WorldWideScience

Sample records for current pharmacological approaches

  1. Current Approaches and New Developments in the Pharmacological Management of Tourette Syndrome.

    Science.gov (United States)

    Quezada, Julio; Coffman, Keith A

    2018-01-01

    Tourette syndrome (TS) is a neurodevelopmental disorder of unknown etiology characterized by spontaneous, involuntary movements and vocalizations called tics. Once thought to be rare, TS affects 0.3-1% of the population. Tics can cause physical discomfort, emotional distress, social difficulties, and can interfere with education and desired activities. The pharmacologic treatment of TS is particularly challenging, as currently the genetics, neurophysiology, and neuropathology of this disorder are still largely unknown. However, clinical experience gained from treating TS has helped us better understand its pathogenesis and, as a result, derive treatment options. The strongest data exist for the antipsychotic agents, both typical and atypical, although their use is often limited in children and adolescents due to their side-effect profiles. There are agents in a variety of other pharmacologic categories that have evidence for the treatment of TS and whose side-effect profiles are more tolerable than the antipsychotics; these include clonidine, guanfacine, baclofen, topiramate, botulinum toxin A, tetrabenazine, and deutetrabenazine. A number of new agents are being developed and tested as potential treatments for TS. These include valbenazine, delta-9-tetrahydrocannabidiol, and ecopipam. Additionally, there are agents with insufficient data for efficacy, as well as agents that have been shown to be ineffective. Those without sufficient data for efficacy include clonazepam, ningdong granule, 5-ling granule, omega-3 fatty acids, and n-acetylcysteine. The agents that have been shown to be ineffective include pramipexole and metoclopramide. We will review all of the established pharmacologic treatments, and discuss those presently in development.

  2. Pharmacological modulations of cardiac ultra-rapid and slowly activating delayed rectifier currents: potential antiarrhythmic approaches.

    Science.gov (United States)

    Islam, Mohammed A

    2010-01-01

    Despite the emerging new insights into our understandings of the cellular mechanisms underlying cardiac arrhythmia, medical therapy for this disease remains unsatisfactory. Atrial fibrillation (AF), the most prevalent arrhythmia, is responsible for significant morbidity and mortality. On the other hand, ventricular fibrillation results in sudden cardiac deaths in many instances. Prolongation of cardiac action potential (AP) is a proven principle of antiarrhythmic therapy. Class III antiarrhythmic agents prolong AP and QT interval by blocking rapidly activating delayed rectifier current (I(Kr)). However, I(Kr) blocking drugs carry the risk of life-threatening proarrhythmia. Recently, modulation of atrial-selective ultra-rapid delayed rectifier current (I(Kur)), has emerged as a novel therapeutic approach to treat AF. A number of I(Kur) blockers are being evaluated for the treatment of AF. The inhibition of slowly activating delayed rectifier current (I(Ks)) has also been proposed as an effective and safer antiarrhythmic approach because of its distinguishing characteristics that differ in remarkable ways from other selective class III agents. Selective I(Ks) block may prolong AP duration (APD) at rapid rates without leading to proarrhythmia. This article reviews the pathophysiological roles of I(Kur) and I(Ks) in cardiac repolarization and the implications of newly developed I(Kur) and I(Ks) blocking agents as promising antiarrhythmic approaches. Several recent patents pertinent to antiarrhythmic drug development have been discussed. Further research will be required to evaluate the efficacy and safety of these agents in the clinical setting.

  3. Safety pharmacology--current and emerging concepts.

    Science.gov (United States)

    Hamdam, Junnat; Sethu, Swaminathan; Smith, Trevor; Alfirevic, Ana; Alhaidari, Mohammad; Atkinson, Jeffrey; Ayala, Mimieveshiofuo; Box, Helen; Cross, Michael; Delaunois, Annie; Dermody, Ailsa; Govindappa, Karthik; Guillon, Jean-Michel; Jenkins, Rosalind; Kenna, Gerry; Lemmer, Björn; Meecham, Ken; Olayanju, Adedamola; Pestel, Sabine; Rothfuss, Andreas; Sidaway, James; Sison-Young, Rowena; Smith, Emma; Stebbings, Richard; Tingle, Yulia; Valentin, Jean-Pierre; Williams, Awel; Williams, Dominic; Park, Kevin; Goldring, Christopher

    2013-12-01

    Safety pharmacology (SP) is an essential part of the drug development process that aims to identify and predict adverse effects prior to clinical trials. SP studies are described in the International Conference on Harmonisation (ICH) S7A and S7B guidelines. The core battery and supplemental SP studies evaluate effects of a new chemical entity (NCE) at both anticipated therapeutic and supra-therapeutic exposures on major organ systems, including cardiovascular, central nervous, respiratory, renal and gastrointestinal. This review outlines the current practices and emerging concepts in SP studies including frontloading, parallel assessment of core battery studies, use of non-standard species, biomarkers, and combining toxicology and SP assessments. Integration of the newer approaches to routine SP studies may significantly enhance the scope of SP by refining and providing mechanistic insight to potential adverse effects associated with test compounds. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Pharmacological approach to acute pancreatitis

    DEFF Research Database (Denmark)

    Bang, U.C.; Semb, S.; Nøjgaard, Camilla

    2008-01-01

    The aim of the present review is to summarize the current knowledge regarding pharmacological prevention and treatment of acute pancreatitis (AP) based on experimental animal models and clinical trials. Somatostatin (SS) and octreotide inhibit the exocrine production of pancreatic enzymes and may...... be useful as prophylaxis against post endoscopic retrograde cholangiopancreatography pancreatitis (PEP). The protease inhibitor gabexate mesilate (GM) is used routinely as treatment to AP in some countries, but randomized clinical trials and a meta-analysis do not support this practice. Nitroglycerin (NGL...

  5. Pharmacological approach to acute pancreatitis

    DEFF Research Database (Denmark)

    Bang, Ulrich-Christian; Semb, Synne; Nojgaard, Camilla

    2008-01-01

    -steroidal anti-inflammatory drugs (NSAID) indomethacin and diclofenac have in randomized studies showed potential as prophylaxis against PEP. Interleukin 10 (IL-10) is a cytokine with anti-inflammatory properties but two trials testing IL-10 as prophylaxis to PEP have returned conflicting results. Antibodies...... pharmacological treatment of AP is limited and studies on the effect of potent anti-inflammatory drugs are warranted....... against tumor necrosis factor-alpha (TNF-alpha) have a potential as rescue therapy but no clinical trials are currently being conducted. The antibiotics beta-lactams and quinolones reduce mortality when necrosis is present in pancreas and may also reduce incidence of infected necrosis. Evidence based...

  6. Non Pharmacological Cognitive Enhancers - Current Perspectives.

    Science.gov (United States)

    Sachdeva, Ankur; Kumar, Kuldip; Anand, Kuljeet Singh

    2015-07-01

    Cognition refers to the mental processes involved in thinking, knowing, remembering, judging, and problem solving. Cognitive dysfunctions are an integral part of neuropsychiatric disorders as well as in healthy ageing. Cognitive Enhancers are molecules that help improve aspects of cognition like memory, intelligence, motivation, attention and concentration. Recently, Non Pharmacological Cognitive Enhancers have gained popularity as effective and safe alternative to various established drugs. Many of these Non Pharmacological Cognitive Enhancers seem to be more efficacious compared to currently available Pharmacological Cognitive Enhancers. This review describes and summarizes evidence on various Non Pharmacological Cognitive Enhancers such as physical exercise, sleep, meditation and yoga, spirituality, nutrients, computer training, brain stimulation, and music. We also discuss their role in ageing and different neuro-psychiatric disorders, and current status of Cochrane database recommendations. We searched the Pubmed database for the articles and reviews having the terms 'non pharmacological and cognitive' in the title, published from 2000 till 2014. A total of 11 results displayed, out of which 10 were relevant to the review. These were selected and reviewed. Appropriate cross-references within the articles along with Cochrane reviews were also considered and studied.

  7. Safety pharmacologyCurrent and emerging concepts

    International Nuclear Information System (INIS)

    Hamdam, Junnat; Sethu, Swaminathan; Smith, Trevor; Alfirevic, Ana; Alhaidari, Mohammad; Atkinson, Jeffrey; Ayala, Mimieveshiofuo; Box, Helen; Cross, Michael; Delaunois, Annie; Dermody, Ailsa; Govindappa, Karthik; Guillon, Jean-Michel; Jenkins, Rosalind; Kenna, Gerry; Lemmer, Björn; Meecham, Ken; Olayanju, Adedamola; Pestel, Sabine; Rothfuss, Andreas

    2013-01-01

    Safety pharmacology (SP) is an essential part of the drug development process that aims to identify and predict adverse effects prior to clinical trials. SP studies are described in the International Conference on Harmonisation (ICH) S7A and S7B guidelines. The core battery and supplemental SP studies evaluate effects of a new chemical entity (NCE) at both anticipated therapeutic and supra-therapeutic exposures on major organ systems, including cardiovascular, central nervous, respiratory, renal and gastrointestinal. This review outlines the current practices and emerging concepts in SP studies including frontloading, parallel assessment of core battery studies, use of non-standard species, biomarkers, and combining toxicology and SP assessments. Integration of the newer approaches to routine SP studies may significantly enhance the scope of SP by refining and providing mechanistic insight to potential adverse effects associated with test compounds. - Highlights: • SP — mandatory non-clinical risk assessments performed during drug development. • SP organ system studies ensure the safety of clinical participants in FiH trials. • Frontloading in SP facilitates lead candidate drug selection. • Emerging trends: integrating SP-Toxicological endpoints; combined core battery tests

  8. Safety pharmacologyCurrent and emerging concepts

    Energy Technology Data Exchange (ETDEWEB)

    Hamdam, Junnat; Sethu, Swaminathan; Smith, Trevor; Alfirevic, Ana; Alhaidari, Mohammad [MRC Centre for Drug Safety Science, University of Liverpool (United Kingdom); Atkinson, Jeffrey [Lorraine University Pharmacolor Consultants Nancy PCN (France); Ayala, Mimieveshiofuo; Box, Helen; Cross, Michael [MRC Centre for Drug Safety Science, University of Liverpool (United Kingdom); Delaunois, Annie [UCB Pharma (Belgium); Dermody, Ailsa; Govindappa, Karthik [MRC Centre for Drug Safety Science, University of Liverpool (United Kingdom); Guillon, Jean-Michel [Sanofi-aventis (France); Jenkins, Rosalind [MRC Centre for Drug Safety Science, University of Liverpool (United Kingdom); Kenna, Gerry [Astra-Zeneca (United Kingdom); Lemmer, Björn [Ruprecht-Karls-Universität Heidelberg (Germany); Meecham, Ken [Huntingdon Life Sciences (United Kingdom); Olayanju, Adedamola [MRC Centre for Drug Safety Science, University of Liverpool (United Kingdom); Pestel, Sabine [Boehringer-Ingelheim (Germany); Rothfuss, Andreas [Roche (Switzerland); and others

    2013-12-01

    Safety pharmacology (SP) is an essential part of the drug development process that aims to identify and predict adverse effects prior to clinical trials. SP studies are described in the International Conference on Harmonisation (ICH) S7A and S7B guidelines. The core battery and supplemental SP studies evaluate effects of a new chemical entity (NCE) at both anticipated therapeutic and supra-therapeutic exposures on major organ systems, including cardiovascular, central nervous, respiratory, renal and gastrointestinal. This review outlines the current practices and emerging concepts in SP studies including frontloading, parallel assessment of core battery studies, use of non-standard species, biomarkers, and combining toxicology and SP assessments. Integration of the newer approaches to routine SP studies may significantly enhance the scope of SP by refining and providing mechanistic insight to potential adverse effects associated with test compounds. - Highlights: • SP — mandatory non-clinical risk assessments performed during drug development. • SP organ system studies ensure the safety of clinical participants in FiH trials. • Frontloading in SP facilitates lead candidate drug selection. • Emerging trends: integrating SP-Toxicological endpoints; combined core battery tests.

  9. Pharmacological approach of the receptors

    International Nuclear Information System (INIS)

    Puech, A.J.

    1989-01-01

    This paper explains the three main goals for clinical positron emission tomography (PET) studies: detection of receptor abnormalities in groups of patients to propose therapeutic indication of new ligands; validation of current hypothesis of drug effect; rational clinical drug development specially for dose-finding studies. (H.W.)

  10. Current status and challenges of cytokine pharmacology

    Czech Academy of Sciences Publication Activity Database

    Zídek, Zdeněk; Anzenbacher, P.; Kmoníčková, Eva

    2009-01-01

    Roč. 157, č. 3 (2009), s. 342-361 ISSN 0007-1188 R&D Projects: GA ČR GA305/08/0535; GA MŠk 1M0508 Institutional research plan: CEZ:AV0Z50390512 Keywords : cytokines * immunotherapy * immunopharmacology Subject RIV: FR - Pharmacology ; Medidal Chemistry Impact factor: 5.204, year: 2009

  11. Human pharmacology of current and new treatments for schizophrenia

    NARCIS (Netherlands)

    Liem-Moolenaar, Marieke

    2012-01-01

    The studies in this thesis together show different ways of studying human pharmacology, give an impression of the current drug development in schizophrenia, and provide examples how human pharmacology can be applied in an early stage of drug development in healthy volunteers. The investigated

  12. Network-based Approaches in Pharmacology.

    Science.gov (United States)

    Boezio, Baptiste; Audouze, Karine; Ducrot, Pierre; Taboureau, Olivier

    2017-10-01

    In drug discovery, network-based approaches are expected to spotlight our understanding of drug action across multiple layers of information. On one hand, network pharmacology considers the drug response in the context of a cellular or phenotypic network. On the other hand, a chemical-based network is a promising alternative for characterizing the chemical space. Both can provide complementary support for the development of rational drug design and better knowledge of the mechanisms underlying the multiple actions of drugs. Recent progress in both concepts is discussed here. In addition, a network-based approach using drug-target-therapy data is introduced as an example. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Clinical pharmacology in Russia-historical development and current state.

    Science.gov (United States)

    Zagorodnikova Goryachkina, Ksenia; Burbello, Aleksandra; Sychev, Dmitry; Frolov, Maxim; Kukes, Vladimir; Petrov, Vladimir

    2015-02-01

    Clinical pharmacology in Russia has long history and is currently active, but rather unrecognized internationally. It is governmentally approved as a teaching/scientific specialty since 1983 and as a medical specialty since 1997. Courses of clinical pharmacology are included in the undergraduate curricula in the 5th and/or 6th year of education at all medical schools in the Russian Federation. Postgraduate education includes initial specialization in internal medicine with further residency in clinical pharmacology. Governmental legislation recommends that every healthcare institution has either a department or a single position of clinical pharmacologist. Major routine duties include information about and monitoring of medication use, consultations in difficult clinical situations, pharmacogenetic counseling, therapeutic drug monitoring, pharmacovigilance, and participation in drug and therapeutics (formulary) committees. There are official experts in clinical pharmacology in Russia responsible for coordinating relevant legislative issues. The chief expert clinical pharmacologist represents the discipline directly at the Ministry of Health. Research in clinical pharmacology in Russia is extensive and variable, but only some of it is published internationally. Russia is a participant of international societies of clinical pharmacology and therapeutics and collaboration is actively ongoing. There are still certain problems related to the development of the discipline in Russia-some healthcare institutions do not see the need for clinical pharmacology. However, the number of clinical pharmacologists in Russia is increasing as well as their role in physicians' education, national healthcare, and research.

  14. Multiple sclerosis: general features and pharmacologic approach

    International Nuclear Information System (INIS)

    Nielsen Lagumersindez, Denis; Martinez Sanchez, Gregorio

    2009-01-01

    Multiple sclerosis is an autoimmune, inflammatory and desmyelinization disease central nervous system (CNS) of unknown etiology and critical evolution. There different etiological hypotheses talking of a close interrelation among predisposing genetic factors and dissimilar environmental factors, able to give raise to autoimmune response at central nervous system level. Hypothesis of autoimmune pathogeny is based on study of experimental models, and findings in biopsies of affected patients by disease. Accumulative data report that the oxidative stress plays a main role in pathogenesis of multiple sclerosis. Oxygen reactive species generated by macrophages has been involved as mediators of demyelinization and of axon damage, in experimental autoimmune encephalomyelitis and strictly in multiple sclerosis. Disease diagnosis is difficult because of there is not a confirmatory unique test. Management of it covers the treatment of acute relapses, disease modification, and symptoms management. These features require an individualized approach, base on evolution of this affection, and tolerability of treatments. In addition to diet, among non-pharmacologic treatments for multiple sclerosis it is recommended physical therapy. Besides, some clinical assays have been performed in which we used natural extracts, nutrition supplements, and other agents with promising results. Pharmacology allowed neurologists with a broad array of proved effectiveness drugs; however, results of research laboratories in past years make probable that therapeutical possibilities increase notably in future. (Author)

  15. Current trends and future development in pharmacologic stress testing

    International Nuclear Information System (INIS)

    Bae, Jin Ho; Lee, Jae Tae

    2005-01-01

    Pharmacologic stress testing for myocardial perfusion imaging is a widely used noninvasive method for the evaluation of known or suspected coronary artery disease. The use of exercise for cardiac stress has been practiced for over 60 years and clinicians are familiar with its using. However, there are inevitable situations in which exercise stress is inappropriate. A large number of patients with cardiac problems are unable to exercise to their full potential due to comorbidity such as osteoarthritis, vascular disease and pulmonary disease and a standard exercise stress test for myocardial perfusion imaging is suboptimal means for assessment of coronary artery disease. This problem has led to the development of the pharmacologic stress test and to a great increase in its popularity. All of the currently used pharmacologic agents have well-documented diagnostic value. This review deals the physiological actions, clinical protocols, safety, nuclear imaging applications of currently available stress agents and future development of new vasodilating agents

  16. Pharmaceutical and pharmacological approaches for bioavailability

    Indian Academy of Sciences (India)

    2014-01-27

    Jan 27, 2014 ... Etoposide posses high plasma protein binding (97%) and is degraded via ... The present article gives insight on pharmaceutical and pharmacological .... caprolactone and were found efficient as drug delivery vehicles.

  17. Veterinary pharmacology: history, current status and future prospects.

    Science.gov (United States)

    Lees, P; Fink-Gremmels, J; Toutain, P L

    2013-04-01

    Veterinary therapeutics, based on the art of Materia Medica, has been practised for countless centuries, but the science of veterinary pharmacology is of very recent origin. This review traces the contribution of Materia Medica to veterinary therapeutics from the Egyptian period through to the Age of Enlightenment. The first tentative steps in the development of the science of veterinary pharmacology were taken in the 18th century, but it was not until the mid 20th century that the science replaced the art of Materia Medica. This review traces the 20th century developments in veterinary pharmacology, with emphasis on the explosion of knowledge in the 35 year period to 2010. The range of factors which have influenced the current status of the discipline are reviewed. Future developments are considered from the perspectives of what might be regarded as desirable and those innovations that might be anticipated. We end with words of encouragement for young colleagues intent upon pursuing a career in veterinary pharmacology. © 2013 Blackwell Publishing Ltd.

  18. Pharmaceutical and pharmacological approaches for bioavailability

    Indian Academy of Sciences (India)

    Much research has been done to determine drug–drug and herb–drug interactions for improving the bioavailability of etoposide. The present article gives insight on pharmaceutical and pharmacological attempts made from time to time to overcome the erratic inter- and intra-patient variability for improving the bioavailability ...

  19. Non-pharmacological approaches to alleviate distress in dementia care.

    Science.gov (United States)

    Mitchell, Gary; Agnelli, Joanne

    2015-11-25

    Distress is one of the most common clinical manifestations associated with dementia. Pharmacological intervention may be appropriate in managing distress in some people. However, best practice guidelines advocate non-pharmacological interventions as the preferred first-line treatment. The use of non-pharmacological interventions encourages healthcare professionals to be more person-centred in their approach, while considering the causes of distress. This article provides healthcare professionals with an overview of some of the non-pharmacological approaches that can assist in alleviating distress for people living with dementia including: reminiscence therapy, reality orientation, validation therapy, music therapy, horticultural therapy, doll therapy and pet therapy. It provides a summary of their use in clinical practice and links to the relevant literature.

  20. Current Pharmacological Advances in the Treatment of Cardiac Arrest

    Directory of Open Access Journals (Sweden)

    Andry Papastylianou

    2012-01-01

    Full Text Available Cardiac arrest is defined as the sudden cessation of spontaneous ventilation and circulation. Within 15 seconds of cardiac arrest, the patient loses consciousness, electroencephalogram becomes flat after 30 seconds, pupils dilate fully after 60 seconds, and cerebral damage takes place within 90–300 seconds. It is essential to act immediately as irreversible damage can occur in a short time. Cardiopulmonary resuscitation (CPR is an attempt to restore spontaneous circulation through a broad range of interventions which are early defibrillation, high-quality and uninterrupted chest compressions, advanced airway interventions, and pharmacological interventions. Drugs should be considered only after initial shocks have been delivered (when indicated and chest compressions and ventilation have been started. During cardiopulmonary resuscitation, no specific drug therapy has been shown to improve survival to hospital discharge after cardiac arrest, and only few drugs have a proven benefit for short-term survival. This paper reviews current pharmacological treatment of cardiac arrest. There are three groups of drugs relevant to the management of cardiac arrest: vasopressors, antiarrhythmics, and other drugs such as sodium bicarbonate, calcium, magnesium, atropine, fibrinolytic drugs, and corticosteroids.

  1. Process Pharmacology: A Pharmacological Data Science Approach to Drug Development and Therapy.

    Science.gov (United States)

    Lötsch, Jörn; Ultsch, Alfred

    2016-04-01

    A novel functional-genomics based concept of pharmacology that uses artificial intelligence techniques for mining and knowledge discovery in "big data" providing comprehensive information about the drugs' targets and their functional genomics is proposed. In "process pharmacology", drugs are associated with biological processes. This puts the disease, regarded as alterations in the activity in one or several cellular processes, in the focus of drug therapy. In this setting, the molecular drug targets are merely intermediates. The identification of drugs for therapeutic or repurposing is based on similarities in the high-dimensional space of the biological processes that a drug influences. Applying this principle to data associated with lymphoblastic leukemia identified a short list of candidate drugs, including one that was recently proposed as novel rescue medication for lymphocytic leukemia. The pharmacological data science approach provides successful selections of drug candidates within development and repurposing tasks. © 2016 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

  2. Tourette Syndrome and comorbid ADHD: current pharmacological treatment options.

    Science.gov (United States)

    Rizzo, Renata; Gulisano, Mariangela; Calì, Paola V; Curatolo, Paolo

    2013-09-01

    Attention Deficit Hyperactivity Disorder (ADHD) is the most common co-morbid condition encountered in people with tics and Tourette Syndrome (TS). The co-occurrence of TS and ADHD is associated with a higher psychopathological, social and academic impairment and the management may represent a challenge for the clinicians. To review recent advances in management of patients with tic, Tourette Syndrome and comorbid Attention Deficit Hyperactivity Disorder. We searched peer reviewed and original medical publications (PUBMED 1990-2012) and included randomized, double-blind, controlled trials related to pharmacological treatment for tic and TS used in children and adolescents with comorbid ADHD. "Tourette Syndrome" or "Tic" and "ADHD", were cross referenced with the words "pharmacological treatment", "α-agonist", "psychostimulants", "selective norepinephrine reuptake inhibitor", "antipsychotics". Three classes of drugs are currently used in the treatment of TS and comorbid ADHD: α-agonists (clonidine and guanfacine), stimulants (amphetamine enantiomers, methylphenidate enantiomers or slow release preparation), and selective norepinephrine reuptake inhibitor (atomoxetine). It has been recently suggested that in a few selected cases partial dopamine agonists (aripiprazole) could be useful. Level A of evidence supported the use of noradrenergic agents (clonidine). Reuptake inhibitors (atomoxetine) and stimulants (methylphenidate) could be, also used for the treatment of TS and comorbid ADHD. Taking into account the risk-benefit profile, clonidine could be used as the first line treatment. However only few studies meet rigorous quality criteria in terms of study design and methodology; most trials have low statistical power due to small sample size or short duration. Treatment should be "symptom targeted" and personalized for each patient. Copyright © 2013 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  3. Pharmacological Approaches for Nonalcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Ionică Floriana Elvira

    2016-09-01

    Full Text Available Background and aims: Nonalcoholic fatty liver disease (NAFDL is a multifactorial condition with a wide spectrum of histological severities, from asymptomatic hepatic steatosis to nonalcoholic steatohepatitis (NASH with or without fibrosis. NAFLD is highly common and potentially serious in children and adolescents and affects approximately one third of the general population. It is closely associated with obesity, insulin resistance and dyslipidemia. NASH is a histological diagnosis and has a great significance because it can progress to cirrhosis, liver failure, and hepatocellular carcinoma (HCC, and is associated with both increased cardiovascular and liver related mortality. The purpose of this review is to summarize the evidence for current potential therapies of NAFLD.

  4. A network pharmacology approach to investigate the pharmacological effects of Guizhi Fuling Wan on uterine fibroids.

    Science.gov (United States)

    Zeng, Liuting; Yang, Kailin; Liu, Huiping; Zhang, Guomin

    2017-11-01

    To investigate the pharmacological mechanism of Guizhi Fuling Wan (GFW) in the treatment of uterine fibroids, a network pharmacology approach was used. Information on GFW compounds was collected from traditional Chinese medicine (TCM) databases, and input into PharmMapper to identify the compound targets. Genes associated with uterine fibroids genes were then obtained from the GeneCards and Online Mendelian Inheritance in Man databases. The interaction data of the targets and other human proteins was also collected from the STRING and IntAct databases. The target data were input into the Database for Annotation, Visualization and Integrated Discovery for gene ontology (GO) and pathway enrichment analyses. Networks of the above information were constructed and analyzed using Cytoscape. The following networks were compiled: A compound-compound target network of GFW; a herb-compound target-uterine fibroids target network of GWF; and a compound target-uterine fibroids target-other human proteins protein-protein interaction network, which were subjected to GO and pathway enrichment analyses. According to this approach, a number of novel signaling pathways and biological processes underlying the effects of GFW on uterine fibroids were identified, including the negative regulation of smooth muscle cell proliferation, apoptosis, and the Ras, wingless-type, epidermal growth factor and insulin-like growth factor-1 signaling pathways. This network pharmacology approach may aid the systematical study of herbal formulae and make TCM drug discovery more predictable.

  5. New approaches in analyzing the pharmacological properties of herbal extracts.

    Science.gov (United States)

    Hamburger, Matthias

    2007-01-01

    Herbal extracts are widely used and accepted in the population. The pharmacological characterization of such products meets some specific challenges, given the chemical complexity of the active ingredient. An overview is given on modern methods and approaches that can be used for that purpose. In particular, HPLC-based activity profiling is discussed as a means to identify pharmacologically active compounds in an extract, and expression profiling is described as a means for global assessment of effects exerted by multi-component mixtures such as extracts. These methods are illustrated with selected axamples from our labs, including woad (Isatis tinctoria), the traditional Chinese herb Danshen (Salvia miltiorrhiza) and black cohosh (Cimicifuga racemosa).

  6. [Treatment of generalized anxiety: new pharmacologic approaches].

    Science.gov (United States)

    Boulenger, J P

    1995-01-01

    . However, it will also be important to know if wether or not the efficacy of these new drugs, like that of buspirone, is associated with some effects on depressive symptomatology, develops only progressively over time and is different in previous BZD users compared to GAD patients who did not receive BZD before the new drug. Among these drugs in development for GAD, the most likely to reach the market in a near future are a BZD partial agonist (abecarnil), 5-HT1A agonists like ipsapirone and 5-HT3 antagonists like ondansetron. However, another area of new developments concerning the drug treatment of GAD is the use of antidepressants, which have demonstrated efficacy in this indication even in patients without depressive features or panic attacks symptoms. Considering the chronic nature of GAD, these drugs, like those acting on the 5-HT-system, would be more adapted than BZD for the long-term management of this condition. If confirmed by clinical trials involving antidepressants other than tricyclics, the efficacy of these drugs in GAD may suggest that common neurobiological mechanisms are involved in the pathogenesis of both anxiety and depressive disorders. Despite the potential interest of these new treatments of GAD, recent years have shown that the development of new anxiolytic drugs often appears limited by high-rates of placebo response in numerous clinical trials. This phenomenon may be related--in part--to the increasingly sophisticated designs used in such trials, such as extensive diagnostic workups, repeated evaluations and inclusion criteria selecting the less severe types of anxiety. As emphasized by other authors, much more research needs to be done to establish what effects various ways of conducting a trial have on the trial's results in order to facilitate the emergence of new psychopharmacological approaches in the treatment of GAD.

  7. Targeting Adenosine Signaling in Parkinson's Disease: From Pharmacological to Non-pharmacological Approaches

    Directory of Open Access Journals (Sweden)

    Luiza R. Nazario

    2017-11-01

    Full Text Available Parkinson's disease (PD is one of the most prevalent neurodegenerative disease displaying negative impacts on both the health and social ability of patients and considerable economical costs. The classical anti-parkinsonian drugs based in dopaminergic replacement are the standard treatment, but several motor side effects emerge during long-term use. This mini-review presents the rationale to several efforts from pre-clinical and clinical studies using adenosine receptor antagonists as a non-dopaminergic therapy. As several studies have indicated that the monotherapy with adenosine receptor antagonists reaches limited efficacy, the usage as a co-adjuvant appeared to be a promising strategy. The formulation of multi-targeted drugs, using adenosine receptor antagonists and other neurotransmitter systems than the dopaminergic one as targets, have been receiving attention since Parkinson's disease presents a complex biological impact. While pharmacological approaches to cure or ameliorate the conditions of PD are the leading strategy in this area, emerging positive aspects have arisen from non-pharmacological approaches and adenosine function inhibition appears to improve both strategies.

  8. Current Status of Undergraduate, Nonprofessional Pharmacology Courses Taught in Colleges of Pharmacy

    Science.gov (United States)

    Gerald, Michael C.

    1976-01-01

    Of the 57 colleges of pharmacy surveyed, 33 are currently offering a total of 44 elective, undergraduate, nonprofessional pharmacology courses, and seven contemplate initiating such courses by 1977. The courses generally cover three areas: social and legal aspects of drug usage and nonprescription consumerism; pharmacology of the drugs of abuse;…

  9. Osteoporosis – a current view of pharmacological prevention and treatment

    Directory of Open Access Journals (Sweden)

    Das S

    2013-05-01

    Full Text Available Subhajit Das, Julie C Crockett Musculoskeletal Research Programme, School of Medicine and Dentistry, University of Aberdeen, Aberdeen, UK Abstract: Postmenopausal osteoporosis is the most common bone disease, associated with low bone mineral density (BMD and pathological fractures which lead to significant morbidity. It is defined clinically by a BMD of 2.5 standard deviations or more below the young female adult mean (T-score = −2.5. Osteoporosis was a huge global problem both socially and economically – in the UK alone, in 2011 £6 million per day was spent on treatment and social care of the 230,000 osteoporotic fracture patients – and therefore viable preventative and therapeutic approaches are key to managing this problem within the aging population of today. One of the main issues surrounding the potential of osteoporosis management is diagnosing patients at risk before they develop a fracture. We discuss the current and future possibilities for identifying susceptible patients, from fracture risk assessment to shape modeling and in relation to the high heritability of osteoporosis now that a plethora of genes have been associated with low BMD and osteoporotic fracture. This review highlights the current therapeutics in clinical use (including bisphosphonates, anti-RANKL [receptor activator of NF-κB ligand], intermittent low dose parathyroid hormone, and strontium ranelate and some of those in development (anti-sclerostin antibodies and cathepsin K inhibitors. By highlighting the intimate relationship between the activities of bone forming (osteoblasts and bone-resorbing (osteoclasts cells, we include an overview and comparison of the molecular mechanisms exploited in each therapy. Keywords: BMD, fracture, bisphosphonate, strontium, denosumab, teriparatide, raloxifene

  10. An Overview of Pharmacological Approaches for Management and Repair of Spinal Cord Injuries

    Directory of Open Access Journals (Sweden)

    Azam Mardani

    2010-11-01

    Full Text Available "nSpinal cord injury (SCI leads to loss of nervous tissue and consequently to catastrophic neurological deficits. Up to now there is no definite treatment available that restores the loss of function to a degree that an independent life can be guaranteed. "nThis justifies the cost of research into the new modalities for a treatment of SCIs. In current paper, recent developments and new approaches in pharmacological therapy have been reviewed

  11. Fournier's gangrene current approaches.

    Science.gov (United States)

    Ozkan, Omer F; Koksal, Neset; Altinli, Ediz; Celik, Atilla; Uzun, Mehmet A; Cıkman, Oztekin; Akbas, Alpaslan; Ergun, Ersin; Kiraz, Hasan A; Karaayvaz, Muammer

    2016-10-01

    Fournier's gangrene is a rare but highly mortal infectious disease characterised by fulminant necrotising fasciitis involving the genital and perineal regions. The objective of this study is to analyse the demographics, clinical feature and treatment approaches as well as outcomes of Fournier's gangrene. Data were collected retrospectively from medical records and operative notes. Patient data were analysed by demographics, aetiological factors, clinical features, treatment approaches and outcomes. Twelve patients (five female and seven male) were enrolled in this study. The most common aetiology was perianal abscess (41·6%). Wound cultures showed a mixture of microorganisms in six (50%) patients. For faecal diversion, while colostomy was performed in six cases (50%), Flexi-Seal was used in two cases (16·6%). In four patients (33·4%), no faecal diversion was performed. Negative pressure wound therapy (NPWT) system was effective in the last four patients (33·4%). The mean hospitalisation period in patients who used NPWT was 18 days, while it was 20 days in the others. NPWT in Fournier's gangrene is a safe dressing method. It promotes granulation formation. Flexi-Seal faecal management is an alternative method to colostomy and provides protection from its associated complications. The combination of two devices (Flexi-Seal and NPWT) is an effective and comfortable method in the management of Fournier's gangrene in appropriate patients. © 2014 The Authors. International Wound Journal © 2014 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

  12. Pharmacological approaches for Alzheimer's disease: neurotransmitter as drug targets.

    Science.gov (United States)

    Prakash, Atish; Kalra, Jaspreet; Mani, Vasudevan; Ramasamy, Kalavathy; Majeed, Abu Bakar Abdul

    2015-01-01

    Alzheimer's disease (AD) is the most common CNS disorder occurring worldwide. There is neither proven effective prevention for AD nor a cure for patients with this disorder. Hence, there is an urgent need to develop safer and more efficacious drugs to help combat the tremendous increase in disease progression. The present review is an attempt at discussing the treatment strategies and drugs under clinical trials governing the modulation of neurotransmitter. Therefore, looking at neurotransmitter abnormalities, there is an urge for developing the pharmacological approaches aimed at correcting those abnormalities and dysfunctioning. In addition, this review also discusses the drugs that are in Phase III trials for the treatment of AD. Despite advances in treatment strategies aimed at correcting neurotransmitter abnormalities, there exists a need for the development of drug therapies focusing on the attempts to remove the pathogenomic protein deposits, thus combating the disease progression.

  13. [New approaches in pharmacology: numerical modelling and simulation].

    Science.gov (United States)

    Boissel, Jean-Pierre; Cucherat, Michel; Nony, Patrice; Dronne, Marie-Aimée; Kassaï, Behrouz; Chabaud, Sylvie

    2005-01-01

    The complexity of pathophysiological mechanisms is beyond the capabilities of traditional approaches. Many of the decision-making problems in public health, such as initiating mass screening, are complex. Progress in genomics and proteomics, and the resulting extraordinary increase in knowledge with regard to interactions between gene expression, the environment and behaviour, the customisation of risk factors and the need to combine therapies that individually have minimal though well documented efficacy, has led doctors to raise new questions: how to optimise choice and the application of therapeutic strategies at the individual rather than the group level, while taking into account all the available evidence? This is essentially a problem of complexity with dimensions similar to the previous ones: multiple parameters with nonlinear relationships between them, varying time scales that cannot be ignored etc. Numerical modelling and simulation (in silico investigations) have the potential to meet these challenges. Such approaches are considered in drug innovation and development. They require a multidisciplinary approach, and this will involve modification of the way research in pharmacology is conducted.

  14. Education and non-pharmacological approaches for gout.

    Science.gov (United States)

    Abhishek, Abhishek; Doherty, Michael

    2018-01-01

    The objectives of this review are as follows: to highlight the gaps in patient and physician knowledge of gout and how this might impede optimal disease management; to provide recommended core knowledge points that should be conveyed to people with gout; and to review non-pharmacological interventions that can be used in gout management. MeSH terms were used to identify eligible studies examining patients' and health-care professionals' knowledge about gout and its management. A narrative review of non-pharmacological management of gout is provided. Many health-care professionals have significant gaps in their knowledge about gout that have the potential to impede optimal management. Likewise, people with gout and the general population lack knowledge about causes, consequences and treatment of this condition. Full explanation about gout, including the potential benefits of urate-lowering treatment (ULT), motivates people with gout to want to start such treatment, and there is evidence, albeit limited, that educational interventions can improve uptake and adherence to ULT. Additionally, several non-pharmacological approaches, such as rest and topical ice application for acute attacks, avoidance of risk factors that can trigger acute attacks, and dietary interventions that may reduce gout attack frequency (e.g. cherry or cherry juice extract, skimmed milk powder or omega-3 fatty acid intake) or lower serum uric acid (e.g. vitamin C), can be used as adjuncts to ULT. There is a pressing need to educate health-care professionals, people with gout and society at large to remove the negative stereotypes associated with gout, which serve as barriers to optimal gout management, and to perceive gout as a significant medical condition. Moreover, there is a paucity of high-quality trial evidence on whether certain simple individual dietary and lifestyle factors can reduce the risk of recurrent gout attacks, and further studies are required in this field. © The Author 2018

  15. [Pharmacological approaches for correction of thyroid dysfunctions in diabetes mellitus].

    Science.gov (United States)

    Shpakov, A O

    2017-05-01

    Thyroid diseases are closely associated with the development of types 1 and 2 diabetes mellitus (DM), and as a consequence, the development of effective approaches for their treatment is one of the urgent problems of endocrinology. Traditionally, thyroid hormones (TH) are used to correct functions of the thyroid system. However, they are characterized by many side effects, such as their negative effect on the cardiovascular system as well as the ability of TH to enhance insulin resistance and to disturb insulin-producing function of pancreas, exacerbating thereby diabetic pathology. Therefore, the analogues of TH, selective for certain types of TH receptors, that do not have these side effects, are being developed. The peptide and low-molecular weight regulators of thyroid-stimulating hormone receptor, which regulate the activity of the thyroid axis at the stage of TH synthesis and secretion in thyrocytes, are being created. Systemic and intranasal administration of insulin, metformin therapy and drugs with antioxidant activity are effective for the treatment of thyroid pathology in types 1 and 2 DM. In the review, the literature data and the results of own investigations on pharmacological approaches for the treatment and prevention of thyroid diseases in patients with types 1 and 2 DM are summarized and analyzed.

  16. Current pharmacological agents for the treatment of premature ejaculation

    Directory of Open Access Journals (Sweden)

    Onur Dede

    2014-06-01

    Full Text Available This study was aimed to review and assess the update studies regarding medical treatment for premature ejaculation (PE. It is the most common sexual problem affecting men. It can affect men at all ages and has a serious impact on the quality of life for men and their partners. A wide variety of therapeutic modalities have been tried for treatment of premature ejaculation. Psychological therapies may be helpful for patients with complaint PE. Several topical therapies have been used including lidocaine cream, lidocaine-prilocaine cream. There has been recent interest in the selective serotonin reuptake inhibitors (SSRI for the treatment of PE, due to the fact that one of their common side effects is delayed ejaculation. Currently used SSRIs have several non-sexual side effects and long half lives, therefore there has been interest in developing a short acting, and efficacious SSRI that can be used on-demand for PE. Dapoxetine has been recently evaluated for the treatment of PE by several groups, and results so far appear promising.

  17. Pharmacological Treatments of Alzheimer’s Disease: Current Medication,

    Directory of Open Access Journals (Sweden)

    Arash Mowla

    2010-12-01

    Full Text Available Background: Alzheimer’s disease (AD that is identified by progressive cognitive deficit and behavioral disturbances (BD are the most common form of dementia. As the population is aging, patients with AD are becoming a serious burden for societies. In this study, current medication for cognitive deficit and behavioral disturbances are reviewed. Also the new treatment strategies for cognitive dysfunction and behavioral disturbances are surveyed. Methods: The method employed in this researh was a systematic bibliographic review, in which only the double-blind placebo-controlled studies or the clinically detailed enough open-labeled studies using validated scales were retained. Results: The efficacy of cholinesterase inhibitors (Tacrine, Rivastigmine, Donapezil and Galantamine has been demonstrated in several double blind placebo controlled clinical trials. They have shown a mild efficacy in mild to moderate AD. Memantine, a NMDA antagonist is the only drug that has demonstrated mild efficacy in moderate to severe AD in controlled clinical trial. Clinical trials surveying the efficacy of active and passive immunization against B amyloid protoin has halted due to serious adverse events. Studies of inducing neurogenesis in brain of AD patients are preliminary. Antipsychotics have shown efficacy for controlling BD of AD patients but they are associated with adverse events. Except for carbamazepine, there is not enough evidence for other anticanvulsants to be effective for behavioral disturbances of AD patients. A controlled clinical trial and some open studies have shown the efficacy of citalopram for BD. Further studies are needed to confirm the efficacy of other medications like trazadon, buspiron and beta blockers for BD. Conclusion: Cholinesterase inhibitors have demonstrated disappointing results. Memantine is only mildly effective for cognitive deficit. To date, no amyloid-modifying therapy has yet been successful in phase 3 clinical trials

  18. An Integrated Approach to Instruction in Pharmacology and Therapeutics

    Science.gov (United States)

    Talbert, Robert L.; Walton, Charles A.

