses are causing a large number of zoonotic diseases. Most prominent examples are reemerging outbreaks of human hemorrhagic fever disease cases caused by arena- and hantaviruses. In addition, rodents are reservoirs for vector-borne pathogens, such as tick-borne encephalitis virus and Borrelia spp., and may carry human pathogenic agents, but likely are not involved in their transmission to human. In our days, next-generation sequencing or high-throughput sequencing (HTS) is revolutionizing the speed of the discovery of novel viruses, but other molecular approaches, such as generic RT-PCR/PCR and rolling circle amplification techniques, contribute significantly to the rapidly ongoing process. However, the current knowledge still represents only the tip of the iceberg, when comparing the known human viruses to those known for rodents, the mammalian taxon with the largest species number. The diagnostic potential of HTS-based metagenomic approaches is illustrated by their use in the discovery and complete genome determination of novel borna- and adenoviruses as causative disease agents in squirrels. In conclusion, HTS, in combination with conventional RT-PCR/PCR-based approaches, resulted in a drastically increased knowledge of the diversity of rodent viruses. Future improvements of the used workflows, including bioinformatics analysis, will further

  1. 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.

  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. 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.

  4. Term infants born at home in Peru are less likely to be hospitalised in the neonatal period than those born in hospital.

    Science.gov (United States)

    Lavin, Tina; Preen, David B

    2017-08-01

    More than 50% of women worldwide give birth at home, but little is known about home birth and subsequent neonatal hospitalisation. The objective of the study was to investigate home birth and neonatal hospitalisation of term neonates in Peru. The relationship between birth setting [home - with or without skilled birth attendant (SBA), health centre, hospital] and neonatal hospitalisation (n = 1656) and incubator care (n = 1651) was investigated using data from the 2002 Young Lives Study. Infants were sampled from 20 sentinel sites across Peru. At each sentinel site 100 households with children aged 6-18 months were randomly sampled (therefore the sample only captured children surviving to 6 months of age). Multivariate regression modelling was used with models adjusted for a range of demographic and clinical factors. After adjustment, the odds of hospitalisation were lower in neonates born at home (with SBA OR 0.20, 95% CI 0.0-0.8, p = 0.021; without SBA OR = 0.4, 95% CI 0.2-0.7, p = 0.002) than in those born in hospital. Socio-demographic factors such as ethnicity, rural living, education, socio-economic status and access to transport did not influence neonatal hospitalisation, time in hospital, incubator care or time under incubator care. Neonates born at home were less likely to be hospitalised after birth owing to neonatal morbidity than neonates born in hospital. It is unclear whether this finding reflects poorer accessibility to hospital care for neonates born at home, or if neonates born at home required hospitalisation less frequently than neonates born in hospital owing to lower neonatal morbidity or other factors such as lower rates of medical intervention for home births. Further research is needed to explore the underlying mechanisms of these findings.

  5. Acquired thrombotic thrombocytopenic purpura: new therapeutic options and their optimal use.

    Science.gov (United States)

    Cataland, S R; Wu, H M

    2015-06-01

    Advances in our understanding of the pathophysiology of both congenital and acquired thrombotic thrombocytopenic purpura (TTP) have led to both an increased understanding of the disease and novel approaches to therapy. The efficacy of rituximab in acquired TTP has led to consideration of rituximab as a prophylactic therapy to prevent relapse of TTP. Novel therapies that target the A1 domain of von Willebrand factor (VWF) to block the formation of microthrombotic disease have also entered clinical study and have demonstrated promise as potential therapeutic options. Additionally, a recombinant ADAMTS13 protease has been developed which may be an important therapeutic option for both congenital and acquired TTP. The development of these new therapeutic options for patients diagnosed with TTP has increased the importance of conducting prospective, randomized studies with these agents to both confirm their efficacy and more importantly understand their most appropriate role in the treatment of patients with TTP. © 2015 International Society on Thrombosis and Haemostasis.

  6. Cancer in children and young adults born after assisted reproductive technology

    DEFF Research Database (Denmark)

    Sundh, Karin Jerhamre; Henningsen, Anna-Karina A; Källen, Karin

    2014-01-01

    STUDY QUESTION: Do children and young adults born after assisted reproductive technology (ART) have an increased risk of cancer? SUMMARY ANSWER: Children born after ART showed no overall increase in the rate of cancer when compared with children born as a result of spontaneous conception. WHAT...... IS KNOWN ALREADY: Children born after ART have more adverse perinatal outcomes, i.e. preterm births, low birthweights and birth defects. Previous studies have shown divergent results regarding the risk of cancer among children born after ART. STUDY DESIGN, SIZE, DURATION: A retrospective Nordic population...... group of children born after spontaneous conception. This control group was almost 4-fold the size of the ART group (n = 358 419) and matched for parity, year of birth and country. Data on perinatal outcomes and cancer were obtained from the National Medical Birth Registries, the Cancer Registries...

  7. 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.

  8. Therapeutic effects of saffron (Crocus sativus L. in digestive disorders: a review

    Directory of Open Access Journals (Sweden)

    Alireza Rezaee Khorasany

    2016-05-01

    Full Text Available Saffron, the dried red-orange stigmas of Crocus sativus L, has been known as a flavoring agent, food coloring and traditional herbal medicine. Pharmacological effects of saffron are mainly attributed to crocin, crocetin, picrocrocin and safranal. These components especially crocin, have significant effects including antidepressant and anticonvulsant, analgesic, anti-cancer and other therapeutic effects on different parts of our body namely cardiovascular, immune, respiratory, genital-urinary and central nervous system. According to the reports and findings, saffron plays a key role to cure different digestive system disorders via chemopreventive, inhibition of cell proliferation, induction of apoptosis, antioxidant effects and radical scavenging, genoprotective property, prevention of lipid peroxidation and anti-inflammatory processes. The outcome of the above mentioned mechanisms shows potential therapeutic properties of saffron against liver cancer, hepatotoxicity, fatty liver, hyperlipidemia, stomach cancer, peptic ulcer, colon cancer, ulcerative colitis, diabetes and pancreas cancer and ileum contractions. According to global statistics, the susceptibility to intestinal diseases is considered as a significant matter and can be important in health planning in any community. Several strategies for treatment and prevention of the digestive system diseases have provided that the use of herbal remedies seems effective and useful. Considering the available findings, the present study aims to introduce saffron as a prophylactic and therapeutic agent against gastrointestinal tract disorders. However, further clinical studies seem necessary in various aspects of saffron effects in different parts of body to verify these findings.

  9. Heat engines for dilatonic Born-Infeld black holes

    Energy Technology Data Exchange (ETDEWEB)

    Bhamidipati, Chandrasekhar; Yerra, Pavan Kumar [Indian Institute of Technology Bhubaneswar, School of Basic Sciences, Bhubaneswar (India)

    2017-08-15

    In the context of dilaton coupled Einstein gravity with a negative cosmological constant and a Born-Infeld field, we study heat engines where a charged black hole is the working substance. Using the existence of a notion of thermodynamic mass and volume (which depend on the dilaton coupling), the mechanical work takes place via the pdV terms present in the first law of extended gravitational thermodynamics. The efficiency is analyzed as a function of dilaton and Born-Infeld couplings, and the results are compared with analogous computations in the related conformal solutions in the Brans-Dicke-Born-Infeld theory and black holes in anti-de Sitter space-time. (orig.)