    1976-01-01

    The impact of the clinical faculty on the content of the pharmacology course is described in a discussion of trends in pharmacology instruction. Interfaculty communication and development of course objectives are reviewed, and descriptions of two baccalaureate courses at the University of Texas College of Pharmacy are appended. (LBH)

  19. From gene networks to drugs: systems pharmacology approaches for AUD.

    Science.gov (United States)

    Ferguson, Laura B; Harris, R Adron; Mayfield, Roy Dayne

    2018-06-01

    The alcohol research field has amassed an impressive number of gene expression datasets spanning key brain areas for addiction, species (humans as well as multiple animal models), and stages in the addiction cycle (binge/intoxication, withdrawal/negative effect, and preoccupation/anticipation). These data have improved our understanding of the molecular adaptations that eventually lead to dysregulation of brain function and the chronic, relapsing disorder of addiction. Identification of new medications to treat alcohol use disorder (AUD) will likely benefit from the integration of genetic, genomic, and behavioral information included in these important datasets. Systems pharmacology considers drug effects as the outcome of the complex network of interactions a drug has rather than a single drug-molecule interaction. Computational strategies based on this principle that integrate gene expression signatures of pharmaceuticals and disease states have shown promise for identifying treatments that ameliorate disease symptoms (called in silico gene mapping or connectivity mapping). In this review, we suggest that gene expression profiling for in silico mapping is critical to improve drug repurposing and discovery for AUD and other psychiatric illnesses. We highlight studies that successfully apply gene mapping computational approaches to identify or repurpose pharmaceutical treatments for psychiatric illnesses. Furthermore, we address important challenges that must be overcome to maximize the potential of these strategies to translate to the clinic and improve healthcare outcomes.

  20. Pharmacologic versus direct-current electrical cardioversion of atrial flutter and fibrillation

    NARCIS (Netherlands)

    Van Gelder, IC; Tuinenburg, AE; Schoonderwoerd, BS; Tieleman, RG; Crijns, HJGM

    1999-01-01

    Conversion of atrial flutter and atrial fibrillation (AF) can be achieved by either pharmacologic or direct-current (DC) electrical cardioversion. DC electrical cardioversion is more effective and restores sinus rhythm instantaneously; however, general anesthesia is necessary, which can cause severe

  1. Applying linked data approaches to pharmacology: Architectural decisions and implementation

    NARCIS (Netherlands)

    Gray, A.J.G; Groth, P.T.; Loizou, A.; Askjaer, S; Brenninkmeijer, C; Burger, K.; Chichester, C.; Evelo, C.T.; Goble, C.A.; Harland, L; Pettifier, S; Thompson, M.; Waagmeester, A; William, A.J

    2014-01-01

    The discovery of new medicines requires pharmacologists to interact with a number of information sources ranging from tabular data to scientific papers, and other specialized formats. In this application report, we describe a linked data platform for integrating multiple pharmacology datasets that

  2. Towards predictive cardiovascular safety : a systems pharmacology approach

    NARCIS (Netherlands)

    Snelder, Nelleke

    2014-01-01

    Cardiovascular safety issues related to changes in blood pressure, arise frequently in drug development. In the thesis “Towards predictive cardiovascular safety – a systems pharmacology approach”, a system-specific model is described to quantify drug effects on the interrelationship between mean

  3. Pharmacologic Approaches Against Advanced Glycation End Products (AGEs) in Diabetic Cardiovascular Disease.

    Science.gov (United States)

    Nenna, Antonio; Nappi, Francesco; Avtaar Singh, Sanjeet Singh; Sutherland, Fraser W; Di Domenico, Fabio; Chello, Massimo; Spadaccio, Cristiano

    2015-05-01

    Advanced Glycation End-Products (AGEs) are signaling proteins associated to several vascular and neurological complications in diabetic and non-diabetic patients. AGEs proved to be a marker of negative outcome in both diabetes management and surgical procedures in these patients. The reported role of AGEs prompted the development of pharmacological inhibitors of their effects, giving rise to a number of both preclinical and clinical studies. Clinical trials with anti-AGEs drugs have been gradually developed and this review aimed to summarize most relevant reports. Evidence acquisition process was performed using PubMed and ClinicalTrials.gov with manually checked articles. Pharmacological approaches in humans include aminoguanidine, pyridoxamine, benfotiamine, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, statin, ALT-711 (alagebrium) and thiazolidinediones. The most recent promising anti-AGEs agents are statins, alagebrium and thiazolidinediones. The role of AGEs in disease and new compounds interfering with their effects are currently under investigation in preclinical settings and these newer anti-AGEs drugs would undergo clinical evaluation in the next years. Compounds with anti-AGEs activity but still not available for clinical scenarios are ALT-946, OPB-9195, tenilsetam, LR-90, TM2002, sRAGE and PEDF. Despite most studies confirm the efficacy of these pharmacological approaches, other reports produced conflicting evidences; in almost any case, these drugs were well tolerated. At present, AGEs measurement has still not taken a precise role in clinical practice, but its relevance as a marker of disease has been widely shown; therefore, it is important for clinicians to understand the value of new cardiovascular risk factors. Findings from the current and future clinical trials may help in determining the role of AGEs and the benefits of anti-AGEs treatment in cardiovascular disease.

  4. Nanorobotics current approaches and techniques

    CERN Document Server

    Ferreira, Antoine

    2013-01-01

    Nanorobot devices now perform a wide variety of tasks at the nanoscale in a wide variety of fields including but not limited to fields such as manufacturing, medicine, supply chain, biology, and outer space. Nanorobotics: Current Approaches and Techniques is a comprehensive overview of this interdisciplinary field with a wide ranging discussion that includes nano-manipulation and industrial nanorobotics, nanorobotics in biology and medicine, nanorobotic sensing, navigation and swarm behavior, and protein and DNA-based nanorobotics. Also included is the latest on topics such as bio-nano-actuators and propulsion and navigation of nanorobotic systems using magnetic fields. Nanorobotics: Current Approaches and Techniques is an ideal book for scientists, researchers, and engineers actively involved in applied and robotic research and development.

  5. Pharmacological Approaches for the Management of Persistent Pain in Older Adults What Nurses Need to Know

    NARCIS (Netherlands)

    Guerriero, Fabio; Bolier, Ruth; van Cleave, Janet H.; Reid, M. Cary

    2016-01-01

    The current article addresses pharmacological treatment issues regarding the management of persistent pain in later life, which is a worldwide problem associated with substantial disability. Recommendations from guidelines were reviewed and data are presented regarding the benefits and risks of

  6. Low current approach to ignition

    International Nuclear Information System (INIS)

    Cenacchi, G.; Sugiyama, L.; Airoldi, A.; Coppi, B.

    1996-01-01

    The open-quotes standardclose quotes path to achieve ignition conditions so far has been that of producing plasmas with the maximum current and poloidal field that axe compatible with the applied toroidal field and the geometry of the adopted configuration (the low q a approach.) The other approach is that motivated by recent experiments with reversed shear configurations, with relatively low currents and high fields corresponding to high values of q a (e-g., q a ≅ 6). While the first approach can be pursued with ohmic heating alone, the second one necessarily involves an auxiliary heating system. One of the advantages of this approach is that the onset of large scale internal modes can be avoided as q(ψ) is kept above 1 over the entire plasma column. Since quite peaked density profiles are produced in the regimes where enhanced confinement is observed, the α-particle power levels for which ignition can be reached and therefore the thermal wall loading on the first wall, can be reduced relatively to the standard, low q a , approach. The possibility is considered that ignition is reached in the reversed shear, high q a , regime and that this is followed by a transition to non-reversed profiles, or even the low q a regime, assuming that the excitation of modes involving magnetic reconnection will not undermine the needed degree of confinement. These results have been demonstrated by numerical transport simulation for the Ignitor-Ult machine, but are applicable to all high field ignition experiments

  7. Approach to pharmacological and clinical applications of Anisi aetheroleum

    Directory of Open Access Journals (Sweden)

    Khaled Mohamed Mohamed Koriem

    2015-01-01

    Full Text Available Anisi aetheroleum is the oil obtained from Pimpinella anisum L. (P. anisum by steam distillation. P. anisum seeds were air-dried, and then the dry seeds were crushed, pulverized, and weighed in sequence for anise oil preparation. P. anisum is one of the oldest medicinal plants that belong to family Apiaceae. The fruit of P. anisum is harvested in August and September. P. anisum is widespread in Asia, Africa and Europe. Local names of P. anisum include anise, anisoon, roomy, saunf, sweet cumin and yansoon. The anise oil odour is aromatic while the oil tastes sweet. The average daily dose of Anisi aetheroleum is 0.3 g. trans-Anethole is the major ingredient of the anise oil. Anisi aetheroleum also displays a protective action against neurotoxicity. In addition, Anisi aetheroleum increases glucose absorption and reduces urine output in the rat. The plant oil have pharmacological (antimicrobial, hepatoprotective, anticonvulsant, anti-inflammatory, antispasmodic, bronchodilator, estrogenic, expectorant and insecticidal effects and clinical effects on nausea, constipation, menopausal period, virus, diabetes, obesity and sedative action. Owing to the wide application of Anisi aetheroleum in pharmacological and clinical fields, it is recommended for more clinical trails to discover a new medication from the active constituents of the plant oil in the future to treat human diseases especially chronic ones.

  8. Pharmacological preconditioning with GYKI 52466: a prophylactic approach to neuroprotection

    Directory of Open Access Journals (Sweden)

    Chelsea S Goulton

    2010-08-01

    Full Text Available Some toxins and drugs can trigger lasting neuroprotective mechanisms that enable neurons to resist a subsequent severe insult. This ‘pharmacological preconditioning’ has far-reaching implications for conditions in which blood flow to the brain is interrupted. We have previously shown that in vitro preconditioning with the AMPA receptor antagonist GYKI 52466 induces tolerance to kainic acid (KA toxicity in hippocampus. This effect persists well after washout of the drug and may be mediated via inverse agonism of G protein linked receptors. Given the amplifying nature of metabotropic modulation, we hypothesised that GYKI 52466 may be effective in reducing seizure severity at doses well below those normally associated with adverse side effects. Here we report that pharmacological preconditioning with low-dose GYKI imparts a significant protection against KA-induced seizures in vivo. GYKI (3 mg/kg, s.c., 90 to 180 min. prior to high-dose KA, markedly reduced seizure scores, virtually abolished all level 3 and level 4 seizures, and completely suppressed KA-induced hippocampal cFOS expression. In addition, preconditioned animals exhibited significant reductions in high frequency/high amplitude spiking and ECoG power in the delta, theta, alpha and beta bands during KA. Adverse behaviours often associated with higher doses of GYKI were not evident during preconditioning. The fact that GYKI is effective at doses well-below, and at pre-administration intervals well-beyond previous studies, suggests that a classical blockade of ionotropic AMPA receptors does not underlie anticonvulsant effects. Low-dose GYKI preconditioning may represent a novel, prophylactic strategy for neuroprotection in a field almost completely devoid of effective pharmaceuticals.

  9. Huntington's disease: current epidemiology and pharmacological management in UK primary care.

    Science.gov (United States)

    Sackley, Catherine; Hoppitt, Thomas J; Calvert, Melanie; Gill, Paramjit; Eaton, Benjamin; Yao, Guiqing; Pall, Hardev

    2011-01-01

    Recent debate suggests Huntington's disease (HD) may be more prevalent than previously reported. In addition, relatively little is known about current disease management. This study aims to provide epidemiological data and describe the pharmacological management of HD in the United Kingdom. A primary care research database was accessed to identify incident and prevalent HD cases between January 1, 2004, and December 31, 2008. Patients with Read codes denoting a definite diagnosis or possible diagnosis, and undiagnosed patients with a positive family history were identified. A subset of patients with a definite diagnosis and prescribed medication indicating symptom onset was also identified. Epidemiological data were estimated. Pharmacological prescriptions to HD patients from 2004 to 2008 were identified, and prescription frequencies were grouped according to the British National Formulary categories. HD incidence estimates ranged from 0.44 to 0.78 per 100,000 person-years, and HD prevalence ranged from 5.96 to 6.54 per 100,000 of the population. Forty-four percent of pharmacological prescriptions targeted the central nervous system. Nearly half of the HD patients were prescribed antidepressants, and over 40% were prescribed analgesics. Although prevalence estimates fell short of figures suggested in recent debate, it is feasible that the true prevalence may be much higher than previously reported. Pharmacological management appears to rely heavily on central nervous system drugs and nutrition support. Many of these drugs are prescribed to HD patients for reasons other than the medication's primary use. Further work is required to evaluate the impact of alternative management strategies, such as therapist intervention, counselling, and organisation support, on the patients' quality of life. Copyright © 2011 S. Karger AG, Basel.

  10. Current approach to liver traumas.

    Science.gov (United States)

    Kaptanoglu, Levent; Kurt, Necmi; Sikar, Hasan Ediz

    2017-03-01

    Liver injuries remain major obstacle for successful treatment, due to size and location of the liver. Requirement for surgery should be determined by clinical factors, most notably hemodynamical state. In this present study we tried to declare our approach to liver traumas. We also tried to emphasize the importance of conservative treatment, since surgeries for liver traumas carry high mortality rates. Patients admitted to the Department of Emergency Surgery at Kartal Research and Education Hospital, due to liver trauma were retrospectively analyzed between 2003 and 2013. Patient demographics, hepatic panel, APTT (activated partial thromboplastin time), PT (prothrombin time), INR (international normalized ratio), fibrinogen, biochemistry panel were recorded. Hemodynamic instability was the most prominent factor for surgery decision, in the lead of current Advanced Trauma Life Support (ATLS) protocols. Operation records and imaging modalities revealed liver injuries according to the Organ Injury Scale of the American Association for the Surgery of Trauma. 300 patients admitted to emergency department were included in our study (187 males and 113 females). Mean age was 47 years (range, 12-87). The overall mortality rate was 13% (40 out of 300). Major factor responsible for mortality rates and outcome was stability of cases on admission. 188 (% 63) patients were counted as stable, whereas 112 (% 37) cases were found unstable (blood pressure ≤ 90, after massive resuscitation). 192 patients were observed conservatively, whereas 108 cases received abdominal surgery. High levels of AST, ALT, LDH, INR, creatinine and low levels of fibrinogen and low platelet counts on admission were found to be associated with mortality and these cases also had Grade 4 and 5 injuries. Hemodynamic instability on admission and the type and grade of injury played major role in mortality rates). Packing was performed in 35 patients, with Grade 4 and 5 injuries. Mortality rate was %13 (40

  11. Introduction to the Theme "New Methods and Novel Therapeutic Approaches in Pharmacology and Toxicology".

    Science.gov (United States)

    Insel, Paul A; Amara, Susan G; Blaschke, Terrence F; Meyer, Urs A

    2017-01-06

    Major advances in scientific discovery and insights can result from the development and use of new techniques, as exemplified by the work of Solomon Snyder, who writes a prefatory article in this volume. The Editors have chosen "New Methods and Novel Therapeutic Approaches in Pharmacology and Toxicology" as the Theme for a number of articles in this volume. These include ones that review the development and use of new experimental tools and approaches (e.g., nanobodies and techniques to explore protein-protein interactions), new types of therapeutics (e.g., aptamers and antisense oligonucleotides), and systems pharmacology, which assembles (big) data derived from omics studies together with information regarding drugs and patients. The application of these new methods and therapeutic approaches has the potential to have a major impact on basic and clinical research in pharmacology and toxicology as well as on patient care.

  12. New pharmacological approaches to the cholinergic system: an overview on muscarinic receptor ligands and cholinesterase inhibitors.

    Science.gov (United States)

    Greig, Nigel H; Reale, Marcella; Tata, Ada M

    2013-08-01

    The cholinergic system is expressed in neuronal and in non-neuronal tissues. Acetylcholine (ACh), synthesized in and out of the nervous system can locally contribute to modulation of various cell functions (e.g. survival, proliferation). Considering that the cholinergic system and its functions are impaired in a number of disorders, the identification of new pharmacological approaches to regulate cholinergic system components appears of great relevance. The present review focuses on recent pharmacological drugs able to modulate the activity of cholinergic receptors and thereby, cholinergic function, with an emphasis on the muscarinic receptor subtype, and additionally covers the cholinesterases, the main enzymes involved in ACh hydrolysis. The presence and function of muscarinic receptor subtypes both in neuronal and non-neuronal cells has been demonstrated using extensive pharmacological data emerging from studies on transgenic mice. The possible involvement of ACh in different pathologies has been proposed in recent years and is becoming an important area of study. Although the lack of selective muscarinic receptor ligands has for a long time limited the definition of therapeutic treatment based on muscarinic receptors as targets, some muscarinic ligands such as cevimeline (patents US4855290; US5571918) or xanomeline (patent, US5980933) have been developed and used in pre-clinical or in clinical studies for the treatment of nervous system diseases (Alzheimer' and Sjogren's diseases). The present review focuses on the potential implications of muscarinic receptors in different pathologies, including tumors. Moreover, the future use of muscarinic ligands in therapeutic protocols in cancer therapy will be discussed, considering that some muscarinic antagonists currently used in the treatment of genitourinary disease (e.g. darifenacin, patent, US5096890; US6106864) have also been demonstrated to arrest tumor progression in nude mice. The involvement of muscarinic

  13. Combining Pharmacological and Psychological Treatments for Binge Eating Disorder: Current Status, Limitations, and Future Directions.

    Science.gov (United States)

    Grilo, Carlos M; Reas, Deborah L; Mitchell, James E

    2016-06-01

    Binge eating disorder (BED) is characterized by recurrent binge eating and marked distress about binge eating without the extreme compensatory behaviors for weight control that characterize other eating disorders. BED is prevalent, associated strongly with obesity, and is associated with heightened levels of psychological, psychiatric, and medical concerns. This article provides an overview of randomized controlled treatments for combined psychological and pharmacological treatment of BED to inform current clinical practice and future treatment research. In contrast to the prevalence and significance of BED, to date, limited research has been performed on combining psychological and pharmacological treatments for BED to enhance outcomes. Our review here found that combining certain medications with cognitive behavioral therapy (CBT) or behavioral weight loss (BWL) interventions produces superior outcomes to pharmacotherapy only but does not substantially improve outcomes achieved with CBT/BWL only. One medication (orlistat) has improved weight losses with CBT/BWL albeit minimally, and only one medication (topiramate) has enhanced reductions achieved with CBT in both binge eating and weight. Implications for future research are discussed.

  14. Therapeutic Enzymes: Applications and Approaches to Pharmacological Improvement.

    Science.gov (United States)

    Yari, Maryam; Ghoshoon, Mohammad B; Vakili, Bahareh; Ghasemi, Younes

    2017-01-01

    Among therapeutic proteins, enzymes represent small and of course profitable market. They can be used to treat important, rare, and deadly diseases. Enzyme therapy is the only available treatment for certain disorders. Here, pharmaceutical enzymes are reviewed. They are categorized in four main groups, enzymes in replacement therapy, enzymes in cancer treatment, enzymes for fibrinolysis, and finally enzymes that are used topically for various treatments. Furthermore, enzyme gene therapy and future perspective of therapeutic enzymes are mentioned in brief. There are many important approved enzymes in pharmaceutical market. Several approaches such as point mutation, fusion protein designing, glycoengineering, and PEGylation were used to achieve improved enzymes. Although sometimes enzymes were engineered to facilitate production and purification process, appropriate delivery to target sites, extending half-life, and reducing immunogenicity are among the main goals of engineering approaches. Overall, enzymes play a critical role in treatment of common and rare diseases. Evaluation of new enzymes as well as improvement of approved enzymes are of the most important challenges in biotechnology. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  15. Novel pharmacological approaches for the treatment of acne vulgaris.

    Science.gov (United States)

    Valente Duarte de Sousa, Isabel Cristina

    2014-10-01

    Acne vulgaris is the most common skin disease worldwide; yet, current treatment options, although effective, are associated with unwanted side effects, chronicity, relapses and recurrences. The adequate control of the four pathogenic mechanisms, involved in the appearance of acne lesions, is paramount to treatment success. The authors discuss and evaluate the pathogenic pathways related to the mechanisms of action of novel molecules, which are currently under investigation for the treatment of acne vulgaris. The manuscript is based on comprehensive searches made through PubMed, GoogleScholar and ClinicalTrial.gov, using different combination of key words, which include acne vulgaris, pathogenesis, treatment, sebogenesis and Propionibacterium acnes. In the near future, more effective treatments with fewer side effects are expected. The use of topical antiandrogens, acetylcholine inhibitors and PPAR modulators seem to be promising options for controlling sebum production. Retinoic acid metabolism-blocking agents and IL-1α inhibitors have the potential to become legitimate alternative options to retinoid therapy in the management of infundibular dyskeratosis. Indeed, the authors believe that there will likely be a decline in the use of antibiotics for controlling P. acnes colonization and targeting the inflammation cascade.

  16. Pharmacologic Treatment of Wet Type Age-related Macular Degeneration; Current and Evolving Therapies.

    Science.gov (United States)

    Shams Najafabadi, Hoda; Daftarian, Narsis; Ahmadieh, Hamid; Soheili, Zahra-Soheila

    2017-08-01

    Age-related macular degeneration as the major cause of blindness in the elderly population has remained at the epicenter of clinical research in ophthalmology. This retinal disorder is characterized by the photoreceptor and retinal pigment epithelial cells loss, occurring within the macula. The disease represents a spectrum of clinical manifestations. It is a multifactorial disease resulting from a combination of genetic predispositions and environmental risk factors. AMD is classified into two different types, dry and wet. Wet AMD is in close relation with angiogenesis and inflammatory processes.A variety of anti-angiogenesis and anti-inflammatory drugs have been proposed for the treatment of the disease. The purpose of this paper is to briefly review the pharmacological therapies of the wet form of AMD and focus on new drugs that are currently in different stages of research and development.

  17. Current strategies for non-pharmacological therapy of long-standing persistent atrial fibrillation

    Directory of Open Access Journals (Sweden)

    Teiichi Yamane, MD, PhD

    2012-06-01

    Full Text Available Non-pharmacological rhythm control of atrial fibrillation (AF is becoming increasingly important in our aging society. Advancement of catheter ablation techniques in the last decade has provided a cure for AF patients, with a nearly established efficiency for paroxysmal cases. However, since ablation of persistent/chronic AF cases is still challenging, early treatment of paroxysmal AF before transformation to the persistent/chronic form is mandatory. Although there is a consensus that pulmonary vein isolation is the first-line approach for ablation of long-standing persistent AF, similar to that for paroxysmal AF, there are still wide variations in the adjunctive approach to modify the atrial substrate of persistent AF (anatomical linear ablation, electrogram-based complex fractionated atrial electrogram ablation, ganglionated plexus ablation, etc.. Since data comparing the effectiveness of these adjunctive approaches are still lacking, large-scale controlled trials evaluating the effect of catheter ablation in diverse patient populations on a long-term basis are needed to establish the appropriate approach for long-standing persistent AF. Furthermore, the development of de novo ablation methods (new energies, new targets, etc. is expected to improve ablation outcome in patients with long-standing persistent AF.

  18. Reconciling current approaches to blindsight

    DEFF Research Database (Denmark)

    Overgaard, Morten; Mogensen, Jesper

    2015-01-01

    After decades of research, blindsight is still a mysterious and controversial topic in consciousness research. Currently, many researchers tend to think of it as an ideal phenomenon to investigate neural correlates of consciousness, whereas others believe that blindsight is in fact a kind...... of degraded vision rather than "truly blind". This article considers both perspectives and finds that both have difficulties understanding all existing evidence about blindsight. In order to reconcile the perspectives, we suggest two specific criteria for a good model of blindsight, able to encompass all...

  19. Current Approach to Child Rights

    Directory of Open Access Journals (Sweden)

    Huseyin Dag

    2015-03-01

    Full Text Available Rights of children, legally or morally all over the world that children are born with; education, health, life, shelter; physical, psychological or sexual exploitation protection of such rights is universal concept used to describethemall. Rights of children is an issue that should be addressed in the concept of human rights. Today, there are many parts of the world that human rights violations, child-size and grew broader, more difficult to intervene in a way that is situated. The idea that children than in adults of different physical, physiological, behavioral and psychological characteristics that continuous growth and improve dawareness that the establishment of thecare of children a society where the problem is and scientific approach everyone with this responsibility should be installed is shaped in Geneva Declaration of Childrens Rights. Today, the international document related to childrens rights is the United Nations Convention on the Rights of the Child adoptedand approved by 193 countries. Child policy in Turkey where 25 million children live is an issue that should be seriously considered. Thus, childrens rights, children working in coordination with the contract on the basis of a policy should be implemented fully. [Cukurova Med J 2015; 40(1.000: 1-5

  20. Current Enlightenment About Etiology and Pharmacological Treatment of Autism Spectrum Disorder

    Directory of Open Access Journals (Sweden)

    Nermin Eissa

    2018-05-01

    Full Text Available Autistic Spectrum Disorder (ASD is a complex neurodevelopmental brain disorder characterized by two core behavioral symptoms, namely impairments in social communication and restricted/repetitive behavior. The molecular mechanisms underlying ASD are not well understood. Recent genetic as well as non-genetic animal models contributed significantly in understanding the pathophysiology of ASD, as they establish autism-like behavior in mice and rats. Among the genetic causes, several chromosomal mutations including duplications or deletions could be possible causative factors of ASD. In addition, the biochemical basis suggests that several brain neurotransmitters, e.g., dopamine (DA, serotonin (5-HT, gamma-amino butyric acid (GABA, acetylcholine (ACh, glutamate (Glu and histamine (HA participate in the onset and progression of ASD. Despite of convincible understanding, risperidone and aripiprazole are the only two drugs available clinically for improving behavioral symptoms of ASD following approval by Food and Drug Administration (FDA. Till date, up to our knowledge there is no other drug approved for clinical usage specifically for ASD symptoms. However, many novel drug candidates and classes of compounds are underway for ASD at different phases of preclinical and clinical drug development. In this review, the diversity of numerous aetiological factors and the alterations in variety of neurotransmitter generation, release and function linked to ASD are discussed with focus on drugs currently used to manage neuropsychiatric symptoms related to ASD. The review also highlights the clinical development of drugs with emphasis on their pharmacological targets aiming at improving core symptoms in ASD.

  1. Current Enlightenment About Etiology and Pharmacological Treatment of Autism Spectrum Disorder.

    Science.gov (United States)

    Eissa, Nermin; Al-Houqani, Mohammed; Sadeq, Adel; Ojha, Shreesh K; Sasse, Astrid; Sadek, Bassem

    2018-01-01

    Autistic Spectrum Disorder (ASD) is a complex neurodevelopmental brain disorder characterized by two core behavioral symptoms, namely impairments in social communication and restricted/repetitive behavior. The molecular mechanisms underlying ASD are not well understood. Recent genetic as well as non-genetic animal models contributed significantly in understanding the pathophysiology of ASD, as they establish autism-like behavior in mice and rats. Among the genetic causes, several chromosomal mutations including duplications or deletions could be possible causative factors of ASD. In addition, the biochemical basis suggests that several brain neurotransmitters, e.g., dopamine (DA), serotonin (5-HT), gamma-amino butyric acid (GABA), acetylcholine (ACh), glutamate (Glu) and histamine (HA) participate in the onset and progression of ASD. Despite of convincible understanding, risperidone and aripiprazole are the only two drugs available clinically for improving behavioral symptoms of ASD following approval by Food and Drug Administration (FDA). Till date, up to our knowledge there is no other drug approved for clinical usage specifically for ASD symptoms. However, many novel drug candidates and classes of compounds are underway for ASD at different phases of preclinical and clinical drug development. In this review, the diversity of numerous aetiological factors and the alterations in variety of neurotransmitter generation, release and function linked to ASD are discussed with focus on drugs currently used to manage neuropsychiatric symptoms related to ASD. The review also highlights the clinical development of drugs with emphasis on their pharmacological targets aiming at improving core symptoms in ASD.

  2. Current Enlightenment About Etiology and Pharmacological Treatment of Autism Spectrum Disorder

    Science.gov (United States)

    Eissa, Nermin; Al-Houqani, Mohammed; Sadeq, Adel; Ojha, Shreesh K.; Sasse, Astrid; Sadek, Bassem

    2018-01-01

    Autistic Spectrum Disorder (ASD) is a complex neurodevelopmental brain disorder characterized by two core behavioral symptoms, namely impairments in social communication and restricted/repetitive behavior. The molecular mechanisms underlying ASD are not well understood. Recent genetic as well as non-genetic animal models contributed significantly in understanding the pathophysiology of ASD, as they establish autism-like behavior in mice and rats. Among the genetic causes, several chromosomal mutations including duplications or deletions could be possible causative factors of ASD. In addition, the biochemical basis suggests that several brain neurotransmitters, e.g., dopamine (DA), serotonin (5-HT), gamma-amino butyric acid (GABA), acetylcholine (ACh), glutamate (Glu) and histamine (HA) participate in the onset and progression of ASD. Despite of convincible understanding, risperidone and aripiprazole are the only two drugs available clinically for improving behavioral symptoms of ASD following approval by Food and Drug Administration (FDA). Till date, up to our knowledge there is no other drug approved for clinical usage specifically for ASD symptoms. However, many novel drug candidates and classes of compounds are underway for ASD at different phases of preclinical and clinical drug development. In this review, the diversity of numerous aetiological factors and the alterations in variety of neurotransmitter generation, release and function linked to ASD are discussed with focus on drugs currently used to manage neuropsychiatric symptoms related to ASD. The review also highlights the clinical development of drugs with emphasis on their pharmacological targets aiming at improving core symptoms in ASD. PMID:29867317

  3. A pharmacology guided approach for setting limits on product-related impurities for bispecific antibody manufacturing.

    Science.gov (United States)

    Rajan, Sharmila; Sonoda, Junichiro; Tully, Timothy; Williams, Ambrose J; Yang, Feng; Macchi, Frank; Hudson, Terry; Chen, Mark Z; Liu, Shannon; Valle, Nicole; Cowan, Kyra; Gelzleichter, Thomas

    2018-04-13

    bFKB1 is a humanized bispecific IgG1 antibody, created by conjoining an anti-Fibroblast Growth Factor Receptor 1 (FGFR1) half-antibody to an anti-Klothoβ (KLB) half-antibody, using the knobs-into-holes strategy. bFKB1 acts as a highly selective agonist for the FGFR1/KLB receptor complex and is intended to ameliorate obesity-associated metabolic defects by mimicking the activity of the hormone FGF21. An important aspect of the biologics product manufacturing process is to establish meaningful product specifications regarding the tolerable levels of impurities that copurify with the drug product. The aim of the current study was to determine acceptable levels of product-related impurities for bFKB1. To determine the tolerable levels of these impurities, we dosed obese mice with bFKB1 enriched with various levels of either HMW impurities or anti-FGFR1-related impurities, and measured biomarkers for KLB-independent FGFR1 signaling. Here, we show that product-related impurities of bFKB1, in particular, high molecular weight (HMW) impurities and anti-FGFR1-related impurities, when purposefully enriched, stimulate FGFR1 in a KLB-independent manner. By taking this approach, the tolerable levels of product-related impurities were successfully determined. Our study demonstrates a general pharmacology-guided approach to setting a product specification for a bispecific antibody whose homomultimer-related impurities could lead to undesired biological effects. Copyright © 2018. Published by Elsevier Inc.

  4. Deciphering the Mechanism of Action of Wrightia tinctoria for Psoriasis Based on Systems Pharmacology Approach.

    Science.gov (United States)

    Sundarrajan, Sudharsana; Lulu, Sajitha; Arumugam, Mohanapriya

    2017-11-01

    Psoriasis is a chronic immune-mediated disorder of the skin. The disease manifests itself with red or silvery scaly plaques distributing over the lower back, scalp, and extensor aspects of limbs. Several medications are available for the treatment of psoriasis; however, high rates of remission and side-effects still persist as a major concern. Siddha, one of the traditional systems of Indian medicine offers cure to many dermatological conditions, including psoriasis. The oil prepared from the leaves of Wrightia tinctoria is prescribed by many healers for the treatment of psoriasis. This work aims to decipher the mechanism of action of the W. tinctoria in curing psoriasis and its associated comorbidities. The work integrates various pharmacology approaches such as drug-likeness evaluation, oral bioavailability predictions, and network pharmacology approaches to understand the roles of various bioactive components of the herb. This work identified 67 compounds of W. tinctoria interacting with 238 protein targets. The compounds were found to act through synergistic mechanism in reviving the disrupted process in the diseased state. The results of this work not only shed light on the pharmacological action of the herb but also validate the usage of safe herbal drugs.

  5. [Note on the epistemology of clinical pharmacology: comparison with the approach of Karl Popper].

    Science.gov (United States)

    Boissel, J P

    1999-01-01

    Is clinical pharmacology a science or only an application of science? Karl Popper suggested a method to identify science and to sort it out from other logical activities such as metaphysics, whereby the falsification criterion he proposed can apply to the theory in such a way that the theory could be refuted. The clinical pharmacologist's approach requires the build-up of a therapeutic model on the basis of two other models: the physiopathologic and the pharmacological. The three-model construct is a theory. Is it scientific in the Popperian sense? From the therapeutic model, one can predict the efficacy of a drug, and the corresponding statement is tested by a clinical trial. Whatever the original statement, it is modified into a refutable one because of the use of the statistical approach in clinical trials. Furthermore, the predicate represents a hypothesis of the model validity, which will then be confronted with 'reality' through clinical experiment. As the therapeutic model is refutable, clinical pharmacology is a science in the Popperian sense.

  6. Diabetic Macular Edema: Current Understanding, Pharmacologic Treatment Options, and Developing Therapies.

    Science.gov (United States)

    Miller, Kevin; Fortun, Jorge A

    2018-01-01

    Diabetic retinopathy and diabetic macular edema comprise a major source of visual disability throughout the developed world. The etiology and pathogenesis of macular edema is intricate and multifactorial, in which the hyperglycemic state in diabetes induces a microangiopathy. Through several inflammatory and vasogenic mediators, including vascular endothelial growth factor (VEGF) upregulation and inflammatory cytokines and chemokines, pathologic changes are induced in the vascular endothelium triggering breakdown of the blood retinal barrier, causing extravasation of fluid into the extracellular space and manifesting clinically as macular edema, resulting in visual loss. The advent of medications targeting the VEGF pathway has led to great clinical improvements compared with the previous standard of care of laser therapy alone, as shown in studies such as RISE, RIDE, VIVID, VISTA, and DRCR. However, analyses have shown that many patients have inadequate response or are nonresponders to anti-VEGF therapy, demonstrating the need for additional therapies to more comprehensively treat this disease. Although corticosteroid treatments and implants have demonstrated some efficacy in adjunctive and supplemental treatment, the need to more adequately treat macular edema remains. Our knowledge of diabetic macular edema continues to grow, leading to new currently available and emerging pharmacotherapies to further enhance our treatment and restore vision in those affected by diabetic macular edema. This review will discuss the pathogenesis of diabetic macular edema and the pharmacologic therapies available for its treatment, including anti-VEGF, steroids, and newer therapies still in development, such as angiopoietin antagonists, Tie2 agonists, kallikrein inhibitors, interleukin inhibitors, and others. Copyright 2018 Asia-Pacific Academy of Ophthalmology.

  7. Where current pharmacological therapies fall short in COPD: symptom control is not enough

    Directory of Open Access Journals (Sweden)

    N. Roche

    2007-09-01

    Full Text Available Chronic obstructive pulmonary disease (COPD is a common and progressive condition that is currently the fourth leading cause of death worldwide. There is now a large body of evidence indicating that both pulmonary and systemic inflammation are present in patients with stable COPD and may underlie both respiratory symptoms and common comorbidities of this disease. Smoking cessation and long-term oxygen therapy have been shown to change the course of COPD and recent results obtained with the combination of fluticasone and salmeterol have indicated that it could decrease mortality and slow the decline in lung function in patients with this disease. However, some pharmacological treatments can significantly improve dyspnoea, exercise tolerance, limitations in activity, rate of exacerbations and quality of life (e.g. long-acting bronchodilators and inhaled corticosteroids combined with a long-acting beta2-agonist. The ability of these agents to modify the rate of disease progression remains to be firmly established in large-scale, long-term trials. The concept of disease modification itself in COPD may need to be revisited and more precisely defined in terms of markers and clinical outcomes, including extrarespiratory manifestations: agents that durably affect symptoms, activities, exacerbations and quality of life should probably be considered as disease modifiers. It is also reasonable to suggest that early diagnosis and treatment of patients with COPD might be the first and potentially most important disease-modifying intervention. There is clearly a need for new therapies that directly target the specific inflammatory processes underlying chronic obstructive pulmonary disease and its pulmonary and extrapulmonary manifestations.

  8. Breaking the Mold: A Review of Mucormycosis and Current Pharmacological Treatment Options.

    Science.gov (United States)

    Riley, Treavor T; Muzny, Christina A; Swiatlo, Edwin; Legendre, Davey P

    2016-09-01

    To review the current literature for the pathogenesis of mucormycosis, discuss diagnostic strategies, and evaluate the efficacy of polyenes, triazoles, and echinocandins as pharmacological treatment options. An electronic literature search was conducted in PubMed using the MESH terms Rhizopus, zygomycetes, zygomycosis, Mucorales and mucormycosis, with search terms amphotericin B, micafungin, anidulafungin, caspofungin, extended infusion amphotericin B, liposomal amphotericin B, combination therapy, triazole, posaconazole, isavuconazole, diagnosis, and clinical manifestations. Studies written in the English language from January 1960 to March 2016 were considered for this review article. All search results were reviewed, and the relevance of each article was determined by the authors independently. Mucormycosis is a rare invasive fungal infection with an exceedingly high mortality and few therapeutic options. It has a distinct predilection for invasion of endothelial cells in the vascular system, which is likely important in dissemination of disease from a primary focus of infection. Six distinct clinical syndromes can occur in susceptible hosts, including rhino-orbital-cerebral, pulmonary, gastrointestinal, cutaneous, widely disseminated, and miscellaneous infection. Diagnosis of mucormycosis is typically difficult to make based on imaging studies, sputum culture, bronchoalveolar lavage culture, or needle aspirate. Surgical debridement prior to dissemination of infection improves clinical outcomes. Surgery combined with early, high-dose systemic antifungal therapy yields greater than a 1.5-fold increase in survival rates. The Mucorales are inherently resistant to most widely used antifungal agents. Amphotericin B is appropriate for empirical therapy, whereas posaconazole and isavuconazole are best reserved for de-escalation, refractory cases, or patients intolerant to amphotericin B. © The Author(s) 2016.

  9. The current burden of cytomegalovirus infection in kidney transplant recipients receiving no pharmacological prophylaxis

    Directory of Open Access Journals (Sweden)

    Claudia Rosso Felipe

    Full Text Available Abstract Cytomegalovirus (CMV infection in kidney transplantation has changed its clinical spectrum, mostly due to the current and more effective immunosuppression. In the absence of preventive strategies it is associated with significant morbi-mortality. Objective: This study evaluated the incidence of CMV events and its effect on outcomes of kidney transplantation in recipients without pharmacological prophylaxis or targeted preemptive treatment. Results: The study cohort comprised 802 recipients of kidney transplants between 04/30/2014 and 04/30/2015. The majority received induction with anti-thymocyte globulin (81.5%, tacrolimus and prednisone in combination with either mycophenolate (46.3% or azathioprine (53.7%. The overall incidence of CMV events was 42% (58.6% infection and 41.4% disease. Patients with CMV showed higher incidence of first treated acute rejection (19 vs. 11%, p = 0,001 compared with those without CMV but no differences in graft loss, death or loss to follow-up. The incidence of delayed graft function was higher (56% vs. 37%, p = 0.000 and the eGFR at 1 (41 ± 21 vs. 54 ± 28 ml/min, p = 0.000 and 12 months (50 ± 19 vs. 61 ± 29 ml/min, p = 0.000 were lower in patients with CMV. Recipients age (OR = 1.03, negative CMV serology (OR = 5.21 and use of mycophenolate (OR = 1.67 were associated with increased risk of CMV. Changes in immunosuppression was more often in patients with CMV (63% vs. 31%, p = 0.000. Conclusion: the incidence of CMV events was high and associated with higher incidence of acute rejection and changes in immunosuppression. Besides traditional risk factors, renal function at 1 month was independently associated with CMV infection.

  10. Current dichotomy between traditional molecular biological and omic research in cancer biology and pharmacology.

    Science.gov (United States)

    Reinhold, William C

    2015-12-10

    There is currently a split within the cancer research community between traditional molecular biological hypothesis-driven and the more recent "omic" forms or research. While the molecular biological approach employs the tried and true single alteration-single response formulations of experimentation, the omic employs broad-based assay or sample collection approaches that generate large volumes of data. How to integrate the benefits of these two approaches in an efficient and productive fashion remains an outstanding issue. Ideally, one would merge the understandability, exactness, simplicity, and testability of the molecular biological approach, with the larger amounts of data, simultaneous consideration of multiple alterations, consideration of genes both of known interest along with the novel, cross-sample comparisons among cell lines and patient samples, and consideration of directed questions while simultaneously gaining exposure to the novel provided by the omic approach. While at the current time integration of the two disciplines remains problematic, attempts to do so are ongoing, and will be necessary for the understanding of the large cell line screens including the Developmental Therapeutics Program's NCI-60, the Broad Institute's Cancer Cell Line Encyclopedia, and the Wellcome Trust Sanger Institute's Cancer Genome Project, as well as the the Cancer Genome Atlas clinical samples project. Going forward there is significant benefit to be had from the integration of the molecular biological and the omic forms or research, with the desired goal being improved translational understanding and application.

  11. Systems-level mechanisms of action of Panax ginseng: a network pharmacological approach.

    Science.gov (United States)

    Park, Sa-Yoon; Park, Ji-Hun; Kim, Hyo-Su; Lee, Choong-Yeol; Lee, Hae-Jeung; Kang, Ki Sung; Kim, Chang-Eop

    2018-01-01

    Panax ginseng has been used since ancient times based on the traditional Asian medicine theory and clinical experiences, and currently, is one of the most popular herbs in the world. To date, most of the studies concerning P. ginseng have focused on specific mechanisms of action of individual constituents. However, in spite of many studies on the molecular mechanisms of P. ginseng , it still remains unclear how multiple active ingredients of P. ginseng interact with multiple targets simultaneously, giving the multidimensional effects on various conditions and diseases. In order to decipher the systems-level mechanism of multiple ingredients of P. ginseng , a novel approach is needed beyond conventional reductive analysis. We aim to review the systems-level mechanism of P. ginseng by adopting novel analytical framework-network pharmacology. Here, we constructed a compound-target network of P. ginseng using experimentally validated and machine learning-based prediction results. The targets of the network were analyzed in terms of related biological process, pathways, and diseases. The majority of targets were found to be related with primary metabolic process, signal transduction, nitrogen compound metabolic process, blood circulation, immune system process, cell-cell signaling, biosynthetic process, and neurological system process. In pathway enrichment analysis of targets, mainly the terms related with neural activity showed significant enrichment and formed a cluster. Finally, relative degrees analysis for the target-disease association of P. ginseng revealed several categories of related diseases, including respiratory, psychiatric, and cardiovascular diseases.