  10. Recent developments in antiviral agents against enterovirus 71 infection.

    Science.gov (United States)

    Tan, Chee Wah; Lai, Jeffrey Kam Fatt; Sam, I-Ching; Chan, Yoke Fun

    2014-02-12

    Enterovirus 71 (EV-71) is the main etiological agent of hand, foot and mouth disease (HFMD). Recent EV-71 outbreaks in Asia-Pacific were not limited to mild HFMD, but were associated with severe neurological complications such as aseptic meningitis and brainstem encephalitis, which may lead to cardiopulmonary failure and death. The absence of licensed therapeutics for clinical use has intensified research into anti-EV-71 development. This review highlights the potential antiviral agents targeting EV-71 attachment, entry, uncoating, translation, polyprotein processing, virus-induced formation of membranous RNA replication complexes, and RNA-dependent RNA polymerase. The strategies for antiviral development include target-based synthetic compounds, anti-rhinovirus and poliovirus libraries screening, and natural compound libraries screening. Growing knowledge of the EV-71 life cycle will lead to successful development of antivirals. The continued effort to develop antiviral agents for treatment is crucial in the absence of a vaccine. The coupling of antivirals with an effective vaccine will accelerate eradication of the disease.

  11. Large baby syndrome in singletons born after frozen embryo transfer (FET)

    DEFF Research Database (Denmark)

    Pinborg, Anja; Henningsen, AA; Loft, A

    2013-01-01

    Are singletons born after frozen embryo transfer (FET) at increased risk of being born large for gestational age (LGA) and if so, is this caused by intrinsic maternal factors or related to the freezing/thawing procedures?......Are singletons born after frozen embryo transfer (FET) at increased risk of being born large for gestational age (LGA) and if so, is this caused by intrinsic maternal factors or related to the freezing/thawing procedures?...

  12. 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

  13. 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.

  14. 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...

  15. Three-dimensional evaluation of soft tissue changes in the orofacial region after tooth-borne and bone-borne surgically assisted rapid maxillary expansion

    NARCIS (Netherlands)

    Nada, R.M.; Loon, B. van; Maal, T.J.J.; Berge, S.J.; Mostafa, Y.A.; Kuijpers-Jagtman, A.M.; Schols, J.G.J.H.

    2013-01-01

    OBJECTIVES: This study seeks to three-dimensionally assess soft tissue changes in the orofacial region following tooth-borne and bone-borne surgically assisted rapid maxillary expansion (SARME). MATERIALS AND METHODS: This prospective cohort study included 40 skeletally mature patients with

  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. The sexual and reproductive health of foreign-born women in the United States.

    Science.gov (United States)

    Tapales, Athena; Douglas-Hall, Ayana; Whitehead, Hannah

    2018-02-14

    To explore the sexual and reproductive health (SRH) behaviors, health insurance coverage and use of SRH services of women in the United States (U.S.) by nativity, disaggregated by race and ethnicity. We analyzed publicly available and restricted data from the National Survey of Family Growth to assess differences and similarities between foreign-born and U.S.-born women, both overall and within Hispanic, non-Hispanic (NH) white, NH black and NH Asian groups. A larger proportion of foreign-born women than U.S.-born women lacked health insurance coverage. Foreign-born women utilized SRH services at lower rates than U.S.-born women; this effect diminished at the multivariate level, although race and ethnicity differences remained. Overall, foreign-born women were less likely to pay for SRH services with private insurance than U.S.-born women. Foreign-born women were less likely to use the most effective contraceptive methods than U.S.-born women, with some variation across race and ethnicity: NH white and NH black foreign-born women were less likely to use highly effective contraceptive methods than their U.S.-born counterparts, but among Hispanic women, the reverse was true. Our findings demonstrate that the SRH behaviors, needs and outcomes of foreign-born women differ from those of U.S-born women within the same race/ethnic group. This paper contributes to the emergent literature on immigrants in the U.S. by laying the foundation for further research on the SRH of the foreign-born population in the country, which is critical for developing public health policies and programs to understand better and serve this growing and diverse population. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  18. Nanocomposite scaffolds with tunable mechanical and degradation capabilities: co-delivery of bioactive agents for bone tissue engineering.

    Science.gov (United States)

    Cattalini, Juan P; Roether, Judith; Hoppe, Alexander; Pishbin, Fatemeh; Haro Durand, Luis; Gorustovich, Alejandro; Boccaccini, Aldo R; Lucangioli, Silvia; Mouriño, Viviana

    2016-10-21

    Novel multifunctional nanocomposite scaffolds made of nanobioactive glass and alginate crosslinked with therapeutic ions such as calcium and copper were developed for delivering therapeutic agents, in a highly controlled and sustainable manner, for bone tissue engineering. Alendronate, a well-known antiresorptive agent, was formulated into microspheres under optimized conditions and effectively loaded within the novel multifunctional scaffolds with a high encapsulation percentage. The size of the cation used for the alginate crosslinking impacted directly on porosity and viscoelastic properties, and thus, on the degradation rate and the release profile of copper, calcium and alendronate. According to this, even though highly porous structures were created with suitable pore sizes for cell ingrowth and vascularization in both cases, copper-crosslinked scaffolds showed higher values of porosity, elastic modulus, degradation rate and the amount of copper and alendronate released, when compared with calcium-crosslinked scaffolds. In addition, in all cases, the scaffolds showed bioactivity and mechanical properties close to the endogenous trabecular bone tissue in terms of viscoelasticity. Furthermore, the scaffolds showed osteogenic and angiogenic properties on bone and endothelial cells, respectively, and the extracts of the biomaterials used promoted the formation of blood vessels in an ex vivo model. These new bioactive nanocomposite scaffolds represent an exciting new class of therapeutic cell delivery carrier with tunable mechanical and degradation properties; potentially useful in the controlled and sustainable delivery of therapeutic agents with active roles in bone formation and angiogenesis, as well as in the support of cell proliferation and osteogenesis for bone tissue engineering.

  19. 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.

  20. 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.

  1. Power in the hypnotic relationship: therapeutic or abusive?

    Science.gov (United States)

    Walling, D P; Levine, R E

    1997-01-01

    The unique relationship between hypnotist and subject has been theorized as one explanation for the effectiveness of hypnosis. This relationship carries a power differential, present in most therapeutic relationships, but accentuated by hypnosis. The power differential is sometimes perceived as the ability of the hypnotist to control the subject. Perceptions of hypnosis offered by stage hypnotists, the popular media, and some clinicians perpetuate the notion that the hypnotist has the ability to exert undue influence upon the client. The present article examines the relationship between hypnotist and subject focusing on issues of power and control. The authors examine the unique dynamics accompanying the use of hypnosis and their impact on the therapeutic dyad. Evidence is offered demonstrating the power differential, and how this differential can serve as either a positive or negative agent of change. Therapists should be aware of the dynamics created by using hypnosis. Implications for training therapists in the use of hypnosis are suggested.

  2. 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.

  3. International Pricing Strategies for Born-Global Firms

    Directory of Open Access Journals (Sweden)

    Michael Neubert

    2017-10-01

    Full Text Available This paper aims to understand how born global firms develop their international pricing strategies, practices, and models. It aims to expand the study of international entrepreneurship and born global firms by including a broader and deeper range of pricing aspects than is normally found in the international entrepreneurship and pricing literature. The paper opted for a multiple case-study research design using different sources of evidence, including four in-depth interviews with CEOs of born global firms. The case-study firms were selected using a purposive selection method. The theoretical framework of Ingenbleek, Frambach & Verhallen is used. The results suggest that successful leaders act as ‘integrating forces’ on two levels: by applying a structured and disciplined price-setting process with regular reviews and by mediating between corporate financial goals and the local market reality. The results support the claim that policy makers should offer insights, training and financial support to give promising born global firms the possibility to select the most efficient international pricing models and strategies. The results are relevant for entrepreneurs to understand the importance of efficient price-modelling processes and the influence of the different price strategies and price models on financial results and sales revenues.