  12. New approaches to the pharmacological treatment of obesity: can they break through the efficacy barrier?

    Science.gov (United States)

    Kennett, G A; Clifton, P G

    2010-11-01

    In this review we assess the range of centrally active anorectics that are either in human clinical trials, or are likely to be so in the near future. We describe their weight loss efficacy, mode of action at both pharmacological and behavioural levels, where understood, together with the range of side effects that might be expected in clinical use. We have however evaluated these compounds against the considerably more rigorous criteria that are now being used by the Federal Drugs Agency and European Medicines Agency to decide approvals and market withdrawals. Several trends are evident. Recent advances in the understanding of energy balance control have resulted in the exploitation of a number of new targets, some of which have yielded promising data in clinical trials for weight loss. A second major trend is derived from the hypothesis that improved weight loss efficacy over current therapy is most likely to emerge from treatments targeting multiple mechanisms of energy balance control. This reasoning has led to the development of a number of new treatments for obesity where multiple mechanisms are targeted, either by a single molecule, such as tesofensine, or through drug combinations such as qnexa, contrave, empatic, and pramlintide+metreleptin. Many of these approaches also utilise advances in formulation technology to widen safety margins. Finally, the practicality of peptide therapies for obesity has become better validated in recent studies and this may allow more rapid exploitation of novel targets, rather than awaiting the development of orally available small molecules. We conclude that novel, more efficacious and better tolerated treatments for obesity may become available in the near future. Copyright © 2010 Elsevier Inc. All rights reserved.

  13. Medicinal significance, pharmacological activities, and analytical aspects of solasodine: A concise report of current scientific literature

    Directory of Open Access Journals (Sweden)

    Kanika Patel

    2013-01-01

    Full Text Available Alkaloids are well known phytoconstituents for their diverse pharmacological properties. Alkaloids are found in all plant parts like roots, stems, leaves, flowers, fruits and seeds. Solasodine occurs as an aglycone part of glycoalkloids, which is a nitrogen analogue to sapogenins. Solanaceae family comprises of a number of plants with variety of natural products of medicinal significance mainly steroidal lactones, glycosides, alkaloids and flavanoids. It is a steroidal alkaloid based on a C27 cholestane skeleton. Literature survey reveals that solasodine has diuretic, anticancer, antifungal, cardiotonic, antispermatogenetic, antiandrogenic, immunomodulatory, antipyretic and various effects on central nervous system. Isolation and quantitative determination was achieved by several analytical techniques. Present review highlights the pharmacological activity of solasodine, with its analytical and tissue culture techniques, which may be helpful to the researchers to develop new molecules for the treatment of various disorders in the future.

  14. Smartphone apps to support hospital prescribing and pharmacology education: a review of current provision.

    Science.gov (United States)

    Haffey, Faye; Brady, Richard R W; Maxwell, Simon

    2014-01-01

    Junior doctors write the majority of hospital prescriptions but many indicate they feel underprepared to assume this responsibility and around 10% of prescriptions contain errors. Medical smartphone apps are now widely used in clinical practice and present an opportunity to provide support to inexperienced prescribers. This study assesses the contemporary range of smartphone apps with prescribing or related content. Six smartphone app stores were searched for apps aimed at the healthcare professional with drug, pharmacology or prescribing content. Three hundred and six apps were identified. 34% appeared to be for use within the clinical environment in order to aid prescribing, 14% out with the clinical setting and 51% of apps were deemed appropriate for both clinical and non-clinical use. Apps with drug reference material, such as textbooks, manuals or medical apps with drug information were the commonest apps found (51%), followed by apps offering drug or infusion rate dose calculation (26%). 68% of apps charged for download, with a mean price of £14.25 per app and a range of £0.62-101.90. A diverse range of pharmacology-themed apps are available and there is further potential for the development of contemporary apps to improve prescribing performance. Personalized app stores may help universities/healthcare organizations offer high quality apps to students to aid in pharmacology education. Users of prescribing apps must be aware of the lack of information regarding the medical expertise of app developers. This will enable them to make informed choices about the use of such apps in their clinical practice. © 2013 The British Pharmacological Society.

  15. Approaches in studying the pharmacology of Chinese Medicine formulas: bottom-up, top-down-and meeting in the middle.

    Science.gov (United States)

    Huang, Tao; Zhong, Linda L D; Lin, Chen-Yuan; Zhao, Ling; Ning, Zi-Wan; Hu, Dong-Dong; Zhang, Man; Tian, Ke; Cheng, Chung-Wah; Bian, Zhao-Xiang

    2018-01-01

    Investigating the pharmacology is key to the modernization of Chinese Medicine (CM) formulas. However, identifying which are the active compound(s) of CM formulas, which biological entities they target, and through which signaling pathway(s) they act to modify disease symptoms, are still difficult tasks for researchers, even when equipped with an arsenal of advanced modern technologies. Multiple approaches, including network pharmacology, pharmaco-genomics, -proteomics, and -metabolomics, have been developed to study the pharmacology of CM formulas. They fall into two general categories in terms of how they tackle a problem: bottom-up and top-down. In this article, we compared these two different approaches in several dimensions by using the case of MaZiRenWan (MZRW, also known as Hemp Seed Pill), a CM herbal formula for functional constipation. Multiple hypotheses are easy to be proposed in the bottom-up approach (e.g. network pharmacology); but these hypotheses are usually false positives and hard to be tested. In contrast, it is hard to suggest hypotheses in the top-down approach (e.g. pharmacometabolomics); however, once a hypothesis is proposed, it is much easier to be tested. Merging of these two approaches could results in a powerful approach, which could be the new paradigm for the pharmacological study of CM formulas.

  16. Systematic Analysis of the Multiple Bioactivities of Green Tea through a Network Pharmacology Approach

    Directory of Open Access Journals (Sweden)

    Shoude Zhang

    2014-01-01

    Full Text Available During the past decades, a number of studies have demonstrated multiple beneficial health effects of green tea. Polyphenolics are the most biologically active components of green tea. Many targets can be targeted or affected by polyphenolics. In this study, we excavated all of the targets of green tea polyphenolics (GTPs though literature mining and target calculation and analyzed the multiple pharmacology actions of green tea comprehensively through a network pharmacology approach. In the end, a total of 200 Homo sapiens targets were identified for fifteen GTPs. These targets were classified into six groups according to their related disease, which included cancer, diabetes, neurodegenerative disease, cardiovascular disease, muscular disease, and inflammation. Moreover, these targets mapped into 143 KEGG pathways, 26 of which were more enriched, as determined though pathway enrichment analysis and target-pathway network analysis. Among the identified pathways, 20 pathways were selected for analyzing the mechanisms of green tea in these diseases. Overall, this study systematically illustrated the mechanisms of the pleiotropic activity of green tea by analyzing the corresponding “drug-target-pathway-disease” interaction network.

  17. A Network Pharmacology Approach to Uncover the Multiple Mechanisms of Hedyotis diffusa Willd. on Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Xinkui Liu

    2018-01-01

    Full Text Available Background. As one of the most frequently diagnosed cancer diseases globally, colorectal cancer (CRC remains an important cause of cancer-related death. Although the traditional Chinese herb Hedyotis diffusa Willd. (HDW has been proven to be effective for treating CRC in clinical practice, its definite mechanisms have not been completely deciphered. Objective. The aim of our research is to systematically explore the multiple mechanisms of HDW on CRC. Methods. This study adopted the network pharmacology approach, which was mainly composed of active component gathering, target prediction, CRC gene collection, network analysis, and gene enrichment analysis. Results. The network analysis showed that 10 targets might be the therapeutic targets of HDW on CRC, namely, HRAS, PIK3CA, KRAS, TP53, APC, BRAF, GSK3B, CDK2, AKT1, and RAF1. The gene enrichment analysis implied that HDW probably benefits patients with CRC by modulating pathways related to cancers, infectious diseases, endocrine system, immune system, nervous system, signal transduction, cellular community, and cell motility. Conclusions. This study partially verified and predicted the pharmacological and molecular mechanism of HDW against CRC from a holistic perspective, which will also lay a foundation for the further experimental research and clinical rational application of HDW.

  18. Multiple sclerosis: general features and pharmacologic approach; Esclerosis multiple: aspectos generales y abordaje farmacologico

    Energy Technology Data Exchange (ETDEWEB)

    Nielsen Lagumersindez, Denis; Martinez Sanchez, Gregorio [Instituto de Farmacia y Alimentos, Universidad de La Habana, La Habana (Cuba)

    2009-07-01

    Multiple sclerosis is an autoimmune, inflammatory and desmyelinization disease central nervous system (CNS) of unknown etiology and critical evolution. There different etiological hypotheses talking of a close interrelation among predisposing genetic factors and dissimilar environmental factors, able to give raise to autoimmune response at central nervous system level. Hypothesis of autoimmune pathogeny is based on study of experimental models, and findings in biopsies of affected patients by disease. Accumulative data report that the oxidative stress plays a main role in pathogenesis of multiple sclerosis. Oxygen reactive species generated by macrophages has been involved as mediators of demyelinization and of axon damage, in experimental autoimmune encephalomyelitis and strictly in multiple sclerosis. Disease diagnosis is difficult because of there is not a confirmatory unique test. Management of it covers the treatment of acute relapses, disease modification, and symptoms management. These features require an individualized approach, base on evolution of this affection, and tolerability of treatments. In addition to diet, among non-pharmacologic treatments for multiple sclerosis it is recommended physical therapy. Besides, some clinical assays have been performed in which we used natural extracts, nutrition supplements, and other agents with promising results. Pharmacology allowed neurologists with a broad array of proved effectiveness drugs; however, results of research laboratories in past years make probable that therapeutical possibilities increase notably in future. (Author)

  19. Clinical Policy Recommendations from the VHA State-of-the-Art Conference on Non-Pharmacological Approaches to Chronic Musculoskeletal Pain.

    Science.gov (United States)

    Kligler, Benjamin; Bair, Matthew J; Banerjea, Ranjana; DeBar, Lynn; Ezeji-Okoye, Stephen; Lisi, Anthony; Murphy, Jennifer L; Sandbrink, Friedhelm; Cherkin, Daniel C

    2018-05-01

    As a large national healthcare system, Veterans Health Administration (VHA) is ideally suited to build on its work to date and develop a safe, evidence-based, and comprehensive approach to the care of chronic musculoskeletal pain conditions that de-emphasizes opioid use and emphasizes non-pharmacological strategies. The VHA Office of Health Services Research and Development (HSR&D) held a state-of-the-art (SOTA) conference titled "Non-pharmacological Approaches to Chronic Musculoskeletal Pain Management" in November 2016. Goals of the conference were (1) to establish consensus on the current state of evidence regarding non-pharmacological approaches to chronic musculoskeletal pain to inform VHA policy in this area and (2) to begin to identify priorities for the future VHA research agenda. Workgroups were established and asked to reach consensus recommendations on clinical and research priorities for the following treatment strategies: psychological/behavioral therapies, exercise/movement therapies, manual therapies, and models for delivering multimodal pain care. Participants in the SOTA identified nine non-pharmacological therapies with sufficient evidence to be implemented across the VHA system as part of pain care. Participants further recommended that effective integration of these non-pharmacological approaches across the VHA and especially into VHA primary care, pain care, and mental health settings should be a priority, and that these treatments should be offered early in the course of pain treatment and delivered in a team-based, multimodal treatment setting concurrently with active self-care and self-management approaches. In addition, we recommend that VHA leadership and policy makers systematically address the barriers to implementation of these approaches by expanding opportunities for clinician and veteran education on the effectiveness of these strategies; supporting and funding further research to determine optimal dosage, duration, sequencing

  20. Childhood obesity: Current and novel approaches.

    Science.gov (United States)

    Sabin, Matthew A; Kiess, Wieland

    2015-06-01

    The prevalence of childhood obesity has increased over the last fifty years by approximately 5% per decade, and approximately a quarter of all children are now either overweight or obese. These children have a significantly increased risk of many future health problems including adult obesity, type 2 diabetes and heart disease. Despite this relentless increase, common-sense approaches aimed at prevention and treatment have failed to solve the problem. Current approaches at prevention have faced major challenges with some progress in implementing smaller scale programs and social marketing, but little action on broad public policy approaches which often appears unpalatable to society or individual governments. Meanwhile, treatment approaches have mainly focused on lifestyle change, and novel approaches are urgently needed. Prevention needs to shift to improving maternal health prior to conception, with more research focussed on the impact of early years in programming offspring to future overweight/obesity. Likewise, treatment paradigms need to move from simply thinking that obesity can be solved by readdressing diet and activity levels. Novel approaches are needed which take into consideration the complex physiology which regulates early childhood growth and the development of obesity in susceptible individuals. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. New advances in pharmacological approaches to the cholinergic system: an overview on muscarinic receptor ligands and cholinesterase inhibitors

    Science.gov (United States)

    Greig, Nigel H.; Reale, Marcella; Tata, Ada Maria

    2016-01-01

    The cholinergic system is expressed in neuronal and in non-neuronal tissues. Acetylcholine (ACh), synthesized in and out of the nervous system can locally contribute to modulation of various cell functions (e.g. survival, proliferation). Considering that the cholinergic system and its functions are impaired in a number of disorders, the identification of new pharmacological approaches to regulate cholinergic system components appears of great relevance. The present review focuses on recent pharmacological drugs able to modulate the activity of cholinergic receptors and thereby, cholinergic function, with an emphasis on the muscarinic receptor subtype, and additionally covers the cholinesterases, the main enzymes involved in ACh hydrolysis. The presence and function of muscarinic receptor subtypes both in neuronal and non-neuronal cells has been demonstrated using extensive pharmacological data emerging from studies on transgenic mice. The possible involvement of ACh in different pathologies has been proposed in recent years and is becoming an important area of study. Although the lack of selective muscarinic receptor ligands has for a long time limited the definition of therapeutic treatment based on muscarinic receptors as targets, some muscarinic ligands such as cevimeline (patents US4855290; US5571918) or xanomeline (patent, US5980933) have been developed and used in pre-clinical or in clinical studies for the treatment of nervous system diseases (Alzheimer’ and Sjogren’s diseases). The present review focuses on the potential implications of muscarinic receptors in different pathologies, including tumors. Moreover, the future use of muscarinic ligands in therapeutic protocols in cancer therapy will be discussed, considering that some muscarinic antagonists currently used in the treatment of genitourinary disease (e.g. darifenacin, patent, US5096890; US6106864) have also been demonstrated to arrest tumor progression in nude mice. The involvement of muscarinic

  2. Current approaches to prevention of venous thromboembolism ...

    African Journals Online (AJOL)

    Various pharmacological and mechanical agents are available locally in both oral and injection forms but there are no standard guidelines or a consensus statement on their utilization. This is the case despite there being a gradual rise in the number of patients who undergo hip and knee replacement surgery in Kenya.

  3. Novel Pharmacological Approaches for Treatment of Neurotoxicity Induced by Chronic Exposure to Depleted Uranium

    National Research Council Canada - National Science Library

    Lasley, Stephen M

    2008-01-01

    .... This hypothesis is consistent with previous observations ensuing from chronic intramuscular DU pellet implants in rats, and is based on the anticipation that specific pharmacological agents will...

  4. Comparing Teaching Approaches About Maxwell's Displacement Current

    Science.gov (United States)

    Karam, Ricardo; Coimbra, Debora; Pietrocola, Maurício

    2014-08-01

    Due to its fundamental role for the consolidation of Maxwell's equations, the displacement current is one of the most important topics of any introductory course on electromagnetism. Moreover, this episode is widely used by historians and philosophers of science as a case study to investigate several issues (e.g. the theory-experiment relationship). Despite the consensus among physics educators concerning the relevance of the topic, there are many possible ways to interpret and justify the need for the displacement current term. With the goal of understanding the didactical transposition of this topic more deeply, we investigate three of its domains: (1) The historical development of Maxwell's reasoning; (2) Different approaches to justify the term insertion in physics textbooks; and (3) Four lectures devoted to introduce the topic in undergraduate level given by four different professors. By reflecting on the differences between these three domains, significant evidence for the knowledge transformation caused by the didactization of this episode is provided. The main purpose of this comparative analysis is to assist physics educators in developing an epistemological surveillance regarding the teaching and learning of the displacement current.

  5. A multilayer approach for turbidity currents

    Science.gov (United States)

    Fernandez-Nieto, Enrique; Castro Díaz, Manuel J.; Morales de Luna, Tomás

    2017-04-01

    When a river that carries sediment in suspension enters into a lake or the ocean it can form a plume that can be classified as hyperpycnal or hypopycnal. Hypopycnal plumes occurs if the combined density of the sediment and interstitial fluid is lower than that of the ambient. Hyperpycnal plumes are a class of sediment-laden gravity current commonly referred to as turbidity currents [7,9]. Some layer-averaged models have been previously developed (see [3, 4, 8] among others). Although this layer-averaged approach gives a fast and valuable information, it has the disadvantage that the vertical distribution of the sediment in suspension is lost. A recent technique based on a multilayer approach [1, 2, 6] has shown to be specially useful to generalize shallow water type models in order to keep track of the vertical components of the averaged variables in the classical shallow water equations. In [5] multilayer model is obtained using a vertical discontinuous Galerkin approach for which the vertical velocity is supposed to be piecewise linear and the horizontal velocity is supposed to be piecewise constant. In this work the technique introduced in [5] is generalized to derive a model for turbidity currents. This model allows to simulate hyperpycnal as well as hypopycnal plumes. Several numerical tests will be presented. References [1] E. Audusse, M. Bristeau, B. Perthame, and J. Sainte-Marie. A multilayer Saint-Venant system with mass exchanges for shallow water flows. derivation and numerical validation. ESAIM: Mathematical Modelling and Numerical Analysis, 45(1):169-200, (2010). [2] E. Audusse, M.-O. Bristeau, M. Pelanti, and J. Sainte-Marie. Approximation of the hydrostatic Navier–Stokes system for density stratified flows by a multilayer model: Kinetic interpretation and numerical solution. Journal of Computational Physics, 230(9):3453-3478, (2011). [3] S. F. Bradford and N. D. Katopodes. Hydrodynamics of turbid underflows. i: Formulation and numerical

  6. The Current State of Empirical Support for the Pharmacological Treatment of Selective Mutism

    Science.gov (United States)

    Carlson, John S.; Mitchell, Angela D.; Segool, Natasha

    2008-01-01

    This article reviews the current state of evidence for the psychopharmacological treatment of children diagnosed with selective mutism within the context of its link to social anxiety disorder. An increased focus on potential medication treatment for this disorder has resulted from significant monetary and resource limitations in typical practice,…

  7. Pharmacological approaches to the management of type 2 diabetes in fasting adults during Ramadan

    Directory of Open Access Journals (Sweden)

    Al Sifri S

    2012-08-01

    Full Text Available Saud Al SifriEndocrinology Department, Alhada Armed Forces Hospital, Taif, Saudi ArabiaI read with great interest the recent review article by AlMaatouq regarding the pharmacological approaches to the management of type 2 diabetes in fasting adults during Ramadan.1 This article stated that "A recent prospective study of more than 1000 patients with T2DMwho fasted during Ramadan found that the risk of hypoglycemia associated with a vildagliptin-based regimen (vildagliptin 100 mg once daily was lower than that of a sulfonylurea-based regimen (both with and without metformin."1 This statement needs to be corrected.Ramadan is the lunar month observed each year in which Muslim adults will fast. This fast includes abstinence from eating, drinking, and smoking from sunrise to sunset. Hypoglycemia during this period represents the greatest health risk for these patients. Recently introduced modulators of the incretin system are the dipeptidylpeptidase-4 inhibitors, which include sitagliptin, vildagliptin, alogliptin, saxagliptin, and linagliptin. These agents are not associated with hypoglycemia.View original paper by AlMaatouq

  8. Computational approaches to analogical reasoning current trends

    CERN Document Server

    Richard, Gilles

    2014-01-01

    Analogical reasoning is known as a powerful mode for drawing plausible conclusions and solving problems. It has been the topic of a huge number of works by philosophers, anthropologists, linguists, psychologists, and computer scientists. As such, it has been early studied in artificial intelligence, with a particular renewal of interest in the last decade. The present volume provides a structured view of current research trends on computational approaches to analogical reasoning. It starts with an overview of the field, with an extensive bibliography. The 14 collected contributions cover a large scope of issues. First, the use of analogical proportions and analogies is explained and discussed in various natural language processing problems, as well as in automated deduction. Then, different formal frameworks for handling analogies are presented, dealing with case-based reasoning, heuristic-driven theory projection, commonsense reasoning about incomplete rule bases, logical proportions induced by similarity an...

  9. Psychological, pharmacological, and combined smoking cessation interventions for smokers with current depression: A systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Roberto Secades-Villa

    Full Text Available We conducted a systematic literature review and meta-analysis (ID: CRD42016051017 of smoking cessation interventions for patients with current depression. We examined the effectiveness of smoking cessation treatments in improving abstinence rates and depressive symptoms. The following electronic databases were used for potentially eligible studies: PUBMED, PSYCINFO, DIALNET and WEB OF KNOWLEDGE. The search terms used were: smoking cessation, depressive disorder, depression, mood, depressive, depressed, smoking, smokers, nicotine, nicotine dependence, and tobacco cigarette smoking. The methodological quality of included studies was assessed using the Effective Public Health Practice Project Quality assessment tool (EPHPP. Of the 6,584 studies identified, 20 were eligible and included in the review. Trial designs of studies were 16 randomized controlled trials and 4 secondary studies. Studies included three types of intervention: psychological (6/30%, pharmacological (6/30% or combined (8/40%. Four trials comprised special populations of smokers. Four studies received a strong methodological quality, 7 were scored as moderate and 9 studies received a weak methodological rating. Analyses of effectiveness showed that smoking cessation interventions appear to increase short-term and long-term smoking abstinence in individuals with current depression. Subgroup analyses revealed stronger effects among studies that provided pharmacological treatments than in studies using psychological treatments. However, the evidence is weak due to the small number of studies. Smoking abstinence appears to be associated with an improvement in depressive symptoms. Heterogeneity in protocols in similar types of treatment also prevent firm conclusions being drawn on the effectiveness of any particular treatment model to optimally manage abstinence among depressed smokers. Further research is required to strengthen the evidence base.

  10. Current diagnostic approaches to subarachnoid haemorrhage

    International Nuclear Information System (INIS)

    U-King-Im, Jean Marie; Koo, Brendan; Trivedi, Rikin A.; Higgins, Nicholas J.; Tay, Keng Y.; Cross, Justin J.; Antoun, Nagui M.; Gillard, Jonathan H.

    2005-01-01

    Over the past decade, significant advances have been made in the field of subarachnoid haemorrhage (SAH). Prompt diagnosis with high-resolution CT and intensive critical care support remain key aspects of good patient management. Early identification and definitive treatment of underlying ruptured aneurysms is generally advocated to reduce the risk of re-bleeding, a complication with high mortality and morbidity. Although intra-arterial digital subtraction angiography (DSA) is still considered the gold standard for sourcing aneurysms, CT angiography, especially with the evolution of multi-slice technology, is slowly gaining acceptance as a rapid, accessible and minimally invasive method which appears likely to replace DSA as first-line modality in the future. Furthermore, the advent of Guglielmi detachable coils and the ISAT trial have revolutionised the treatment of ruptured aneurysms, with a significant trend towards endovascular coiling away from operative clipping. Improvements in clinical experience, coiling technology and assistive devices now allow interventionalists to potentially treat the majority of aneurysms, including wide-necked or complex lesions. The uncertain long-term results of coiling, however, still fuel strong debate and controversy. This review summarises current diagnostic approaches to SAH from a radiological perspective, with an emphasis on aneurysmal SAH and an evidence-based approach to the role of imaging and interventional radiology in diagnosis, treatment and follow-up. (orig.)

  11. Current diagnostic approaches to subarachnoid haemorrhage

    Energy Technology Data Exchange (ETDEWEB)

    U-King-Im, Jean Marie; Koo, Brendan; Trivedi, Rikin A.; Higgins, Nicholas J.; Tay, Keng Y.; Cross, Justin J.; Antoun, Nagui M.; Gillard, Jonathan H. [Addenbrooke' s Hospital, University Department of Radiology, Cambridge (United Kingdom)

    2005-06-01

    Over the past decade, significant advances have been made in the field of subarachnoid haemorrhage (SAH). Prompt diagnosis with high-resolution CT and intensive critical care support remain key aspects of good patient management. Early identification and definitive treatment of underlying ruptured aneurysms is generally advocated to reduce the risk of re-bleeding, a complication with high mortality and morbidity. Although intra-arterial digital subtraction angiography (DSA) is still considered the gold standard for sourcing aneurysms, CT angiography, especially with the evolution of multi-slice technology, is slowly gaining acceptance as a rapid, accessible and minimally invasive method which appears likely to replace DSA as first-line modality in the future. Furthermore, the advent of Guglielmi detachable coils and the ISAT trial have revolutionised the treatment of ruptured aneurysms, with a significant trend towards endovascular coiling away from operative clipping. Improvements in clinical experience, coiling technology and assistive devices now allow interventionalists to potentially treat the majority of aneurysms, including wide-necked or complex lesions. The uncertain long-term results of coiling, however, still fuel strong debate and controversy. This review summarises current diagnostic approaches to SAH from a radiological perspective, with an emphasis on aneurysmal SAH and an evidence-based approach to the role of imaging and interventional radiology in diagnosis, treatment and follow-up. (orig.)

  12. Systems Pharmacology-Based Approach of Connecting Disease Genes in Genome-Wide Association Studies with Traditional Chinese Medicine.

    Science.gov (United States)

    Kim, Jihye; Yoo, Minjae; Shin, Jimin; Kim, Hyunmin; Kang, Jaewoo; Tan, Aik Choon

    2018-01-01

    Traditional Chinese medicine (TCM) originated in ancient China has been practiced over thousands of years for treating various symptoms and diseases. However, the molecular mechanisms of TCM in treating these diseases remain unknown. In this study, we employ a systems pharmacology-based approach for connecting GWAS diseases with TCM for potential drug repurposing and repositioning. We studied 102 TCM components and their target genes by analyzing microarray gene expression experiments. We constructed disease-gene networks from 2558 GWAS studies. We applied a systems pharmacology approach to prioritize disease-target genes. Using this bioinformatics approach, we analyzed 14,713 GWAS disease-TCM-target gene pairs and identified 115 disease-gene pairs with q value < 0.2. We validated several of these GWAS disease-TCM-target gene pairs with literature evidence, demonstrating that this computational approach could reveal novel indications for TCM. We also develop TCM-Disease web application to facilitate the traditional Chinese medicine drug repurposing efforts. Systems pharmacology is a promising approach for connecting GWAS diseases with TCM for potential drug repurposing and repositioning. The computational approaches described in this study could be easily expandable to other disease-gene network analysis.

  13. Pharmacological modulation of cortical excitability shifts induced by transcranial direct current stimulation in humans.

    Science.gov (United States)

    Nitsche, M A; Fricke, K; Henschke, U; Schlitterlau, A; Liebetanz, D; Lang, N; Henning, S; Tergau, F; Paulus, W

    2003-11-15

    Transcranial direct current stimulation (tDCS) of the human motor cortex results in polarity-specific shifts of cortical excitability during and after stimulation. Anodal tDCS enhances and cathodal stimulation reduces excitability. Animal experiments have demonstrated that the effect of anodal tDCS is caused by neuronal depolarisation, while cathodal tDCS hyperpolarises cortical neurones. However, not much is known about the ion channels and receptors involved in these effects. Thus, the impact of the sodium channel blocker carbamazepine, the calcium channel blocker flunarizine and the NMDA receptor antagonist dextromethorphane on tDCS-elicited motor cortical excitability changes of healthy human subjects were tested. tDCS-protocols inducing excitability alterations (1) only during tDCS and (2) eliciting long-lasting after-effects were applied after drug administration. Carbamazepine selectively eliminated the excitability enhancement induced by anodal stimulation during and after tDCS. Flunarizine resulted in similar changes. Antagonising NMDA receptors did not alter current-generated excitability changes during a short stimulation, which elicits no after-effects, but prevented the induction of long-lasting after-effects independent of their direction. These results suggest that, like in other animals, cortical excitability shifts induced during tDCS in humans also depend on membrane polarisation, thus modulating the conductance of sodium and calcium channels. Moreover, they suggest that the after-effects may be NMDA receptor dependent. Since NMDA receptors are involved in neuroplastic changes, the results suggest a possible application of tDCS in the modulation or induction of these processes in a clinical setting. The selective elimination of tDCS-driven excitability enhancements by carbamazepine proposes a role for this drug in focussing the effects of cathodal tDCS, which may have important future clinical applications.

  14. Schizoaffective disorder: a review of current research themes and pharmacological management.

    Science.gov (United States)

    Kantrowitz, Joshua T; Citrome, Leslie

    2011-04-01

    Despite a clear recognition of the existence of patients with co-morbid psychotic and mood symptoms, many studies conclude that schizoaffective disorder as a distinct diagnosis does not exist. Regardless of one's opinion on schizoaffective disorder, psychiatrists remain dependent on phenomenological descriptions for diagnosing psychiatric disorders, and these phenomenological criteria are also used for clinical trial entry. On the other hand, many psychiatrists prescribe for specific target symptoms and do not always rigidly follow diagnostic systems and, moreover, there have been very few trials that have specifically studied schizoaffective disorder. Despite recent intriguing work in epidemiology, genetics, neurocognition and electrophysiology, the diagnosis of schizoaffective disorder remains controversial. Taken together, these studies suggest that even if schizoaffective disorder exists as a separate diagnosis, it may not be useful clinically due to considerable variation in the general use of this term. It is possible that diagnostic criteria in the future will include genetic, imaging and electrophysiological components, and that this will allow for better differentiation of disease states among the heterogeneous pool of patients currently believed to have schizophrenia, schizoaffective disorder or bipolar disorder. Although it is likely that most, if not all, antipsychotics are effective for schizoaffective disorder, given recent regulatory approval of a specific antipsychotic agent for the acute treatment of schizoaffective disorder, greater attention is now being focused on the entity of schizoaffective disorder and potential treatment decisions. However, based on the limited extant evidence, it is not yet possible to make definitive treatment recommendations for schizoaffective disorder. Additional clinical trials that include other antipsychotics, mood stabilizers and antidepressants are desirable and necessary before clear and comprehensive evidence

  15. Ulipristal acetate: a novel pharmacological approach for the treatment of uterine fibroids

    Directory of Open Access Journals (Sweden)

    Biglia N

    2014-02-01

    Full Text Available Nicoletta Biglia,1 Silvestro Carinelli,2 Antonio Maiorana,3 Marta D'Alonzo,1 Giuseppe Lo Monte,4 Roberto Marci4 1Department of Obstetrics and Gynaecology, Mauriziano "Umberto I" Hospital, University of Turin, Turin, 2Department of Pathology, European Institute of Oncology, Milan, 3Department of Obstetrics and Gynecology, ARNAS Civico Hospital, Palermo, 4Department of Morphology, Surgery and Experimental Medicine, Section of Obstetrics and Gynecology, Infertility Unit, University of Ferrara, Ferrara, Italy Abstract: Uterine fibroids are the most common benign tumors of the female genital tract. The management of symptomatic fibroids has traditionally been surgical; however, alternative pharmacological approaches have been proposed to control symptoms. To date, gonadotropin-releasing hormone analogs are the only available drugs for the preoperative treatment of fibroids. However, the US Food and Drug Administration recently authorized ulipristal acetate (UPA, an oral selective progesterone-receptor modulator, for the same indication. UPA is a new, effective, and well-tolerated option for the preoperative treatment of moderate and severe symptoms of uterine fibroids in women of reproductive age. According to clinical data, UPA shows several advantages: it is faster than leuprolide in reducing the fibroid-associated bleeding, it significantly improves hemoglobin and hematocrit levels in anemic patients, and it grants a significant reduction in the size of fibroids, which lasts for at least 6 months after the end of the treatment. Furthermore, UPA displays a better tolerability profile when compared to leuprolide; in fact, it keeps estradiol levels at mid follicular phase range, thereby reducing the incidence of hot flushes and exerting no impact on bone turnover. On the grounds of this evidence, the administration of 5 mg/day ulipristal acetate for 3 months is suggested for different patient categories and allows for planning a treatment strategy

  16. Narcolepsy: current treatment options and future approaches

    Science.gov (United States)

    Billiard, Michel

    2008-01-01

    The management of narcolepsy is presently at a turning point. Three main avenues are considered in this review: 1) Two tendencies characterize the conventional treatment of narcolepsy. Modafinil has replaced methylphenidate and amphetamine as the first-line treatment of excessive daytime sleepiness (EDS) and sleep attacks, based on randomized, double blind, placebo-controlled clinical trials of modafinil, but on no direct comparison of modafinil versus traditional stimulants. For cataplexy, sleep paralysis, and hypnagogic hallucinations, new antidepressants tend to replace tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs) in spite of a lack of randomized, double blind, placebo-controlled clinical trials of these compounds; 2) The conventional treatment of narcolepsy is now challenged by sodium oxybate, the sodium salt of gammahydroxybutyrate, based on a series of randomized, double-blind, placebo-controlled clinical trials and a long-term open label study. This treatment has a fairly good efficacy and is active on all symptoms of narcolepsy. Careful titration up to an adequate level is essential both to obtain positive results and avoid adverse effects; 3) A series of new treatments are currently being tested, either in animal models or in humans, They include novel stimulant and anticataplectic drugs, endocrine therapy, and, more attractively, totally new approaches based on the present state of knowledge of the pathophysiology of narcolepsy with cataplexy, hypocretine-based therapies, and immunotherapy. PMID:18830438

  17. Pharmacological versus microvascular decompression approaches for the treatment of trigeminal neuralgia: clinical outcomes and direct costs

    Directory of Open Access Journals (Sweden)

    Almeida A

    2011-08-01

    therapies, while after MDV surgery several patients showed important side effects. Data reinforce that, (1 TN patients should be carefully evaluated before choosing therapy for pain control, (2 different pharmacological approaches are available to initiate pain control at low costs, and (3 criteria for surgical interventions should be clearly defined due to important side effects, with the initial higher costs being strongly reduced with time.Keywords: trigeminal neuralgia, carbamazepine, gabapentin associated with ropivacaine, microvascular decompression, clinical outcomes, direct costs 

  18. Linearized dynamical approach to current algebra

    International Nuclear Information System (INIS)

    Scadron, M.D.

    1995-07-01

    We study the original motivations searching for a nonlinear chiral Lagrangian to replace the linear sigma model while manifesting all the successful properties of current algebra and partial conservation of axial currents (PCAC). (author). 26 refs

  19. Narcolepsy: current treatment options and future approaches

    Directory of Open Access Journals (Sweden)

    Michel Billiard

    2008-06-01

    Full Text Available Michel BilliardDepartment of Neurology, Gui de Chauliac Hospital, Montpellier, FranceAbstract: The management of narcolepsy is presently at a turning point. Three main avenues are considered in this review: 1 Two tendencies characterize the conventional treatment of narcolepsy. Modafinil has replaced methylphenidate and amphetamine as the first-line treatment of excessive daytime sleepiness (EDS and sleep attacks, based on randomized, double blind, placebo-controlled clinical trials of modafinil, but on no direct comparison of modafinil versus traditional stimulants. For cataplexy, sleep paralysis, and hypnagogic hallucinations, new antidepressants tend to replace tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs in spite of a lack of randomized, double blind, placebo-controlled clinical trials of these compounds; 2 The conventional treatment of narcolepsy is now challenged by sodium oxybate, the sodium salt of gammahydroxybutyrate, based on a series of randomized, double-blind, placebo-controlled clinical trials and a long-term open label study. This treatment has a fairly good efficacy and is active on all symptoms of narcolepsy. Careful titration up to an adequate level is essential both to obtain positive results and avoid adverse effects; 3 A series of new treatments are currently being tested, either in animal models or in humans, They include novel stimulant and anticataplectic drugs, endocrine therapy, and, more attractively, totally new approaches based on the present state of knowledge of the pathophysiology of narcolepsy with cataplexy, hypocretine-based therapies, and immunotherapy.Keywords: narcolepsy, treatment, conventional drugs, modafinil, sodium oxybate, future treatments

  20. Efficacy, tolerability, and safety of non-pharmacological therapies for chronic pain: An umbrella review on various CAM approaches.

    Science.gov (United States)

    Houzé, Bérengère; El-Khatib, Héjar; Arbour, Caroline

    2017-10-03

    Complementary and alternative medicine (CAM) therapies may be used as a non-pharmacological approach to chronic pain management. While hundreds of trials about individual CAM modality have been conducted, a comprehensive overview of their results is currently lacking for pain clinicians and researchers. This umbrella review synthesized the quality of meta-analytic evidence supporting the efficacy, tolerability and safety of CAM therapies for the management of chronic pain. MEDLINE, EMBASE, CINAHL, and CENTRAL were searched from October 1991 to November 2016. Reviews of clinical trials (randomized and non-randomized) with meta-analysis investigating the utility of any CAM modality for chronic pain were eligible. Pain relief post-intervention was the main outcome and secondary outcomes included patients' adherence and incidence of adverse effects during CAM protocol. Twenty-six reviews (207 clinical trials, >12,000 participants) about 18 CAM modalities, falling under natural products, mind and body practices or other complementary health approaches were included. Inhaled cannabis, graded motor imagery, and Compound Kushen injection (a form of Chinese medicine) were found the most efficient (with moderate-to-high effect sizes and low heterogeneity) and tolerable (≥80% of adherence to study protocols) for chronic pain relief. When reported, adverse effects related to these CAM were minor. Although several CAM were found effective for chronic pain relief, it remains unclear when these modalities are a reasonable choice against or in conjunction with mainstream treatments. In that sense, future research with a clear emphasis on concurrent evaluation of CAM overall efficacy and patient adherence/tolerance is needed. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Ethno-diversity within current ethno-pharmacology as part of Israeli traditional medicine – A review

    Directory of Open Access Journals (Sweden)

    Lev Efraim

    2006-01-01

    Full Text Available Abstract The Holy Land has absorbed millions of immigrants in recent centuries: Jews from East and West, Druze, Circassians, Muslim and Christian Arabs. The land is unique and diverse in geographical location and ethnic groups, and also in its cultural characteristics, including traditional medicine and use of materia medica. However, these traditions have waned over the years. The young state of Israel adopted a "melting pot" approach to fashion Jews from all over the world into Israelis. The traditional medicine and materia medica of different ethnic groups (Yemenite, Iranian, and Iraqi Jews are reviewed in this paper, as well as the ethno-botanical survey (first conducted in the 1980s, covering Bedouins, Druze, Circassians, and Muslim and Christian Arabs, and the matching ethno-pharmacological survey (conducted in the late 1990s covering the medicines sold in stores. Present-day healers are usually not young and are believed to be the end of the chain of traditional medical knowledge. The ethno-diversity of Israel is becoming blurred; modernity prevails, and ethnic characteristics are fading. The characteristic lines of traditional medicine and materia medica have hardly lasted three generations. A salient former dividing line between ethnic groups, namely their use of different medicinal substances, paradoxically becomes a bridge for conservative users of all groups and religions. Shops selling these substances have become centers for "nostalgia" and preserving the oriental heritage, traditional medicine, and medicinal substances!

  2. Current approaches to assessing intangible assets

    OpenAIRE

    Урусова, Зінаїда Петрівна

    2013-01-01

    The article analyzes methods of assessing intangible assets in Ukraine as well as in accordance with International Financial Reporting Standards. Contemporary approaches to assessing intangible assets have been researched.

  3. ECAPS - Eddy Current Approach and Proximity Satellites

    Data.gov (United States)

    National Aeronautics and Space Administration — Multiple, energized coils in a small satellite will generate eddy currents in the skin of the International Space Station (ISS). This will create repulsive forces...

  4. Pharmacologic Approaches to Weight Management: Recent Gains and Shortfalls in Combating Obesity.

    Science.gov (United States)

    Saunders, Katherine H; Kumar, Rekha B; Igel, Leon I; Aronne, Louis J

    2016-07-01

    Obesity is a growing epidemic in the USA with over one third of adults presently classified as obese. Obesity-related comorbidities include many leading causes of preventable death such as heart disease, stroke, type 2 diabetes, and certain types of cancer. Modest weight loss of 5-10 % of body weight is sufficient to produce clinically relevant improvements in cardiovascular disease risk factors among patients with overweight and obesity. Until recently, there were limited pharmacologic options approved by the Food and Drug Administration to treat obesity. Phentermine/topiramate ER and lorcaserin were approved in 2012, and naltrexone SR/bupropion SR and liraglutide 3.0 mg were approved in 2014. This article reviews recent literature in the field of Obesity Medicine and highlights important findings from clinical trials. Future directions in the pharmacologic management of obesity are presented along with new diabetes medications that promote weight loss and reduce cardiovascular mortality.

  5. Pharmacological Approach for Managing Pain in Irritable Bowel Syndrome: A Review Article

    OpenAIRE

    Chen, Longtu; Ilham, Sheikh J.; Feng, Bin

    2017-01-01

    Context Visceral pain is a leading symptom for patients with irritable bowel syndrome (IBS) that affects 10% - 20 % of the world population. Conventional pharmacological treatments to manage IBS-related visceral pain is unsatisfactory. Recently, medications have emerged to treat IBS patients by targeting the gastrointestinal (GI) tract and peripheral nerves to alleviate visceral pain while avoiding adverse effects on the central nervous system (CNS). Several investigational drugs for IBS also...

  6. Anxiety and Depression: Mouse Genetics and Pharmacological Approaches to the Role of GABAA Receptor Subtypes

    Science.gov (United States)

    Smith, Kiersten S.; Rudolph, Uwe

    2012-01-01

    GABAA receptors mediate fast synaptic inhibitory neurotransmission throughout the central nervous system. Recent work indicates a role for GABAA receptors in physiologically modulating anxiety and depression levels. In this review, we summarize research that led to the identification of the essential role of GABAA receptors in counteracting trait anxiety and depression-related behaviors, and research aimed at identifying individual GABAA receptor subtypes involved in physiological and pharmacological modulation of emotions. PMID:21810433

  7. Rational pharmacological approaches for cognitive dysfunction and depression in Parkinson's disease.

    Science.gov (United States)

    Sandoval-Rincón, Maritza; Sáenz-Farret, Michel; Miguel-Puga, Adán; Micheli, Federico; Arias-Carrión, Oscar

    2015-01-01

    Parkinson's disease (PD) is not a single entity but rather a heterogeneous neurodegenerative disorder. The present study aims to conduct a critical systematic review of the literature to describe the main pharmacological strategies to treat cognitive dysfunction and major depressive disorder in PD patients. We performed a search of articles cited in PubMed from 2004 to 2014 using the following MeSH terms (Medical subject headings) "Parkinson disease"; "Delirium," "Dementia," "Amnestic," "Cognitive disorders," and "Parkinson disease"; "depression," "major depressive disorder," "drug therapy." We found a total of 71 studies related to pharmacological treatment in cognitive dysfunction and 279 studies for pharmacological treatment in major depressive disorder. After fulfillment of all the inclusion and exclusion criteria, 13 articles remained for cognitive dysfunction and 11 for major depressive disorder, which are presented and discussed in this study. Further research into non-motor symptoms of PD may provide insights into mechanisms of neurodegeneration, and provide better quality of life by using rational drugs.

  8. Rational Pharmacological Approaches for Cognitive Dysfunction and Depression in Parkinson’s Disease

    Science.gov (United States)

    Sandoval-Rincón, Maritza; Sáenz-Farret, Michel; Miguel-Puga, Adán; Micheli, Federico; Arias-Carrión, Oscar

    2015-01-01

    Parkinson’s disease (PD) is not a single entity but rather a heterogeneous neurodegenerative disorder. The present study aims to conduct a critical systematic review of the literature to describe the main pharmacological strategies to treat cognitive dysfunction and major depressive disorder in PD patients. We performed a search of articles cited in PubMed from 2004 to 2014 using the following MeSH terms (Medical subject headings) “Parkinson disease”; “Delirium,” “Dementia,” “Amnestic,” “Cognitive disorders,” and “Parkinson disease”; “depression,” “major depressive disorder,” “drug therapy.” We found a total of 71 studies related to pharmacological treatment in cognitive dysfunction and 279 studies for pharmacological treatment in major depressive disorder. After fulfillment of all the inclusion and exclusion criteria, 13 articles remained for cognitive dysfunction and 11 for major depressive disorder, which are presented and discussed in this study. Further research into non-motor symptoms of PD may provide insights into mechanisms of neurodegeneration, and provide better quality of life by using rational drugs. PMID:25873910

  9. Current approaches to gene regulatory network modelling

    Directory of Open Access Journals (Sweden)

    Brazma Alvis

    2007-09-01

    Full Text Available Abstract Many different approaches have been developed to model and simulate gene regulatory networks. We proposed the following categories for gene regulatory network models: network parts lists, network topology models, network control logic models, and dynamic models. Here we will describe some examples for each of these categories. We will study the topology of gene regulatory networks in yeast in more detail, comparing a direct network derived from transcription factor binding data and an indirect network derived from genome-wide expression data in mutants. Regarding the network dynamics we briefly describe discrete and continuous approaches to network modelling, then describe a hybrid model called Finite State Linear Model and demonstrate that some simple network dynamics can be simulated in this model.

  10. Current approaches in atrial fibrillation treatment

    Directory of Open Access Journals (Sweden)

    Cenk Sarı

    2014-09-01

    Full Text Available Atrial fibrillation (AF is the most common sustained arrhythmia encountered in clinical practice. Its incidence increases with age. AF is classified into subtypes according to the duration and/or able to provide sinus rhytym. İnitially, patients should be evaluated for rhythm or rate control for appropriate treatment. Second stage of strategy aimed to investigate the feasibility of anticoagulation therapy. Recently, due to the progress made in treatment with rhythm control and anticoagulation therapy, either American or European guidelines have been renovated. These developments have taken place in the newly published guide. In this article, the current change in the management of AF is discussed.

  11. Predicting new indications of compounds with a network pharmacology approach: Liuwei Dihuang Wan as a case study.

    Science.gov (United States)

    Wang, Yin-Ying; Bai, Hong; Zhang, Run-Zhi; Yan, Hong; Ning, Kang; Zhao, Xing-Ming

    2017-11-07

    With the ever increasing cost and time required for drug development, new strategies for drug development are highly demanded, whereas repurposing old drugs has attracted much attention in drug discovery. In this paper, we introduce a new network pharmacology approach, namely PINA, to predict potential novel indications of old drugs based on the molecular networks affected by drugs and associated with diseases. Benchmark results on FDA approved drugs have shown the superiority of PINA over traditional computational approaches in identifying new indications of old drugs. We further extend PINA to predict the novel indications of Traditional Chinese Medicines (TCMs) with Liuwei Dihuang Wan (LDW) as a case study. The predicted indications, including immune system disorders and tumor, are validated by expert knowledge and evidences from literature, demonstrating the effectiveness of our proposed computational approach.

  12. Multidisciplinary management of intrahepatic cholangiocarcinoma: Current approaches.

    Science.gov (United States)

    Guro, Hanisah; Kim, Jin Won; Choi, YoungRok; Cho, Jai Young; Yoon, Yoo-Seok; Han, Ho-Seong

    2017-06-01

    Intrahepatic cholangiocarcinoma (ICC) is a common primary hepatic tumor. However, its outcomes are usually worse than those of hepatocellular carcinoma owing to its non-specific presentation and detection at an advanced stage. The most widely used serum marker, carbohydrate antigen 19-9, is non-specific. Furthermore, imaging studies rarely identify any pathognomonic features. Surgery is the only treatment option that offers a chance of long-term survival. However, the resectability rate is low owing to the high frequencies of intrahepatic metastases, peritoneal carcinomatosis, or extrahepatic metastases. Surgical treatment should be tailored according to the macroscopic classification of ICC (e.g. mass-forming, periductal infiltrating, and intraductal growth types) because it reflects the tumor's dissemination pattern. Although lymph node metastasis is a negative prognostic factor, the importance and extent of lymph node dissection is still controversial. To improve patient survival, liver transplantation is considered in some patients with unresectable ICC, especially in those with an insufficient remnant liver volume. Minimally invasive procedures, including laparoscopic and robotic liver resection, have been tested and achieved comparable outcomes to conventional surgery in preliminary studies. No randomized trials have confirmed the efficacy of adjuvant chemotherapy in ICC, and several trials have evaluated molecular-targeted agents as monotherapy or in combination with cytotoxic chemotherapy. Multidisciplinary approaches are necessary to improve the outcomes of ICC. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. CURRENT APPROACHES TO CHEMORADIOTHERAPY FOR MALIGNANT GLIOMAS

    Directory of Open Access Journals (Sweden)

    Ye. L. Choinzonov

    2014-01-01

    Full Text Available High-grade malignant gliomas (WHO grade G III–IV account for more than 50% of all primary brain tumors. Despite aggressive treatment, survival rates are still very low with a median reported survival of no more than 1.5 years.Radiation therapy is an integral part of the combined treatment, but often does not influence lethally on resistant tumor cells. Thereby, in recent decades there has been an active search for novel approaches to the treatment of malignant gliomas (chemotherapeutic drugs, biological modifiers, local hyperthermia. Experimental data showed that the effect of high temperatures has both a direct damaging effect on tumor cells and a sensitizing effect. Significant advantages are achieved when the complex treatment of different malignant tumorsincludes local hyperthermia. However data on the treatment of patients with primary and recurrent gliomas G III–IV using local hyperthermia are scarce.The literature review is given in the article provides an overview of the existing treatment methods for brain tumors.

  14. Pulp regeneration: Current approaches and future challenges

    Directory of Open Access Journals (Sweden)

    Jingwen eYANG

    2016-03-01

    Full Text Available Regenerative endodontics aims to replace inflamed/necrotic pulp tissues with regenerated pulp-like tissues to revitalize teeth and improve life quality. Pulp revascularization case reports, which showed successful clinical and radiographic outcomes, indicated the possible clinical application of pulp regeneration via cell homing strategy. From a clinical point of view, functional pulp-like tissues should be regenerated with the characterization of vascularization, re-innervation, and dentin deposition with a regulated rate similar to that of normal pulp. Efficient root canal disinfection and proper size of the apical foramen are the two requisite preconditions for pulp regeneration. Progress has been made on pulp regeneration via cell homing strategies. This review focused on the requisite preconditions and cell homing strategies for pulp regeneration. In addition to the traditionally used mechanical preparation and irrigation, antibiotics, irrigation assisted with EndoVac apical negative-pressure system, and ultrasonic and laser irradiation are now being used in root canal disinfection. In addition, pulp-like tissues could be formed with the apical foramen less than 1 mm, although more studies are needed to determine the appropriate size. Moreover, signaling molecules including stromal cell derived factor (SDF-1α, basic Fibroblast Growth Factor (bFGF, Platelet Derived Growth Factor (PDGF, stem cell factor (SCF, and Granulocyte Colony-Stimulating Factor (G-CSF were used to achieve pulp-like tissue formation via a cell homing strategy. Studies on the cell sources of pulp regeneration might give some indications on the signaling molecular selection. The active recruitment of endogenous cells into root canals to regenerate pulp-like tissues is a novel concept that may offer an unprecedented opportunity for the near-term clinical translation of current biology-based therapies for dental pulp regeneration.

  15. An integrated approach to uncover quality marker underlying the effects of Alisma orientale on lipid metabolism, using chemical analysis and network pharmacology.

    Science.gov (United States)

    Liao, Maoliang; Shang, Haihua; Li, Yazhuo; Li, Tian; Wang, Miao; Zheng, Yanan; Hou, Wenbin; Liu, Changxiao

    2018-06-01

    Quality control of traditional Chinese medicines is currently a great concern, due to the correlation between the quality control indicators and clinic effect is often questionable. According to the "multi-components and multi-targets" property of TCMs, a new special quality and bioactivity evaluation system is urgently needed. Present study adopted an integrated approach to provide new insights relating to uncover quality marker underlying the effects of Alisma orientale (AO) on lipid metabolism. In this paper, guided by the concept of the quality marker (Q-marker), an integrated strategies "effect-compound-target-fingerprint" was established to discovery and screen the potential quality marker of AO based on network pharmacology and chemical analysis. Firstly, a bioactivity evaluation was performed to screen the main active fractions. Then the chemical compositions were rapidly identified by chemical analysis. Next, networks were constructed to illuminate the interactions between these component and their targets for lipid metabolism, and the potential Q-marker of AO was initially screened. Finally, the activity of the Q-markers was validated in vitro. 50% ethanol extract fraction was found to have the strongest lipid-lowering activity. Then, the network pharmacology was used to clarify the unique relationship between the Q-markers and their integral pharmacological action. Combined with the results obtained, five active ingredients in the 50% ethanol extract fraction were given special considerations to be representative Q-markers: Alisol A, Alisol B, Alisol A 23-acetate, Alisol B 23-acetate and Alisol A 24-acetate, respectively. The chromatographic fingerprints based Q-marker was establishment. The integrated Q-marker screen may offer an alternative quality assessment of herbal medicines. Copyright © 2018. Published by Elsevier GmbH.

  16. Systematic Understanding of Mechanisms of a Chinese Herbal Formula in Treatment of Metabolic Syndrome by an Integrated Pharmacology Approach.

    Science.gov (United States)

    Chen, Meimei; Yang, Fafu; Yang, Xuemei; Lai, Xinmei; Gao, Yuxing

    2016-12-16

    Metabolic syndrome (MS) is becoming a worldwide health problem. Wendan decoction (WDD)-a famous traditional Chinese medicine formula-has been extensively employed to relieve syndromes related to MS in clinical practice in China. However, its pharmacological mechanisms still remain vague. In this study, a comprehensive approach that integrated chemomics, principal component analysis, molecular docking simulation, and network analysis was established to elucidate the multi-component and multi-target mechanism of action of WDD in treatment of MS. The compounds in WDD were found to possess chemical diversity, complexity and drug-likeness compared to MS drugs. Six nuclear receptors were obtained to have strong binding affinity with 217 compounds of five herbs in WDD. The importance roles of targets and herbs were also identified due to network parameters. Five compounds from Radix Glycyrrhizae Preparata can hit all six targets, which can assist in screening new MS drugs. The pathway network analysis demonstrated that the main pharmacological effects of WDD might lie in maintaining lipid and glucose metabolisms and anticancer activities as well as immunomodulatory and hepatoprotective effects. This study provided a comprehensive system approach for understanding the multi-component, multi-target and multi-pathway mechanisms of WDD during the treatment of MS.

  17. Systematic Understanding of Mechanisms of a Chinese Herbal Formula in Treatment of Metabolic Syndrome by an Integrated Pharmacology Approach

    Directory of Open Access Journals (Sweden)

    Meimei Chen

    2016-12-01

    Full Text Available Metabolic syndrome (MS is becoming a worldwide health problem. Wendan decoction (WDD—a famous traditional Chinese medicine formula—has been extensively employed to relieve syndromes related to MS in clinical practice in China. However, its pharmacological mechanisms still remain vague. In this study, a comprehensive approach that integrated chemomics, principal component analysis, molecular docking simulation, and network analysis was established to elucidate the multi-component and multi-target mechanism of action of WDD in treatment of MS. The compounds in WDD were found to possess chemical diversity, complexity and drug-likeness compared to MS drugs. Six nuclear receptors were obtained to have strong binding affinity with 217 compounds of five herbs in WDD. The importance roles of targets and herbs were also identified due to network parameters. Five compounds from Radix Glycyrrhizae Preparata can hit all six targets, which can assist in screening new MS drugs. The pathway network analysis demonstrated that the main pharmacological effects of WDD might lie in maintaining lipid and glucose metabolisms and anticancer activities as well as immunomodulatory and hepatoprotective effects. This study provided a comprehensive system approach for understanding the multi-component, multi-target and multi-pathway mechanisms of WDD during the treatment of MS.

  18. Current treatment approaches in patients with ankylosing spondylitis

    Directory of Open Access Journals (Sweden)

    Bilal Elbey

    2015-03-01

    Full Text Available Ankylosing spondylitis (AS is a chronic, inflammatory, rheumatic disease that mainly affects sacroiliac joints and spine. AS predominantly occurs more often in males and typically begins in the second or third decade. The mainstay of therapy in AS are nonsteroidal anti-inflammatory drugs, which reduce inflammation and pain. Disease modifying antirheumatic drugs (DMARD did not have enough evidence to prove their effect in AS treatment. The use of DMARD may not sufficient to improve the treatment and symptoms. Currently, TNF-blockers such as, Golimumab Etanersept Adalimumab İnfliksimab have promising results in the treatment of AS. TNF-blockers improve the clinical signs and symptoms, and improve the patients’ physical function and quality of life. This manuscript is focused that Current pharmacological treatments in patients with ankylosing spondylitis.

  19. A Network Pharmacology Approach to Determine the Active Components and Potential Targets of Curculigo Orchioides in the Treatment of Osteoporosis.

    Science.gov (United States)

    Wang, Nani; Zhao, Guizhi; Zhang, Yang; Wang, Xuping; Zhao, Lisha; Xu, Pingcui; Shou, Dan

    2017-10-27

    BACKGROUND Osteoporosis is a complex bone disorder with a genetic predisposition, and is a cause of health problems worldwide. In China, Curculigo orchioides (CO) has been widely used as a herbal medicine in the prevention and treatment of osteoporosis. However, research on the mechanism of action of CO is still lacking. The aim of this study was to identify the absorbable components, potential targets, and associated treatment pathways of CO using a network pharmacology approach. MATERIAL AND METHODS We explored the chemical components of CO and used the five main principles of drug absorption to identify absorbable components. Targets for the therapeutic actions of CO were obtained from the PharmMapper server database. Pathway enrichment analysis was performed using the Comparative Toxicogenomics Database (CTD). Cytoscape was used to visualize the multiple components-multiple target-multiple pathways-multiple disease network for CO. RESULTS We identified 77 chemical components of CO, of which 32 components could be absorbed in the blood. These potential active components of CO regulated 83 targets and affected 58 pathways. Data analysis showed that the genes for estrogen receptor alpha (ESR1) and beta (ESR2), and the gene for 11 beta-hydroxysteroid dehydrogenase type 1, or cortisone reductase (HSD11B1) were the main targets of CO. Endocrine regulatory factors and factors regulating calcium reabsorption, steroid hormone biosynthesis, and metabolic pathways were related to these main targets and to ten corresponding compounds. CONCLUSIONS The network pharmacology approach used in our study has attempted to explain the mechanisms for the effects of CO in the prevention and treatment of osteoporosis, and provides an alternative approach to the investigation of the effects of this complex compound.

  20. Pharmacologic Approach to Defective Protein Trafficking in the E637K-hERG Mutant with PD-118057 and Thapsigargin.

    Directory of Open Access Journals (Sweden)

    Haiyan Mao

    Full Text Available Treatment of LQT2 is inadequate. Many drugs which can pharmacologically rescue defective protein trafficking in LQT2 also result in potent blockade of HERG current, negating their therapeutic benefit. It is reported that PD-118057 and thapsigargin can rescue LQT2 without hERG channel blockade, but the precise mechanism of action is unknown. Furthermore, the effect of PD-118057 and thapsigargin on the dominant negative E637K-hERG mutant has not been previously investigated.IN THIS STUDY, WE INVESTIGATED: (a the effect of PD-118057 and thapsigargin on the current amplitudes of WT-hERG and WT/E637K-hERG channels; (b the effect of PD-118057 and thapsigargin on the biophysical properties of WT-hERG and WT/E637K-hERG channels; (c whether drug treatment can rescue channel processing and trafficking defects of the WT/E637K-hERG mutant.The whole-cell Patch-clamp technique was used to assess the effect of PD-118057 and thapsigargin on the electrophysiological characteristics of the rapidly activating delayed rectifier K(+ current (Ikr of the hERG protein channel. Western blot was done to investigate pharmacological rescue on hERG protein channel function.In our study, PD-118057 was shown to significantly enhance both the maximum current amplitude and tail current amplitude, but did not alter the gating and kinetic properties of the WT-hERG channel, with the exception of accelerating steady-state inactivation. Additionally, thapsigargin shows a similar result as PD-118057 for the WT-hERG channel, but with the exception of attenuating steady-state inactivation. However, for the WT/E637K-hERG channel, PD-118057 had no effect on either the current or on the gating and kinetic properties. Furthermore, thapsigargin treatment did not alter the current or the gating and kinetic properties of the WT/E637K-hERG channel, with the exception of opening at more positive voltages.Our findings illustrate that neither PD-118057 nor thapsigargin play a role in correcting

  1. Management of Irritable Bowel Syndrome: Novel Approaches to the Pharmacology of Gut Motility

    Directory of Open Access Journals (Sweden)

    Carmelo Scarpignato

    1999-01-01

    receptors on GI smooth muscle and, therefore, act as motilin agonists. This antibiotic accelerates gastric emptying and shortens orocecal transit time. In the large bowel a significant decrease in transit is observed only in the right colon, which suggests a shift in fecal distribution. Several ‘motilinomimetics’ have been synthesized. Their development depends on the lack of antimicrobial activity and the absence of fading of the prokinetic effect during prolonged administration. 5-hydroxytryptamine (5-HT4 agonists with significant pharmacological effects on the mid- and distal gut (such as prucalopride and tegaserod are available for human use. These ‘enterokinetic’ compounds are useful for treating constipation- predominant IBS patients. 5-HT3 receptor antagonists also possess a number of interesting pharmacological properties that may make them suitable for treatment of IBS. Besides decreasing colonic sensitivity to distension, these drugs prolong intestinal transit and may be particularly useful in diarrhea-predominant IBS. Finally, when administered in small pulsed doses, octreotide, besides reducing the perception of rectal distension, accelerates intestinal transit, although other evidence disputes such an effect.

  2. Pharmacological Approach for Managing Pain in Irritable Bowel Syndrome: A Review Article

    Science.gov (United States)

    Chen, Longtu; Ilham, Sheikh J.; Feng, Bin

    2017-01-01

    Context Visceral pain is a leading symptom for patients with irritable bowel syndrome (IBS) that affects 10% - 20 % of the world population. Conventional pharmacological treatments to manage IBS-related visceral pain is unsatisfactory. Recently, medications have emerged to treat IBS patients by targeting the gastrointestinal (GI) tract and peripheral nerves to alleviate visceral pain while avoiding adverse effects on the central nervous system (CNS). Several investigational drugs for IBS also target the periphery with minimal CNS effects. Evidence of Acquisition In this paper, reputable internet databases from 1960 - 2016 were searched including Pubmed and ClinicalTrials.org, and 97 original articles analyzed. Search was performed based on the following keywords and combinations: irritable bowel syndrome, clinical trial, pain, visceral pain, narcotics, opioid, chloride channel, neuropathy, primary afferent, intestine, microbiota, gut barrier, inflammation, diarrhea, constipation, serotonin, visceral hypersensitivity, nociceptor, sensitization, hyperalgesia. Results Certain conventional pain managing drugs do not effectively improve IBS symptoms, including NSAIDs, acetaminophen, aspirin, and various narcotics. Anxiolytic and antidepressant drugs (Benzodiazepines, TCAs, SSRI and SNRI) can attenuate pain in IBS patients with relevant comorbidities. Clonidine, gabapentin and pregabalin can moderately improve IBS symptoms. Lubiprostone relieves constipation predominant IBS (IBS-C) while loperamide improves diarrhea predominant IBS (IBS-D). Alosetron, granisetron and ondansetron can generally treat pain in IBS-D patients, of which alosetron needs to be used with caution due to cardiovascular toxicity. The optimal drugs for managing pain in IBS-D and IBS-C appear to be eluxadoline and linaclotide, respectively, both of which target peripheral GI tract. Conclusions Conventional pain managing drugs are in general not suitable for treating IBS pain. Medications that target

  3. Resins and Gums in Historical Iatrosophia Texts from Cyprus - A Botanical and Medico-pharmacological Approach.

    Science.gov (United States)

    Lardos, Andreas; Prieto-Garcia, José; Heinrich, Michael

    2011-01-01

    This study explores historical iatrosophia texts from Cyprus from a botanical and medico-pharmacological point of view focusing on remedies containing resins and gums. The iatrosophia are a genre of Greek medical literature of Byzantine origin and can be described as medicine handbooks which serve as therapeutic repositories containing recipes or advice. To extract and analyze information on plant usage in such sources - which are largely unedited texts and so far have not been translated - we investigate (i) the relationship of the iatrosophia to Dioscorides' De Materia Medica as well as historic pharmaceutical books or standard texts on modern phytotherapy and (ii) the validity of the remedies by comparing them to modern scientific data on reported biological activities. In the six texts investigated 27 substances incorporating plant exudates are mentioned. They are obtained from over 43 taxa of higher plants and in particular are used to treat dermatological, gastrointestinal, and respiratory tract conditions. The comparison to historic pharmaceutical books and phytotherapy texts reflects the gradual decline of the use of plant exudates in Western medicine. While remarkable parallels to Dioscorides' text exist, the non-Dioscoridean influence suggests a complex pattern of knowledge exchange. Overall, this resulted in an integration of knowledge from so far poorly understood sources. The comparison with bioscientific data reveals a fragmentary picture and highlights the potential of these unexplored substances and their uses. Where relevant bioscientific data are available, we generally found a confirmation. This points to a largely rational use of the associated remedies. Taken together, the iatrosophia are a valuable resource for ethnopharmacological and natural product research. Most importantly they contribute to the understanding of the development of herbal medicines in the (Eastern) Mediterranean and Europe.

  4. Life context of pharmacological academic performance enhancement among university students--a qualitative approach.

    Science.gov (United States)

    Hildt, Elisabeth; Lieb, Klaus; Franke, Andreas Günter

    2014-03-07

    Academic performance enhancement or cognitive enhancement (CE) via stimulant drug use has received increasing attention. The question remains, however, whether CE solely represents the use of drugs for achieving better academic or workplace results or whether CE also serves various other purposes. The aim of this study was to put the phenomenon of pharmacological academic performance enhancement via prescription and illicit (psycho-) stimulant use (Amphetamines, Methylphenidate) among university students into a broader context. Specifically, we wanted to further understand students' experiences, the effects of use on students and other factors, such as pressure to perform in their academic and private lives. A sample of 18 healthy university students reporting the non-medical use of prescription and illicit stimulants for academic performance enhancement was interviewed in a face-to-face setting. The leading questions were related to the situations and context in which the students considered the non-medical use of stimulants. Based on the resultant transcript, two independent raters identified six categories relating to the life context of stimulant use for academic performance enhancement: Context of stimulant use beyond academic performance enhancement, Subjective experience of enhancement, Timing of consumption, Objective academic results, Side effects, Pressure to perform. The answers reveal that academic performance enhancement through the use of stimulants is not an isolated phenomenon that solely aims at enhancing cognition to achieve better academic results but that the multifaceted life context in which it is embedded is of crucial relevance. The participants not only considered the stimulants advantageous for enhancing academic performance, but also for leading an active life with a suitable balance between studying and time off. The most common reasons given for stimulant use were to maximize time, to increase motivation and to cope with memorizing

  5. A feasibility study of a new approach to clinical radiosensitisation: hypothermia and hyperbaric oxygen in combination with pharmacological vasodilatation

    International Nuclear Information System (INIS)

    Sealy, R.; Harrison, G.G.; Morrell, D.; Cape Town Univ.

    1986-01-01

    It is proposed that hyperbaric oxygen fails in the clinical situation due to a high proportion (greater than 33%) of hypoxic cells in human tumours. The means of overcoming this problem are reviewed. Additional to hyperbaric oxygenation, moderate hypothermia (30 0 C) to allow redistribution of oxygen in the tumour is proposed. A system of externally controlled intravenous anaesthesia has been developed for the single-subject hypervaric cylinder. Pharmacological vasodilatation is induced in the anaesthetised patient who is then fluid loaded and cooled. Initial single-sensitising treatments are advocated. Twenty-nine patients with advanced mouth cancer have completed a course of this treatment, of whom five of nine were free of disease after 2 years and 10 of 21 at 1 year, with three intercurrent deaths. Fifteen have experienced local failure. This approach would appear to be practical, safe and promising. (author)

  6. Application of Several Multimedia Approaches to the Teaching of CNS Pharmacology: Parkinson's Disease and Antiparkinsonism Drugs.

    Science.gov (United States)

    Faulkner, Thomas P.; Sprague, Jon E.

    1996-01-01

    A multimedia approach to drug therapy for Parkinson's Disease, part of a pharmacy school central nervous system course, integrated use of lecture, textbook, video/graphic technology, the movie "Awakenings," Internet and World Wide Web, and an interactive animated movie. A followup questionnaire found generally positive student attitudes…

  7. Current Approaches to the Management of Pediatric Overweight and Obesity

    Science.gov (United States)

    Ridolfi, Danielle R.; Hayes, Jacqueline F.; St Paul, Michelle; Wilfley, Denise E.

    2015-01-01

    Opinion Statement Family-based behavioral intervention has been demonstrated to be an effective and safe treatment for childhood obesity and should be considered a first-line treatment option. However, access to such intensive evidence-based treatment is limited and, currently, obesity care is dominated by high intensity behavioral treatment implemented in specialty clinics or less effective, low intensity treatments implemented in primary care. However, capitalizing on the established and ongoing relationship between primary care providers and families, primary care providers hold an invaluable role in early identification of overweight and obesity, and subsequent referral to an evidence-based treatment. key aspects of effective treatment include: early intervention, moderate- to high-intensity intervention of sufficient duration, multi-component intervention targeting dietary modification, physical activity and behavioral strategies, family involvement and goals targeting family members, and follow-up contact during maintenance. The purpose of this review is to present the current empirically supported treatment options for pediatric obesity including primary care-based interventions and diagnostic tools, multi-component behavioral intervention with a focus on family-based behavioral intervention, immersion treatment, and pharmacologic and surgical management. PMID:25205083

  8. Pharmacological management of chronic obstructive pulmonary ...

    African Journals Online (AJOL)

    The main objective of treatment is to relieve daily symptoms, improve quality of life and importantly decrease the risk of future exacerbations. Current guidelines are based on grade A and B evidence. Pneumococcal and annual influenza vaccinations are encouraged. A holistic approach that augments pharmacological ...

  9. A linguistic rule-based approach to extract drug-drug interactions from pharmacological documents.

    Science.gov (United States)

    Segura-Bedmar, Isabel; Martínez, Paloma; de Pablo-Sánchez, César

    2011-03-29

    A drug-drug interaction (DDI) occurs when one drug influences the level or activity of another drug. The increasing volume of the scientific literature overwhelms health care professionals trying to be kept up-to-date with all published studies on DDI. This paper describes a hybrid linguistic approach to DDI extraction that combines shallow parsing and syntactic simplification with pattern matching. Appositions and coordinate structures are interpreted based on shallow syntactic parsing provided by the UMLS MetaMap tool (MMTx). Subsequently, complex and compound sentences are broken down into clauses from which simple sentences are generated by a set of simplification rules. A pharmacist defined a set of domain-specific lexical patterns to capture the most common expressions of DDI in texts. These lexical patterns are matched with the generated sentences in order to extract DDIs. We have performed different experiments to analyze the performance of the different processes. The lexical patterns achieve a reasonable precision (67.30%), but very low recall (14.07%). The inclusion of appositions and coordinate structures helps to improve the recall (25.70%), however, precision is lower (48.69%). The detection of clauses does not improve the performance. Information Extraction (IE) techniques can provide an interesting way of reducing the time spent by health care professionals on reviewing the literature. Nevertheless, no approach has been carried out to extract DDI from texts. To the best of our knowledge, this work proposes the first integral solution for the automatic extraction of DDI from biomedical texts.

  10. Identification of novel anti-inflammatory agents from Ayurvedic medicine for prevention of chronic diseases: "reverse pharmacology" and "bedside to bench" approach.

    Science.gov (United States)

    Aggarwal, Bharat B; Prasad, Sahdeo; Reuter, Simone; Kannappan, Ramaswamy; Yadev, Vivek R; Park, Byoungduck; Kim, Ji Hye; Gupta, Subash C; Phromnoi, Kanokkarn; Sundaram, Chitra; Prasad, Seema; Chaturvedi, Madan M; Sung, Bokyung

    2011-10-01

    Inflammation, although first characterized by Cornelius Celsus, a physician in first Century Rome, it was Rudolf Virchow, a German physician in nineteenth century who suggested a link between inflammation and cancer, cardiovascular diseases, diabetes, pulmonary diseases, neurological diseases and other chronic diseases. Extensive research within last three decades has confirmed these observations and identified the molecular basis for most chronic diseases and for the associated inflammation. The transcription factor, Nuclear Factor-kappaB (NF-kappaB) that controls over 500 different gene products, has emerged as major mediator of inflammation. Thus agents that can inhibit NF-kappaB and diminish chronic inflammation have potential to prevent or delay the onset of the chronic diseases and further even treat them. In an attempt to identify novel anti-inflammatory agents which are safe and effective, in contrast to high throughput screen, we have turned to "reverse pharmacology" or "bed to benchside" approach. We found that Ayurveda, a science of long life, almost 6,000 years old, can serve as a "goldmine" for novel anti-inflammatory agents used for centuries to treat chronic diseases. The current review is an attempt to provide description of various Ayurvedic plants currently used for treatment, their active chemical components, and the inflammatory pathways that they inhibit.

  11. Systems Pharmacological Approach of Pulsatillae Radix on Treating Crohn’s Disease

    Directory of Open Access Journals (Sweden)

    Su Yeon Suh

    2017-01-01

    Full Text Available In East Asian traditional medicine, Pulsatillae Radix (PR is widely used to treat amoebic dysentery and renowned for its anti-inflammatory effects. This study aimed to confirm evidence regarding the potential therapeutic effect of PR on Crohn’s disease using a system network level based in silico approach. Study results showed that the compounds in PR are highly connected to Crohn’s disease related pathways, biological processes, and organs, and these findings were confirmed by compound-target network, target-pathway network, and gene ontology analysis. Most compounds in PR have been reported to possess anti-inflammatory, anticancer, and antioxidant effects, and we found that these compounds interact with multiple targets in a synergetic way. Furthermore, the mRNA expressions of genes targeted by PR are elevated significantly in immunity-related organ tissues, small intestine, and colon. Our results suggest that the anti-inflammatory and repair and immune system enhancing effects of PR might have therapeutic impact on Crohn’s disease.

  12. [Pharmacological approach to desychronization of the sleep-wakefulness cycle in the military and sport environment].

    Science.gov (United States)

    Lagarde, D

    2007-07-01

    Sports and military environments have many common features - intense physical activity, rigorous physical environment (heat, cold, high or low pressure, hypoxia, acceleration...), specific psychosocial atmosphere, team spirit. If combined with jet lag syndrome, these specific conditions can favor altered physical and mental performance. There is always the temptation to use drugs as a simple way to reduce the penalizing effects. The available compounds known to affect sleep and wakefulness include hypnotics, benzodiazepines and non benzodiazepines such as temazepam, zolopidem, and zopiclone, stimulants such as amphetamine and amphetamine-like agents, adrafinil, modafinil, caffeine and chronobiotics substances such as melatonin and, more recently, slow release caffeine. In the sports area, all of these substances except caffeine are on the list of forbidden products, although special authorizations linked to known disease conditions are allowed. In the military setting, the environment may be similar, but the context of use is very different. In the context of a rescue mission, the current practice in the French military organization is to place modafinil pills in the ejection seat of fight planes and in rescue boats. A second context is the use of anti-sleep agents under orders; the debate continues on this and the appropriate recommendations in this context. Self-medication is a third condition, in which case no rules have been defined.

  13. A new approach to determining pharmacologic adulteration of herbal weight loss products.

    Science.gov (United States)

    De Carvalho, L M; Cohen, P A; Silva, C V; Moreira, A P L; Falcão, T M; Dal Molin, T R; Zemolin, G; Martini, M

    2012-01-01

    Pharmaceutical adulterants are commonly found in herbal weight loss products, and analytical techniques for detecting these adulterants have become increasingly important to the public health community. Previously we reported a novel analytical method for the determination of adulterants in herbal formulations by capillary electrophoresis with contactless conductivity detection. The current study refines this previously described technique by testing if anxiolytics, diuretics, and laxatives interfered with the detection of anorectics and antidepressants. A survey of herbal weight loss products sold by compounding pharmacies in Brazil were analysed to determine the presence of pharmaceutical adulterants. A total of 106 herbal products, collected from 73 pharmacies in nine Brazilian states, were analysed for amfepramone, sibutramine, fenproporex, fluoxetine, paroxetine, sertraline and bupropion using the new analytical method. The method permitted the rapid and selective screening for the seven adulterants. Of the 106 weight loss products sampled, four (3.8%) were found to be adulterated by fenproporex or sibutramine. The adulterated samples were compounded by four different pharmacies located in three different Brazilian states. The novel capillary electrophoresis method we developed may be a useful tool for public health organisations tasked with analysing herbal weight loss products.

  14. A partial Hamiltonian approach for current value Hamiltonian systems

    Science.gov (United States)

    Naz, R.; Mahomed, F. M.; Chaudhry, Azam

    2014-10-01

    We develop a partial Hamiltonian framework to obtain reductions and closed-form solutions via first integrals of current value Hamiltonian systems of ordinary differential equations (ODEs). The approach is algorithmic and applies to many state and costate variables of the current value Hamiltonian. However, we apply the method to models with one control, one state and one costate variable to illustrate its effectiveness. The current value Hamiltonian systems arise in economic growth theory and other economic models. We explain our approach with the help of a simple illustrative example and then apply it to two widely used economic growth models: the Ramsey model with a constant relative risk aversion (CRRA) utility function and Cobb Douglas technology and a one-sector AK model of endogenous growth are considered. We show that our newly developed systematic approach can be used to deduce results given in the literature and also to find new solutions.

  15. Current approaches to the management of idiopathic pulmonary fibrosis.

    Science.gov (United States)

    Raghu, Ganesh; Richeldi, Luca

    2017-08-01

    Idiopathic pulmonary fibrosis (IPF) is a progressive and ultimately fatal lung disease associated with dyspnoea, cough and impaired quality of life. Currently, the aims of patient care are to improve outcomes for patients by slowing the progression of the disease, extending life, and improving quality of life. A prompt, accurate diagnosis is important to enable patients to receive treatment early in the course of the disease and to be considered for lung transplantation. Two anti-fibrotic drugs, nintedanib and pirfenidone, have been shown to reduce decline in lung function in patients with IPF. In addition to pharmacological therapy, optimal management of IPF includes treatment of comorbidities, symptom relief, pulmonary rehabilitation, and palliative care. Patient education is important to enable patients to make decisions about their care and to help them manage their disease and the side-effects of anti-fibrotic drugs. Research continues into new treatments and combinations of treatments that may improve outcomes for patients with this devastating disease. Copyright © 2017. Published by Elsevier Ltd.

  16. Adjoint current-based approaches to prostate brachytherapy optimization

    International Nuclear Information System (INIS)

    Roberts, J. A.; Henderson, D. L.

    2009-01-01

    This paper builds on previous work done at the Univ. of Wisconsin - Madison to employ the adjoint concept of nuclear reactor physics in the so-called greedy heuristic of brachytherapy optimization. Whereas that previous work focused on the adjoint flux, i.e. the importance, this work has included use of the adjoint current to increase the amount of information available in optimizing. Two current-based approaches were developed for 2-D problems, and each was compared to the most recent form of the flux-based methodology. The first method aimed to take a treatment plan from the flux-based greedy heuristic and adjust via application of the current-displacement, or a vector displacement based on a combination of tissue (adjoint) and seed (forward) currents acting as forces on a seed. This method showed promise in improving key urethral and rectal dosimetric quantities. The second method uses the normed current-displacement as the greedy criterion such that seeds are placed in regions of least force. This method, coupled with the dose-update scheme, generated treatment plans with better target irradiation and sparing of the urethra and normal tissues than the flux-based approach. Tables of these parameters are given for both approaches. In summary, these preliminary results indicate adjoint current methods are useful in optimization and further work in 3-D should be performed. (authors)

  17. An In Silico Knockout Model for Gastrointestinal Absorption Using a Systems Pharmacology Approach - Development and Application for Ketones.

    Directory of Open Access Journals (Sweden)

    Vittal Shivva

    Full Text Available Gastrointestinal absorption and disposition of ketones is complex. Recent work describing the pharmacokinetics (PK of d-β-hydroxybutyrate (BHB following oral ingestion of a ketone monoester ((R-3-hydroxybutyl (R-3-hydroxybutyrate found multiple input sites, nonlinear disposition and feedback on endogenous production. In the current work, a human systems pharmacology model for gastrointestinal absorption and subsequent disposition of small molecules (monocarboxylic acids with molecular weight < 200 Da was developed with an application to a ketone monoester. The systems model was developed by collating the information from the literature and knowledge gained from empirical population modelling of the clinical data. In silico knockout variants of this systems model were used to explore the mechanism of gastrointestinal absorption of ketones. The knockouts included active absorption across different regions in the gut and also a passive diffusion knockout, giving 10 gut knockouts in total. Exploration of knockout variants has suggested that there are at least three distinct regions in the gut that contribute to absorption of ketones. Passive diffusion predominates in the proximal gut and active processes contribute to the absorption of ketones in the distal gut. Low doses are predominantly absorbed from the proximal gut by passive diffusion whereas high doses are absorbed across all sites in the gut. This work has provided mechanistic insight into the absorption process of ketones, in the form of unique in silico knockouts that have potential for application with other therapeutics. Future studies on absorption process of ketones are suggested to substantiate findings in this study.

  18. Pharmacological analysis of the activation and receptor properties of the tonic GABA(CR current in retinal bipolar cell terminals.

    Directory of Open Access Journals (Sweden)

    Stefanie M Jones

    Full Text Available GABAergic inhibition in the central nervous system (CNS can occur via rapid, transient postsynaptic currents and via a tonic increase in membrane conductance, mediated by synaptic and extrasynaptic GABA(A receptors (GABA(ARs respectively. Retinal bipolar cells (BCs exhibit a tonic current mediated by GABA(CRs in their axon terminal, in addition to synaptic GABA(AR and GABA(CR currents, which strongly regulate BC output. The tonic GABA(CR current in BC terminals (BCTs is not dependent on vesicular GABA release, but properties such as the alternative source of GABA and the identity of the GABA(CRs remain unknown. Following a recent report that tonic GABA release from cerebellar glial cells is mediated by Bestrophin 1 anion channels, we have investigated their role in non-vesicular GABA release in the retina. Using patch-clamp recordings from BCTs in goldfish retinal slices, we find that the tonic GABA(CR current is not reduced by the anion channel inhibitors NPPB or flufenamic acid but is reduced by DIDS, which decreases the tonic current without directly affecting GABA(CRs. All three drugs also exhibit non-specific effects including inhibition of GABA transporters. GABA(CR ρ subunits can form homomeric and heteromeric receptors that differ in their properties, but BC GABA(CRs are thought to be ρ1-ρ2 heteromers. To investigate whether GABA(CRs mediating tonic and synaptic currents may differ in their subunit composition, as is the case for GABA(ARs, we have examined the effects of two antagonists that show partial ρ subunit selectivity: picrotoxin and cyclothiazide. Tonic and synaptic GABA(CR currents were differentially affected by both drugs, suggesting that a population of homomeric ρ1 receptors contributes to the tonic current. These results extend our understanding of the multiple forms of GABAergic inhibition that exist in the CNS and contribute to visual signal processing in the retina.

  19. Anesthetic pharmacology

    National Research Council Canada - National Science Library

    Evers, Alex S; Maze, M; Kharasch, Evan D

    2011-01-01

    ...: Section 1 introduces the principles of drug action, Section 2 presents the molecular, cellular and integrated physiology of the target organ/functional system and Section 3 reviews the pharmacology...

  20. Pharmacological activation of rapid delayed rectifier potassium current suppresses bradycardia-induced triggered activity in the isolated guinea pig heart

    DEFF Research Database (Denmark)

    Hansen, Rie Schultz; Olesen, Søren-Peter; Grunnet, Morten

    2007-01-01

    arrhythmias. We present here data that support that NS3623 affects native I(Kr) and report the effects that activating this potassium current have in the intact guinea pig heart. In Langendorff-perfused hearts, the compound showed a concentration-dependent shortening of action potential duration, which...

  1. A progressive approach to discrete trial teaching: Some current guidelines

    Directory of Open Access Journals (Sweden)

    Justin B. Leaf

    2016-12-01

    Full Text Available Discrete trial teaching (DTT is one of the cornerstones of applied behavior analysis (ABA based interventions. Conventionally, DTT is commonly implemented within a prescribed, fixed manner in which the therapist is governed by a strict set of rules. In contrast to conventional DTT, a progressive approach to DTT allows the therapist to remain flexible, making in-the-moment analyses and changes based on several variables (e.g., individual responding, current and previous history. The present paper will describe some guidelines to a progressive approach to DTT. The guidelines presented here should not be taken as a set of rules or as an exhaustive list.

  2. A Progressive Approach to Discrete Trial Teaching: Some Current Guidelines

    Directory of Open Access Journals (Sweden)

    Justin B. LEAF

    2016-12-01

    Full Text Available Discrete trial teaching (DTT is one of the cornerstones of applied behavior analysis (ABA based interventions. Conventionally, DTT is commonly implemented within a prescribed, fixed manner in which the therapist is governed by a strict set of rules. In contrast to conventional DTT, a progressive approach to DTT allows the therapist to remain flexible, making in-the-moment analyses and changes based on several variables (e.g., individual responding, current and previous history. The present paper will describe some guidelines to a progressive approach to DTT. The guidelines presented here should not be taken as a set of rules or as an exhaustive list.