  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. Current and Emerging Topical Antibacterials and Antiseptics: Agents, Action, and Resistance Patterns.

    Science.gov (United States)

    Williamson, Deborah A; Carter, Glen P; Howden, Benjamin P

    2017-07-01

    Bacterial skin infections represent some of the most common infectious diseases globally. Prevention and treatment of skin infections can involve application of a topical antimicrobial, which may be an antibiotic (such as mupirocin or fusidic acid) or an antiseptic (such as chlorhexidine or alcohol). However, there is limited evidence to support the widespread prophylactic or therapeutic use of topical agents. Challenges involved in the use of topical antimicrobials include increasing rates of bacterial resistance, local hypersensitivity reactions (particularly to older agents, such as bacitracin), and concerns about the indiscriminate use of antiseptics potentially coselecting for antibiotic resistance. We review the evidence for the major clinical uses of topical antibiotics and antiseptics. In addition, we review the mechanisms of action of common topical agents and define the clinical and molecular epidemiology of antimicrobial resistance in these agents. Moreover, we review the potential use of newer and emerging agents, such as retapamulin and ebselen, and discuss the role of antiseptic agents in preventing bacterial skin infections. A comprehensive understanding of the clinical efficacy and drivers of resistance to topical agents will inform the optimal use of these agents to preserve their activity in the future. Copyright © 2017 American Society for Microbiology.

  6. Screening of Anti-Obesity Agent from Herbal Mixtures

    Directory of Open Access Journals (Sweden)

    Sung-Kee Jo

    2012-03-01

    Full Text Available Globally, one in three of the World’s adults are overweight and one in 10 is obese. By 2015, World Health Organization (WHO estimates the number of chubby adults will balloon to 2.3 billion—Equal to the combined populations of China, Europe and the United States. The discovery of bioactive compounds from herbs is one possible way to control obesity and to prevent or reduce the risks of developing various obesity-related diseases. In this study, we screened anti-obesity agents such as methyl gallate from the herbal composition known as HemoHIM that actively inhibits lipid formation as evidenced by Oil Red O staining and triglyceride (TG contents in 3T3-L1 adipocytes, suggesting their use as an anti-obesity agent. Furthermore, the amount of glycerol released from cells into the medium had increased by treatment of methyl gallate in a concentration-dependent manner. The present study suggests that a promising anti-obesity agent like methyl gallate might be of therapeutic interest for the treatment of obesity.

  7. Screening of anti-obesity agent from herbal mixtures.

    Science.gov (United States)

    Roh, Changhyun; Jung, Uhee; Jo, Sung-Kee

    2012-03-23

    Globally, one in three of the World's adults are overweight and one in 10 is obese. By 2015, World Health Organization (WHO) estimates the number of chubby adults will balloon to 2.3 billion--Equal to the combined populations of China, Europe and the United States. The discovery of bioactive compounds from herbs is one possible way to control obesity and to prevent or reduce the risks of developing various obesity-related diseases. In this study, we screened anti-obesity agents such as methyl gallate from the herbal composition known as HemoHIM that actively inhibits lipid formation as evidenced by Oil Red O staining and triglyceride (TG) contents in 3T3-L1 adipocytes, suggesting their use as an anti-obesity agent. Furthermore, the amount of glycerol released from cells into the medium had increased by treatment of methyl gallate in a concentration-dependent manner. The present study suggests that a promising anti-obesity agent like methyl gallate might be of therapeutic interest for the treatment of obesity.

  8. Birth origin differentially affects depressive-like behaviours: are captive-born cynomolgus monkeys more vulnerable to depression than their wild-born counterparts?

    Directory of Open Access Journals (Sweden)

    Sandrine M J Camus

    Full Text Available BACKGROUND: Adverse early-life experience might lead to the expression of abnormal behaviours in animals and the predisposition to psychiatric disorder (e.g. major depressive disorder in Humans. Common breeding processes employ weaning and housing conditions different from what happens in the wild. METHODS: The present study, therefore, investigated whether birth origin impacts the possible existence of spontaneous atypical/abnormal behaviours displayed by 40 captive-born and 40 wild-born socially-housed cynomolgus macaques in farming conditions using an unbiased ethological scan-sampling analysis followed by multifactorial correspondence and hierarchical clustering analyses. RESULTS: We identified 10 distinct profiles (groups A to J that significantly differed on several behaviours, body postures, body orientations, distances between individuals and locations in the cage. Data suggest that 4 captive-born and 1 wild-born animals (groups G and J present depressive-like symptoms, unnatural early life events thereby increasing the risk of developing pathological symptoms. General differences were also highlighted between the captive- and wild-born populations, implying the expression of differential coping mechanisms in response to the same captive environment. CONCLUSIONS: Birth origin thus impacts the development of atypical ethologically-defined behavioural profiles, reminiscent of certain depressive-like symptoms. The use of unbiased behavioural observations might allow the identification of animal models of human mental/behavioural disorders and their most appropriate control groups.

  9. First- and second-born adolescents' decision-making autonomy throughout adolescence.

    Science.gov (United States)

    Campione-Barr, Nicole; Lindell, Anna K; Short, Stephen D; Greer, Kelly Bassett; Drotar, Scott D

    2015-12-01

    First- and second-born adolescents' and their parents' perceptions of adolescents' decision-making autonomy were compared from ages 12 to 19 in a longitudinal sample of 145 predominantly White, middle class families. Utilizing a multivariate, multilevel modeling approach, differences in perceptions of adolescents' autonomy between parents and each adolescent, as well as by social-cognitive domain were examined. The present study found that when comparing parents' perceptions of their children at the same age, second-borns were granted more autonomy regarding conventional issues than first-borns during early adolescence, but by later adolescence first-borns were granted more autonomy regarding prudential issues than second-borns. However, comparisons between adolescents' and siblings' perceptions showed no differences. Potential reasons for, and implications of, differences in perceptions of adolescent autonomy are discussed. Copyright © 2015 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

  10. Towards new therapeutic approaches for malignant melanoma.

    Science.gov (United States)

    Pacheco, Ivan; Buzea, Cristina; Tron, Victor

    2011-11-01

    Recent progress in understanding the molecular mechanisms of the initiation and progression of melanoma has created new opportunities for developing novel therapeutic modalities to manage this potentially lethal disease. Although at first glance, melanoma carcinogenesis appears to be a chaotic system, it is indeed, arguably, a deterministic multistep process involving sequential alterations of proto-oncogenes, tumour suppressors and miRNA genes. The scope of this article is to discuss the most recent and significant advances in melanoma molecular therapeutics. It is apparent that using single agents targeting solely individual melanoma pathways might be insufficient for long-term survival. However, the outstanding results on melanoma survival observed with novel selective inhibitors of B-RAF, such as PLX4032 give hope that melanoma can be cured. The fact that melanoma develops acquired resistance to PLX4032 emphasises the importance of simultaneously targeting several pathways. Because the most striking feature of melanoma is its unsurpassed ability to metastasise, it is important to implement newer systems for drug delivery adapted from research on stem cells and nanotechnology.

  11. Dried blood spot analysis for therapeutic drug monitoring of linezolid in patients with multidrug-resistant tuberculosis

    NARCIS (Netherlands)

    Vu, D H; Bolhuis, M S; Koster, R A; Greijdanus, B; de Lange, W C M; van Altena, R; Brouwers, J R B J; Uges, D R A; Alffenaar, J W C

    2012-01-01

    Linezolid is a promising antimicrobial agent for the treatment of multidrug-resistant tuberculosis (MDR-TB), but its use is limited by toxicity. Therapeutic drug monitoring (TDM) may help to minimize toxicity while adequate drug exposure is maintained. Conventional plasma sampling and monitoring

  12. 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

  13. Emerging vector borne diseases – incidence through vectors

    Directory of Open Access Journals (Sweden)

    Sara eSavic

    2014-12-01

    Full Text Available Vector borne diseases use to be a major public health concern only in tropical and subtropical areas, but today they are an emerging threat for the continental and developed countries also. Nowdays, in intercontinetal countries, there is a struggle with emerging diseases which have found their way to appear through vectors. Vector borne zoonotic diseases occur when vectors, animal hosts, climate conditions, pathogens and susceptible human population exist at the same time, at the same place. Global climate change is predicted to lead to an increase in vector borne infectious diseases and disease outbreaks. It could affect the range and popultion of pathogens, host and vectors, transmission season, etc. Reliable surveilance for diseases that are most likely to emerge is required. Canine vector borne diseases represent a complex group of diseases including anaplasmosis, babesiosis, bartonellosis, borreliosis, dirofilariosis, erlichiosis, leishmaniosis. Some of these diseases cause serious clinical symptoms in dogs and some of them have a zoonotic potential with an effect to public health. It is expected from veterinarians in coordination with medical doctors to play a fudamental role at primeraly prevention and then treatment of vector borne diseases in dogs. The One Health concept has to be integrated into the struggle against emerging diseases.During a four year period, from 2009-2013, a total number of 551 dog samples were analysed for vector borne diseases (borreliosis, babesiosis, erlichiosis, anaplasmosis, dirofilariosis and leishmaniasis in routine laboratory work. The analysis were done by serological tests – ELISA for borreliosis, dirofilariosis and leishmaniasis, modified Knott test for dirofilariosis and blood smear for babesiosis, erlichiosis and anaplasmosis. This number of samples represented 75% of total number of samples that were sent for analysis for different diseases in dogs. Annually, on avarege more then half of the samples

  14. High cancer mortality for US-born Latinos: evidence from California and Texas.

    Science.gov (United States)

    Pinheiro, Paulo S; Callahan, Karen E; Gomez, Scarlett Lin; Marcos-Gragera, Rafael; Cobb, Taylor R; Roca-Barcelo, Aina; Ramirez, Amelie G

    2017-07-11

    Latinos born in the US, 36 million, comprise 65% of all US Latinos. Yet their cancer experience is nearly always analyzed together with their foreign-born counterparts, 19 million, who constitute a steady influx of truly lower-risk populations from abroad. To highlight specific cancer vulnerabilities for US-born Latinos, we compare their cancer mortality to the majority non-Latino white (NLW) population, foreign-born Latinos, and non-Latino blacks. We analyzed 465,751 cancer deaths from 2008 to 2012 occurring among residents of California and Texas, the two most populous states, accounting for 47% of US Latinos. This cross-sectional analysis, based on granular data obtained from death certificates on cause of death, age, race, ethnicity and birthplace, makes use of normal standardization techniques and negative binomial regression models. While Latinos overall have lower all-cancers-combined mortality rates than NLWs, these numbers were largely driven by low rates among the foreign born while mortality rates for US-born Latinos approach those of NLWs. Among Texas males, rates were 210 per 100,000 for NLWs and 166 for Latinos combined, but 201 per 100,000 for US-born Latinos and 125 for foreign-born Latinos. Compared to NLWs, US-born Latino males in California had mortality rate ratios of 2.83 (95% CI: 2.52-3.18) for liver cancer, 1.44 (95% CI: 1.30-1.61) for kidney cancer, and 1.25 (95% CI: 1.17-1.34) for colorectal cancer (CRC). Texas results showed a similar site-specific pattern. Specific cancer patterns for US-born Latinos, who have relatively high cancer mortality, similar overall to NLWs, are masked by aggregation of all Latinos, US-born and foreign-born. While NLWs had high mortality for lung cancer, US-born Latinos had high mortality for liver, kidney and male colorectal cancers. HCV testing and reinforcement of the need for CRC screening should be a priority in this specific and understudied population. The unprecedented proximity of overall rates between

  15. Therapeutic Options for the Management of the Cardiorenal Syndrome

    Directory of Open Access Journals (Sweden)

    Katerina Koniari

    2011-01-01

    Full Text Available Patients with heart failure often present with impaired renal function, which is a predictor of poor outcome. The cardiorenal syndrome is the worsening of renal function, which is accelerated by worsening of heart failure or acute decompensated heart failure. Although it is a frequent clinical entity due to the improved survival of heart failure patients, still its pathophysiology is not well understood, and thus its therapeutic approach remains controversial and sometimes ineffective. Established therapeutic strategies, such as diuretics and inotropes, are often associated with resistance and limited clinical success. That leads to an increasing concern about novel options, such as the use of vasopressin antagonists, adenosine A1 receptor antagonists, and renal-protective dopamine. Initial clinical trials have shown quite encouraging results in some heart failure subpopulations but have failed to demonstrate a clear beneficial role of these agents. On the other hand, ultrafiltration appears to be a more promising therapeutic procedure that will improve volume regulation, while preserving renal and cardiac function. Further clinical studies are required in order to determine their net effect on renal function and potential cardiovascular outcomes. Until then, management of the cardiorenal syndrome remains quite empirical.

  16. Molecular hydrogen in sports medicine: new therapeutic perspectives.

    Science.gov (United States)

    Ostojic, S M

    2015-04-01

    In the past 2 decades, molecular hydrogen emerged as a novel therapeutic agent, with antioxidant, anti-inflammatory and anti-apoptotic effects demonstrated in plethora of animal disease models and human studies. Beneficial effects of molecular hydrogen in clinical environment are observed especially in oxidative stress-mediated diseases, such as diabetes mellitus, brain stem infarction, rheumatoid arthritis, or neurodegenerative diseases. A number of more recent studies have reported that molecular hydrogen affects cell signal transduction and acts as an alkalizing agent, with these newly identified mechanisms of action having the potential to widen its application in clinical medicine even further. In particular, hydrogen therapy may be an effective and specific innovative treatment for exercise-induced oxidative stress and sports injury, with potential for the improvement of exercise performance. This review will summarize recent research findings regarding the clinical aspects of molecular hydrogen use, emphasizing its application in the field of sports medicine. © Georg Thieme Verlag KG Stuttgart · New York.

  17. Topologically nontrivial black holes in Lovelock-Born-Infeld gravity

    Science.gov (United States)

    Farhangkhah, N.