  3. Current Therapeutic Strategies and Novel Approaches in Osteosarcoma

    International Nuclear Information System (INIS)

    Ando, Kosei; Heymann, Marie-Françoise; Stresing, Verena; Mori, Kanji; Rédini, Françoise; Heymann, Dominique

    2013-01-01

    Osteosarcoma is the most frequent malignant primary bone tumor and a main cause of cancer-related death in children and adolescents. Although long-term survival in localized osteosarcoma has improved to about 60% during the 1960s and 1970s, long-term survival in both localized and metastatic osteosarcoma has stagnated in the past several decades. Thus, current conventional therapy consists of multi-agent chemotherapy, surgery and radiation, which is not fully adequate for osteosarcoma treatment. Innovative drugs and approaches are needed to further improve outcome in osteosarcoma patients. This review describes the current management of osteosarcoma as well as potential new therapies

  4. Cost-utility analysis of antiviral use under pandemic influenza using a novel approach - linking pharmacology, epidemiology and heath economics.

    Science.gov (United States)

    Wu, D B C; Chaiyakunapruk, N; Pratoomsoot, C; Lee, K K C; Chong, H Y; Nelson, R E; Smith, P F; Kirkpatrick, C M; Kamal, M A; Nieforth, K; Dall, G; Toovey, S; Kong, D C M; Kamauu, A; Rayner, C R

    2018-03-01

    Simulation models are used widely in pharmacology, epidemiology and health economics (HEs). However, there have been no attempts to incorporate models from these disciplines into a single integrated model. Accordingly, we explored this linkage to evaluate the epidemiological and economic impact of oseltamivir dose optimisation in supporting pandemic influenza planning in the USA. An HE decision analytic model was linked to a pharmacokinetic/pharmacodynamics (PK/PD) - dynamic transmission model simulating the impact of pandemic influenza with low virulence and low transmissibility and, high virulence and high transmissibility. The cost-utility analysis was from the payer and societal perspectives, comparing oseltamivir 75 and 150 mg twice daily (BID) to no treatment over a 1-year time horizon. Model parameters were derived from published studies. Outcomes were measured as cost per quality-adjusted life year (QALY) gained. Sensitivity analyses were performed to examine the integrated model's robustness. Under both pandemic scenarios, compared to no treatment, the use of oseltamivir 75 or 150 mg BID led to a significant reduction of influenza episodes and influenza-related deaths, translating to substantial savings of QALYs. Overall drug costs were offset by the reduction of both direct and indirect costs, making these two interventions cost-saving from both perspectives. The results were sensitive to the proportion of inpatient presentation at the emergency visit and patients' quality of life. Integrating PK/PD-EPI/HE models is achievable. Whilst further refinement of this novel linkage model to more closely mimic the reality is needed, the current study has generated useful insights to support influenza pandemic planning.

  5. Current management of oral cancer. A multidisciplinary approach.

    Science.gov (United States)

    Ord, R A; Blanchaert, R H

    2001-11-01

    Recent basic science discoveries have contributed to our understanding of the etiology of oral cancer and allowed us to consider innovative approaches to therapy. The authors evaluated and summarized current approaches to the management of oral cancer, emphasizing the multidisciplinary team approach to coordinate surgery, radiation therapy and chemotherapy. Current concepts in management, including complications of therapy, are described. State-of-the-art surgical techniques can spare patients with oral cancer from much of the morbidity and complications common in the past. The refinement of treatment strategies reduces complications and improves efficacy. Many exciting new clinical trials in the areas of gene therapy and immunomodulation are showing promise. Management of oral cancer has undergone radical change in the past 10 years and continues to evolve rapidly. Discoveries in molecular biology, diagnosis, surgery, radiation therapy and medical oncology have altered many traditional concepts and practices. General dental practitioners need to understand current treatment modalities for oral and pharyngeal cancers to determine to whom they should refer patients for the most appropriate treatment, and to make recommendations regarding complications associated with these cancers.

  6. Pharmacological modulation of the short-lasting effects of antagonistic direct current-stimulation over the human motor cortex

    Directory of Open Access Journals (Sweden)

    Leila eChaieb

    2012-07-01

    Full Text Available Combined administration of transcranial direct current stimulation (tDCS with either pergolide (PGL or D-cycloserine (D-CYC can prolong the excitability-diminishing effects of cathodal, or the excitability enhancing effect of anodal stimulation for up to 24hrs poststimulation. However, it remains unclear whether the potentiation of the observed aftereffects is dominated by the polarity and duration of the stimulation, or the dual application of combined stimulation and drug administration. The present study looks at whether the aftereffects of oral administration of PGL (a D1/D2 agonist or D-CYC (a partial NMDA receptor agonist, in conjunction with the short duration antagonistic application of tDCS (either 5 min cathodal followed immediately by 5 min anodal or vice versa, that alone only induces short lasting aftereffects, can modulate cortical excitability in healthy human subjects, as revealed by a single-pulse MEP (motor-evoked-potential paradigm. Results indicate that the antagonistic application of DC currents induces short-term neuroplastic aftereffects that are dependent upon the polarity of the second application of short-duration tDCS. The application of D-cycloserine resulted in a reversal of this trend and so consequently a marked inhibition of cortical excitability with the cathodal-anodal stimulation order was observed. The administration of pergolide showed no significant aftereffects in either case. These results emphasise that the aftereffects of tDCS are dependent upon the stimulation orientation, and mirror the findings of other studies reporting the neuroplasticity inducing aftereffects of tDCS, and their prolongation when combined with the administration of CNS active drugs.

  7. Esclerosis múltiple: aspectos generales y abordaje farmacológico Multiple sclerosis: general features and pharmacologic approach

    Directory of Open Access Journals (Sweden)

    Nielsen Lagumersindez Denis

    2009-08-01

    disease of central nervous system (CNS of unknown etiology and critical evolution. There are different etiological hypotheses talking of a close interrelation among predisposing genetic factors and dissimilar environmental factors, able to give raise to autoimmune response at central nervous system level. Hypothesis of autoimmune pathogeny is based on study of experimental models, and findings in biopsies of affected patients by disease. Accumulative data report that the oxidative stress plays a main role in pathogenesis of multiple sclerosis. Oxygen reactive species generated by macrophages has been involved as mediators of demyelinization and of axon damage, in experimental autoimmune encephalomyelitis and strictly in multiple sclerosis. Disease diagnosis is difficult because of there is not a confirmatory unique test. Management of it covers the treatment of acute relapses, disease modification, and symptoms management. These features require an individualized approach, base on evolution of this affection, and tolerability of treatments. In addition to diet, among non-pharmacologic treatments for multiple sclerosis it is recommended physical therapy. Besides, some clinical assays have been performed in which we used natural extracts, nutrition supplements, and other agents with promising results. Pharmacology allowed neurologists with a broad array of proved effectiveness drugs; however, results of research laboratories in past years make probable that therapeutical possibilities increase notably in future.

  8. Optimizing nitrogen fertilizer use: Current approaches and simulation models

    International Nuclear Information System (INIS)

    Baethgen, W.E.

    2000-01-01

    Nitrogen (N) is the most common limiting nutrient in agricultural systems throughout the world. Crops need sufficient available N to achieve optimum yields and adequate grain-protein content. Consequently, sub-optimal rates of N fertilizers typically cause lower economical benefits for farmers. On the other hand, excessive N fertilizer use may result in environmental problems such as nitrate contamination of groundwater and emission of N 2 O and NO. In spite of the economical and environmental importance of good N fertilizer management, the development of optimum fertilizer recommendations is still a major challenge in most agricultural systems. This article reviews the approaches most commonly used for making N recommendations: expected yield level, soil testing and plant analysis (including quick tests). The paper introduces the application of simulation models that complement traditional approaches, and includes some examples of current applications in Africa and South America. (author)

  9. Breast cancer treatment: historical review and current approaches

    International Nuclear Information System (INIS)

    Kulakowski, A.

    1994-01-01

    The evolution and development of opinions on the diagnosis and treatment of breast cancer since Galen to present time is presented. The concept of breast cancer as a local disease has been replaced by the understanding of its systemic character. On this background described are the methods of surgical treatment beginning from early - supraradical, to present -conservative approaches. The ''milestones'' in diagnosis and treatment of breast cancer of the last 40 years are presented. Current methods of breast cancer management include correct diagnosis (clinical examination, mammography, ultrasound, fine needle aspiration biopsy), TNM staging, adequate loco-regional therapy, systemic therapy, rehabilitation, reconstruction and careful follow-up. (author)

  10. Low-energy hadronic interactions beyond the current algebra approach

    International Nuclear Information System (INIS)

    Ivanov, A.N.; Troitskaya, N.I.; Nagy, M.

    1993-06-01

    The new low-energy AP 3 -interaction, which is produced by convergent box-constituent-quark-loop diagrams, is obtained within chiral perturbation theory at the quark level (CHPT) q with linear realization of chiral U(3) x U(3) symmetry. Its contributions to processes of low-energy interactions of low-lying mesons are investigated. The new interaction goes beyond the framework of the low-energy current algebra approach and of the effective chiral Lagrangians with linear realization of chiral symmetry, constructed at the hadronic level. (author). 17 refs, 3 figs

  11. Electrostatic Discharge Current Linear Approach and Circuit Design Method

    Directory of Open Access Journals (Sweden)

    Pavlos K. Katsivelis

    2010-11-01

    Full Text Available The Electrostatic Discharge phenomenon is a great threat to all electronic devices and ICs. An electric charge passing rapidly from a charged body to another can seriously harm the last one. However, there is a lack in a linear mathematical approach which will make it possible to design a circuit capable of producing such a sophisticated current waveform. The commonly accepted Electrostatic Discharge current waveform is the one set by the IEC 61000-4-2. However, the over-simplified circuit included in the same standard is incapable of producing such a waveform. Treating the Electrostatic Discharge current waveform of the IEC 61000-4-2 as reference, an approximation method, based on Prony’s method, is developed and applied in order to obtain a linear system’s response. Considering a known input, a method to design a circuit, able to generate this ESD current waveform in presented. The circuit synthesis assumes ideal active elements. A simulation is carried out using the PSpice software.

  12. Genomics and systems biology - How relevant are the developments to veterinary pharmacology, toxicology and therapeutics?

    NARCIS (Netherlands)

    Witkamp, R.F.

    2005-01-01

    This review discusses some of the recent developments in genomics and its current and future relevance for veterinary pharmacology and toxicology. With the rapid progress made in this field several new approaches in pharmacological and toxicological research have developed and drug discovery and

  13. Students' perception of an integrated approach of teaching entire sequence of medicinal chemistry, pharmacology, and pharmacotherapeutics courses in PharmD curriculum.

    Science.gov (United States)

    Islam, Mohammed A; Schweiger, Teresa A

    2015-04-01

    To develop an integrated approach of teaching medicinal chemistry, pharmacology, and pharmacotherapeutics and to evaluate students' perceptions of integration as they progress through the PharmD curriculum. Instructors from each discipline jointly mapped the course contents and sequenced the course delivery based on organ systems/disease states. Medicinal chemistry and pharmacology contents were integrated and aligned with respective pharmacotherapeutics contents to deliver throughout second and third year of the curriculum. In addition to classroom lectures, active learning strategies such as recitation, case studies, online-discussion boards, open book quizzes, and writing patient progress notes were incorporated to enhance student learning. Student learning was assessed by examination scores, patient progress notes, and writing assignments. The impact of course integration was evaluated by a Web-based survey. One hundred and sixty-nine students completed the survey. Students exhibited positive attitude toward the integrated approach of teaching medicinal chemistry, pharmacology, and therapeutics. The P3 and P4 students better appreciated the benefits of integration compared to P2 students (P < .05). Students perceived the course integration as an effective way of learning. This study supports course improvement and the viability of expanding the concept of integration to other courses in the curriculum. © The Author(s) 2014.

  14. Personalizing Type 2 Diabetes Management: Use of a Patient-Centered Approach to Individualizing A1C Goals and Pharmacological Regimens.

    Science.gov (United States)

    Lahiri, Sharon W

    2017-12-01

    IN BRIEF Caring for people with type 2 diabetes requires a patient-centered approach to treatment targets and medication regimens. Focusing on patients' individual characteristics, needs, and treatment responses can improve compliance and clinical outcomes. Medication selection can be guided by the mechanisms of action, advantages, disadvantages, and costs of available options; patients' behavioral and psychological variables, personal preferences, and socioeconomic status also should be taken into account. This article provides an overview of patient-centered and individualized diabetes management, offers pharmacological recommendations for specific clinical scenarios, and describes a complicated case illustrating the patient-centered approach in clinical practice.

  15. Respiratory sensitization and allergy: Current research approaches and needs

    International Nuclear Information System (INIS)

    Boverhof, Darrell R.; Billington, Richard; Gollapudi, B. Bhaskar; Hotchkiss, John A.; Krieger, Shannon M.; Poole, Alan; Wiescinski, Connie M.; Woolhiser, Michael R.

    2008-01-01

    There are currently no accepted regulatory models for assessing the potential of a substance to cause respiratory sensitization and allergy. In contrast, a number of models exist for the assessment of contact sensitization and allergic contact dermatitis (ACD). Research indicates that respiratory sensitizers may be identified through contact sensitization assays such as the local lymph node assay, although only a small subset of the compounds that yield positive results in these assays are actually respiratory sensitizers. Due to the increasing health concerns associated with occupational asthma and the impending directives on the regulation of respiratory sensitizers and allergens, an approach which can identify these compounds and distinguish them from contact sensitizers is required. This report discusses some of the important contrasts between respiratory allergy and ACD, and highlights several prominent in vivo, in vitro and in silico approaches that are being applied or could be further developed to identify compounds capable of causing respiratory allergy. Although a number of animal models have been used for researching respiratory sensitization and allergy, protocols and endpoints for these approaches are often inconsistent, costly and difficult to reproduce, thereby limiting meaningful comparisons of data between laboratories and development of a consensus approach. A number of emerging in vitro and in silico models show promise for use in the characterization of contact sensitization potential and should be further explored for their ability to identify and differentiate contact and respiratory sensitizers. Ultimately, the development of a consistent, accurate and cost-effective model will likely incorporate a number of these approaches and will require effective communication, collaboration and consensus among all stakeholders

  16. Current Approaches to the Establishment of Credit Risk Specific Provisions

    Directory of Open Access Journals (Sweden)

    Ion Nitu

    2008-10-01

    Full Text Available The aim of the new Basel II and IFRS approaches is to make the operations of financial institutions more transparent and thus to create a better basis for the market participants and supervisory authorities to acquire information and make decisions. In the banking sector, a continuous debate is being led, related to the similarities and differences between IFRS approach on loan loss provisions and Basel II approach on calculating the capital requirements, judging against the classical method regarding loan provisions, currently used by the Romanian banks following the Central Bank’s regulations.Banks must take into consideration that IFRS and Basel II objectives are fundamentally different. While IFRS aims to ensure that the financial papers reflect adequately the losses recorded at each balance sheet date, the Basel II objective is to ensure that the bank has enough provisions or capital in order to face expected losses in the next 12 months and eventual unexpected losses.Consequently, there are clear differences between the objectives of the two models. Basel II works on statistical modeling of expected losses while IFRS, although allowing statistical models, requires a trigger event to have occurred before they can be used. IAS 39 specifically states that losses that are expected as a result of future events, no matter how likely, are not recognized. This is a clear and fundamental area of difference between the two frameworks.

  17. Towards an Airframe Noise Prediction Methodology: Survey of Current Approaches

    Science.gov (United States)

    Farassat, Fereidoun; Casper, Jay H.

    2006-01-01

    In this paper, we present a critical survey of the current airframe noise (AFN) prediction methodologies. Four methodologies are recognized. These are the fully analytic method, CFD combined with the acoustic analogy, the semi-empirical method and fully numerical method. It is argued that for the immediate need of the aircraft industry, the semi-empirical method based on recent high quality acoustic database is the best available method. The method based on CFD and the Ffowcs William- Hawkings (FW-H) equation with penetrable data surface (FW-Hpds ) has advanced considerably and much experience has been gained in its use. However, more research is needed in the near future particularly in the area of turbulence simulation. The fully numerical method will take longer to reach maturity. Based on the current trends, it is predicted that this method will eventually develop into the method of choice. Both the turbulence simulation and propagation methods need to develop more for this method to become useful. Nonetheless, the authors propose that the method based on a combination of numerical and analytical techniques, e.g., CFD combined with FW-H equation, should also be worked on. In this effort, the current symbolic algebra software will allow more analytical approaches to be incorporated into AFN prediction methods.

  18. An approach to and the rationale for the pharmacological management of behavioral and psychological symptoms of dementia

    Directory of Open Access Journals (Sweden)

    Tripathi Manjari

    2010-10-01

    Full Text Available The behavioral and psychological symptoms of dementia (BPSD have been a difficult management area for neurologists and psychiatrists alike. The correct identification of each symptom and the underlying precipitating cause is the key to proper management-nonpharmacological as well as pharmacological. BPSD has been well documented in all types of dementia in various stages of the disease and in all dementias at an advanced stage. The proper management is not only rewarding in terms of responsiveness in an otherwise "incurable" and progressive disease, but also improves the quality of life of the patients and the caregivers alike. The caregiver burden is greatly decreased by an efficient management of BPSD. This review discusses the implications and boundaries of the term BPSD and unravels each symptom and its identification. Manifestations of psychological symptoms such as delusion, hallucination, misidentification, psychosis, depression, apathy, and anxiety are briefly described. Correct identification of behavior symptoms such as wandering, agitation, catastrophic reaction, disinhibition, and delirium has been outlined. While the subtle differences in each entity make the precise identification difficult, the different therapeutics of each make the exercise necessary. Pharmacological recommendations and side effects of medications have been mentioned thereafter. The review will help in the identification and correct pharmacological management of BPSD.

  19. Current Approaches for Control Room I and C Modernization

    International Nuclear Information System (INIS)

    Lopez, Alberto; Jimenez, Alfonso

    2002-01-01

    In general, instrumentation and control (I and C) systems for nuclear power plants were made using analogic systems and relays, since this was the only technology available by the time these systems were designed. This fact impacts on the operational and maintenance capabilities required to these systems. For this reason, nuclear power plants are facing nowadays two challenges: on one hand, the obsolescence of these systems contributes to the increase in the operation and maintenance costs - due to the difficulties for getting spare parts and support from the system vendors -. On the other hand, there has been an increase in the utilities competitiveness due to the electric power market liberalization. All this, of course, along with the commitment to maintain the current safety levels and meet the new requirements and standards that may arise in the near future. The application of current technologies, especially digital technology, solves the obsolescence problems and allows for a more functional and updated human-machine interface. Nevertheless, the cost associated to these modifications makes it necessary to develop strategies to determine which systems need to be modified and how to implement modifications effectively, so that these systems can work jointly with others using different technologies. Other issues inherent to digital technology must be considered, such as verification and validation of the software and of the human-machine interface, which are required for its licensing. This presentation describes the current approaches for I and C modernization, the main reasons, technologies and implementation plans, focusing on the control room and on the impact on operations. The main issues to be considered for developing a specific modernization plan are analysed. The goals and status of the 'Feasibility Study of the Control Room I and C Modernization' are described. This study is currently being developed by Endesa, Iberdrola and Tecnatom, and is included

  20. Two complementary approaches to right-handed currents

    International Nuclear Information System (INIS)

    Gemmler, Katrin M.

    2012-01-01

    Flavour observables impose strong constraints on models of new physics. We study whether right-handed currents can provide a realistic extension to the Standard Model. We analyse two complementary models. These setups lead to new flavour violating interactions in the right-handed sector. We first consider a bottom-up approach assuming a left-right symmetric flavour group broken only by the Yukawa couplings. In this model the vertical stroke V ub vertical stroke problem can be solved. Secondly we study the Left-Right Model. We perform a comprehensive numerical analysis, including all known experimental constraints from ΔF=2 observables and the decay B →X s γ simultaneously. We observe that there exist regions in parameter space in accordance with the all data. In this model all flavour anomalies can be resolved except the vertical stroke V ub vertical stroke problem.

  1. OSTEOARTHRITIS: CURRENT CLINICAL CONCEPT AND SOME PROMISING THERAPEUTIC APPROACHES

    Directory of Open Access Journals (Sweden)

    A. E. Karateev

    2018-01-01

    Full Text Available In recent years, there has been a trend toward changing the clinical concept of osteoarthritis (OA. This disease has been considered as an age-related disease and the long-term result of a current pathological process for a very long time. However, many experts are now inclined to consider it necessary to identify the early, pre-X-ray stage of OA, when adequate treatment may not only halt the progression, but also achieve the regression of joint structural changes. This review deals with a number of pathogenetic and clinical aspects of the early stages of OA, which are important for timely diagnosis and pathogenetic therapy choice. It also considers some therapeutic approaches, both a "classic" and recently actively discussed methods for using platelet-rich plasma and autologous chondrocyte transplantation.

  2. Two complementary approaches to right-handed currents

    Energy Technology Data Exchange (ETDEWEB)

    Gemmler, Katrin M.

    2012-04-17

    Flavour observables impose strong constraints on models of new physics. We study whether right-handed currents can provide a realistic extension to the Standard Model. We analyse two complementary models. These setups lead to new flavour violating interactions in the right-handed sector. We first consider a bottom-up approach assuming a left-right symmetric flavour group broken only by the Yukawa couplings. In this model the vertical stroke V{sub ub} vertical stroke problem can be solved. Secondly we study the Left-Right Model. We perform a comprehensive numerical analysis, including all known experimental constraints from {Delta}F=2 observables and the decay B {yields}X{sub s}{gamma} simultaneously. We observe that there exist regions in parameter space in accordance with the all data. In this model all flavour anomalies can be resolved except the vertical stroke V{sub ub} vertical stroke problem.

  3. DIABETIC POLYNEUROPATHY: CURRENT APPROACHES TO DIAGNOSIS AND PATHOGENETIC THERAPY

    Directory of Open Access Journals (Sweden)

    O. S. Levin

    2014-07-01

    Full Text Available The paper considers the current views of the prevalence, clinical picture, approaches to the diagnosis and treatment of one of the most commonneurological complications of diabetes mellitus – diabetic polyneuropathy, and both its somatic and autonomous manifestations. Neuropathy ismost common in diabetic patients and its clinical forms reflect the severe course of diabetes mellitus and serve as an unfavorable prognostic signthat is associated with an approximately 5-fold increase in mortality. At the same time, the timely detection and adequate correction of the manifestations of neuropathy may substantially improve quality of life in the patients. The possibilities of pathogenetic therapy for diabetic polyneuropathy associated mainly with the use of benfotiamine and alpha-lipoic acid, as well as symptomatic therapy for its individual manifestationsare considered.

  4. DIABETIC POLYNEUROPATHY: CURRENT APPROACHES TO DIAGNOSIS AND PATHOGENETIC THERAPY

    Directory of Open Access Journals (Sweden)

    O. S. Levin

    2013-01-01

    Full Text Available The paper considers the current views of the prevalence, clinical picture, approaches to the diagnosis and treatment of one of the most commonneurological complications of diabetes mellitus – diabetic polyneuropathy, and both its somatic and autonomous manifestations. Neuropathy ismost common in diabetic patients and its clinical forms reflect the severe course of diabetes mellitus and serve as an unfavorable prognostic signthat is associated with an approximately 5-fold increase in mortality. At the same time, the timely detection and adequate correction of the manifestations of neuropathy may substantially improve quality of life in the patients. The possibilities of pathogenetic therapy for diabetic polyneuropathy associated mainly with the use of benfotiamine and alpha-lipoic acid, as well as symptomatic therapy for its individual manifestationsare considered.

  5. [Pharmacological treatment].

    Science.gov (United States)

    Arriola Manchola, Enrique; Álaba Trueba, Javier

    2016-06-01

    Alzheimer's disease (AD) is a chronic degenerative and inflammatory process leading to synapticdysfunction and neuronal death. A review about the pharmacological treatment alternatives is made: acetylcholinesterase inhibitors (AChEI), a nutritional supplement (Souvenaid) and Ginkgo biloba. A special emphasis on Ginkgo biloba due to the controversy about its use and the approval by the European Medicines Agency is made. Copyright © 2016 Sociedad Española de Geriatría y Gerontología. Publicado por Elsevier España, S.L.U. All rights reserved.

  6. Weight management in type 2 diabetes: current and emerging approaches to treatment.

    Science.gov (United States)

    Van Gaal, Luc; Scheen, André

    2015-06-01

    Diabetes is a growing global health concern, as is obesity. Diabetes and obesity are intrinsically linked: obesity increases the risk of diabetes and also contributes to disease progression and cardiovascular disease. Although the benefits of weight loss in the prevention of diabetes and as a critical component of managing the condition are well established, weight reduction remains challenging for individuals with type 2 diabetes due to a host of metabolic and psychological factors. For many patients, lifestyle intervention is not enough to achieve weight loss, and alternative options, such as pharmacotherapy, need to be considered. However, many traditional glucose-lowering medications may lead to weight gain. This article focuses on the potential of currently available pharmacological strategies and on emerging approaches in development to support the glycemic and weight-loss goals of individuals with type 2 diabetes. Two pharmacotherapy types are considered: those developed primarily for blood glucose control that have a favorable effect on body weight and those developed primarily to induce weight loss that have a favorable effect on blood glucose control. Finally, the potential of combination therapies for the management of obese patients with type 2 diabetes is discussed. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  7. Treatment of Thrombotic Antiphospholipid Syndrome: The Rationale of Current Management-An Insight into Future Approaches.

    Science.gov (United States)

    Chighizola, Cecilia Beatrice; Ubiali, Tania; Meroni, Pier Luigi

    2015-01-01

    Vascular thrombosis and pregnancy morbidity represent the clinical manifestations of antiphospholipid syndrome (APS), which is serologically characterized by the persistent positivity of antiphospholipid antibodies (aPL). Antiplatelet and anticoagulant agents currently provide the mainstay of APS treatment. However, the debate is still open: controversies involve the intensity and the duration of anticoagulation and the treatment of stroke and refractory cases. Unfortunately, the literature cannot provide definite answers to these controversial issues as it is flawed by many limitations, mainly due to the recruitment of patients not fulfilling laboratory and clinical criteria for APS. The recommended therapeutic management of different aPL-related clinical manifestations is hereby presented, with a critical appraisal of the evidence supporting such approaches. Cutting edge therapeutic strategies are also discussed, presenting the pioneer reports about the efficacy of novel pharmacological agents in APS. Thanks to a better understanding of aPL pathogenic mechanisms, new therapeutic targets will soon be explored. Much work is still to be done to unravel the most controversial issues about APS management: future studies are warranted to define the optimal management according to aPL risk profile and to assess the impact of a strict control of cardiovascular risk factors on disease control.

  8. Treatment of Thrombotic Antiphospholipid Syndrome: The Rationale of Current Management—An Insight into Future Approaches

    Science.gov (United States)

    Ubiali, Tania; Meroni, Pier Luigi

    2015-01-01

    Vascular thrombosis and pregnancy morbidity represent the clinical manifestations of antiphospholipid syndrome (APS), which is serologically characterized by the persistent positivity of antiphospholipid antibodies (aPL). Antiplatelet and anticoagulant agents currently provide the mainstay of APS treatment. However, the debate is still open: controversies involve the intensity and the duration of anticoagulation and the treatment of stroke and refractory cases. Unfortunately, the literature cannot provide definite answers to these controversial issues as it is flawed by many limitations, mainly due to the recruitment of patients not fulfilling laboratory and clinical criteria for APS. The recommended therapeutic management of different aPL-related clinical manifestations is hereby presented, with a critical appraisal of the evidence supporting such approaches. Cutting edge therapeutic strategies are also discussed, presenting the pioneer reports about the efficacy of novel pharmacological agents in APS. Thanks to a better understanding of aPL pathogenic mechanisms, new therapeutic targets will soon be explored. Much work is still to be done to unravel the most controversial issues about APS management: future studies are warranted to define the optimal management according to aPL risk profile and to assess the impact of a strict control of cardiovascular risk factors on disease control. PMID:26075289

  9. Current and evolving approaches for improving the oral permeability of BCS Class III or analogous molecules.

    Science.gov (United States)

    Dave, Vivek S; Gupta, Deepak; Yu, Monica; Nguyen, Phuong; Varghese Gupta, Sheeba

    2017-02-01

    The Biopharmaceutics Classification System (BCS) classifies pharmaceutical compounds based on their aqueous solubility and intestinal permeability. The BCS Class III compounds are hydrophilic molecules (high aqueous solubility) with low permeability across the biological membranes. While these compounds are pharmacologically effective, poor absorption due to low permeability becomes the rate-limiting step in achieving adequate bioavailability. Several approaches have been explored and utilized for improving the permeability profiles of these compounds. The approaches include traditional methods such as prodrugs, permeation enhancers, ion-pairing, etc., as well as relatively modern approaches such as nanoencapsulation and nanosizing. The most recent approaches include a combination/hybridization of one or more traditional approaches to improve drug permeability. While some of these approaches have been extremely successful, i.e. drug products utilizing the approach have progressed through the USFDA approval for marketing; others require further investigation to be applicable. This article discusses the commonly studied approaches for improving the permeability of BCS Class III compounds.

  10. Current Perspectives on Desmoid Tumors: The Mayo Clinic Approach

    Directory of Open Access Journals (Sweden)

    Scott Okuno

    2011-08-01

    Full Text Available Desmoid tumors are a rare group of locally aggressive, non malignant tumors of fibroblastic origin that can lead to significant morbidity due to local invasion. Despite advances in the understanding of these tumors, their natural history is incompletely understood and the optimal treatment is still a matter of debate. Local control is the main goal of treatment and there has been a change in philosophy regarding the management of these tumors from aggressive surgical resection to function preservation. A multidisciplinary approach is essential to plan local control with acceptable morbidity. The current Mayo Clinic algorithm for the treatment of these tumors is based on institutional experience and the available evidence in the literature: asymptomatic/non progressive lesions away from vital structures are managed with observation and regular imaging; primary or recurrent desmoid tumors which are symptomatic or progressive or near vital structures are managed with wide surgical resection when wide surgical margins are possible with minimal functional and cosmetic loss. When positive or close surgical margins are likely, surgical resection with adjuvant radiotherapy or definitive radiotherapy is preferred. If likely functional or cosmetic deficit is unacceptable, radiotherapy is the treatment of choice. Unresectable lesions are considered for radiotherapy, chemotherapy or newer modalities however an unresectable lesion associated with a painful, functionless, infected extremity is managed with an amputation.

  11. Current Perspectives on Desmoid Tumors: The Mayo Clinic Approach

    International Nuclear Information System (INIS)

    Joglekar, Siddharth B.; Rose, Peter S.; Sim, Franklin; Okuno, Scott; Petersen, Ivy

    2011-01-01

    Desmoid tumors are a rare group of locally aggressive, non malignant tumors of fibroblastic origin that can lead to significant morbidity due to local invasion. Despite advances in the understanding of these tumors, their natural history is incompletely understood and the optimal treatment is still a matter of debate. Local control is the main goal of treatment and there has been a change in philosophy regarding the management of these tumors from aggressive surgical resection to function preservation. A multidisciplinary approach is essential to plan local control with acceptable morbidity. The current Mayo Clinic algorithm for the treatment of these tumors is based on institutional experience and the available evidence in the literature: asymptomatic/non progressive lesions away from vital structures are managed with observation and regular imaging; primary or recurrent desmoid tumors which are symptomatic or progressive or near vital structures are managed with wide surgical resection when wide surgical margins are possible with minimal functional and cosmetic loss. When positive or close surgical margins are likely, surgical resection with adjuvant radiotherapy or definitive radiotherapy is preferred. If likely functional or cosmetic deficit is unacceptable, radiotherapy is the treatment of choice. Unresectable lesions are considered for radiotherapy, chemotherapy or newer modalities however an unresectable lesion associated with a painful, functionless, infected extremity is managed with an amputation

  12. Pubertal induction in hypogonadism: Current approaches including use of gonadotrophins.

    Science.gov (United States)

    Zacharin, Margaret

    2015-06-01

    Primary disorders of the gonad or those secondary to abnormalities of the hypothalamic pituitary axis result in hypogonadism. The range of health problems of childhood and adolescence that affect this axis has increased, as most children now survive chronic illness, but many have persisting deficits in gonadal function as a result of their underlying condition or its treatment. An integrated approach to hormone replacement is needed to optimize adult hormonal and bone health, and to offer opportunities for fertility induction and preservation that were not considered possible in the past. Timing of presentation ranges from birth, with disorders of sexual development, through adolescent pubertal failure, to adult fertility problems. This review addresses diagnosis and management of hypogonadism and focuses on new management strategies to address current concerns with fertility preservation. These include Turner syndrome, and fertility presevation prior to childhood cancer treatment. New strategies for male hormone replacement therapy that may impinge upon future fertility are emphasized. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. [Procedural pain perception of preterm newborn in neonatal intensive care unit: assessment and non-pharmacological approaches].

    Science.gov (United States)

    Bernardini, V; De Liso, P; Santoro, F; Allemand, F; Allemand, A

    2011-08-01

    The aim of this study was to evaluate the reaction to the procedural pain of preterm newborn and to demonstrate the different effectiveness of the two analgesic and not pharmacological techniques of recent clinical acquisition, the use of glucose solution and the sensorial saturation, in order to identify an optimal strategy for the prevention and pain treatment. We take a sample of 28 preterm newborns of 30-35 weeks. The subjects are divided in two randomized groups following the kind of analgesia used during the hematic sample from heel: the first group (group A) included 14 subjects, who received glucose solution associated to no nutritive suction; the second group (group B) included 14 subjects who received the sensorial saturation. The symptoms associated with pain at the moment of venous sample are measured through premature infant pain profile (PIPP) scale. Results show that the score was lower in the group treated with sensorial saturation (media 6.52; Pneonatal age could develop.

  14. Pharmacological Targeting SHP-1-STAT3 Signaling Is a Promising Therapeutic Approach for the Treatment of Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Li-Ching Fan

    2015-09-01

    Full Text Available STAT3 activation is associated with poor prognosis in human colorectal cancer (CRC. Our previous data demonstrated that regorafenib (Stivarga is a pharmacological agonist of SH2 domain-containing phosphatase 1 (SHP-1 that enhances SHP-1 activity and induces apoptosis by targeting STAT3 signals in CRC. This study aimed to find a therapeutic drug that is more effective than regorafenib for CRC treatment. Here, we showed that SC-43 was more effective than regorafenib at inducing apoptosis in vitro and suppressing tumorigenesis in vivo. SC-43 significantly increased SHP-1 activity, downregulated p-STAT3Tyr705 level, and induced apoptosis in CRC cells. An SHP-1 inhibitor or knockdown of SHP-1 by siRNA both significantly rescued the SC-43–induced apoptosis and decreased p-STAT3Tyr705 level. Conversely, SHP-1 overexpression increased the effects of SC-43 on apoptosis and p-STAT3Tyr705 level. These data suggest that SC-43–induced apoptosis mediated through the loss of p-STAT3Tyr705 was dependent on SHP-1 function. Importantly, SC-43–enhanced SHP-1 activity was because of the docking potential of SC-43, which relieved the autoinhibited N-SH2 domain of SHP-1 and inhibited p-STAT3Tyr705 signals. Importantly, we observed that a significant negative correlation existed between SHP-1 and p-STAT3Tyr705expression in CRC patients (P = .038. Patients with strong SHP-1 and weak p-STAT3Tyr705 expression had significantly higher overall survival compared with patients with weak SHP-1 and strong p-STAT3Tyr705 expression (P = .029. In conclusion, SHP-1 is suitable to be a useful prognostic marker and a pharmacological target for CRC treatment. Targeting SHP-1-STAT3 signaling by SC-43 may serve as a promising pharmacotherapy for CRC.

  15. Current approaches to nuclear power plant life management in Japan

    International Nuclear Information System (INIS)

    Noda, T.; Tajima, K.; Ishikawa, M.; Koyama, M.

    2002-01-01

    extracted additional maintenance measures and incorporated them into their long-term maintenance plans, thereby reinforcing their current maintenance activities. Considering the latest information including domestic and overseas operating experiences and knowledge of academics and experts consigned by the Minister of Economy, Trade and Industry (METI), the Nuclear and Industry Safety Agency (NISA) of the METI reviewed and studied the technical evaluation and long-term maintenance plans of these electric utility companies. This paper describes the outlines of the NISA's report and related activities on current approaches to cope with the ageing of nuclear power plants in Japan. (Note) In 2001, the MITI was reorganized to the Ministry of Economy, Trade and Industry (METI). (author)

  16. Current approach to diagnosis and treatment of delirium after cardiac surgery

    Science.gov (United States)

    Evans, Adam S.; Weiner, Menachem M.; Arora, Rakesh C.; Chung, Insung; Deshpande, Ranjit; Varghese, Robin; Augoustides, John; Ramakrishna, Harish

    2016-01-01

    Delirium after cardiac surgery remains a common occurrence that results in significant short- and long-term morbidity and mortality. It continues to be underdiagnosed given its complex presentation and multifactorial etiology; however, its prevalence is increasing given the aging cardiac surgical population. This review highlights the perioperative risk factors, tools to assist in diagnosing delirium, and current pharmacological and nonpharmacological therapy options. PMID:27052077

  17. CURRENT APPROACHES FOR RESEARCH OF MULTIPLE SCLEROSIS BIOMARKERS

    Directory of Open Access Journals (Sweden)

    Kolyada T.I

    2016-12-01

    Full Text Available Current data concerning features of multiple sclerosis (MS etiology, pathogenesis, clinical course and treatment of disease indicate the necessity of personalized approach to the management of MS patients. These features are the variety of possible etiological factors and mechanisms that trigger the development of MS, different courses of disease, and significant differences in treatment efficiency. Phenotypic and pathogenetic heterogeneity of MS requires, on the one hand, the stratification of patients into groups with different treatment depending on a number of criteria including genetic characteristics, disease course, stage of the pathological process, and forms of the disease. On the other hand, it requires the use of modern methods for assessment of individual risk of developing MS, its early diagnosis, evaluation and prognosis of the disease course and the treatment efficiency. This approach is based on the identification and determination of biomarkers of MS including the use of systems biology technology platforms such as genomics, proteomics, metabolomics and bioinformatics. Research and practical use of biomarkers of MS in clinical and laboratory practice requires the use of a wide range of modern medical and biological, mathematical and physicochemical methods. The group of "classical" methods used to study MS biomarkers includes physicochemical and immunological methods aimed at the selection and identification of single molecular biomarkers, as well as methods of molecular genetic analysis. This group of methods includes ELISA, western blotting, isoelectric focusing, immunohistochemical methods, flow cytometry, spectrophotometric and nephelometric methods. These techniques make it possible to carry out both qualitative and quantitative assay of molecular biomarkers. The group of "classical methods" can also include methods based on polymerase chain reaction (including multiplex and allele-specific PCR and genome sequencing

  18. Activation of adenosine receptors and inhibition of cyclooxygenases: two recent pharmacological approaches to modulation of radiation suppressed hematopoiesis

    International Nuclear Information System (INIS)

    Hofer, M.; Pospisil, M.; Vacek, A.; Hola, J.; Weiterova, L.; Streitova, D.; Znojil, V.

    2008-01-01

    Searching for drugs conforming to requirements for protection and/or treatment of radiation-induced damage belongs to the most important tasks of current radiobiology. In the Laboratory of Experimental Hematology, Institute of Biophysics, v.v.i., Academy of Sciences of the Czech Republic, Brno, Czech Republic, two original approaches for stimulation of radiation-suppressed hematopoiesis have been tested in recent years, namely activation of adenosine receptors and inhibition of cyclooxygenases. Non-selective activation of adenosine receptors, induced by combined administration of dipyridamole, a drug preventing adenosine uptake and supporting thus its extracellular receptor-mediated action, and adenosine monophosphate, an adenosine prodrug, has been found to stimulate hematopoiesis when the drugs were given either pre- or post-irradiation. When synthetic adenosine receptor agonists selective for individual adenosine receptor subtypes were tested, stimulatory effects in myelosuppressed mice have been found after administration of IB-MECA, a selective adenosine A3 receptor agonist. Non-selective cyclooxygenase inhibitors, inhibiting both cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2), indomethacin, diclofenac, or flurbiprofen, have been observed to act positively on radiation-perturbed hematopoiesis in sublethally irradiated mice. However, their undesirable gastrointestinal side effects have been found to negatively influence survival of lethally irradiated animals. Recently tested selective COX-2 inhibitor meloxicam, preserving protective action of COX-1-synthesized prostaglandins in the gastrointestinal tissues, has been observed to retain the hematopoiesis-stimulating effects of non-selective cyclooxygenase inhibitors and to improve the survival of animals exposed to lethal radiation doses. These findings bear evidence for the possibility to use selective adenosine A3 receptor agonists and selective COX-2 inhibitors in human practice for treatment of

  19. Current pharmacotherapeutic approaches for the treatment of Tourette syndrome.

    Science.gov (United States)

    Egolf, A; Coffey, B J

    2014-02-01

    Tourette syndrome is a childhood onset neurodevelopmental disorder characterized by multiple motor and vocal tics. Although many youth experience attenuation or even remission of tics in adolescence and young adulthood, some individuals experience persistent tics which can be debilitating or disabling. The majority of patients also have one or more psychiatric comorbid disorders, such as attention deficit hyperactivity disorder and/or obsessive-compulsive disorder. Treatment is multimodal, including both pharmacotherapy and cognitive behavioral treatment, and requires disentanglement of tics and the comorbid symptoms. Although the only two formally approved medications in the United States are haloperidol and pimozide, these treatments are generally not used as first-line interventions due to their significant potential for adverse effects. The α-adrenoceptor agonists guanfacine and clonidine have an established evidence base for both efficacy and tolerability, and are usually recommended as initial pharmacotherapy. Atypical neuroleptics, such as aripiprazole or risperidone, are typically used if the α-adrenoceptor agonists are ineffective or intolerable. However, many other pharmacological agents reviewed in this manuscript have been studied as treatment alternatives. Copyright 2014 Prous Science, S.A.U. or its licensors. All rights reserved.

  20. MELiSSA Food Characterization general approach and current status

    Science.gov (United States)

    Weihreter, Martin; Chaerle, Laury; Secco, Benjamin; Molders, Katrien; van der Straeten, Dominique; Duliere, Eric; Pieters, Serge; Maclean, Heather; Dochain, Denis; Quinet, Muriel; Lutts, Stanley; Graham, Thomas; Stasiak, Michael; Rondeau Vuk, Theresa; Zheng, Youbin; Dixon, Mike; Laniau, Martine; Larreture, Alain; Timsit, Michel; Aronne, Giovanna; Barbieri, Giancarlo; Buonomo, Roberta; Veronica; Paradiso, Roberta; de Pascale, Stafania; Galbiati, Massimo; Troia, A. R.; Nobili, Matteo; Bucchieri, Lorenzo; Page, Valérie; Feller, Urs; Lasseur, Christophe

    . Available MELiSSA closed environment crop growth data were used to develop a first photosynthetic model representing the basic carbon fixation mechanisms. This model will be further elaborated in the course of this study to predict yield, oxygen production and transpi-ration. As an ultimate goal the model is intended to simulate the composition of the different plant organs (root, shoot, fruit/seed or tuber) for each crop under various conditions. For the validation of this model an extensive amount of data sets are needed. Current plant growth bench test setups will provide part of the required data. To gain more precise and detailed datasets, a highly closed plant growth chamber (Plant Characterization Unit, PCU) is under development. The PCU will provide accurate mass balances for carbon, water, oxygen and other elements with statistical reliability. This reliability is achieved through a high degree of closure and environment homogeneity. The PCU will also provide data for the above described plant characterization studies. The general work approach, the current status and future steps will be illustrated.

  1. Systems Pharmacology in Small Molecular Drug Discovery

    Directory of Open Access Journals (Sweden)

    Wei Zhou

    2016-02-01

    Full Text Available Drug discovery is a risky, costly and time-consuming process depending on multidisciplinary methods to create safe and effective medicines. Although considerable progress has been made by high-throughput screening methods in drug design, the cost of developing contemporary approved drugs did not match that in the past decade. The major reason is the late-stage clinical failures in Phases II and III because of the complicated interactions between drug-specific, human body and environmental aspects affecting the safety and efficacy of a drug. There is a growing hope that systems-level consideration may provide a new perspective to overcome such current difficulties of drug discovery and development. The systems pharmacology method emerged as a holistic approach and has attracted more and more attention recently. The applications of systems pharmacology not only provide the pharmacodynamic evaluation and target identification of drug molecules, but also give a systems-level of understanding the interaction mechanism between drugs and complex disease. Therefore, the present review is an attempt to introduce how holistic systems pharmacology that integrated in silico ADME/T (i.e., absorption, distribution, metabolism, excretion and toxicity, target fishing and network pharmacology facilitates the discovery of small molecular drugs at the system level.

  2. Pharmacologic therapy for acute pancreatitis

    Science.gov (United States)

    Kambhampati, Swetha; Park, Walter; Habtezion, Aida

    2014-01-01

    While conservative management such as fluid, bowel rest, and antibiotics is the mainstay of current acute pancreatitis management, there is a lot of promise in pharmacologic therapies that target various aspects of the pathogenesis of pancreatitis. Extensive review of preclinical studies, which include assessment of therapies such as anti-secretory agents, protease inhibitors, anti-inflammatory agents, and anti-oxidants are discussed. Many of these studies have shown therapeutic benefit and improved survival in experimental models. Based on available preclinical studies, we discuss potential novel targeted pharmacologic approaches that may offer promise in the treatment of acute pancreatitis. To date a variety of clinical studies have assessed the translational potential of animal model effective experimental therapies and have shown either failure or mixed results in human studies. Despite these discouraging clinical studies, there is a great clinical need and there exist several preclinical effective therapies that await investigation in patients. Better understanding of acute pancreatitis pathophysiology and lessons learned from past clinical studies are likely to offer a great foundation upon which to expand future therapies in acute pancreatitis. PMID:25493000

  3. Beyond (eco)design : Current approaches to sustainable packaging design

    NARCIS (Netherlands)

    Wever, R.

    2014-01-01

    Packaging has always received a lot of attention within the field of design for sustainability. The classical approach has been to mainly focus on reducing the impact of the packaging. This approach stems from the ill-informed position that packaging is superfluous, or at best there only for

  4. A current approach to heart failure in Duchenne muscular dystrophy.

    Science.gov (United States)

    D'Amario, Domenico; Amodeo, Antonio; Adorisio, Rachele; Tiziano, Francesco Danilo; Leone, Antonio Maria; Perri, Gianluigi; Bruno, Piergiorgio; Massetti, Massimo; Ferlini, Alessandra; Pane, Marika; Niccoli, Giampaolo; Porto, Italo; D'Angelo, Gianluca A; Borovac, Josip Anđelo; Mercuri, Eugenio; Crea, Filippo

    2017-11-01

    Duchenne muscular dystrophy (DMD) is a genetic, progressive neuromuscular condition that is marked by the long-term muscle deterioration with significant implications of pulmonary and cardiac dysfunction. As such, end-stage heart failure (HF) in DMD is increasingly becoming the main cause of death in this population. The early detection of cardiomyopathy is often challenging, due to a long subclinical phase of ventricular dysfunction and difficulties in assessment of cardiovascular symptomatology in these patients who usually loose ambulation during the early adolescence. However, an early diagnosis of cardiovascular disease in patients with DMD is decisive since it allows a timely initiation of cardioprotective therapies that can mitigate HF symptoms and delay detrimental heart muscle remodelling. Echocardiography and ECG are standardly used for screening and detection of cardiovascular abnormalities in these patients, although these tools are not always adequate to detect an early, clinically asymptomatic phases of disease progression. In this regard, cardiovascular magnetic resonance (CMR) with late gadolinium enhancement is emerging as a promising method for the detection of early cardiac involvement in patients with DMD. The early detection of cardiac dysfunction allows the therapeutic institution of various classes of drugs such as corticosteroids, beta-blockers, ACE inhibitors, antimineralocorticoid diuretics and novel pharmacological and surgical solutions in the multimodal and multidisciplinary care for this group of patients. This review will focus on these challenges and available options for HF in patients with DMD. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  5. New Approaches to Circulating Current Controllers for Modular Multilevel Converters

    Directory of Open Access Journals (Sweden)

    Miguel Moranchel

    2017-01-01

    Full Text Available In the next years, modular multilevel converters (MMCs are going to be a next generation multilevel converters for medium to high voltage conversion applications, such as medium voltage motor drives, medium voltage flexible AC transmission systems (FACTS and high voltage direct current transmission. They provide advantages such as high modularity, availability, low generation of harmonics, etc. However, the circulating current distorts the leg currents and increases the rated current of power devices, which further increases system cost. This paper focuses on analysis and suppression of these currents in a MMC using two algorithms for tracking of harmonics. For this work resonant controllers and repetitive controllers have been selected. Both controllers are analyzed and simulations results are presented. Moreover, the controllers have been tested and validated for a three phase MMC operating as an inverter using a real processing platform based on Zynq by Xilinx and designed to control large multilevel converters and in a real MMC prototype. These results are provided to demonstrate the feasibility of the proposed method.

  6. An evaluation of current approaches to nursing home capital reimbursement.

    Science.gov (United States)

    Cohen, J; Holahan, J

    1986-01-01

    One of the more controversial issues in reimbursement policy is how to set the capital cost component of facilities rates. In this article we examine in detail the various approaches used by states to reimburse nursing homes for capital costs. We conclude that newer approaches that recognize the increasing value of nursing home assets over time, commonly called fair rental systems, are preferable to the methodologies that have been used historically in both the Medicare and the Medicaid programs to set capital rates. When properly designed, fair rental systems should provide more rational incentives and less encouragement of property manipulation than do more traditional systems, with little or no increase in state costs.

  7. Space Pharmacology

    CERN Document Server

    Wotring, Virginia E

    2012-01-01

    “Space Pharmacology” is a review of the current knowledge regarding the use of pharmaceuticals during spaceflights. It is a comprehensive review of the literature, addressing each area of pharmacokinetics and each major physiological system in turn. Every section begins with a topic overview, and is followed by a discussion of published data from spaceflight, and from ground experiments meant to model the spaceflight situation. Includes a discussion looking forward to the new medical challenges we are likely to face on longer duration exploration missions. This book is a snapshot of our current knowledge that also highlights areas of unknown.

  8. Current approach to diagnosis and management of osteoarthritis ...

    African Journals Online (AJOL)

    There is extreme variability in presentation at different joint sites and between individuals. Management of OA involves a comprehensive approach consisting of preventative measures and numerous therapeutic modalities which should be tailored to individual needs. The family practitioner plays a vital role in the diagnosis ...

  9. A Progressive Approach to Discrete Trial Teaching: Some Current Guidelines

    Science.gov (United States)

    Leaf, Justin B.; Cihon, Joseph H.; Leaf, Ronald; McEachin, John; Taubman, Mitchell

    2016-01-01

    Discrete trial teaching (DTT) is one of the cornerstones of applied behavior analysis (ABA) based interventions. Conventionally, DTT is commonly implemented within a prescribed, fixed manner in which the therapist is governed by a strict set of rules. In contrast to conventional DTT, a progressive approach to DTT allows the therapist to remain…

  10. Ewing Sarcoma: Current Management and Future Approaches Through Collaboration

    NARCIS (Netherlands)

    Gaspar, Nathalie; Hawkins, Douglas S.; Dirksen, Uta; Lewis, Ian J.; Ferrari, Stefano; Le Deley, Marie-Cecile; Kovar, Heinrich; Grimer, Robert; Whelan, Jeremy; Claude, Line; Delattre, Olivier; Paulussen, Michael; Picci, Piero; Sundby Hall, Kirsten; van den Berg, Hendrik; Ladenstein, Ruth; Michon, Jean; Hjorth, Lars; Judson, Ian; Luksch, Roberto; Bernstein, Mark L.; Marec-Bérard, Perrine; Brennan, Bernadette; Craft, Alan W.; Womer, Richard B.; Juergens, Heribert; Oberlin, Odile

    2015-01-01

    Ewing sarcoma (ES) is an aggressive sarcoma of bone and soft tissue occurring at any age with a peak incidence in adolescents and young adults. The treatment of ES relies on a multidisciplinary approach, coupling risk-adapted intensive neoadjuvant and adjuvant chemotherapies with surgery and/or

  11. Current approaches to gastric cancer in Peru and Mexico.

    Science.gov (United States)

    Santos, Erlan

    2017-01-01

    In Peru, the incidence of gastric cancer is reported to be around 15.8 per 100,000 inhabitants and it is the second most common oncological disease in men and the third one in women. Additionally, a high mortality index was reported, especially among poor people. To address this issue, in 2008, Peru initiated several insurance treatment plans of oncological diseases with promising results. In Mexico, there is a high predominance of gastric cancer in male gender compared to female gender, even reaching a 2/1 ratio, and the detection rate of early gastric cancer is low (10% to 20%) which results in a mainly palliative treatment with an overall survival rate in 5 years about 10% to 15% only. In Peru, the average age at diagnosis is around 62.96±14.75 years old and the most frequent symptoms includes abdominal pain, indigestion, loss of appetite, weight loss and gastrointestinal bleeding, while in Mexico, some studies reported an average age at diagnosis around 60.3±4.1 years old (range, 23-78 years old) and the most frequent symptoms were postprandial fullness (74.4%), abdominal pain (37.2%), weight loss (18.6%), and melena (4.6%). The anemia rate was 65.1% with a mean Hb level of 6.14 g/dL. In Peru, the most common gastric cancer type is the intestinal-type adenocarcinoma (around 34%), followed by the diffuse-type adenocarcinoma (18.7%), whilst among Mexicans, the diffuse-type was reported in 55.2% of cases, the intestinal-type was reported in 28.2% and the undifferentiated-type corresponded to 6%. In both, Peru and Mexico, 90% of the associated factors includes tabaquismo, diets rich in salt, smoked foods, and a sedentary lifestyle. Family inheritance and advanced age and pharmacological-resistant Helicobacter pylori infection are also important. Poverty has been heavily associated with a higher incidence of gastric cancer. The management of gastric cancer patients in Peru is carried out by general surgeons or general surgical oncologists. In recent years, efforts

  12. Experimental typography : reviewing the modernist and the current approaches

    OpenAIRE

    Makal, Eray

    1993-01-01

    Ankara : The Department of Graphic Design and Institute of Fine Arts, Bilkent Univ., 1993. Thesis (Master's) -- Bilkent University, 1993. Includes bibliographical references leaves 65-66. The intention of this study is to evaluate the experimental typography within the history of graphic design by taking in consideration of two epochs. The Modernist and The Current. Makal, Eray M.S.

  13. Forecasting Water Waves and Currents: A Space-time Approach

    NARCIS (Netherlands)

    Ambati, V.R.

    2008-01-01

    Forecasting water waves and currents in near shore and off shore regions of the seas and oceans is essential to maintain and protect our environment and man made structures. In wave hydrodynamics, waves can be classified as shallow and deep water waves based on its water depth. The mathematical

  14. Online Learning Integrity Approaches: Current Practices and Future Solutions

    Science.gov (United States)

    Lee-Post, Anita; Hapke, Holly

    2017-01-01

    The primary objective of this paper is to help institutions respond to the stipulation of the Higher Education Opportunity Act of 2008 by adopting cost-effective academic integrity solutions without compromising the convenience and flexibility of online learning. Current user authentication solutions such as user ID and password, security…

  15. Methodological Approaches in Conducting Overviews: Current State in HTA Agencies

    Science.gov (United States)

    Pieper, Dawid; Antoine, Sunya-Lee; Morfeld, Jana-Carina; Mathes, Tim; Eikermann, Michaela

    2014-01-01

    Objectives: Overviews search for reviews rather than for primary studies. They might have the potential to support decision making within a shorter time frame by reducing production time. We aimed to summarize available instructions for authors intending to conduct overviews as well as the currently applied methodology of overviews in…

  16. Religious Approaches on Business Ethics: Current Situation and Future Perspectives

    OpenAIRE

    Melé, Domènec

    2015-01-01

    The Business Ethics Movement began in the mid-1970s. For the first two decades philosophical theories were dominant, but in recent years an increasing presence of religious approaches, in both empirical and conceptual research, can be noted, in spite of some objections to the presence of religions in the business ethics field. Empirical research, generally based on psychological and sociological studies, shows the influence of religious faith on several business issues. Conceptual research in...

  17. Current diagnostic approach of bone tumors in childhood

    International Nuclear Information System (INIS)

    Torre, Marcia Barbosa; Scatigno Neto, Andre

    1995-01-01

    The authors analyze the magnetic resonance imaging (MRI) as the imaging modality of choice for evaluation of patients with bone tumors or soft tissue tumors. The advent of such a sensitive imaging modality is fortuitous and coincides with a recent change in the therapeutic approach to primary bone tumors. MRI is extremely valuable in monitoring the tumor response to the initial chemotherapy and is accurate defining the margins of tumor, facilitating planning of limb salvage surgical procedures. (author). 5 refs., 8 figs

  18. Implementation of the RCM approach at EDF NPPs: Current status

    International Nuclear Information System (INIS)

    Dubreuil-Chambardel, A.; Martin-Onraet, M.; Degrave, C.

    2001-01-01

    To ensure safest possible operation and to get best overall economic performance of its Nuclear Power Plants, 10 years ago Electricite de France launched a Reliability Centered Maintenance (RCM) project to optimize the preventive maintenance programs. The principles underlying the RCM approach are based on common sense: failures must be prevented by preventive maintenance operations in all cases when the repercussions for the installation could be serious or critical in term of safety, availability or maintenance costs. The approach is a 3-phases process: 1. Evaluation of the functional consequences of failures 2. Evaluation of performances based on the analysis of experience feedback 3. Optimization of the preventive maintenance tasks The new preventive maintenance programs are presently almost completed and progressively implemented. Here and now, the implementation of the RCM approach allows to emphasize some benefits: 1. Same or increased level of safety 2. Same or increased level of plant availability 3. ALARA principles better taken into account 4. Cost control 5. Positive change in maintenance culture. Some new studies are in progress, such as the development of a 'Risk Based In Service Inspection' for passive components. (author)

  19. Treatment for spasmodic dysphonia: limitations of current approaches

    Science.gov (United States)

    Ludlow, Christy L.

    2009-01-01

    Purpose of review Although botulinum toxin injection is the gold standard for treatment of spasmodic dysphonia, surgical approaches aimed at providing long-term symptom control have been advancing over recent years. Recent findings When surgical approaches provide greater long-term benefits to symptom control, they also increase the initial period of side effects of breathiness and swallowing difficulties. However, recent analyses of quality-of-life questionnaires in patients undergoing regular injections of botulinum toxin demonstrate that a large proportion of patients have limited relief for relatively short periods due to early breathiness and loss-of-benefit before reinjection. Summary Most medical and surgical approaches to the treatment of spasmodic dysphonia have been aimed at denervation of the laryngeal muscles to block symptom expression in the voice, and have both adverse effects as well as treatment benefits. Research is needed to identify the central neuropathophysiology responsible for the laryngeal muscle spasms in order target treatment towards the central neurological abnormality responsible for producing symptoms. PMID:19337127

  20. A "genome-to-lead" approach for insecticide discovery: pharmacological characterization and screening of Aedes aegypti D(1-like dopamine receptors.

    Directory of Open Access Journals (Sweden)

    Jason M Meyer

    2012-01-01

    Full Text Available BACKGROUND: Many neglected tropical infectious diseases affecting humans are transmitted by arthropods such as mosquitoes and ticks. New mode-of-action chemistries are urgently sought to enhance vector management practices in countries where arthropod-borne diseases are endemic, especially where vector populations have acquired widespread resistance to insecticides. METHODOLOGY/PRINCIPAL FINDINGS: We describe a "genome-to-lead" approach for insecticide discovery that incorporates the first reported chemical screen of a G protein-coupled receptor (GPCR mined from a mosquito genome. A combination of molecular and pharmacological studies was used to functionally characterize two dopamine receptors (AaDOP1 and AaDOP2 from the yellow fever mosquito, Aedes aegypti. Sequence analyses indicated that these receptors are orthologous to arthropod D(1-like (Gα(s-coupled receptors, but share less than 55% amino acid identity in conserved domains with mammalian dopamine receptors. Heterologous expression of AaDOP1 and AaDOP2 in HEK293 cells revealed dose-dependent responses to dopamine (EC(50: AaDOP1 = 3.1±1.1 nM; AaDOP2 = 240±16 nM. Interestingly, only AaDOP1 exhibited sensitivity to epinephrine (EC(50 = 5.8±1.5 nM and norepinephrine (EC(50 = 760±180 nM, while neither receptor was activated by other biogenic amines tested. Differential responses were observed between these receptors regarding their sensitivity to dopamine agonists and antagonists, level of maximal stimulation, and constitutive activity. Subsequently, a chemical library screen was implemented to discover lead chemistries active at AaDOP2. Fifty-one compounds were identified as "hits," and follow-up validation assays confirmed the antagonistic effect of selected compounds at AaDOP2. In vitro comparison studies between AaDOP2 and the human D(1 dopamine receptor (hD(1 revealed markedly different pharmacological profiles and identified amitriptyline and doxepin as AaDOP2

  1. Compared effects of missense mutations in Very-Long-Chain Acyl-CoA Dehydrogenase deficiency: Combined analysis by structural, functional and pharmacological approaches.

    Science.gov (United States)

    Gobin-Limballe, Stéphanie; McAndrew, Ryan P; Djouadi, Fatima; Kim, Jung-Ja; Bastin, Jean

    2010-05-01

    Very-Long-Chain Acyl-CoA Dehydrogenase deficiency (VLCADD) is an autosomal recessive disorder considered as one of the more common ss-oxidation defects, possibly associated with neonatal cardiomyopathy, infantile hepatic coma, or adult-onset myopathy. Numerous gene missense mutations have been described in these VLCADD phenotypes, but only few of them have been structurally and functionally analyzed, and the molecular basis of disease variability is still poorly understood. To address this question, we first analyzed fourteen disease-causing amino acid changes using the recently described crystal structure of VLCAD. The predicted effects varied from the replacement of amino acid residues lining the substrate binding cavity, involved in holoenzyme-FAD interactions or in enzyme dimerisation, predicted to have severe functional consequences, up to amino acid substitutions outside key enzyme domains or lying on near enzyme surface, with predicted milder consequences. These data were combined with functional analysis of residual fatty acid oxidation (FAO) and VLCAD protein levels in patient cells harboring these mutations, before and after pharmacological stimulation by bezafibrate. Mutations identified as detrimental to the protein structure in the 3-D model were generally associated to profound FAO and VLCAD protein deficiencies in the patient cells, however, some mutations affecting FAD binding or monomer-monomer interactions allowed a partial response to bezafibrate. On the other hand, bezafibrate restored near-normal FAO rates in some mutations predicted to have milder consequences on enzyme structure. Overall, combination of structural, biochemical, and pharmacological analysis allowed assessment of the relative severity of individual mutations, with possible applications for disease management and therapeutic approach. Copyright 2010 Elsevier B.V. All rights reserved.

  2. Pharmacological approach to the mechanisms of transcranial DC-stimulation-induced after-effects of human motor cortex excitability.

    Science.gov (United States)

    Liebetanz, David; Nitsche, Michael A; Tergau, Frithjof; Paulus, Walter

    2002-10-01

    Weak transcranial direct current stimulation (tDCS) induces persisting excitability changes in the human motor cortex. These plastic excitability changes are selectively controlled by the polarity, duration and current strength of stimulation. To reveal the underlying mechanisms of direct current (DC)-induced neuroplasticity, we combined tDCS of the motor cortex with the application of Na(+)-channel-blocking carbamazepine (CBZ) and the N-methyl-D-aspartate (NMDA)-receptor antagonist dextromethorphan (DMO). Monitored by transcranial magnetic stimulation (TMS), motor cortical excitability changes of up to 40% were achieved in the drug-free condition. Increase of cortical excitability could be selected by anodal stimulation, and decrease by cathodal stimulation. Both types of excitability change lasted several minutes after cessation of current stimulation. DMO suppressed the post-stimulation effects of both anodal and cathodal DC stimulation, strongly suggesting the involvement of NMDA receptors in both types of DC-induced neuroplasticity. In contrast, CBZ selectively eliminated anodal effects. Since CBZ stabilizes the membrane potential voltage-dependently, the results reveal that after-effects of anodal tDCS require a depolarization of membrane potentials. Similar to the induction of established types of short- or long-term neuroplasticity, a combination of glutamatergic and membrane mechanisms is necessary to induce the after-effects of tDCS. On the basis of these results, we suggest that polarity-driven alterations of resting membrane potentials represent the crucial mechanisms of the DC-induced after-effects, leading to both an alteration of spontaneous discharge rates and to a change in NMDA-receptor activation.

  3. Current approaches to treatments for schizophrenia spectrum disorders, part I: an overview and medical treatments

    Directory of Open Access Journals (Sweden)

    Chien WT

    2013-09-01

    Full Text Available Wai Tong Chien, Annie LK Yip School of Nursing, Faculty of Health and Social Sciences, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong Abstract: During the last three decades, an increasing understanding of the etiology, psychopathology, and clinical manifestations of schizophrenia spectrum disorders, in addition to the introduction of second-generation antipsychotics, has optimized the potential for recovery from the illness. Continued development of various models of psychosocial intervention promotes the goal of schizophrenia treatment from one of symptom control and social adaptation to an optimal restoration of functioning and/or recovery. However, it is still questionable whether these new treatment approaches can address the patients' needs for treatment and services and contribute to better patient outcomes. This article provides an overview of different treatment approaches currently used in schizophrenia spectrum disorders to address complex health problems and a wide range of abnormalities and impairments resulting from the illness. There are different treatment strategies and targets for patients at different stages of the illness, ranging from prophylactic antipsychotics and cognitive–behavioral therapy in the premorbid stage to various psychosocial interventions in addition to antipsychotics for relapse prevention and rehabilitation in the later stages of the illness. The use of antipsychotics alone as the main treatment modality may be limited not only in being unable to tackle the frequently occurring negative symptoms and cognitive impairments but also in producing a wide variety of adverse effects to the body or organ functioning. Because of varied pharmacokinetics and treatment responsiveness across agents, the medication regimen should be determined on an individual basis to ensure an optimal effect in its long-term use. This review also highlights that the recent practice guidelines and standards have

  4. Treatment for primary hypothyroidism: current approaches and future possibilities

    Science.gov (United States)

    Chakera, Ali J; Pearce, Simon HS; Vaidya, Bijay

    2012-01-01

    Primary hypothyroidism is the most common endocrine disease. Although the diagnosis and treatment of hypothyroidism is often considered simple, there are large numbers of people with this condition who are suboptimally treated. Even in those people with hypothyroidism who are biochemically euthyroid on levothyroxine replacement there is a significant proportion who report poorer quality of life. This review explores the historical and current treatment options for hypothyroidism, reasons for and potential solutions to suboptimal treatment, and future possibilities in the treatment of hypothyroidism. PMID:22291465

  5. Current approaches to antithrombotic therapy in patients with cardioembolic stroke

    Directory of Open Access Journals (Sweden)

    Oleg Ivanovich Vinogradov

    2013-01-01

    Full Text Available The rate of cardiogenic embolism among all ischemic strokes is as high as 38%. Cardioembolic strokes are characterized by the higher magnitude of neurological deficit, the high risk of recurrent acute stroke, and a lethal outcome. This review deals with the etiopathogenesis of thrombus formation in the heart chambers, with current criteria for the verification of cardioembolic strokes, with the results of trials of new oral anticoagulants, and latest guidelines for antithrombotic therapy to prevent stroke. Special focus is given to secondary stroke prevention in patients with nonvalvular atrial fibrillation since it is atrial fibrillation that is the most common cause of cardioembolic stroke.

  6. Current approach for urinary system stone disease in pregnant women

    Directory of Open Access Journals (Sweden)

    Orcun Celik

    2016-01-01

    Full Text Available Urinary system stones can be classified according to size, location, X-ray characteristics, aetiology of formation, composition, and risk of recurrence. Especially urolithiasis during pregnancy is a diagnostic and therapeutic challenge. In most cases, it becomes symptomatic in the second or third trimester. Diagnostic options in pregnant women are limited due to the possible teratogenic, carcinogenic, and mutagenic risk of foetal radiation exposure. Clinical management of a pregnant urolithiasis patient is complex and demands close collaboration between patient, obstetrician and urologist. We would like to review current diagnosis and treatment modalities of stone disease of pregnant woman.

  7. Current concepts and future approaches to vestibular rehabilitation.

    Science.gov (United States)

    Tjernström, Fredrik; Zur, Oz; Jahn, Klaus

    2016-04-01

    Over the last decades methods of vestibular rehabilitation to enhance adaptation to vestibular loss, habituation to changing sensory conditions, and sensory reweighting in the compensation process have been developed. However, the use of these techniques still depends to a large part on the educational background of the therapist. Individualized assessment of deficits and specific therapeutic programs for different disorders are sparse. Currently, vestibular rehabilitation is often used in an unspecific way in dizzy patients irrespective of the clinical findings. When predicting the future of vestibular rehabilitation, it is tempting to foretell advances in technology for assessment and treatment only, but the current intense exchange between clinicians and basic scientists also predicts advances in truly understanding the complex interactions between the peripheral senses and central adaptation mechanisms. More research is needed to develop reliable techniques to measure sensory dependence and to learn how this knowledge can be best used--by playing off the patient's sensory strength or working on the weakness. To be able using the emerging concepts, the neuro-otological community must strive to educate physicians, physiotherapists and nurses to perform the correct examinations for assessment of individual deficits and to look for factors that might impede rehabilitation.

  8. Ebola virus vaccines: an overview of current approaches

    Science.gov (United States)

    Marzi, Andrea; Feldmann, Heinz

    2016-01-01

    Ebola hemorrhagic fever is one of the most fatal viral diseases worldwide affecting humans and nonhuman primates. Although infections only occur frequently in Central Africa, the virus has the potential to spread globally and is classified as a category A pathogen that could be misused as a bioterrorism agent. As of today there is no vaccine or treatment licensed to counteract Ebola virus infections. DNA, subunit and several viral vector approaches, replicating and non-replicating, have been tested as potential vaccine platforms and their protective efficacy has been evaluated in nonhuman primate models for Ebola virus infections, which closely resemble disease progression in humans. Though these vaccine platforms seem to confer protection through different mechanisms, several of them are efficacious against lethal disease in nonhuman primates attesting that vaccination against Ebola virus infections is feasible. PMID:24575870

  9. [Our current approach in the treatment of sigmoid colon volvulus].

    Science.gov (United States)

    Taviloğlu, Korhan; Aydin, Erol; Ertekin, Cemalettin; Güloğlu, Recep; Kurtoğlu, Mehmet

    2002-04-01

    Our aim was to emphasize the role of endoscopic detorsion in the treatment of sigmoid colon volvulus, which we currently apply in the majority of our cases. The data of 37 patients were analyzed in a retrospective manner, during a 86-month period, between May 1994 and July 2001. The patients were classified into three groups. The first group consisted of 9 patients with resection and anastomosis, the second group consisted of 20 patients with Hartmann's procedure, and the third group consisted of 8 patients with endoscopic detorsion. Complications were encountered in 7 patients (19%), and 3 patients (8%) died following treatment. We favor colonic resection following endoscopic treatment. Resection should be preferred, if endoscopic detorsion is not successful or in the presence of a complication.

  10. Current approaches and future directions in the treatment of leprosy

    Directory of Open Access Journals (Sweden)

    Worobec SM

    2012-08-01

    Full Text Available Sophie M WorobecDepartment of Dermatology, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, USAAbstract: This review surveys current treatments and future treatment trends in leprosy from a clinical perspective. The World Health Organization provides a multidrug treatment regimen that targets the Mycobacterium leprae bacillus which causes leprosy. Several investigational drugs are available for the treatment of drug-resistant M. leprae. Future directions in leprosy treatment will focus on: the molecular signaling mechanism M. leprae uses to avoid triggering an immune response; prospective studies of the side effects experienced during multiple-drug therapy; recognition of relapse rates post-completion of designated treatments; combating multidrug resistance; vaccine development; development of new diagnostic tests; and the implications of the recent discovery of a genetically distinct leprosy-causing bacillus, Mycobacterium lepromatosis.Keywords: epidemiology, leprosy, Hansen’s disease, multidrug resistance, multidrug therapy

  11. The trilayer approach of teaching physiology, pathophysiology, and pharmacology concepts in a first-year pharmacy course: the TLAT model.

    Science.gov (United States)

    Islam, Mohammed A; Sabnis, Gauri; Farris, Fred

    2017-09-01

    This paper describes the development, implementation, and students' perceptions of a new trilayer approach of teaching (TLAT). The TLAT model involved blending lecture, in-class group activities, and out-of-class assignments on selected content areas and was implemented initially in a first-year integrated pharmacy course. Course contents were either delivered by traditional lectures or by the TLAT. A survey instrument was distributed by SurveyMonkey to determine students' perceptions of the TLAT model. Descriptive statistics were used for data analysis. Students' performance in a total of 225 examination and quiz questions was analyzed to evaluate whether the TLAT model improved students' learning. Students' ( n = 98) performance scores for TLAT-based and lecture-based questions were 83.3 ± 10.2 and 79.5 ± 14.0, respectively ( P Physiological Society.

  12. Current approaches to challenging scenarios in myeloproliferative neoplasms.

    Science.gov (United States)

    Zimran, Eran; Hoffman, Ronald; Kremyanskaya, Marina

    2018-06-01

    The Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) including polycythemia vera, essential thrombocythemia and primary myelofibrosis are clonal hematological malignancies that originate at the level of the hematopoietic stem cell, and are characterized by excessive proliferation of cells belonging to one or more of the myeloid lineages. Central to the pathogenesis of the MPNs is constitutive activation of the JAK/STAT signaling pathway due to a family of driver mutations affecting JAK2, CALR or MPL. These disorders share common clinical and laboratory features, a significant burden of systemic symptoms, increased risk of developing arterial and venous thrombotic events, and the potential to progress to myelofibrosis and acute leukemia. Areas covered: We identified four clinical situations which represent challenging management dilemmas for patients with MPNs. Our conclusions and recommendations are based on a literature search using MEDLINE and recent meeting abstracts using the keywords, focusing on publications directly addressing these scenarios and on recent contributions to the field. Expert commentary: Multi-center efforts to study large cohorts of MPN patients have led to more uniform and evidence-based approaches to key aspects in MPN management. However, treatment strategies to deal with specific clinical scenarios are lacking.

  13. Current approach to the treatment of chronic myeloid leukaemia.

    Science.gov (United States)

    Pasic, Ivan; Lipton, Jeffrey H

    2017-04-01

    Of all the cancers, chronic myeloid leukaemia (CML) has witnessed the most rapid evolution of the therapeutic milieu in recent decades. The introduction of tyrosine kinase inhibitors (TKIs) as a therapeutic option has profoundly changed patient experience and outcome. The availability of multiple new highly effective therapies has increasingly underscored the importance of a good understanding of the underlying pathophysiological basis in CML, as well as patient-specific factors in choosing the right treatment for every individual. The treatment of CML has migrated in many jurisdictions from the office of a highly specialized malignant hematologist to the general hematologist or even a general practitioner. The goal of this review is to offer an overview of the modern approach to the treatment of CML, with an emphasis on chronic phase (CP) CML, including both TKI-based therapies such as imatinib, dasatinib, nilotinib, bosutinib and ponatinib, and non-TKI medications, such as omacetaxine. We discuss evidence behind each drug, most common and material adverse reactions and outline how this information can be used in selecting the right drug for the right patient. We also discuss evidence as it relates to other therapies, including stem cell transplant (SCT), and patients in accelerated (AP) and blastic phase (BP). Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. New approaches to business cycle theory in current economic science

    Directory of Open Access Journals (Sweden)

    Monica DOBRESCU

    2012-07-01

    Full Text Available In modern economies, current research generally acknowledges that the central issues in macroeconomics are essentially the same as those identified by Keynes in the General Theory of Employment, Interest and Money. One way or the other, economists are trying to address the same macroeconomic issues that they did seven decades ago: How can we account for the different growth rates and various fluctuations observed in national economies? Which are the economic policies most suitable to solve the issues of growth and cyclic behavior? Both the new classicals and the new Keynesians have made considerable progress within their research paradigms: to explain economic fluctuations, the new classicals focus on technological perturbations, the intertemporal substitution of leisure and real business cycles; on the other hand, the new Keynesians speak in terms of monopolistic competition, menu costs or efficiency wages. On the whole, the new classicals believe that the business cycle can best be understood within the market-clearing model, whereas the new keynesians believe that business fluctuations are due to certain market failures of various sorts.The present paper focuses on the main directions of research of the new classical school on the business cycle, given that the theoretical progress in this field has been significant and relevant for economic policy during the past four decades.

  15. Current approaches to diagnosing and treating major neurocognitive disorder

    Directory of Open Access Journals (Sweden)

    A. A. Kulesh

    2017-01-01

    Full Text Available The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5 replaces the term «dementia» with «major neurocognitive disorder» (MNCD, which can reduce the  stigmatization of patients and focus the attention of specialists on  the preserved abilities of patients rather than deficit symptoms. In  the next 35 years, the number of patients with MNCD in the world is  predicted to almost triple. The article considers the concept,  epidemiology, and etiological pattern of this syndrome. It  characterizes in detail Alzheimer's disease (AD that is a cause of  MNCD in 50–70% of cases. The current diagnostic criteria and  clinical presentations of the disease are given. The presence of early and significant episodic memory disorders as both alone or  concurrent with other cognitive and behavioral changes reflects the  main clinical phenotype of AD. Magnetic resonance morphometry,  amyloid positron emission tomography, and estimation of  cerebrospinal fluid β-amyloid and tau protein levels find increasing  applications in research and routine practice. Drug and non-drug  treatments for MNCD are considered. The use of akatinol memantine to treat this disorder and the issues related to the comprehensive management of patients with severe cognitive impairment are analyzed.

  16. Treatment of cutaneous melanoma: current approaches and future prospects

    International Nuclear Information System (INIS)

    Algazi, Alain P; Soon, Christopher W; Daud, Adil I

    2010-01-01

    Melanoma is the most aggressive and deadly type of skin cancer. Surgical resection with or without lymph node sampling is the standard of care for primary cutaneous melanoma. Adjuvant therapy decisions may be informed by careful consideration of prognostic factors. High-dose adjuvant interferon alpha-2b increases disease-free survival and may modestly improve overall survival. Less toxic alternatives for adjuvant therapy are currently under study. External beam radiation therapy is an option for nodal beds where the risk of local recurrence is very high. In-transit melanoma metastases may be treated locally with surgery, immunotherapy, radiation, or heated limb perfusion. For metastatic melanoma, the options include chemotherapy or immunotherapy; targeted anti-BRAF and anti-KIT therapy is under active investigation. Standard chemotherapy yields objective tumor responses in approximately 10%–20% of patients, and sustained remissions are uncommon. Immunotherapy with high-dose interleukin-2 yields objective tumor responses in a minority of patients; however, some of these responses may be durable. Identification of activating mutations of BRAF, NRAS, c-KIT, and GNAQ in distinct clinical subtypes of melanoma suggest that these are molecularly distinct. Emerging data from clinical trials suggest that substantial improvements in the standard of care for melanoma may be possible

  17. Ocular Behçet disease: current therapeutic approaches.

    Science.gov (United States)

    Evereklioglu, Cem

    2011-11-01

    To alert physician to timely recognition and current treatment of recurrent hypopyon iridocyclitis or panuveitis in ocular Behçet disease (OBD). Interferon-α, rituximab, intravitreal triamcinolone, and biological response modifiers by tumor necrosis factor inhibitors such as infliximab and adalimumab are being used increasingly for the treatment of severe sight-threatening ocular inflammation including retinal vasculitis and cystoid macular edema (CME). Biological agents offer tremendous potential in the treatment of OBD. Given that OBD predominantly afflicts the younger adults in their most productive years, dermatologist, rheumatologist, internist, or general practitioners supervising patients with oculo-articulo-oromucocutaneous syndromes should be aware of systemic Behçet disease. Early recognition of ocular involvement is important and such patients should strongly be instructed to visit immediately an ophthalmologist, as uveitis management differs from extraocular involvements with high ocular morbidity from sight-threatening complications due to relapsing inflammatory attacks in the posterior segment of the eye. A single infliximab infusion should be considered for the control of acute panuveitis, whereas repeated long-term infliximab infusions were proved to be more effective in reducing the number of episodes in refractory uveoretinitis with faster regression and complete remission of CME.

  18. The aetiology ofautism spectrum disorders. An overview of current approaches

    Directory of Open Access Journals (Sweden)

    Paulina Gołaska

    2013-03-01

    Full Text Available Despite the great popularity of autism among researchers, its main cause still remains unknown. However, there are many theories which describe the mechanisms of this disorder. On the other hand, one who tries to integrate them seems to be helpless according to their contradictory and – in most cases – hypothetical status. In a context of this inac‑ curacy, focusing only on one of the concepts would be probably very disadvantageous. As many researchers suggest, the etiology of autism is complex and it is the interaction of multiple factors which implies the disorder appears. It seems that the nature of autism is equifinal and heterogeneous. Thus, the aim of this article is to present a review of current biological theories of autism etiology and to indicate the environmental as well as innate risk factors which may disturb the natural pathway of child development: prenatal (which increase the probability of autism emergence as early as in the first or second year of life or perinatal ones (low birth weight, hypoxia, age of the mother, her educational sta‑ tus. The foetal testosterone theory of autism and its general consequences for the child development will be described also. Finally, the neurological, neurochemical and neuroanatomical dysfunctions in autism will be presented.

  19. Pancreaticoduodenal injuries: re-evaluating current management approaches.

    Science.gov (United States)

    Chinnery, G E; Madiba, T E

    2010-02-01

    Pancreaticoduodenal injuries are uncommon owing to the protected position of the pancreas and duodenum in the retroperitoneum. Management depends on the extent of injury. This study was undertaken to document outcome of pancreaticoduodenal injuries and to re-evaluate our approach. A prospective study of all patients treated for pancreaticoduodenal trauma in one surgical ward at King Edward VIII hospital over a 7-year period (1998 - 2004). Demographic data, clinical presentation, findings at laparotomy and outcome were documented. Prophylactic antibiotics were given at induction of anaesthesia. A total of 488 patients underwent laparotomy over this period, 43 (9%) of whom (all males) had pancreatic and duodenal injuries. Injury mechanisms were gunshot (30), stabbing (10) and blunt trauma (3). Their mean age was 30.1+9.6 years. Delay before laparotomy was 12.8+29.1 hours. Seven were admitted in shock. Mean Injury Severity Score (ISS) was 14+8.6. Management of 20 duodenal injuries was primary repair (14), repair and pyloric exclusion (3) and conservative (3). Management of 15 pancreatic injuries was drainage alone (13), conservative management of pseudocyst (1) and distal pancreatectomy (1). Management of 8 combined pancreaticoduodenal injuries was primary duodenal repair and pancreatic drainage (5) and repair with pyloric exclusion of duodenal injury and pancreatic drainage (3). Twenty-one patients (49%) developed complications, and 28 required ICU admission with a median ICU stay of 4 days. Ten patients died (23%). Mean hospital stay was 18.3+24.4 days. The overall mortality was comparable with that in the world literature. We still recommend adequate exploration of the pancreas and duodenum and conservative operative management where possible.

  20. Subthreshold pharmacological and genetic approaches to analyzing CaV2.1-mediated NMDA receptor signaling in short-term memory.

    Science.gov (United States)

    Takahashi, Eiki; Niimi, Kimie; Itakura, Chitoshi

    2010-10-25

    Ca(V)2.1 is highly expressed in the nervous system and plays an essential role in the presynaptic modulation of neurotransmitter release machinery. Recently, the antiepileptic drug levetiracetam was reported to inhibit presynaptic Ca(V)2.1 functions, reducing glutamate release in the hippocampus, although the precise physiological role of Ca(V)2.1-regulated synaptic functions in cognitive performance at the system level remains unknown. This study examined whether Ca(V)2.1 mediates hippocampus-dependent spatial short-term memory using the object location and Y-maze tests, and perirhinal cortex-dependent nonspatial short-term memory using the object recognition test, via a combined pharmacological and genetic approach. Heterozygous rolling Nagoya (rol/+) mice carrying the Ca(V)2.1alpha(1) mutation had normal spatial and nonspatial short-term memory. A 100mg/kg dose of levetiracetam, which is ineffective in wild-type controls, blocked spatial short-term memory in rol/+ mice. At 5mg/kg, the N-methyl-D-aspartate (NMDA) receptor blocker (+/-)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), which is ineffective in wild-type controls, also blocked the spatial short-term memory in rol/+ mice. Furthermore, a combination of subthreshold doses of levetiracetam (25 mg/kg) and CPP (2.5mg/kg) triggered a spatial short-term memory deficit in rol/+ mice, but not in wild-type controls. Similar patterns of nonspatial short-term memory were observed in wild-type and rol/+ mice when injected with levetiracetam (0-300 mg/kg). These results indicate that Ca(V)2.1-mediated NMDA receptor signaling is critical in hippocampus-dependent spatial short-term memory and differs in various regions. The combination subthreshold pharmacological and genetic approach presented here is easily performed and can be used to study functional signaling pathways in neuronal circuits. Copyright © 2010 Elsevier B.V. All rights reserved.