    2018-04-01

    We present the black hole solutions possessing horizon with nonconstant-curvature and additional scalar restrictions on the base manifold in Lovelock gravity coupled to Born-Infeld (BI) nonlinear electrodynamics. The asymptotic and near origin behavior of the metric is presented and we analyze different behaviors of the singularity. We find that, in contrast to the case of black hole solutions of BI-Lovelock gravity with constant curvature horizon and Maxwell-Lovelock gravity with non constant horizon which have only timelike singularities, spacelike, and timelike singularities may exist for BI-Lovelock black holes with nonconstant curvature horizon. By calculating the thermodynamic quantities, we study the effects of nonlinear electrodynamics via the Born-Infeld action. Stability analysis shows that black holes with positive sectional curvature, κ , possess an intermediate unstable phase and large and small black holes are stable. We see that while Ricci flat Lovelock-Born-Infeld black holes having exotic horizons are stable in the presence of Maxwell field or either Born Infeld field with large born Infeld parameter β , unstable phase appears for smaller values of β , and therefore nonlinearity brings in the instability.

  18. Black hole solutions in mimetic Born-Infeld gravity.

    Science.gov (United States)

    Chen, Che-Yu; Bouhmadi-López, Mariam; Chen, Pisin

    2018-01-01

    The vacuum, static, and spherically symmetric solutions in the mimetic Born-Infeld gravity are studied. The mimetic Born-Infeld gravity is a reformulation of the Eddington-inspired-Born-Infeld (EiBI) model under the mimetic approach. Due to the mimetic field, the theory contains non-trivial vacuum solutions different from those in Einstein gravity. We find that with the existence of the mimetic field, the spacelike singularity inside a Schwarzschild black hole could be altered to a lightlike singularity, even though the curvature invariants still diverge at the singularity. Furthermore, in this case, the maximal proper time for a timelike radially-infalling observer to reach the singularity is found to be infinite.

  19. Black hole solutions in mimetic Born-Infeld gravity

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Che-Yu [National Taiwan University, Department of Physics and Center for Theoretical Sciences, Taipei (China); LeCosPA, National Taiwan University, Taipei (China); Bouhmadi-Lopez, Mariam [University of the Basque Country UPV/EHU, Department of Theoretical Physics, Bilbao (Spain); IKERBASQUE, Basque Foundation for Science, Bilbao (Spain); Chen, Pisin [National Taiwan University, Department of Physics and Center for Theoretical Sciences, Taipei (China); LeCosPA, National Taiwan University, Taipei (China); Stanford University, Kavli Institute for Particle Astrophysics and Cosmology, SLAC National Accelerator Laboratory, Stanford, CA (United States)

    2018-01-15

    The vacuum, static, and spherically symmetric solutions in the mimetic Born-Infeld gravity are studied. The mimetic Born-Infeld gravity is a reformulation of the Eddington-inspired-Born-Infeld (EiBI) model under the mimetic approach. Due to the mimetic field, the theory contains non-trivial vacuum solutions different from those in Einstein gravity. We find that with the existence of the mimetic field, the spacelike singularity inside a Schwarzschild black hole could be altered to a lightlike singularity, even though the curvature invariants still diverge at the singularity. Furthermore, in this case, the maximal proper time for a timelike radially-infalling observer to reach the singularity is found to be infinite. (orig.)

  20. Therapeutic Effect of Caffeine Treatment Immediately Following Neonatal Hypoxic-Ischemic Injury on Spatial Memory in Male Rats

    Directory of Open Access Journals (Sweden)

    R. Holly Fitch

    2013-03-01

    Full Text Available Hypoxia Ischemia (HI refers to the disruption of blood and/or oxygen delivery to the brain. Term infants suffering perinatal complications that result in decreased blood flow and/or oxygen delivery to the brain are at risk for HI. Among a variety of developmental delays in this population, HI injured infants demonstrate subsequent memory deficits. The Rice-Vannucci rodent HI model can be used to explore behavioral deficits following early HI events, as well as possible therapeutic agents to help reduce deleterious outcomes. Caffeine is an adenosine receptor antagonist that has recently shown promising results as a therapeutic agent following HI injury. The current study sought to investigate the therapeutic benefit of caffeine following early HI injury in male rats. On post-natal day (P 7, HI injury was induced (cauterization of the right common carotid artery, followed by two hours of 8% oxygen. Male sham animals received only a midline incision with no manipulation of the artery followed by room air exposure for two hours. Subsets of HI and sham animals then received either an intraperitoneal (i.p. injection of caffeine (10 mg/kg, or vehicle (sterile saline immediately following hypoxia. All animals later underwent testing on the Morris Water Maze (MWM from P90 to P95. Results show that HI injured animals (with no caffeine treatment displayed significant deficits on the MWM task relative to shams. These deficits were attenuated by caffeine treatment when given immediately following the induction of HI. We also found a reduction in right cortical volume (ipsilateral to injury in HI saline animals as compared to shams, while right cortical volume in the HI caffeine treated animals was intermediate. These findings suggest that caffeine is a potential therapeutic agent that could be used in HI injured infants to reduce brain injury and preserve subsequent cognitive function.

  1. First-born siblings show better second language skills than later born siblings

    Science.gov (United States)

    Keller, Karin; Troesch, Larissa M.; Grob, Alexander

    2015-01-01

    We examined the extent to which three sibling structure variables number of siblings, birth order, and presence of an older sibling at school age are linked to the second language skills of bilingual children. The research questions were tested using an ethnically heterogeneous sample of 1209 bilingual children with German as a second language. Controlling for children’s age, sex, nationality, number of children’s books at home, family language and parental German language skills, hierarchical regression analyses showed an inverse relationship between the number of siblings and second language skills: the more siblings a child had, the lower was his/her second language proficiency. This relationship was mediated by attendance in early education institutions. Moreover, first-born siblings showed better second language skills than later born siblings. The current study revealed that the resource dilution model, i.e., the decrease in resources for every additional sibling, holds for second language acquisition. Moreover, the results indicate that bilingual children from families with several children benefit from access to early education institutions. PMID:26089806

  2. First-born siblings show better second language skills than later born siblings

    Directory of Open Access Journals (Sweden)

    Karin eKeller

    2015-06-01

    Full Text Available We examined the extent to which three sibling structure variables number of siblings, birth order and presence of an older sibling at school age are linked to the second language skills of bilingual children. The research questions were tested using an ethnically heterogeneous sample of 1209 bilingual children with German as a second language. Controlling for children’s age, sex, nationality, number of children’s books at home, family language and parental German language skills, hierarchical regression analyses showed an inverse relationship between the number of siblings and second language skills: The more siblings a child had, the lower was his/her second language proficiency. This relationship was mediated by attendance in early education institutions. Moreover, first-born siblings showed better second language skills than later born siblings.The current study revealed that the resource dilution model, i.e., the decrease in resources for every additional sibling, holds for second language acquisition. Moreover, the results indicate that bilingual children from families with several children benefit from access to early education institutions.

  3. Functional Representation for the Born-Oppenheimer Diagonal Correction and Born-Huang Adiabatic Potential Energy Surfaces for Isotopomers of H3

    International Nuclear Information System (INIS)

    Mielke, Steven L.; Schwenke, David; Schatz, George C.; Garrett, Bruce C.; Peterson, Kirk A.