  1. Cough in Children: Current Approaches to the Treatment

    Directory of Open Access Journals (Sweden)

    O.O. Rechkina

    2016-03-01

    Full Text Available Introduction. Cough is one of the most common symptoms in the practice of doctors of various specialties, including pediatricians. Cough treatment should be started with the identification of its cause and correct diagnosis. Most often, cough in children is due to the increased viscosity of bronchial secretions, i.e. violation of sputum transport in the bronchial tree, and insufficient activity of ciliated epithelium. The main objective of the treatment of productive cough is dilution of sputum, bronchial secretion and excretion, thus necessitating the administration of mucolytics. Currently, one of the most famous mucolytics is acetylcysteine, cysteine amino acid product, such as ACC®. However, today the question of ACC® (acetylcysteine application in infants and young children is still debatable. This article presents a study whose objective was to evaluate the therapeutic efficacy and tolerability of ACC® (20 mg/ml solution in the treatment of bronchopulmonary diseases in children aged 2 to 6 years. Materials and methods. The study involved 60 children with acute tracheitis, simple bronchitis, acute obstructive bronchitis, recurrent bronchitis in the acute phase, community-acquired pneumonia, asthma exacerbation, cystic fibrosis. Patients of the main groups (n = 40 received ACC® (20 mg/ml solution at the age-specific dosage 3 times a day in combined treatment. Therapy of patients in the control group (n = 20 was conducted without ACC®. Results. During follow-up, patients who received ACC® had significant positive changes in the nature of cough, sputum viscosity and its amount as opposed to a comparison group of patients. Complete disappearance of cough was achieved on day 5–8 from the beginning of treatment, while in the control group patients, this time was longer. The evaluation of the effectiveness of the study drug showed that very good efficacy was achieved in 75 % of patients and good — in 20 %, and among patients who

  2. An integrative pharmacological approach to radio telemetry and blood sampling in pharmaceutical drug discovery and safety assessment.

    Science.gov (United States)

    Litwin, Dennis C; Lengel, David J; Kamendi, Harriet W; Bialecki, Russell A

    2011-01-18

    A successful integration of the automated blood sampling (ABS) and telemetry (ABST) system is described. The new ABST system facilitates concomitant collection of physiological variables with blood and urine samples for determination of drug concentrations and other biochemical measures in the same rat without handling artifact. Integration was achieved by designing a 13 inch circular receiving antenna that operates as a plug-in replacement for the existing pair of DSI's orthogonal antennas which is compatible with the rotating cage and open floor design of the BASi Culex® ABS system. The circular receiving antenna's electrical configuration consists of a pair of electrically orthogonal half-toroids that reinforce reception of a dipole transmitter operating within the coil's interior while reducing both external noise pickup and interference from other adjacent dipole transmitters. For validation, measured baclofen concentration (ABST vs. satellite (μM): 69.6 ± 23.8 vs. 76.6 ± 19.5, p = NS) and mean arterial pressure (ABST vs. traditional DSI telemetry (mm Hg): 150 ± 5 vs.147 ± 4, p = NS) variables were quantitatively and qualitatively similar between rats housed in the ABST system and traditional home cage approaches. The ABST system offers unique advantages over traditional between-group study paradigms that include improved data quality and significantly reduced animal use. The superior within-group model facilitates assessment of multiple physiological and biochemical responses to test compounds in the same animal. The ABST also provides opportunities to evaluate temporal relations between parameters and to investigate anomalous outlier events because drug concentrations, physiological and biochemical measures for each animal are available for comparisons.

  3. A quantitative systems pharmacology approach, incorporating a novel liver model, for predicting pharmacokinetic drug-drug interactions.

    Science.gov (United States)

    Cherkaoui-Rbati, Mohammed H; Paine, Stuart W; Littlewood, Peter; Rauch, Cyril

    2017-01-01

    All pharmaceutical companies are required to assess pharmacokinetic drug-drug interactions (DDIs) of new chemical entities (NCEs) and mathematical prediction helps to select the best NCE candidate with regard to adverse effects resulting from a DDI before any costly clinical studies. Most current models assume that the liver is a homogeneous organ where the majority of the metabolism occurs. However, the circulatory system of the liver has a complex hierarchical geometry which distributes xenobiotics throughout the organ. Nevertheless, the lobule (liver unit), located at the end of each branch, is composed of many sinusoids where the blood flow can vary and therefore creates heterogeneity (e.g. drug concentration, enzyme level). A liver model was constructed by describing the geometry of a lobule, where the blood velocity increases toward the central vein, and by modeling the exchange mechanisms between the blood and hepatocytes. Moreover, the three major DDI mechanisms of metabolic enzymes; competitive inhibition, mechanism based inhibition and induction, were accounted for with an undefined number of drugs and/or enzymes. The liver model was incorporated into a physiological-based pharmacokinetic (PBPK) model and simulations produced, that in turn were compared to ten clinical results. The liver model generated a hierarchy of 5 sinusoidal levels and estimated a blood volume of 283 mL and a cell density of 193 × 106 cells/g in the liver. The overall PBPK model predicted the pharmacokinetics of midazolam and the magnitude of the clinical DDI with perpetrator drug(s) including spatial and temporal enzyme levels changes. The model presented herein may reduce costs and the use of laboratory animals and give the opportunity to explore different clinical scenarios, which reduce the risk of adverse events, prior to costly human clinical studies.

  4. A quantitative systems pharmacology approach, incorporating a novel liver model, for predicting pharmacokinetic drug-drug interactions.

    Directory of Open Access Journals (Sweden)

    Mohammed H Cherkaoui-Rbati

    Full Text Available All pharmaceutical companies are required to assess pharmacokinetic drug-drug interactions (DDIs of new chemical entities (NCEs and mathematical prediction helps to select the best NCE candidate with regard to adverse effects resulting from a DDI before any costly clinical studies. Most current models assume that the liver is a homogeneous organ where the majority of the metabolism occurs. However, the circulatory system of the liver has a complex hierarchical geometry which distributes xenobiotics throughout the organ. Nevertheless, the lobule (liver unit, located at the end of each branch, is composed of many sinusoids where the blood flow can vary and therefore creates heterogeneity (e.g. drug concentration, enzyme level. A liver model was constructed by describing the geometry of a lobule, where the blood velocity increases toward the central vein, and by modeling the exchange mechanisms between the blood and hepatocytes. Moreover, the three major DDI mechanisms of metabolic enzymes; competitive inhibition, mechanism based inhibition and induction, were accounted for with an undefined number of drugs and/or enzymes. The liver model was incorporated into a physiological-based pharmacokinetic (PBPK model and simulations produced, that in turn were compared to ten clinical results. The liver model generated a hierarchy of 5 sinusoidal levels and estimated a blood volume of 283 mL and a cell density of 193 × 106 cells/g in the liver. The overall PBPK model predicted the pharmacokinetics of midazolam and the magnitude of the clinical DDI with perpetrator drug(s including spatial and temporal enzyme levels changes. The model presented herein may reduce costs and the use of laboratory animals and give the opportunity to explore different clinical scenarios, which reduce the risk of adverse events, prior to costly human clinical studies.

  5. Pharmacological and non-pharmacological treatment options for depression and depressive symptoms in hemodialysis patients

    Directory of Open Access Journals (Sweden)

    Stefania S. Grigoriou

    2015-04-01

    Full Text Available Depression is a mental disorder with a high prevalence among patients with end stage renal disease (ESRD. It is reported that depression afflicts approximately 20-30% of this patient population, being associated, amongst other, with high mortality rate, low adherence to medication and low perceived quality of life. There is a variety of medications known to be effective for the treatment of depression but due to poor adherence to treatment as well as due to the high need for medications addressing other ESRD comorbidities, depression often remains untreated. According to the literature, depression is under-diagnosed and undertreated in the majority of the patients with chronic kidney disease. In the current review the main pharmacological and non-pharmacological approaches and research outcomes for the management of depressive symptoms in hemodialysis patients are discussed.

  6. Network Pharmacology-Based Approach to Investigate the Analgesic Efficacy and Molecular Targets of Xuangui Dropping Pill for Treating Primary Dysmenorrhea

    Directory of Open Access Journals (Sweden)

    Jihan Huang

    2017-01-01

    Full Text Available This study aimed to evaluate the clinical analgesic efficacy and identify the molecular targets of XGDP for treating primary dysmenorrhea (PD by a network pharmacology approach. Analysis of pain disappearance rate of XGDP in PD treatment was conducted based on data from phase II and III randomized, double-blind, double-simulation, and positive parallel controlled clinical trials. The bioactive compounds were obtained by the absorption, distribution, metabolism, and excretion processes with oral bioavailability (OB and drug-likeness (DL evaluation. Subsequently, target prediction, pathway identification, and network construction were employed to clarify the mechanisms of the analgesic effect of XGDP on PD. The pain disappearance rates in phase II and III clinical trials of XGDP in PD treatment were 62.5% and 55.8%, respectively, yielding a significant difference (P<0.05 when compared with the control group using Tongjingbao granules (TJBG. Among 331 compounds, 53 compounds in XGDP were identified as the active compounds related to PD through OB, DL, and target prediction. The active compounds and molecular targets of XGDP were identified, and our study showed that XGDP may exert its therapeutic effects on PD through the regulation of the targets related to anti-inflammation analgesia and central analgesia and relieving smooth muscle contraction.

  7. Phyto-constituents, Pharmacological Properties and Biotechnological Approaches for Conservation of the Anti-diabetic Functional Food Medicinal Plant Salacia: A Review Note

    Directory of Open Access Journals (Sweden)

    Majid Bagnazari

    2017-01-01

    Full Text Available Background and Objective: Genus Salacia L. (Celastraceae is a woody climbing medicinal plant consisting of about 200 species with many endangered species located throughout the world’s tropical areas. Various parts of the plant as food, functional food additive and tea have been extensively used to treat a variety of ailments like diabetes and obesity as well as inflammatory and skin diseases. The present work reviews the phytochemical properties, pharmacological activities, biotechnological strategy for conservation and safety evaluation of this valuable genus.Results and Conclusion: More efforts are needed to isolate new phytoconstituents from this important medicinal plant. The  echanism of anti-diabetic action has not been done at molecular and cellular levels, thus the fundamental biological understanding is required for future applications. Though the safety of plant species has been well documented and has been confirmed by many toxicological studies, further toxicity research and clinical trials arerecommended. In order to sustain harvest and conservation, agronomic practices for cultivation have to be developed. Establishment of more efficient protocols for in vitro propagation is necessary too. Approaches like genetic manipulation, hairy root culture, media standardization, and use of inducers/precursors for elevation of secondary metabolite levels could also be attractive.Conflict of interest: The authors report no conflicts of interest.

  8. Time to lack of persistence with pharmacological treatment among patients with current depressive episodes: a natural study with 1-year follow-up

    Directory of Open Access Journals (Sweden)

    Li K

    2016-10-01

    Full Text Available Kanglai Li,1,* Qinling Wei,2,* Guanying Li,2 Xiangjun He,2 Yingtao Liao,2 Zhaoyu Gan2 1Very Important Patient Department, 2Department of Psychiatry, The Third Affiliated Hospital of Sun Yat-sen University, Tianhe District, Guangzhou, Guangdong, People’s Republic of China *These authors contributed equally to this work Introduction: Medication nonadherence remains a big challenge for depressive patients. This study aims to assess and compare the medication persistence between unipolar depression (UD and bipolar depression (BD. Methods: A total of 146 UD and 187 BD patients were recruited at their first index prescription. Time to lack of persistence with pharmacological treatment (defined as a gap of at least 60 days without taking any medication was calculated, and clinical characteristics were collected. Final diagnosis was made at the end of 1-year follow-up. Results: A total of 101 (69.2% UD and 126 (67.4% BD patients discontinued the treatment, with a median duration of 36 days and 27 days, respectively. No significant difference was found between UD and BD in terms of time to lack of persistence with pharmacological treatment. The highest discontinuation rate (>40% occurred in the first 3 months for both groups of patients. For UD patients, those with a higher risk of suicide (odds ratio [OR] =0.696, P=0.035 or comorbidity of any anxiety disorder (OR =0.159, P<0.001 were less likely to prematurely drop out (drop out within the first 3 months, while those with onset in the summer (OR =4.702, P=0.049 or autumn (OR =7.690, P=0.012 were more likely to prematurely drop out than those with onset in the spring (OR =0.159, P<0.001. For BD patients, being female (OR =2.250, P=0.012 and having a history of spontaneous remission or switch to hypomania (OR =2.470, P=0.004 were risk factors for premature drop out, while hospitalization (OR =0.304, P=0.023 and misdiagnosis as UD (OR =0.283, P<0.001 at the first index prescription were protective

  9. Pharmacological isolation of postsynaptic currents mediated by NR2A- and NR2B-containing NMDA receptors in the anterior cingulate cortex

    Directory of Open Access Journals (Sweden)

    Cao Xiaoyan

    2007-04-01

    Full Text Available Abstract NMDA receptors (NMDARs are involved in excitatory synaptic transmission and plasticity associated with a variety of brain functions, from memory formation to chronic pain. Subunit-selective antagonists for NMDARs provide powerful tools to dissect NMDAR functions in neuronal activities. Recently developed antagonist for NR2A-containing receptors, NVP-AAM007, triggered debates on its selectivity and involvement of the NMDAR subunits in bi-directional synaptic plasticity. Here, we re-examined the pharmacological properties of NMDARs in the anterior cingulate cortex (ACC using NVP-AAM007 as well as ifenprodil, a selective antagonist for NR2B-containing NMDARs. By alternating sequence of drug application and examining different concentrations of NVP-AAM007, we found that the presence of NVP-AAM007 did not significantly affect the effect of ifenprodil on NMDAR-mediated EPSCs. These results suggest that NVP-AAM007 shows great preference for NR2A subunit and could be used as a selective antagonist for NR2A-containing NMDARs in the ACC.

  10. Current knowledge of Schisandra chinensis (Turcz.) Baill. (Chinese magnolia vine) as a medicinal plant species: a review on the bioactive components, pharmacological properties, analytical and biotechnological studies.

    Science.gov (United States)

    Szopa, Agnieszka; Ekiert, Radosław; Ekiert, Halina

    2017-01-01

    Schisandra chinensis Turcz. (Baill.) is a plant species whose fruits have been well known in Far Eastern medicine for a long time. However, schisandra seems to be a plant still underestimated in contemporary therapy still in the countries of East Asia. The article presents latest available information on the chemical composition of this plant species. Special attention is given to dibenzo cyclooctadiene lignans. In addition, recent studies of the biological activity of dibenzocyclooctadiene lignans and schisandra fruit extracts are recapitulated. The paper gives a short resume of their beneficial effects in biological systems in vitro, in animals, and in humans, thus underlining their medicinal potential. The cosmetic properties are depicted, too. The analytical methods used for assaying schisandra lignans in the scientific studies and also in industry are also presented. Moreover, special attention is given to the information on the latest biotechnological studies of this plant species. The intention of this review is to contribute to a better understanding of the huge potential of the pharmacological relevance of S. chinensis.

  11. Current and future pharmacologic options for the management of patients unable to achieve low-density lipoprotein-cholesterol goals with statins

    NARCIS (Netherlands)

    El Harchaoui, Karim; Akdim, Fatima; Stroes, Erik S. G.; Trip, Mieke D.; Kastelein, John J. P.

    2008-01-01

    Low-density lipoprotein-cholesterol (LDL-C) lowering is the mainstay of the current treatment guidelines in the management of cardiovascular risk. HMG-CoA reductase inhibitors (statins) are Currently the most effective LDL-C-lowering drugs. However, a substantial number of patients do not reach

  12. Neurofeedback in children with attention-deficit/hyperactivity disorder (ADHD)--a controlled multicenter study of a non-pharmacological treatment approach.

    Science.gov (United States)

    Holtmann, Martin; Pniewski, Benjamin; Wachtlin, Daniel; Wörz, Sonja; Strehl, Ute

    2014-08-13

    Attention-deficit/hyperactivity disorder (ADHD) is the most common neurobehavioral disorder of childhood and has often a chronic course persisting into adulthood. However, up to 30% of children treated with stimulants either fail to show an improvement or suffer adverse side effects, including decreased appetite, insomnia and irritability and there is no evidence of long term efficacy of stimulants for ADHD. A series of studies has shown that neurofeedback is an effective additional or alternative treatment for children with ADHD, leading to e.g. significant and stable improvement in behavior, attention and IQ. Significant treatment effects of neurofeedback have also been verified in meta-analyses. Most of the trials, however, have been criticized for methodological difficulties, particularly lacking appropriate control conditions and number of patients included. This randomized study examines the efficacy of slow cortical potentials (SCP) -neurofeedback, controlling unspecific effects of the setting by comparing two active treatment modalities. A total of 144 patients with ADHD, older than six and younger than ten years, in some cases with additional pharmacological treatment, are included in this trial. In five trial centres patients are treated either with SCP-feedback or electromyographic (EMG) -feedback in 25 sessions within 3 months. A comprehensive test battery is conducted before and after treatment and at follow-up 6 month later, to assess core symptoms of ADHD, general psychopathology, attentional performance, comorbid symptoms, intelligence, quality of life and cortical arousal. The efficacy of SCP-feedback training for children with ADHD is evaluated in this randomized controlled study. In addition to behavior ratings and psychometric tests neurophysiological parameters serve as dependent variables. Further, the choice of EMG-biofeedback as an active control condition is debated. Current Controlled Trials ISRCTN76187185. Registered 5 February 2009.

  13. Future pharmacological therapy in hypertension.

    Science.gov (United States)

    Stewart, Merrill H; Lavie, Carl J; Ventura, Hector O

    2018-04-26

    Hypertension (HTN) is a widespread and growing disease, with medication intolerance and side-effect present among many. To address these obstacles novel pharmacotherapy is an active area of drug development. This review seeks to explore future drug therapy for HTN in the preclinical and clinical arenas. The future of pharmacological therapy in HTN consists of revisiting old pathways to find new targets and exploring wholly new approaches to provide additional avenues of treatment. In this review, we discuss the current status of the most recent drug therapy in HTN. New developments in well trod areas include novel mineralocorticoid antagonists, aldosterone synthase inhibitors, aminopeptidase-A inhibitors, natriuretic peptide receptor agonists, or the counter-regulatory angiotensin converting enzyme 2/angiotensin (Ang) (1-7)/Mas receptor axis. Neprilysin inhibitors popularized for heart failure may also still hold HTN potential. Finally, we examine unique systems in development never before used in HTN such as Na/H exchange inhibitors, vasoactive intestinal peptide agonists, and dopamine beta hydroxylase inhibitors. A concise review of future directions of HTN pharmacotherapy.

  14. Skills Training for School Leavers: Some Alternative Approaches. Current Issues Brief No. 2.

    Science.gov (United States)

    Fraser, Doug

    In the face of escalating youth unemployment, some new approaches are needed for training out-of-school youth in Australia. The current system of apprenticeship has become outmoded because many of the skilled trades that the system prepares young people for will soon be non-existent. One approach to this problem has been implementation of…

  15. A non-pharmacologic approach to address challenging behaviors of Veterans with dementia: description of the tailored activity program-VA randomized trial.

    Science.gov (United States)

    Gitlin, Laura N; Mann, William C; Vogel, W Bruce; Arthur, Paul B

    2013-09-23

    Behavioral symptoms accompanying dementia are associated with increased health care costs, reduced quality of life and daily functioning, heightened family caregiver burden, and nursing home placement. Standard care typically involves pharmacologic agents, but these are, at best, modestly effective, carry serious risks, including mortality, and do not address behavioral symptoms families consider most distressful and which may prompt nursing home placement. Given dementia's devastating effects and the absence of an imminent cure, the Veterans Administration has supported the development and testing of new approaches to manage challenging behaviors at home. The Tailored Activity Program - Veterans Administration is a Phase III efficacy trial designed to reduce behavioral symptoms in Veterans with dementia living with their caregivers in the community. The study uses a randomized two-group parallel design with 160 diverse Veterans and caregivers. The experimental group receives a transformative patient-centric intervention designed to reduce the burden of behavioral symptoms in Veterans with dementia. An occupational therapist conducts an assessment to identify a Veteran's preserved capabilities, deficit areas, previous roles, habits, and interests to develop activities tailored to the Veteran. Family caregivers are then trained to incorporate activities into daily care. The attention-control group receives bi-monthly telephone contact where education on topics relevant to dementia is provided to caregivers. Key outcomes include reduced frequency and severity of behavioral symptoms using the 12-item Neuropsychiatric Inventory (primary endpoint), reduced caregiver burden, enhanced skill acquisition, efficacy using activities, and time spent providing care at 4 months; and long-term effects (8 months) on the Veteran's quality of life and frequency and severity of behavioral symptoms, and caregiver use of activities. The programs' impact of Veterans Administration cost

  16. Pharmacology of pediatric resuscitation.

    Science.gov (United States)

    Ushay, H M; Notterman, D A

    1997-02-01

    The resuscitation of children from cardiac arrest and shock remains a challenging goal. The pharmacologic principles underlying current recommendations for intervention in pediatric cardiac arrest have been reviewed. Current research efforts, points of controversy, and accepted practices that may not be most efficacious have been described. Epinephrine remains the most effective resuscitation adjunct. High-dose epinephrine is tolerated better in children than in adults, but its efficacy has not received full analysis. The preponderance of data continues to point toward the ineffectiveness and possible deleterious effects of overzealous sodium bicarbonate use. Calcium chloride is useful in the treatment of ionized hypocalcemia but may harm cells that have experienced asphyxial damage. Atropine is an effective agent for alleviating bradycardia induced by increased vagal tone, but because most bradycardia in children is caused by hypoxia, improved oxygenation is the intervention of choice. Adenosine is an effective and generally well-tolerated agent for the treatment of supraventricular tachycardia. Lidocaine is the drug of choice for ventricular dysrhythmias, and bretylium, still relatively unexplored, is in reserve. Many pediatricians use dopamine for shock in the postresuscitative period, but epinephrine is superior. Most animal research on cardiac arrest is based on models with ventricular fibrillation that probably are not reflective of cardiac arrest situations most often seen in pediatrics.

  17. Current insights into the molecular systems pharmacology of lncRNA-miRNA regulatory interactions and implications in cancer translational medicine

    Directory of Open Access Journals (Sweden)

    Sujit Nair

    2016-04-01

    Full Text Available In recent times, the role(s of microRNAs (miRNAs and long noncoding RNAs (lncRNAs in the pathogenesis of various cancers has received great attention. Indeed, there is also a growing recognition of regulatory RNA cross-talk, i.e., lncRNA-miRNA interactions, that may modulate various events in carcinogenesis and progression to metastasis. This review summarizes current evidence in the literature of lncRNA-miRNA interactions in various cancers such as breast, liver, stomach, lung, prostate, bladder, colorectal, blood, brain, skin, kidney, cervical, laryngeal, gall bladder, and bone. Further, the potential prognostic and theragnostic clinical applications of lncRNA-miRNA interactions in cancer are discussed along with an overview of noncoding RNA (ncRNA-based studies that were presented at the American Society of Clinical Oncology (ASCO 2015. Interestingly, the last decade has seen tremendous innovation, as well as increase in complexity, of the cancer biological network(s from mRNA- to miRNA- and lncRNA-based networks. Thus, biological networks devoted to understanding regulatory interactions between these ncRNAs would be the next frontier in better elucidating the contributions of lncRNA-miRNA interactions in cancer. Herein, a cancer biological network of lncRNA-miRNA interactions is presented wherein “edges” connect interacting lncRNA-miRNA pairs, with each ncRNA serving as a discrete “node” of the network. In conclusion, the untapped potential of lncRNA-miRNA interactions in terms of its diagnostic, prognostic and therapeutic potential as targets for clinically actionable intervention as well as biomarker validation in discovery pipelines remains to be explored. Future research will likely harness this potential so as to take us closer to the goal of “precision” and “personalized medicine” which is tailor-made to the unique needs of each cancer patient, and is clearly the way forward going into the future.

  18. [Non-Pharmacological Interventions for Pregnancy-Related Sleep Disturbances].

    Science.gov (United States)

    Hung, Hsuan-Man; Chiang, Hsiao-Ching

    2017-02-01

    Most women experience the worse sleep quality of their life during pregnancy and the early postpartum period. Although pregnancy typically accounts for a relatively short part of a woman's life, the related sleep disturbances may have a significant and negative impact on her long-term health. Approximately 78-80% of pregnant women experience sleep disturbances, including interruptions in deep sleep, decreased total sleep time, poor subjective sleep quality, frequent night waking, and reduced sleep efficacy. Sleep disturbances during pregnancy start during the first trimester and become prevalent during the third trimester. Related factors include physiological and psychosocial changes and an unhealthy lifestyle. As non-pharmacological interventions have the potential to improve sleep quality in 70% to 80% of patients with insomnia, this is the main approached that is currently used to treat pregnancy-related sleep disturbances. Examples of these non-pharmacological interventions include music therapy, aerobic exercise, massage, progressive muscle relaxation, multi-modal interventions, and the use of a maternity support belt. The efficacy and safety of other related non-pharmacological interventions such as auricular acupressure, cognitive therapy, tai chi, and aromatherapy remain uncertain, with more empirical research required. Additionally, non-pharmacological interventions do not effectively treat sleep disturbances in all pregnant women.

  19. Problems of pharmacological supply of disaster medicine

    International Nuclear Information System (INIS)

    Sabaev, V.V.; Il'ina, S.L.

    1995-01-01

    The paper reviews a number of pharmacological problems, being important for the disaster medicine, of theoretical and practical nature, the settlement of which would promote more efficient rendering emergency medical aid to the injured persons in the conditions of emergency situations and further expert medical care. On the example of radiation accidents there are studied methodical approaches to organization of drug prophylaxis and therapy of the injured persons in emergency situations. The authors have proved the necessity of arranging proper pharmacological supply of disaster medicine which is to settle the whole complex of scientific-applied and organizational questions relating to the competence of pharmacology and pharmacy. 17 refs

  20. Nanotechnology Based Theranostic Approaches in Alzheimer's Disease Management: Current Status and Future Perspective.

    Science.gov (United States)

    Ahmad, Javed; Akhter, Sohail; Rizwanullah, Md; Khan, Mohammad Ahmed; Pigeon, Lucie; Addo, Richard T; Greig, Nigel H; Midoux, Patrick; Pichon, Chantal; Kamal, Mohammad Amjad

    2017-01-01

    Alzheimer's disease (AD), a cognitive dysfunction/dementia state amongst the elders is characterized by irreversible neurodegeneration due to varied pathophysiology. Up till now, anti-AD drugs having different pharmacology have been developed and used in clinic. Yet, these medications are not curative and only lowering the AD associated symptoms. Improvement in treatment outcome required drug targeting across the blood-brain barrier (BBB) to the central nervous system (CNS) in optimal therapeutic concentration. Nanotechnology based diagnostic tools, drug carriers and theranostics offer highly sensitive molecular detection, effective drug targeting and their combination. Over the past decade, significant works have been done in this area and we have seen very remarkable outocome in AD therapy. Various nanoparticles from organic and inorganic nanomaterial category have successfully been investigated against AD. This paper discussed the role of nanoparticles in early detection of AD, effective drug targeting to brain and theranostic (diagnosis and therapy) approaches in AD's management. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  1. Targeting HIV latency: pharmacologic strategies toward eradication

    Science.gov (United States)

    Xing, Sifei; Siliciano, Robert F.

    2013-01-01

    The latent reservoir for HIV-1 in resting CD4+ T cells remains a major barrier to HIV-1 eradication, even though highly active antiretroviral therapy (HAART) can successfully reduce plasma HIV-1 levels to below the detection limit of clinical assays and reverse disease progression. Proposed eradication strategies involve reactivation of this latent reservoir. Multiple mechanisms are believed to be involved in maintaining HIV-1 latency, mostly through suppression of transcription. These include cytoplasmic sequestration of host transcription factors and epigenetic modifications such as histone deacetylation, histone methylation and DNA methylation. Therefore, strategies targeting these mechanisms have been explored for reactivation of the latent reservoir. In this review, we discuss current pharmacological approaches toward eradication, focusing on small molecule latency-reversing agents, their mechanisms, advantages and limitations. PMID:23270785

  2. [Pharmacological treatment of obesity].

    Science.gov (United States)

    Gomis Barbará, R

    2004-01-01

    The pharmacological treatment of obesity should be considered when cannot be achieved a 10% weight loss with diet therapy and physical activity. The drugs effective in obesity treatment may act by different mechanisms such as reduction in food intake, inhibition of fat absorption, increase of thermogenesis and stimulation of adipocyte apoptosis. At present, we only have two marketed drugs for obesity treatment. Sibutramine is an inhibitor of norepinephrine, dopamine and serotonina reuptake which inhibits food intake and increases thermogenesis. Sibutramine administration for a year can induce a weight loss of 4-7%. Its main side effects are hypertension, headache, insomnia and constipation. Orlistat is an inhibitor of pancreatic lipase which is able to block the absorption of 30% of ingested fat. Its administration induces weight loss and reduction of ulterior weight regain. Also, this drug improves hypertension dyslipdaemia and helps to prevent diabetes in 52% of cases when administered over four years. The increase in frequency of stools and interference with vitamin absorption are its main side effects. Glucagon-like peptide 1, which increases insulin sensitivity and satiety, adiponectin and PPAR-gamma agonists which reduce insulin resistance and modulates adipocyte generation are the basis for future therapeutic approaches of obesity. Phosphatase inhibitors induce PPAR-gamma phosphorylation and UCP-1 expression leading to an increase in thermogenesis and reduction in appetite.

  3. Pharmacological therapy of spondyloarthritis.

    Science.gov (United States)

    Palazzi, Carlo; D'Angelo, Salvatore; Gilio, Michele; Leccese, Pietro; Padula, Angela; Olivieri, Ignazio

    2015-01-01

    The current pharmacological therapy of spondyloarthritis (SpA) includes several drugs: Non-steroidal anti-inflammatory drugs, corticosteroids, traditional disease-modifying antirheumatic drugs and biologic drugs. A systematic literature search was completed using the largest electronic databases (Medline, Embase and Cochrane), starting from 1995, with the aim to review data on traditional and biologic agents commercialised for SpA treatment. Randomised controlled trials and large observational studies were considered. In addition, studies performed in SpA patients treated with other, still unapproved, drugs (rituximab, anti-IL6 agents, apremilast, IL17 inhibitors and anakinra) were also taken into account. Biologic agents, especially anti-TNF drugs, have resulted in significant progress in improving clinical symptoms and signs, reducing inflammatory features in laboratory tests and imaging findings, and recovering all functional indexes. Anti-TNF drugs have radically changed the evolution of radiographic progression in peripheral joints; the first disappointing data concerning their efficacy on new bone formation of axial SpA has been recently challenged by studies enrolling patients who have been earlier diagnosed and treated. The opportunity to extend the interval of administration or to reduce the doses of anti-TNF agents can favourably influence the costs. Ustekinumab, the first non-anti-TNF biologic drug commercialised for psoriatic arthritis, offers new chances to patients that are unresponsive to anti-TNF.

  4. Quantum dot as a spin-current diode: A master-equation approach

    DEFF Research Database (Denmark)

    Souza, F.M.; Egues, J.C.; Jauho, Antti-Pekka

    2007-01-01

    We report a study of spin-dependent transport in a system composed of a quantum dot coupled to a normal metal lead and a ferromagnetic lead NM-QD-FM. We use the master equation approach to calculate the spin-resolved currents in the presence of an external bias and an intradot Coulomb interaction....... We find that for a range of positive external biases current flow from the normal metal to the ferromagnet the current polarization =I↑−I↓ / I↑+I↓ is suppressed to zero, while for the corresponding negative biases current flow from the ferromagnet to the normal metal attains a relative maximum value....... The system thus operates as a rectifier for spin-current polarization. This effect follows from an interplay between Coulomb interaction and nonequilibrium spin accumulation in the dot. In the parameter range considered, we also show that the above results can be obtained via nonequilibrium Green functions...

  5. A clinical trial with combined transcranial direct current stimulation and alcohol approach bias retraining

    NARCIS (Netherlands)

    den Uyl, T.E.; Gladwin, T.E.; Rinck, M.; Lindenmeyer, J.; Wiers, R.W.

    2017-01-01

    Two studies showed an improvement in clinical outcomes after alcohol approach bias retraining, a form of Cognitive Bias Modification (CBM). We investigated whether transcranial direct current stimulation (tDCS) could enhance effects of CBM. TDCS is a neuromodulation technique that can increase

  6. State Higher Education Funding Models: An Assessment of Current and Emerging Approaches

    Science.gov (United States)

    Layzell, Daniel T.

    2007-01-01

    This article provides an assessment of the current and emerging approaches used by state governments in allocating funding for higher education institutions and programs. It reviews a number of desired characteristics or outcomes for state higher education funding models, including equity, adequacy, stability, and flexibility. Although there is…

  7. Biological and Pharmacological properties

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. Biological and Pharmacological properties. NOEA inhibits Ceramidase. Anandamide inhibits gap junction conductance and reduces sperm fertilizing capacity. Endogenous ligands for Cannabinoid receptors (anandamide and NPEA). Antibacterial and antiviral ...

  8. Pharmacology Goes Concept-Based: Course Design, Implementation, and Evaluation.

    Science.gov (United States)

    Lanz, Amelia; Davis, Rebecca G

    Although concept-based curricula are frequently discussed in the nursing education literature, little information exists to guide the development of a concept-based pharmacology course. Traditionally, nursing pharmacology courses are taught with an emphasis on drug class where a prototype drug serves as an exemplar. When transitioning pharmacology to a concept-based course, special considerations are in order. How can educators successfully integrate essential pharmacological content into a curriculum structured around nursing concepts? This article presents one approach to the design and implementation of a concept-based undergraduate pharmacology course. Planning methods, supportive teaching strategies, and course evaluation procedures are discussed.

  9. Challenging the current strategy of radiological protection of the environment: arguments for an ecosystem approach

    International Nuclear Information System (INIS)

    Brechignac, F.; Doi, Masahiro

    2009-01-01

    The system of radiological protection of the environment that is currently under development is one contribution to the general need to adequately protect the environment against stress. Dominated by operational goals, it emphasizes conceptual and methodological approaches that are readily accessible today: reference organisms supported by individual-based traditional ecotoxicological data. Whilst there are immediate advantages to this approach (pragmatism, consistency with other approaches in use for man and biota), there are also clear limitations, especially in a longer run perspective, that need to be acknowledged and further considered. One can mention a few: uncertainties generated by the need for various extrapolations (from lower to higher levels of biological organisation, ...), various features missed such as potential ecological impact through impairment of ecosystem processes, trans-generational impacts as mediated through genomic instability, indirect effects mediated through trophic interactions or disruption of ecological balances, ... Such limitations have already been faced in other fields of environmental protection against other stressors, pushing a number of environment professionals to assign stronger emphasis on more systemic approaches. This review discusses the advantages and limitations of the current approach designed for the radiological protection of non-human biota in the broader context of environment protection as a whole, with especial reference to upcoming trends and evolutions. This leads in particular to advocating the need to boost scientific and methodological approaches featuring the ecosystem concept as a mean to access a unified goal of protection: preserving life sustainability through protection of ecosystem structure and functioning.

  10. Challenging the current strategy of radiological protection of the environment: arguments for an ecosystem approach

    Energy Technology Data Exchange (ETDEWEB)

    Brechignac, F., E-mail: francois.brechignac@irsn. [Institute for Radioprotection and Nuclear Safety (IRSN), Centre d' Etudes de Cadarache, Blg 229, 13115 Saint-Paul-lez-Durance (France); Doi, Masahiro [National Institute of Radiological Sciences, NIRS, Center for Radiation Protection, Regulatory Sciences Research Group, 4-9-1, Anagawa, Inage, Chiba, 263-8555 (Japan)

    2009-12-15

    The system of radiological protection of the environment that is currently under development is one contribution to the general need to adequately protect the environment against stress. Dominated by operational goals, it emphasizes conceptual and methodological approaches that are readily accessible today: reference organisms supported by individual-based traditional ecotoxicological data. Whilst there are immediate advantages to this approach (pragmatism, consistency with other approaches in use for man and biota), there are also clear limitations, especially in a longer run perspective, that need to be acknowledged and further considered. One can mention a few: uncertainties generated by the need for various extrapolations (from lower to higher levels of biological organisation, ...), various features missed such as potential ecological impact through impairment of ecosystem processes, trans-generational impacts as mediated through genomic instability, indirect effects mediated through trophic interactions or disruption of ecological balances, ... Such limitations have already been faced in other fields of environmental protection against other stressors, pushing a number of environment professionals to assign stronger emphasis on more systemic approaches. This review discusses the advantages and limitations of the current approach designed for the radiological protection of non-human biota in the broader context of environment protection as a whole, with especial reference to upcoming trends and evolutions. This leads in particular to advocating the need to boost scientific and methodological approaches featuring the ecosystem concept as a mean to access a unified goal of protection: preserving life sustainability through protection of ecosystem structure and functioning.

  11. A Phase Current Reconstruction Approach for Three-Phase Permanent-Magnet Synchronous Motor Drive

    Directory of Open Access Journals (Sweden)

    Hao Yan

    2016-10-01

    Full Text Available Three-phase permanent-magnet synchronous motors (PMSMs are widely used in renewable energy applications such as wind power generation, tidal energy and electric vehicles owing to their merits such as high efficiency, high precision and high reliability. To reduce the cost and volume of the drive system, techniques of reconstructing three-phase current using a single current sensor have been reported for three-phase alternating current (AC control system using the power converts. In existing studies, the reconstruction precision is largely influenced by reconstructing dead zones on the Space Vector Pulse Width Modulation (SVPWM plane, which requires other algorithms to compensate either by modifying PWM modulation or by phase-shifting of the PWM signal. In this paper, a novel extended phase current reconstruction approach for PMSM drive is proposed. Six novel installation positions are obtained by analyzing the sampling results of the current paths between each two power switches. By arranging the single current sensor at these positions, the single current sensor is sampled during zero voltage vectors (ZVV without modifying the PWM signals. This proposed method can reconstruct the three-phase currents without any complex algorithms and is available in the sector boundary region and low modulation region. Finally, this method is validated by experiments.

  12. Environmental release of living modified organisms: current approaches and case studies.

    Science.gov (United States)

    Thomas, E; Nickson, Ph D

    2005-01-01

    Agricultural biotechnology is being rapidly adopted as evidenced by the acreage of genetically modified (GM) crops planted and tonnes of product (grain and fiber) harvested. Concurrent with this technological progress, is a growing concern that the worlds biological diversity is coming under increasing threat from human activities. As such, ecological risk assessment approaches are being developed for GM crop plants as international agreements regulating the transboundary movements of these products are being implemented. This paper reviews the ecological risk assessment approach that has been used to date to approve GM crops to date. The process has been case-by-case, using a comparative, science-based approach balancing the potential risks and benefits of the new technology versus those present with the currently accepted practices. The approach used to evaluate and approve these products is consistent with the conditions and requirements outlined in the Cartagena Protocol.

  13. Towards Current Profile Control in ITER: Potential Approaches and Research Needs

    Science.gov (United States)

    Schuster, E.; Barton, J. E.; Wehner, W. P.

    2014-10-01

    Many challenging plasma control problems still need to be addressed in order for the ITER Plasma Control System (PCS) to be able to successfully achieve the ITER project goals. For instance, setting up a suitable toroidal current density profile is key for one possible advanced scenario characterized by noninductive sustainment of the plasma current and steady-state operation. The nonlinearity and high dimensionality exhibited by the plasma demand a model-based current-profile control synthesis procedure that can accommodate this complexity through embedding the known physics within the design. The development of a model capturing the dynamics of the plasma relevant for control design enables not only the design of feedback controllers for regulation or tracking but also the design of optimal feedforward controllers for a systematic model-based approach to scenario planning, the design of state estimators for a reliable real-time reconstruction of the plasma internal profiles based on limited and noisy diagnostics, and the development of a fast predictive simulation code for closed-loop performance evaluation before implementation. Progress towards control-oriented modeling of the current profile evolution and associated control design has been reported following both data-driven and first-principles-driven approaches. An overview of these two approaches will be provided, as well as a discussion on research needs associated with each one of the model applications described above. Supported by the US Department of Energy under DE-SC0001334 and DE-SC0010661.

  14. Management of Neuropsychiatric Systemic Lupus Erythematosus: Current Approaches and Future Perspectives.

    Science.gov (United States)

    Magro-Checa, César; Zirkzee, Elisabeth J; Huizinga, Tom W; Steup-Beekman, Gerda M

    2016-03-01

    Neuropsychiatric systemic lupus erythematosus (NPSLE) is a generic definition referring to a series of neurological and psychiatric symptoms directly related to systemic lupus erythematosus (SLE). NPSLE includes heterogeneous and rare neuropsychiatric (NP) manifestations involving both the central and peripheral nervous system. Due to the lack of a gold standard, the attribution of NP symptoms to SLE represents a clinical challenge that obligates the strict exclusion of any other potential cause. In the acute setting, management of these patients does not differ from other non-SLE subjects presenting with the same NP manifestation. Afterwards, an individualized therapeutic strategy, depending on the presenting manifestation and severity of symptoms, must be started. Clinical trials in NPSLE are scarce and most of the data are extracted from case series and case reports. High-dose glucocorticoids and intravenous cyclophosphamide remain the cornerstone for patients with severe symptoms that are thought to reflect inflammation or an underlying autoimmune process. Rituximab, intravenous immunoglobulins, or plasmapheresis may be used if response is not achieved. When patients present with mild to moderate NP manifestations, or when maintenance therapy is warranted, azathioprine and mycophenolate may be considered. When symptoms are thought to reflect a thrombotic underlying process, anticoagulation and antiplatelet agents are the mainstay of therapy, especially if antiphospholipid antibodies or antiphospholipid syndrome are present. Recent trials on SLE using new biologicals, based on newly understood SLE mechanisms, have shown promising results. Based on what we currently know about its pathogenesis, it is tempting to speculate how these new therapies may affect the management of NPSLE patients. This article provides a comprehensive and critical review of the literature on the epidemiology, pathophysiology, diagnosis, and management of NPSLE. We describe the most

  15. Are Current Accounts of Asian Economies Mean-reverting?: Nonlinear Unit Root Test Approach

    Directory of Open Access Journals (Sweden)

    Bonghan Kim

    2005-12-01

    Full Text Available This paper tests the mean reverting property of current account in the financial crisis-affected 5 counties of southeast Asia using nonlinear unit root tests of Park and shintani(2004. Our approach is based on the idea that a conventional unit root test has lower power in detecting the nonlinear mean reverting behavior if the current account follows a nonlinear mean reversion process. We obtained following empirical results. First, for the pre-crisis period (1981Q1-1996Q4, the current accounts of Indonesia, Malaysia and Philippines are mean-reverting but those of Korea and Thailand are not mean-reverting. Second, for the full sample period (1981Q1-2003Q4, the ADF test fails to reject the unit root of the current account in all countries except Philippines. However, unit root is rejected in favor of nonlinear mean reversion except Thailand. This nonlinear unit root test result implies that crisis-affected Asian countries except Thailand have sustainable paths of current accounts. Third, when the current accounts of East Asian countries are nonlinear mean-reverting, the mean reverting process can be well described by the ESTAR model, instead of the DTAR or DLSTAR model. The nonlinear unit root test results imply smooth nonlinear mean-reversion behaviors of East Asian current accounts. Finally, the shape of estimated impulse response functions becomes steeper as the size of shock increases, which is the very characteristic of the nonlinear process.