    2009-01-01

    Multireference configuration interaction (MRCI) calculations of the Born-Oppenheimer diagonal correction (BODC) for H3 were performed at 1397 symmetry-unique configurations using the Born-Huang approach; isotopic substitution leads to 4041 symmetry-unique configurations for the DH2 mass combination. These results were then fit to a functional form that permits calculation of the BODC for any combination of isotopes. Mean unsigned fitting errors on a test grid of configurations not included in the fitting process were 0.14, 0.12, and 0.65 cm-1 for the H3, DH2, and MuH2 isotopomers, respectively. This representation can be combined with any Born-Oppenheimer potential energy surface (PES) to yield Born-Huang (BH) PESs; herein we choose the CCI potential energy surface, the uncertainties of which (∼0.01 kcal/mol) are much smaller than the magnitude of the BODC. FORTRAN routines to evaluate these BH surfaces are provided. Variational transition state theory calculations are presented comparing thermal rate constants for reactions on the BO and BH surfaces to provide an initial estimate of the significance of the diagonal correction for the dynamics.

  4. Monoclonal Antibody Fragments for Targeting Therapeutics to Growth Plate Cartilage | NCI Technology Transfer Center | TTC

    Science.gov (United States)

    Researchers at The Eunice Kennedy Shriver National Institute on Child Health and Human Development (NICHD) have discovered monoclonal antibodies that bind to matrilin-3, a protein specifically expressed in cartilage tissue, that could be used for treating or inhibiting growth plate disorders, such as a skeletal dysplasia or short stature. The monoclonal antibodies can also be used to target therapeutic agents, such as anti-arthritis agents, to cartilage tissue. NICHD seeks statements of capability or interest from parties interested in collaborative research to co-develop, evaluate, or commercialize treatment of skeletal disorders using targeting antibodies.

  5. Practical solutions to implementing "Born Semantic" data systems

    Science.gov (United States)

    Leadbetter, A.; Buck, J. J. H.; Stacey, P.

    2015-12-01

    The concept of data being "Born Semantic" has been proposed in recent years as a Semantic Web analogue to the idea of data being "born digital"[1], [2]. Within the "Born Semantic" concept, data are captured digitally and at a point close to the time of creation are annotated with markup terms from semantic web resources (controlled vocabularies, thesauri or ontologies). This allows heterogeneous data to be more easily ingested and amalgamated in near real-time due to the standards compliant annotation of the data. In taking the "Born Semantic" proposal from concept to operation, a number of difficulties have been encountered. For example, although there are recognised methods such as Header, Dictionary, Triples [3] for the compression, publication and dissemination of large volumes of triples these systems are not practical to deploy in the field on low-powered (both electrically and computationally) devices. Similarly, it is not practical for instruments to output fully formed semantically annotated data files if they are designed to be plugged into a modular system and the data to be centrally logged in the field as is the case on Argo floats and oceanographic gliders where internal bandwidth becomes an issue [2]. In light of these issues, this presentation will concentrate on pragmatic solutions being developed to the problem of generating Linked Data in near real-time systems. Specific examples from the European Commission SenseOCEAN project where Linked Data systems are being developed for autonomous underwater platforms, and from work being undertaken in the streaming of data from the Irish Galway Bay Cable Observatory initiative will be highlighted. Further, developments of a set of tools for the LogStash-ElasticSearch software ecosystem to allow the storing and retrieval of Linked Data will be introduced. References[1] A. Leadbetter & J. Fredericks, We have "born digital" - now what about "born semantic"?, European Geophysical Union General Assembly, 2014

  6. Reconsidering the classification of tick-borne encephalitis virus within the Siberian subtype gives new insights into its evolutionary history.

    Science.gov (United States)

    Kovalev, S Y; Mukhacheva, T A

    2017-11-01

    Tick-borne encephalitis is widespread in Eurasia and transmitted by Ixodes ticks. Classification of its causative agent, tick-borne encephalitis virus (TBEV), includes three subtypes, namely Far-Eastern, European, and Siberian (TBEV-Sib), as well as a group of 886-84-like strains with uncertain taxonomic status. TBEV-Sib is subdivided into three phylogenetic lineages: Baltic, Asian, and South-Siberian. A reason to reconsider TBEV-Sib classification was the analysis of 186 nucleotide sequences of an E gene fragment submitted to GenBank during the last two years. Within the South-Siberian lineage, we have identified a distinct group with prototype strains Aina and Vasilchenko as an individual lineage named East-Siberian. The analysis of reclassified lineages has promoted a new model of the evolutionary history of TBEV-Sib lineages and TBEV-Sib as a whole. Moreover, we present arguments supporting separation of 886-84-like strains into an individual TBEV subtype, which we propose to name Baikalian (TBEV-Bkl). Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Designer exosomes produced by implanted cells intracerebrally deliver therapeutic cargo for Parkinson's disease treatment.

    Science.gov (United States)

    Kojima, Ryosuke; Bojar, Daniel; Rizzi, Giorgio; Hamri, Ghislaine Charpin-El; El-Baba, Marie Daoud; Saxena, Pratik; Ausländer, Simon; Tan, Kelly R; Fussenegger, Martin

    2018-04-03

    Exosomes are cell-derived nanovesicles (50-150 nm), which mediate intercellular communication, and are candidate therapeutic agents. However, inefficiency of exosomal message transfer, such as mRNA, and lack of methods to create designer exosomes have hampered their development into therapeutic interventions. Here, we report a set of EXOsomal transfer into cells (EXOtic) devices that enable efficient, customizable production of designer exosomes in engineered mammalian cells. These genetically encoded devices in exosome producer cells enhance exosome production, specific mRNA packaging, and delivery of the mRNA into the cytosol of target cells, enabling efficient cell-to-cell communication without the need to concentrate exosomes. Further, engineered producer cells implanted in living mice could consistently deliver cargo mRNA to the brain. Therapeutic catalase mRNA delivery by designer exosomes attenuated neurotoxicity and neuroinflammation in in vitro and in vivo models of Parkinson's disease, indicating the potential usefulness of the EXOtic devices for RNA delivery-based therapeutic applications.

  8. Shattered Shangri-la: differences in depressive and anxiety symptoms in students born in Tibet compared to Tibetan students born in exile.

    Science.gov (United States)

    Evans, Dabney; Buxton, David C; Borisov, Andrey; Manatunga, Amita K; Ngodup, Dawa; Raison, Charles L

    2008-06-01

    As a result of ongoing political tensions within Tibetan regions of the People's Republic of China, several thousand Tibetans escape across the Himalayas every year to seek refuge in India and Nepal. Prior studies have found a high prevalence of depressive and anxiety symptoms in these refugees, many of whom are young and have been exposed to significant trauma. However, it is not known whether depressive and anxiety symptoms are more prevalent in these refugees than in ethnic Tibetans born and raised in the relative political and social stability of exile communities in North India and Nepal. We conducted a cross-sectional survey of a convenience sample of 319 students attending school at the Tibetan Children's Villages in Northern India to test the a priori hypothesis that adolescents and young adults who escaped from Tibet to India would demonstrate increased depressive and anxiety symptoms when compared to ethnic Tibetans born and raised in exile. The Hopkins Symptom Checklist-25 (HSCL-25) was used to measure depressive and anxiety symptoms. In addition, demographic information on age, sex, country of birth and frequency of family contact was collected. Students born in Tibet had higher mean HSCL-25 depressive and anxiety symptom scores than did ethnic Tibetans born in exile. Female students demonstrated higher depressive and anxiety scores, as did those with limited contact with immediate family. After adjusting for sex, age and frequency of family contact, being born in Tibet was associated with increased HSCL-25 depressive and anxiety symptom scores (depression: F[2, 316] = 29.96, P < 0.0001; anxiety: F[4, 316] = 43.57, P < 0.0001). The experience of being raised in Tibet and escaping to India appears to be a risk factor for increased depressive and anxiety symptoms when compared to being born and raised within an exile community in India or Nepal.

  9. Effects of treatment with antimicrobial agents on the human colonic microflora

    Directory of Open Access Journals (Sweden)

    Fatemeh Rafii

    2008-12-01

    Full Text Available Fatemeh Rafii, John B Sutherland, Carl E CernigliaDivision of Microbiology, National Center for Toxicological Research, FDA, Jefferson, AR, USAAbstract: Antimicrobial agents are the most valuable means available for treating bacterial infections. However, the administration of therapeutic doses of antimicrobial agents to patients is a leading cause of disturbance of the normal gastrointestinal microflora. This disturbance results in diminishing the natural defense mechanisms provided by the colonic microbial ecosystem, making the host vulnerable to infection by commensal microorganisms or nosocomial pathogens. In this minireview, the impacts of antimicrobials, individually and in combinations, on the human colonic microflora are discussed.Keywords: antibiotics, intestinal bacteria

  10. Social development of children born very preterm: a systematic review.

    Science.gov (United States)

    Ritchie, Kirsten; Bora, Samudragupta; Woodward, Lianne J

    2015-10-01

    To review systematically studies examining the development of social competence in children born very preterm (VPT) (gestation skills. Twenty-three studies were included. Seven focused on social competence and another 16 examined social competence within a range of outcomes. Study quality was low. Limitations included reliance on single informant data, cross-sectional measurement, use of brief screening tools, absence of child or peer report, and no conceptual model. In terms of social adjustment, 16 out of 21 studies found children born VPT had more peer problems and social withdrawal. Findings of social performance were mixed, with some studies suggesting differences in prosocial behavior (4/14) and others not. Social skills were assessed in four studies and showed children born VPT had poorer skills than children born at term. Predictors of social competence included gestational age, neonatal brain abnormalities, and family socio-economic status. Children born VPT have poorer social competence. These difficulties emerge early and persist throughout childhood. © 2015 Mac Keith Press.

  11. Copper-64 Dichloride as Theranostic Agent for Glioblastoma Multiforme: A Preclinical Study

    Directory of Open Access Journals (Sweden)

    Cristina Ferrari

    2015-01-01

    Full Text Available Glioblastoma multiforme (GBM is the most common primary malignant brain tumor in adults with a median survival time less than one year. To date, there are only a limited number of effective agents available for GBM therapy and this does not seem to add much survival advantage over the conventional approach based on surgery and radiotherapy. Therefore, the development of novel therapeutic approaches to GBM is essential and those based on radionuclide therapy could be of significant clinical impact. Experimental evidence has clearly demonstrated that cancer cells have a particularly high fractional content of copper inside the nucleus compared to normal cells. This behavior can be conveniently exploited both for diagnosis and for delivering therapeutic payloads (theranostic of the radionuclide copper-64 into the nucleus of cancerous cells by intravenous administration of its simplest chemical form as dichloride salt [64Cu]CuCl2. To evaluate the potential theranostic role of [64Cu]CuCl2 in GBM, the present work reports results from a preclinical study carried out in a xenografted GBM tumor mouse model. Biodistribution data of this new agent were collected using a small-animal PET tomograph. Subsequently, groups of tumor implanted nude mice were treated with [64Cu]CuCl2 to simulate single- and multiple-dose therapy protocols, and results were analyzed to estimate therapeutic efficacy.

  12. Biological and therapeutic activities, and anticancer properties of curcumin.

    Science.gov (United States)

    Perrone, Donatella; Ardito, Fatima; Giannatempo, Giovanni; Dioguardi, Mario; Troiano, Giuseppe; Lo Russo, Lucio; DE Lillo, Alfredo; Laino, Luigi; Lo Muzio, Lorenzo

    2015-11-01

    Curcumin (diferuloylmethane) is a polyphenol derived from the Curcuma longa plant. Curcumin has been used extensively in Ayurvedic medicine, as it is nontoxic and exhibits a variety of therapeutic properties, including antioxidant, analgesic, anti-inflammatory and antiseptic activities. Recently, certain studies have indicated that curcumin may exert anticancer effects in a variety of biological pathways involved in mutagenesis, apoptosis, tumorigenesis, cell cycle regulation and metastasis. The present study reviewed previous studies in the literature, which support the therapeutic activity of curcumin in cancer. In addition, the present study elucidated a number of the challenges concerning the use of curcumin as an adjuvant chemotherapeutic agent. All the studies reviewed herein suggest that curcumin is able to exert anti-inflammatory, antiplatelet, antioxidative, hepatoprotective and antitumor activities, particularly against cancers of the liver, skin, pancreas, prostate, ovary, lung and head neck, as well as having a positive effect in the treatment of arthritis.

  13. Promising novel therapeutic approaches in the management of gastrointestinal stromal tumors.

    Science.gov (United States)

    Szucs, Zoltan; Thway, Khin; Fisher, Cyril; Bulusu, Ramesh; Constantinidou, Anastasia; Benson, Charlotte; van der Graaf, Winette Ta; Jones, Robin L

    2017-01-01

    Primary and secondary resistance to currently available licensed tyrosine kinase inhibitors poses a real clinical challenge in the management of advanced gastrointestinal stromal tumors. Within the frame of early phase clinical trials novel systemic treatments are currently being evaluated to target both the well explored and novel emerging downstream effectors of KIT and PDGFRA signaling. Alternative therapeutic approaches also include exploring novel inhibitors of the KIT/PDGFRA receptors, immune checkpoint and cyclin-dependent kinase inhibitors. The final clinical trial outcome data for these agents are highly anticipated. Integration of new diagnostic techniques into routine clinical practice can potentially guide tailored delivery of agents in the treatment of a highly polyclonal, heterogeneous disease such as heavily pretreated advanced gastrointestinal stromal tumor.

  14. Horizon structure of rotating Einstein-Born-Infeld black holes and shadow

    Energy Technology Data Exchange (ETDEWEB)

    Atamurotov, Farruh [Institute of Nuclear Physics, Tashkent (Uzbekistan); Inha University in Tashkent, Tashkent (Uzbekistan); Ulugh Beg Astronomical Institute, Tashkent (Uzbekistan); National University of Uzbekistan, Tashkent (Uzbekistan); Ghosh, Sushant G. [Jamia Millia Islamia, Centre for Theoretical Physics, New Delhi (India); University of Kwa-Zulu-Natal, Astrophysics and Cosmology Research Unit, School of Mathematical Sciences, Private Bag 54001, Durban (South Africa); Ahmedov, Bobomurat [Institute of Nuclear Physics, Tashkent (Uzbekistan); Ulugh Beg Astronomical Institute, Tashkent (Uzbekistan); National University of Uzbekistan, Tashkent (Uzbekistan)

    2016-05-15

    We investigate the horizon structure of the rotating Einstein-Born-Infeld solution which goes over to the Einstein-Maxwell's Kerr-Newman solution as the Born-Infeld parameter goes to infinity (β → ∞). We find that for a given β, mass M, and charge Q, there exist a critical spinning parameter a{sub E} and r{sub H}{sup E}, which corresponds to an extremal Einstein-Born-Infeld black hole with degenerate horizons, and a{sub E} decreases and r{sub H}{sup E} increases with increase of the Born-Infeld parameter β, while a < a{sub E} describes a non-extremal Einstein-Born-Infeld black hole with outer and inner horizons. Similarly, the effect of β on the infinite redshift surface and in turn on the ergo-region is also included. It is well known that a black hole can cast a shadow as an optical appearance due to its strong gravitational field. We also investigate the shadow cast by the both static and rotating Einstein-Born-Infeld black hole and demonstrate that the null geodesic equations can be integrated, which allows us to investigate the shadow cast by a black hole which is found to be a dark zone covered by a circle. Interestingly, the shadow of an Einstein-Born-Infeld black hole is slightly smaller than for the Reissner-Nordstrom black hole, which consists of concentric circles, for different values of the Born-Infeld parameter β, whose radius decreases with increase of the value of the parameter β. Finally, we have studied observable distortion parameter for shadow of the rotating Einstein-Born-Infeld black hole. (orig.)

  15. Horizon structure of rotating Einstein-Born-Infeld black holes and shadow

    International Nuclear Information System (INIS)

    Atamurotov, Farruh; Ghosh, Sushant G.; Ahmedov, Bobomurat

    2016-01-01

    We investigate the horizon structure of the rotating Einstein-Born-Infeld solution which goes over to the Einstein-Maxwell's Kerr-Newman solution as the Born-Infeld parameter goes to infinity (β → ∞). We find that for a given β, mass M, and charge Q, there exist a critical spinning parameter a E and r H E , which corresponds to an extremal Einstein-Born-Infeld black hole with degenerate horizons, and a E decreases and r H E increases with increase of the Born-Infeld parameter β, while a < a E describes a non-extremal Einstein-Born-Infeld black hole with outer and inner horizons. Similarly, the effect of β on the infinite redshift surface and in turn on the ergo-region is also included. It is well known that a black hole can cast a shadow as an optical appearance due to its strong gravitational field. We also investigate the shadow cast by the both static and rotating Einstein-Born-Infeld black hole and demonstrate that the null geodesic equations can be integrated, which allows us to investigate the shadow cast by a black hole which is found to be a dark zone covered by a circle. Interestingly, the shadow of an Einstein-Born-Infeld black hole is slightly smaller than for the Reissner-Nordstrom black hole, which consists of concentric circles, for different values of the Born-Infeld parameter β, whose radius decreases with increase of the value of the parameter β. Finally, we have studied observable distortion parameter for shadow of the rotating Einstein-Born-Infeld black hole. (orig.)

  16. Canine vector-borne co-infections: Ehrlichia canis and Hepatozoon canis in the same host monocytes.

    Science.gov (United States)

    Baneth, Gad; Harrus, Shimon; Gal, Arnon; Aroch, Itamar

    2015-02-28

    The protozoon Hepatozoon canis and the rickettsia Ehrlichia canis are tick-borne pathogens, transmitted by Rhipicephalus sanguineus, which cause canine hepatozoonosis and canine monocytic ehrlichiosis, respectively. Co-infection of the same host monocytes with H. canis and E. canis confirmed by molecular characterization of the infecting agents and quantitative assessment of co-infected cells is described for the first time in three naturally-infected dogs. Blood smear evaluation indicated that at least 50% of the leukocytes infected with H. canis gamonts contained E. canis morulae. Co-infection of the same host cell demonstrated in this report suggests that infection with one pathogen may permit or enhance invasion or prolonged cellular survival of the other. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Alkylating chemotherapeutic agents cyclophosphamide and melphalan cause functional injury to human bone marrow-derived mesenchymal stem cells.

    Science.gov (United States)

    Kemp, Kevin; Morse, Ruth; Sanders, Kelly; Hows, Jill; Donaldson, Craig

    2011-07-01

    The adverse effects of melphalan and cyclophosphamide on hematopoietic stem cells are well-known; however, the effects on the mesenchymal stem cells (MSCs) residing in the bone marrow are less well characterised. Examining the effects of chemotherapeutic agents on patient MSCs in vivo is difficult due to variability in patients and differences in the drug combinations used, both of which could have implications on MSC function. As drugs are not commonly used as single agents during high-dose chemotherapy (HDC) regimens, there is a lack of data comparing the short- or long-term effects these drugs have on patients post treatment. To help address these problems, the effects of the alkylating chemotherapeutic agents cyclophosphamide and melphalan on human bone marrow MSCs were evaluated in vitro. Within this study, the exposure of MSCs to the chemotherapeutic agents cyclophosphamide or melphalan had strong negative effects on MSC expansion and CD44 expression. In addition, changes were seen in the ability of MSCs to support hematopoietic cell migration and repopulation. These observations therefore highlight potential disadvantages in the use of autologous MSCs in chemotherapeutically pre-treated patients for future therapeutic strategies. Furthermore, this study suggests that if the damage caused by chemotherapeutic agents to marrow MSCs is substantial, it would be logical to use cultured allogeneic MSCs therapeutically to assist or repair the marrow microenvironment after HDC.

  18. Developmental outcomes of Japanese children born through Assisted Reproductive Technology (ART) in toddlerhood.

    Science.gov (United States)

    Aoki, Sayaka; Hashimoto, Keiji; Ogawa, Kohei; Horikawa, Reiko; Sago, Haruhiko

    2018-05-01

    This study aimed to investigate developmental outcomes of Japanese babies born through Assisted Reproductive Technology (ART) at ages 2 and 3. The data were gathered from 1085 children in a hospital-based cohort study conducted in Japan. The children's level of development was assessed through a parent-rated questionnaire, the Kinder Infant Development Scale, which consists of nine developmental domains. We compared the development of children born through ART and those born naturally by conducting analyses of covariance. For the analyses, the effect of maternal age, family income, parental education and multiple birth were controlled for. At 24 months, no significant difference was found between children born through ART and those born naturally in development in any domain. At 36 months, a significant difference was found in development of Receptive language (F (1, 845) = 6.148, P = 0.013), Expressive language (F (1, 845) = 4.060, P = 0.044) and Language concept (F (1, 845) = 6.968, P = 0.008). For these domains, children born through ART had a significantly higher developmental age compared to children born naturally. At age 2, no significant difference was found between the children born through ART and those born naturally in nine developmental domains, although at age 3, the children born through ART showed significantly better language development than the children born naturally. © 2018 Japan Society of Obstetrics and Gynecology.

  19. Biocontrol efficacy of different isolates of Trichoderma against soil borne pathogen Rhizoctonia solani.

    Science.gov (United States)

    Asad, Saeed Ahmad; Ali, Naeem; Hameed, Abdul; Khan, Sabaz Ali; Ahmad, Rafiq; Bilal, Muhammad; Shahzad, Muhammad; Tabassum, Ayesha

    2014-01-01

    In this study, the biocontrol abilities of water-soluble and volatile metabolites of three different isolates of Trichoderma (T. asperellum, T. harzianum and Trichoderma spp.) against soil borne plant pathogen Rhizoctonia solani were investigated both in vitro and in vivo. The results showed for the first time that mycelial growth inhibition of the pathogen was 74.4-67.8% with water-soluble metabolites as compared to 15.3-10.6% with volatile metabolites in vitro. In vivo antagonistic activity of Trichoderma isolates against R. solani was evaluated on bean plants under laboratory and greenhouse conditions. We observed that T. asperellum was more effective and consistent, lowering disease incidence up to 19.3% in laboratory and 30.5% in green house conditions. These results showed that three isolates of Trichoderma could be used as effective biocontrol agents against R. solani.

  20. 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.