  16. Light-cone gauge approach to arbitrary spin fields, currents and shadows

    International Nuclear Information System (INIS)

    Metsaev, R R

    2014-01-01

    Totally symmetric arbitrary spin fields in AdS space, conformal fields, conformal currents, and shadow fields in flat space are studied. Light-cone gauge formulations for such fields, currents and shadows are obtained. Use of the Poincaré parametrization of AdS space and ladder operators allows us to treat fields in flat and AdS spaces on an equal footing. Light-cone gauge realization of relativistic symmetries for fields, currents and shadows is also obtained. The light-cone gauge formulation for fields is obtained by using the gauge invariant Lagrangian which is presented in terms of modified de Donder divergence, while the light-cone gauge formulation for currents and shadows is obtained by using the gauge invariant approach to currents and shadows. This allows us to demonstrate explicitly how the ladder operators entering the gauge invariant formulation of fields, currents and shadows manifest themselves in the light-cone gauge formulation for fields, currents and shadows. (paper)

  17. Current Methods Applied to Biomaterials - Characterization Approaches, Safety Assessment and Biological International Standards.

    Science.gov (United States)

    Oliveira, Justine P R; Ortiz, H Ivan Melendez; Bucio, Emilio; Alves, Patricia Terra; Lima, Mayara Ingrid Sousa; Goulart, Luiz Ricardo; Mathor, Monica B; Varca, Gustavo H C; Lugao, Ademar B

    2018-04-10

    Safety and biocompatibility assessment of biomaterials are themes of constant concern as advanced materials enter the market as well as products manufactured by new techniques emerge. Within this context, this review provides an up-to-date approach on current methods for the characterization and safety assessment of biomaterials and biomedical devices from a physicalchemical to a biological perspective, including a description of the alternative methods in accordance with current and established international standards. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  18. Pharmacological screening technologies for venom peptide discovery.

    Science.gov (United States)

    Prashanth, Jutty Rajan; Hasaballah, Nojod; Vetter, Irina

    2017-12-01

    Venomous animals occupy one of the most successful evolutionary niches and occur on nearly every continent. They deliver venoms via biting and stinging apparatuses with the aim to rapidly incapacitate prey and deter predators. This has led to the evolution of venom components that act at a number of biological targets - including ion channels, G-protein coupled receptors, transporters and enzymes - with exquisite selectivity and potency, making venom-derived components attractive pharmacological tool compounds and drug leads. In recent years, plate-based pharmacological screening approaches have been introduced to accelerate venom-derived drug discovery. A range of assays are amenable to this purpose, including high-throughput electrophysiology, fluorescence-based functional and binding assays. However, despite these technological advances, the traditional activity-guided fractionation approach is time-consuming and resource-intensive. The combination of screening techniques suitable for miniaturization with sequence-based discovery approaches - supported by advanced proteomics, mass spectrometry, chromatography as well as synthesis and expression techniques - promises to further improve venom peptide discovery. Here, we discuss practical aspects of establishing a pipeline for venom peptide drug discovery with a particular emphasis on pharmacology and pharmacological screening approaches. This article is part of the Special Issue entitled 'Venom-derived Peptides as Pharmacological Tools.' Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Noise exposure and oxidative balance in auditory and extra-auditory structures in adult and developing animals. Pharmacological approaches aimed to minimize its effects.

    Science.gov (United States)

    Molina, S J; Miceli, M; Guelman, L R

    2016-07-01

    Noise coming from urban traffic, household appliances or discotheques might be as hazardous to the health of exposed people as occupational noise, because may likewise cause hearing loss, changes in hormonal, cardiovascular and immune systems and behavioral alterations. Besides, noise can affect sleep, work performance and productivity as well as communication skills. Moreover, exposure to noise can trigger an oxidative imbalance between reactive oxygen species (ROS) and the activity of antioxidant enzymes in different structures, which can contribute to tissue damage. In this review we systematized the information from reports concerning noise effects on cell oxidative balance in different tissues, focusing on auditory and non-auditory structures. We paid specific attention to in vivo studies, including results obtained in adult and developing subjects. Finally, we discussed the pharmacological strategies tested by different authors aimed to minimize the damaging effects of noise on living beings. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Integrodifferential approach to solution of eddy currents in linear structures with motion

    Czech Academy of Sciences Publication Activity Database

    Doležel, Ivo; Karban, P.; Donátová, M.; Šolín, Pavel

    2010-01-01

    Roč. 80, č. 8 (2010), s. 1636-1646 ISSN 0378-4754 R&D Projects: GA ČR(CZ) GA102/07/0496 Institutional research plan: CEZ:AV0Z20570509 Keywords : eddy currents * integrodifferential approach * numerical analysis Subject RIV: JA - Electronics ; Optoelectronics, Electrical Engineering Impact factor: 0.812, year: 2010 www.elsevier.com/locate/matcom

  1. Auroral Substorms: Search for Processes Causing the Expansion Phase in Terms of the Electric Current Approach

    Science.gov (United States)

    Akasofu, Syun-Ichi

    2017-10-01

    Auroral substorms are mostly manifestations of dissipative processes of electromagnetic energy. Thus, we consider a sequence of processes consisting of the power supply (dynamo), transmission (currents/circuits) and dissipations (auroral substorms-the end product), namely the electric current line approach. This work confirms quantitatively that after accumulating magnetic energy during the growth phase, the magnetosphere unloads the stored magnetic energy impulsively in order to stabilize itself. This work is based on our result that substorms are caused by two current systems, the directly driven (DD) current system and the unloading system (UL). The most crucial finding in this work is the identification of the UL (unloading) current system which is responsible for the expansion phase. A very tentative sequence of the processes leading to the expansion phase (the generation of the UL current system) is suggested for future discussions. (1) The solar wind-magnetosphere dynamo enhances significantly the plasma sheet current when its power is increased above 10^{18} erg/s (10^{11} w). (2) The magnetosphere accumulates magnetic energy during the growth phase, because the ionosphere cannot dissipate the increasing power because of a low conductivity. As a result, the magnetosphere is inflated, accumulating magnetic energy. (3) When the power reaches 3-5× 10^{18} erg/s (3-5× 10^{11} w) for about one hour and the stored magnetic energy reaches 3-5×10^{22} ergs (10^{15} J), the magnetosphere begins to develop perturbations caused by current instabilities (the current density {≈}3× 10^{-12} A/cm2 and the total current {≈}106 A at 6 Re). As a result, the plasma sheet current is reduced. (4) The magnetosphere is thus deflated. The current reduction causes partial B/partial t > 0 in the main body of the magnetosphere, producing an earthward electric field. As it is transmitted to the ionosphere, it becomes equatorward-directed electric field which drives both

  2. VALUE-BASED APPROACH TO MANAGING CURRENT ASSETS OF CORPORATE CONSTRUCTION COMPANIES

    Directory of Open Access Journals (Sweden)

    Galyna Shapoval

    2017-09-01

    Full Text Available In modern conditions of management, the value of an enterprise becomes the main indicator, which is learned not only by scientists, but also by owners of enterprise and potential investors. Current assets take a very important place among the factors that affect the value of an enterprise, so management of current assets becomes more acute from the point of their impact on enterprise value. The purpose of the paper is to develop a system of value-based management of corporate construction companies’ current assets. The main tasks are: the study of current assets impact on the value of corporate construction companies, the definition of value-based approach to managing current assets of corporate enterprises and development of value-based management system of corporate construction companies’ current assets by elements. General scientific and special research methods were used while writing the work. Value-based management of current assets involves value-based management of the elements of current assets. The value-based inventory management includes the following stages of management: the assessment of reliability and choice of supplier according to the criterion of cash flow maximization, the classification of stocks in management accounting according to the rhythm of supply and the establishment of periodicity of supplies in accordance with the needs of the construction process. The value-based management of accounts receivable includes the following stages of management: assessment of the efficiency of investment of working capital into accounts receivable, the assessment of customers' loyalty and the definition of credit conditions and monitoring of receivables by construction and debt instruments. Value-based cash management involves determining the required level of cash to ensure the continuity of the construction process, assessing the effectiveness of cash use according to the criterion of maximizing cash flow, as well as budget

  3. Current Approaches in the Treatment of Relapsed and Refractory Acute Myeloid Leukemia

    Science.gov (United States)

    Ramos, Nestor R.; Mo, Clifton C.; Karp, Judith E.; Hourigan, Christopher S.

    2015-01-01

    The limited sensitivity of the historical treatment response criteria for acute myeloid leukemia (AML) has resulted in a different paradigm for treatment compared with most other cancers presenting with widely disseminated disease. Initial cytotoxic induction chemotherapy is often able to reduce tumor burden to a level sufficient to meet the current criteria for “complete” remission. Nevertheless, most AML patients ultimately die from their disease, most commonly as clinically evident relapsed AML. Despite a variety of available salvage therapy options, prognosis in patients with relapsed or refractory AML is generally poor. In this review, we outline the commonly utilized salvage cytotoxic therapy interventions and then highlight novel investigational efforts currently in clinical trials using both pathway-targeted agents and immunotherapy based approaches. We conclude that there is no current standard of care for adult relapsed or refractory AML other than offering referral to an appropriate clinical trial. PMID:25932335

  4. A frequency domain approach to analyzing passive battery-ultracapacitor hybrids supplying periodic pulsed current loads

    International Nuclear Information System (INIS)

    Kuperman, Alon; Aharon, Ilan; Kara, Avi; Malki, Shalev

    2011-01-01

    Highlights: → Passive battery-ultracapacitor hybrids are examined. → Frequency domain analysis is employed. → The ultracapacitor branch operates as a low-pass filter for the battery. → The battery supplies the average load demand. → Design requirements are discussed. - Abstract: A Fourier-based analysis of passive battery-ultracapacitor hybrid sources is introduced in the manuscript. The approach is first introduced for a general load, and then is followed by a study for a case of periodic pulsed current load. It is shown that the ultracapacitor branch is perceived by the battery as a low-pass filter, which absorbs the majority of the high frequency harmonic current and letting the battery to supply the average load demand in addition to the small part of dynamic current. Design requirements influence on the ultracapacitor capacitance and internal resistance choice are quantitatively discussed. The theory is enforced by simulation and experimental results, showing an excellent agreement.

  5. Limitations Of The Current State Space Modelling Approach In Multistage Machining Processes Due To Operation Variations

    Science.gov (United States)

    Abellán-Nebot, J. V.; Liu, J.; Romero, F.

    2009-11-01

    The State Space modelling approach has been recently proposed as an engineering-driven technique for part quality prediction in Multistage Machining Processes (MMP). Current State Space models incorporate fixture and datum variations in the multi-stage variation propagation, without explicitly considering common operation variations such as machine-tool thermal distortions, cutting-tool wear, cutting-tool deflections, etc. This paper shows the limitations of the current State Space model through an experimental case study where the effect of the spindle thermal expansion, cutting-tool flank wear and locator errors are introduced. The paper also discusses the extension of the current State Space model to include operation variations and its potential benefits.

  6. Investigating students' view on STEM in learning about electrical current through STS approach

    Science.gov (United States)

    Tupsai, Jiraporn; Yuenyong, Chokchai

    2018-01-01

    This study aims to investigate Grade 11 students' views on Science Technology Engineering Mathematics (STEM) with the integration of learning about electrical current based on Science Technology Society (STS) approach [8]. The participants were 60 Grade 11 students in Demonstration Secondary School, Khon Kaen University, Khon Kaen Province, Thailand. The methodology is in the respect of interpretive paradigm. The teaching and learning about Electrical Current through STS approach carried out over 6 weeks. The Electrical Current unit through STS approach was developed based on framework[8] that consists of five stages including (1) identification of social issues, (2) identification of potential solutions, (3) need for knowledge, (4) decision making, and (5) socialization stage. To start with, the question "what if this world is lack of electricity" was challenged in the class in order to move students to find the problem of how to design Electricity Generation from Clean Energy. Students were expected to apply scientific and other knowledge to design of Electricity Generation. Students' views on STEM were collected during their learning by participant' observation and students' tasks. Their views on STEM were categorized when they applied their knowledge for designing the Electricity Generation. The findings indicated that students cooperatively work to solve the problem when applying knowledge about the content of Science and Mathematics and processing skill of Technology and Engineering. It showed that students held the integration of science, technology, engineering and mathematics to design their possible solutions in learning about Electrical Current. The paper also discusses implications for science teaching and learning through STS in Thailand.

  7. Exploring the Therapeutic Mechanism of Desmodium styracifolium on Oxalate Crystal-Induced Kidney Injuries Using Comprehensive Approaches Based on Proteomics and Network Pharmacology

    Directory of Open Access Journals (Sweden)

    Jiebin Hou

    2018-06-01

    Full Text Available Purpose: As a Chinese medicinal herb, Desmodium styracifolium (Osb. Merr (DS has been applied clinically to alleviate crystal-induced kidney injuries, but its effective components and their specific mechanisms still need further exploration. This research first combined the methods of network pharmacology and proteomics to explore the therapeutic protein targets of DS on oxalate crystal-induced kidney injuries to provide a reference for relevant clinical use.Methods: Oxalate-induced kidney injury mouse, rat, and HK-2 cell models were established. Proteins differentially expressed between the oxalate and control groups were respectively screened using iTRAQ combined with MALDI-TOF-MS. The common differential proteins of the three models were further analyzed by molecular docking with DS compounds to acquire differential targets. The inverse docking targets of DS were predicted through the platform of PharmMapper. The protein–protein interaction (PPI relationship between the inverse docking targets and the differential proteins was established by STRING. Potential targets were further validated by western blot based on a mouse model with DS treatment. The effects of constituent compounds, including luteolin, apigenin, and genistein, were investigated based on an oxalate-stimulated HK-2 cell model.Results: Thirty-six common differentially expressed proteins were identified by proteomic analysis. According to previous research, the 3D structures of 15 major constituents of DS were acquired. Nineteen differential targets, including cathepsin D (CTSD, were found using molecular docking, and the component-differential target network was established. Inverse-docking targets including p38 MAPK and CDK-2 were found, and the network of component-reverse docking target was established. Through PPI analysis, 17 inverse-docking targets were linked to differential proteins. The combined network of component-inverse docking target-differential proteins was

  8. An interdisciplinary review of current and future approaches to improving human-predator relations.

    Science.gov (United States)

    Pooley, S; Barua, M; Beinart, W; Dickman, A; Holmes, G; Lorimer, J; Loveridge, A J; Macdonald, D W; Marvin, G; Redpath, S; Sillero-Zubiri, C; Zimmermann, A; Milner-Gulland, E J

    2017-06-01

    In a world of shrinking habitats and increasing competition for natural resources, potentially dangerous predators bring the challenges of coexisting with wildlife sharply into focus. Through interdisciplinary collaboration among authors trained in the humanities, social sciences, and natural sciences, we reviewed current approaches to mitigating adverse human-predator encounters and devised a vision for future approaches to understanding and mitigating such encounters. Limitations to current approaches to mitigation include too much focus on negative impacts; oversimplified equating of levels of damage with levels of conflict; and unsuccessful technical fixes resulting from failure to engage locals, address hidden costs, or understand cultural (nonscientific) explanations of the causality of attacks. An emerging interdisciplinary literature suggests that to better frame and successfully mitigate negative human-predator relations conservation professionals need to consider dispensing with conflict as the dominant framework for thinking about human-predator encounters; work out what conflicts are really about (they may be human-human conflicts); unravel the historical contexts of particular conflicts; and explore different cultural ways of thinking about animals. The idea of cosmopolitan natures may help conservation professionals think more clearly about human-predator relations in both local and global context. These new perspectives for future research practice include a recommendation for focused interdisciplinary research and the use of new approaches, including human-animal geography, multispecies ethnography, and approaches from the environmental humanities notably environmental history. Managers should think carefully about how they engage with local cultural beliefs about wildlife, work with all parties to agree on what constitutes good evidence, develop processes and methods to mitigate conflicts, and decide how to monitor and evaluate these. Demand for

  9. CLINICAL PHARMACOLOGY OF DIURETICS

    Directory of Open Access Journals (Sweden)

    I. V. Soldatenko

    2014-06-01

    Full Text Available Clinical pharmacology of diuretics in the international system of ATC (anatomic-therapeutic-chemical is presented. Classification of this group by the action mechanism and caused effects is provided. Pharmacokinetics and pharmacodynamics features, indications and principles of diuretics usage in clinics are considered. Contraindications, side effects and interaction with other drugs of this group are discussed in detail.

  10. Developmental paediatric anaesthetic pharmacology

    DEFF Research Database (Denmark)

    Hansen, Tom Giedsing

    2015-01-01

    Safe and effective drug therapy in neonates, infants and children require detailed knowledge about the ontogeny of drug disposition and action as well how these interact with genetics and co-morbidity of children. Recent advances in developmental pharmacology in children follow the increased...

  11. Delirium in the elderly: A systematic review of pharmacological and non-pharmacological treatments

    Directory of Open Access Journals (Sweden)

    Cecília Carboni Tardelli Cerveira

    Full Text Available ABSTRACT Delirium is a common disorder associated with poor prognosis, especially in the elderly. The impact of different treatment approaches for delirium on morbimortality and long-term welfare is not completely understood. OBJECTIVE: To determine the efficacy of pharmacological and non-pharmacological treatments in elderly patients with delirium. METHODS: This systematic review compared pharmacological and non-pharmacological treatments in patients over 60 years old with delirium. Databases used were: MEDLINE (PubMed, EMBASE, Cochrane CENTRAL and LILACS from inception to January 6th, 2016. RESULTS: A total of ten articles were selected. The six non-pharmacological intervention studies showed no impact on duration of delirium, mortality or institutionalization, but a decrease in severity of delirium and improvement in medium-term cognitive function were observed. The most commonly used interventions were temporal-spatial orientation, orientation to self and others, early mobilization and sleep hygiene. The four studies with pharmacological interventions found that rivastigmine reduced the duration of delirium, improved cognitive function and reduced caregiver burden; olanzapine and haloperidol decreased the severity of delirium; droperidol reduced length of hospitalization and improved delirium remission rate. CONCLUSION: Although the pharmacological approach has been used in the treatment of delirium among elderly, there have been few studies assessing its efficacy, involving a small number of patients. However, the improvements in delirium duration and severity suggest these drugs are effective in treating the condition. Once delirium has developed, non-pharmacological treatment seems less effective in controlling symptoms, and there is a lack of studies describing different non-pharmacological interventions.

  12. The pharmacology of gynaecology.

    Science.gov (United States)

    Tothill, A

    1980-09-01

    Focus in this discussion of the pharmacology of gynecology is on the following: vaginal infections; genital herpes; genital warts; pelvic inflammatory disease; urinary infections; pruritus vulvae; menstrual problems; infertility; oral contraception; and hormone replacement therapy. Doctors in England working in Local Authority Family Planning Clinics are debarred from prescribing, and any patient with a vaginal infection has to be referred either to a special clinic or to her general practitioner which is often preferable as her medical history will be known. Vaginal discharge is a frequent complaint, and it is necessary to obtain full details. 1 of the most common infections is vaginal candidosis. Nystatin pessaries have always been a useful 1st-line treatment and are specific for this type of infection. Trichomonas infection also occurs frequently and responds well to metronidazole in a 200 mg dosage, 3 times daily for 7 days. It is necessary to treat the consort at the same time. Venereal diseases such as syphilis and gonorrhea always require vigorous treatment. Patients are now presenting with herpes genitalis far more often. The only treatment which is currently available, and is as good as any, is the application of warm saline to the vaginal area. Genital warts may be discovered on routine gynecological examination or may be reported to the doctor by the patient. 1 application of a 20% solution of podophyllum, applied carefully to each wart, usually effects a cure. Pelvic inflammatory disease seems to be on the increase. Provided any serious disease is ruled out a course of systemic antibiotics is often effective. Urinary infections are often seen in the gynecologic clinic, and many of these will respond well to 2 tablets of co-trimoxazole, 2 times daily for 14 days. In pruritus vulvae it is important to determine whether the cause is general or local. Menstrual problems regularly occur and have been increased by the IUD and the low-dose progesterone pill

  13. Clozapine-resistant schizophrenia – non pharmacological augmentation methods

    Directory of Open Access Journals (Sweden)

    Gałaszkiewicz Joanna

    2017-12-01

    Full Text Available Clozapine is the drug of choice for drug-resistant schizophrenia, but despite its use, 30-40% patients fail to achieve satisfactory therapeutic effects. In such situations, augmentation attempts are made by both pharmacological and non-pharmacological methods. To date, most of the work has been devoted to pharmacological strategies, much less to augemantation of clozapine with electroconvulsive therapy (C+ECT, transcranial direct current stimulation (tDCS or transcranial magnetic stimulation (TMS.

  14. A systems biology-based approach to uncovering the molecular mechanisms underlying the effects of dragon's blood tablet in colitis, involving the integration of chemical analysis, ADME prediction, and network pharmacology.

    Directory of Open Access Journals (Sweden)

    Haiyu Xu

    Full Text Available Traditional Chinese medicine (TCM is one of the oldest East Asian medical systems. The present study adopted a systems biology-based approach to provide new insights relating to the active constituents and molecular mechanisms underlying the effects of dragon's blood (DB tablets for the treatment of colitis. This study integrated chemical analysis, prediction of absorption, distribution, metabolism, and excretion (ADME, and network pharmacology. Firstly, a rapid, reliable, and accurate ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry method was employed to identify 48 components of DB tablets. In silico prediction of the passive absorption of these compounds, based on Caco-2 cell permeability, and their P450 metabolism enabled the identification of 22 potentially absorbed components and 8 metabolites. Finally, networks were constructed to analyze interactions between these DB components/metabolites absorbed and their putative targets, and between the putative DB targets and known therapeutic targets for colitis. This study provided a great opportunity to deepen the understanding of the complex pharmacological mechanisms underlying the effects of DB in colitis treatment.

  15. [Pharmacological therapy of obesity].

    Science.gov (United States)

    Pagotto, Uberto; Vanuzzo, Diego; Vicennati, Valentina; Pasquali, Renato

    2008-04-01

    Obesity is reaching epidemic proportions worldwide and it is correlated with various comorbidities, among which the most relevant are diabetes mellitus, arterial hypertension, and cardiovascular diseases. Obesity management is a modern challenge because of the rapid evolution of unfavorable lifestyles and unfortunately there are no effective treatments applicable to the large majority of obese/overweight people. The current medical attitude is to treat the complications of obesity (e.g. dyslipidemia, hypertension, diabetes, and cardiovascular diseases). However, the potential of treating obesity is enormous, bearing in mind that a volitional weight loss of 10 kg is associated with important risk factor improvement: blood pressure -10 mmHg, total cholesterol -10%, LDL cholesterol -15%, triglycerides -30%, fasting glucose -50%, HDL cholesterol +8%. Drug treatment for obesity is an evolving branch of pharmacology, burdened by severe side effects and consequences of the early drugs, withdrawn from the market, and challenged by the lack of long-term data on the effect of medications on obesity-related morbidity and mortality, first of all cardiovascular diseases. In Europe three antiobesity drugs are currently licensed: sibutramine, orlistat, and rimonabant; important trials with clinical endpoints are ongoing for sibutramine and rimonabant. While waiting for their results, it is convenient to evaluate these drugs for their effects on body weight and cardiometabolic risk factors. Sibutramine is a centrally acting serotonin/noradrenaline reuptake inhibitor that mainly increases satiety. At the level of brown adipose tissue, sibutramine can also facilitate energy expenditure by increasing thermogenesis. The long-term studies (five) documented a mean differential weight reduction of 4.45 kg for sibutramine vs placebo. Considering the principal studies, attrition rate was 43%. This drug not only reduces body weight and waist circumference, but it decreases triglycerides and

  16. Current approaches to the diagnosis, treatment, and reporting of trichomoniasis and candidosis.

    Science.gov (United States)

    O'Connor, B H; Adler, M W

    1979-02-01

    The current approach to the management of trichomoniasis and candidosis in sexually transmitted disease (STD) clinics in England and Wales is described. Microscopy alone was used in the diagnosis of trichomoniasis in 44% of clinics and of candidosis in 35% of clinics. Oral metronidazole was used for the treatment of trichomoniasis in women in 92% of clinics. Vaginal pessaries containing nystatin or clotrimazole were routinely used to treat candidosis in 95% of clinics. Male sexual contacts of female patients with candidosis and trichomoniasis were invited to attend for examination in 88% of clinics. Physicians in 81% of clinics prescribed treatment on epidemiological grounds for male contacts of female patients with trichomoniasis. A more uniform approach to the diagnostic categories used for the quarterly returns for cases treated epidemiologically is recommended.

  17. Multilevel Molecular Modeling Approach for a Rational Design of Ionic Current Sensors for Nanofluidics.

    Science.gov (United States)

    Kirch, Alexsandro; de Almeida, James M; Miranda, Caetano R

    2018-05-10

    The complexity displayed by nanofluidic-based systems involves electronic and dynamic aspects occurring across different size and time scales. To properly model such kind of system, we introduced a top-down multilevel approach, combining molecular dynamics simulations (MD) with first-principles electronic transport calculations. The potential of this technique was demonstrated by investigating how the water and ionic flow through a (6,6) carbon nanotube (CNT) influences its electronic transport properties. We showed that the confinement on the CNT favors the partially hydrated Na, Cl, and Li ions to exchange charge with the nanotube. This leads to a change in the electronic transmittance, allowing for the distinguishing of cations from anions. Such an ionic trace may handle an indirect measurement of the ionic current that is recorded as a sensing output. With this case study, we are able to show the potential of this top-down multilevel approach, to be applied on the design of novel nanofluidic devices.

  18. How is the Current Nano/Microscopic Knowledge Implemented in Model Approaches?

    International Nuclear Information System (INIS)

    Rotenberg, Benjamin

    2013-01-01

    The recent developments of experimental techniques have opened new opportunities and challenges for the modelling and simulation of clay materials, on various scales. In this communication, several aspects of the interaction between experimental and modelling approaches will be presented and dis-cussed. What levels of modelling are available depending on the target property and what experimental input is required? How can experimental information be used to validate models? What knowledge can modelling on different scale bring to the knowledge on the physical properties of clays? Finally, what can we do when experimental information is not available? Models implement the current nano/microscopic knowledge using experimental input, taking advantage of multi-scale approaches, and providing data or insights complementary to experiments. Future work will greatly benefit from the recent experimental developments, in particular for 3D-imaging on intermediate scales, and should also address other properties, e.g. mechanical or thermal properties. (authors)

  19. Modelling chloride penetration in concrete using electrical voltage and current approaches

    Directory of Open Access Journals (Sweden)

    Juan Lizarazo-Marriaga

    2011-03-01

    Full Text Available This paper reports a research programme aimed at giving a better understanding of the phenomena involved in the chloride penetration in cement-based materials. The general approach used was to solve the Nernst-Planck equation numerically for two physical ideal states that define the possible conditions under which chlorides will move through concrete. These conditions are named in this paper as voltage control and current control. For each condition, experiments and simulations were carried out in order to establish the importance of electrical variables such as voltage and current in modelling chloride transport in concrete. The results of experiments and simulations showed that if those electrical variables are included as key parameters in the modelling of chloride penetration through concrete, a better understanding of this complex phenomenon can be obtained.

  20. Moment approach to neoclassical flows, currents and transport in auxiliary heated tokamaks

    International Nuclear Information System (INIS)

    Kim, Yil Bong.

    1988-02-01

    The moment approach is utilized to derive the full complement of neoclassical transport processes in auxiliary heated tokamaks. The effects of auxiliary heating [neutral beam injection (NBI) and ion cyclotron resonance heating (ICRH)] considered arise from the collisional interaction between the background plasma species and the fast-ion-tail species. From a known fast ion distribution function we evaluate the parallel (to the magnetic field) momentum and heat flow inputs to the background plasma. Then, through the momentum and heat flow balance equations, we can determine the induced parallel flows (and current) and radial transpot fluxes in ''equilibrium'' (on the time scale much longer than the collisional relaxation time, i.e., t >> 1ν/sub ii/). In addition to the fast-ion-induced current, the total neoclassical current includes the boostap current, which is driven by the pressure and temperature gradients, the Pfirsch-Schlueter current which is required for charge neutrality, and the neoclassical (including trapped particle effects) Spitzer current due to the parallel electric field. The radial transport fluxes also include off-diagonal compnents in the transport matrix which correspond to the Ware (neoclassical) pinch due to the inductive applied electric field an the fast-ion-induced radial fluxes, in addition to the usual pressure- and temperature-gradient-driven fluxes (particle diffusion and heat conduction). Once the tranport coefficient are completely determined, the radial fluxes and the heat fluxes can be substituted into the density and energy evolution equations to provide a complete description of ''equilibrium'' (δδt << ν/sub ii/) neoclassical transport processes in a plasma. 47 refs., 14 figs

  1. A Study of Frequency Mixing Approaches for Eddy Current Testing of Steam Generator Tubes

    International Nuclear Information System (INIS)

    Jung, Hee Jun; Song, Sung Jin; Kim, Chang Hwan; Kim, Dae Kwang

    2009-01-01

    The multifrequency eddy current testing(ECT) have been proposed various frequency mixing algorithms. In this study, we compare these approaches to frequency mixing of ECT signals from steam generator tubes; time-domain optimization, discrete cosine transform-domain optimization. Specifically, in this study, two different frequency mixing algorithms, a time-domain optimization method and a discrete cosine transform(DCT) optimization method, are investigated using the experimental signals captured from the ASME standard tube. The DCT domain optimization method is computationally fast but produces larger amount of residue.

  2. Implementation of systematic training approach in Kozloduy Training Centre - Current situation. Presentation of Bulgaria

    International Nuclear Information System (INIS)

    Kosturkov, L.

    1993-01-01

    To identify the needs in implementation of the systematic training approach, a relation between the number of trainees, duration of the training and the type of training should be made. In other hand, as it was stated in the TWG-T(93) Status Report, in order to be better identified outstanding training needs, the existing capabilities and other related projects should be taken into account. This report is pointed to give more details for the current situation in Bulgaria and to clarify the needs of international assistance. 3 refs, 3 tabs

  3. Simple engineering design for complex thermoelectric generators based on reduced current approach

    DEFF Research Database (Denmark)

    Wijesooriyage, Waruna Dissanayaka; Rezaniakolaei, Alireza; Rosendahl, Lasse

    2015-01-01

    Thermoelectric generators (TEGs) are niche candidate for the field of energy management as electrical generator devices. Generally, comprehensive and accurate design techniques for TEGs (thermoelectric generators), such as reduced current approach (RCA), are complex and time consuming processes....... This study develops a simple, comprehensive and accurate TEG designing technique based on RCA. The proposed method can predict the most efficient TEG architecture with more than 97% accuracy comparing to the RCA over wide range of possible temperature and zT for present TEG applications. Moreover...

  4. Dhat syndrome: Evolution of concept, current understanding, and need of an integrated approach

    Directory of Open Access Journals (Sweden)

    Sujita Kumar Kar

    2015-01-01

    Full Text Available Dhat syndrome has often been construed as a culture-bound sexual neurosis of the Indian subcontinent. Symptoms similar to that of Dhat syndrome has been described in other cultures across different time periods. The present paper looks at the evolution of the concept of Dhat syndrome in India. The review also takes an overview of the current understanding of this syndrome in terms of nosological status as a distinct entity and its "culture-bound" status. The narrative finally attempts to discuss the integrated approach for the treatment of this disorder.

  5. Non-pharmacological intervention for memory decline

    Directory of Open Access Journals (Sweden)

    Maria eCotelli

    2012-03-01

    Full Text Available Non-pharmacological treatment of memory difficulties in healthy older adults, as well as those with brain damage and neurodegenerative disorders, has gained much attention in recent years (Ball et al., 2002, Willis et al., 2006, Acevedo and Loewenstein, 2007. The two main reasons that explain this growing interest in memory rehabilitation are the limited efficacy of current drug therapies and the plasticity of the human central nervous system (Cotelli et al., 2011c and the discovery that during aging, the connections in the brain are not fixed but retain the capacity to change with learning.Moreover, several studies have reported enhanced cognitive performance in patients with neurological disease, following non-invasive brain stimulation (i.e., repetitive transcranial magnetic stimulation (rTMS and transcranial direct current stimulation (tDCS to specific cortical areas. The present review provides an overview of memory rehabilitation in individuals with Mild Cognitive Impairment (MCI and in patients with Alzheimer’s Disease (AD with particular regard to cognitive rehabilitation interventions focused on memory and non-invasive brain stimulation. Reviewed data suggest that in patients with memory deficits, memory intervention therapy could lead to performance improvements in memory, nevertheless further studies need to be conducted in order to establish the real value of this approach.

  6. An adaptive mesh refinement approach for average current nodal expansion method in 2-D rectangular geometry

    International Nuclear Information System (INIS)

    Poursalehi, N.; Zolfaghari, A.; Minuchehr, A.

    2013-01-01

    Highlights: ► A new adaptive h-refinement approach has been developed for a class of nodal method. ► The resulting system of nodal equations is more amenable to efficient numerical solution. ► The benefit of the approach is reducing computational efforts relative to the uniform fine mesh modeling. ► Spatially adaptive approach greatly enhances the accuracy of the solution. - Abstract: The aim of this work is to develop a spatially adaptive coarse mesh strategy that progressively refines the nodes in appropriate regions of domain to solve the neutron balance equation by zeroth order nodal expansion method. A flux gradient based a posteriori estimation scheme has been utilized for checking the approximate solutions for various nodes. The relative surface net leakage of nodes has been considered as an assessment criterion. In this approach, the core module is called in by adaptive mesh generator to determine gradients of node surfaces flux to explore the possibility of node refinements in appropriate regions and directions of the problem. The benefit of the approach is reducing computational efforts relative to the uniform fine mesh modeling. For this purpose, a computer program ANRNE-2D, Adaptive Node Refinement Nodal Expansion, has been developed to solve neutron diffusion equation using average current nodal expansion method for 2D rectangular geometries. Implementing the adaptive algorithm confirms its superiority in enhancing the accuracy of the solution without using fine nodes throughout the domain and increasing the number of unknown solution. Some well-known benchmarks have been investigated and improvements are reported

  7. A Unified Current Loop Tuning Approach for Grid-Connected Photovoltaic Inverters

    Directory of Open Access Journals (Sweden)

    Weiyi Zhang

    2016-09-01

    Full Text Available High level penetration of renewable energy sources has reshaped modern electrical grids. For the future grid, distributed renewable power generation plants can be integrated in a larger scale. Control of grid-connected converters is required to achieve fast power reference tracking and further to present grid-supporting and fault ride-through performance. Among all of the aspects for converter control, the inner current loop for grid-connected converters characterizes the system performance considerably. This paper proposes a unified current loop tuning approach for grid-connected converters that is generally applicable in different cases. A direct discrete-time domain tuning procedure is used, and particularly, the selection of the phase margin and crossover frequency is analyzed, which acts as the main difference compared with the existing studies. As a general method, the approximation in the modeling of the controller and grid filter is avoided. The effectiveness of the tuning approach is validated in both simulation and experimental results with respect to power reference tracking, frequency and voltage supporting.

  8. Regenerative endodontics as a tissue engineering approach: past, current and future.

    Science.gov (United States)

    Malhotra, Neeraj; Mala, Kundabala

    2012-12-01

    With the reported startling statistics of high incidence of tooth decay and tooth loss, the current interest is focused on the development of alternate dental tissue replacement therapies. This has led to the application of dental tissue engineering as a clinically relevant method for the regeneration of dental tissues and generation of bioengineered whole tooth. Although, tissue engineering approach requires the three main key elements of stem cells, scaffold and morphogens, a conductive environment (fourth element) is equally important for successful engineering of any tissue and/or organ. The applications of this science has evolved continuously in dentistry, beginning from the application of Ca(OH)(2) in vital pulp therapy to the development of a fully functional bioengineered tooth (mice). Thus, with advances in basic research, recent reports and studies have shown successful application of tissue engineering in the field of dentistry. However, certain practical obstacles are yet to be overcome before dental tissue regeneration can be applied as evidence-based approach in clinics. The article highlights on the past achievements, current developments and future prospects of tissue engineering and regenerative therapy in the field of endodontics and bioengineered teeth (bioteeth). © 2012 The Authors. Australian Endodontic Journal © 2012 Australian Society of Endodontology.

  9. Angular approach combined to mechanical model for tool breakage detection by eddy current sensors

    Science.gov (United States)

    Ritou, M.; Garnier, S.; Furet, B.; Hascoet, J. Y.

    2014-02-01

    The paper presents a new complete approach for Tool Condition Monitoring (TCM) in milling. The aim is the early detection of small damages so that catastrophic tool failures are prevented. A versatile in-process monitoring system is introduced for reliability concerns. The tool condition is determined by estimates of the radial eccentricity of the teeth. An adequate criterion is proposed combining mechanical model of milling and angular approach.Then, a new solution is proposed for the estimate of cutting force using eddy current sensors implemented close to spindle nose. Signals are analysed in the angular domain, notably by synchronous averaging technique. Phase shifts induced by changes of machining direction are compensated. Results are compared with cutting forces measured with a dynamometer table.The proposed method is implemented in an industrial case of pocket machining operation. One of the cutting edges has been slightly damaged during the machining, as shown by a direct measurement of the tool. A control chart is established with the estimates of cutter eccentricity obtained during the machining from the eddy current sensors signals. Efficiency and reliability of the method is demonstrated by a successful detection of the damage.

  10. Modeling radiation loads in the ILC main linac and a novel approach to treat dark current

    Energy Technology Data Exchange (ETDEWEB)

    Mokhov, Nilolai V. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Rakhno, Igor L. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Tropin, Igor S. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States)

    2017-09-11

    Electromagnetic and hadron showers generated by electrons of dark current (DC) can represent a significant radiation threat to the ILC linac equipment and personnel. In this study, a commissioning scenario is analysed which is considered as the worst-case scenario for the main linac regarding the DC contribution to the radiation environment in the tunnel. A normal operation scenario is analysed as well. An emphasis is made on radiation load to sensitive electronic equipment—cryogenic thermometers inside the cryomodules. Prompt and residual dose rates in the ILC main linac tunnels were also calculated in these new high-statistics runs. A novel approach was developed—as a part of general purpose Monte Carlo code MARS15—to model generation, acceleration and transport of DC electrons in electromagnetic fields inside SRF cavities. Comparisons were made with a standard approach when a set of pre-calculated DC electron trajectories is used, with a proper normalization, as a source for Monte Carlo modelling. Results of MARS15 Monte Carlo calculations, performed for the current main linac tunnel design, reveal that the peak absorbed dose in the cryogenic thermometers in the main tunnel for 20 years of operation is about 0.8 MGy. The calculated contact residual dose on cryomodules and tunnel walls in the main tunnel for typical irradiation and cooling conditions is 0.1 and 0.01 mSv/hr, respectively.

  11. Some Pharmacological Aspects of Antimalarial Drugs

    African Journals Online (AJOL)

    1974-06-15

    Jun 15, 1974 ... Some Pharmacological Aspects of Antimalarial. Drugs. D.BOTHA. SUMMARY. A short review is given of antimalarial drugs currently in use. S. Air. Med. l., 48, 1263 (1974). CLASSIFICATION. The chemotherapy of malaria may be conveniently classi- fied as (i) casual prophylaxis; (ii) suppressive treatment;.

  12. Pharmacological interactions of vasoconstrictors.

    Science.gov (United States)

    Gómez-Moreno, Gerardo; Guardia, Javier; Cutando, Antonio; Calvo-Guirado, José Luis

    2009-01-01

    This article is the first of a series on pharmacological interactions involving medicaments commonly prescribed and/or used in odontology: vasoconstrictors in local anaesthetics and anti-inflammatory and anti-microbial analgesics. The necessity for the odontologist to be aware of adverse reactions as a result of the pharmacological interactions is due to the increase in medicament consumption by the general population. There is a demographic change with greater life expectancy and patients have increased chronic health problems and therefore have increased medicament intake. The presence of adrenaline (epinephrine) and other vasoconstrictors in local odontological anaesthetics is beneficial in relation to the duration and depth of anaesthesia and reduces bleeding and systemic toxicity of the local anaesthetic. However, it might produce pharmacological interactions between the injected vasoconstrictors and the local anaesthetic and adrenergic medicament administered exogenically which the odontologist should be aware of, especially because of the risk of consequent adverse reactions. Therefore the importance of conducting a detailed clinical history of the general state of health and include all medicaments, legal as well as illegal, taken by the patient.

  13. Pharmacological effects of biotin.

    Science.gov (United States)

    Fernandez-Mejia, Cristina

    2005-07-01

    In the last few decades, more vitamin-mediated effects have been discovered at the level of gene expression. Increasing knowledge on the molecular mechanisms of these vitamins has opened new perspectives that form a connection between nutritional signals and the development of new therapeutic agents. Besides its role as a carboxylase prosthetic group, biotin regulates gene expression and has a wide repertoire of effects on systemic processes. The vitamin regulates genes that are critical in the regulation of intermediary metabolism: Biotin has stimulatory effects on genes whose action favors hypoglycemia (insulin, insulin receptor, pancreatic and hepatic glucokinase); on the contrary, biotin decreases the expression of hepatic phosphoenolpyruvate carboxykinase, a key gluconeogenic enzyme that stimulates glucose production by the liver. The findings that biotin regulates the expression of genes that are critical in the regulation of intermediary metabolism are in agreement with several observations that indicate that biotin supply is involved in glucose and lipid homeostasis. Biotin deficiency has been linked to impaired glucose tolerance and decreased utilization of glucose. On the other hand, the diabetic state appears to be ameliorated by pharmacological doses of biotin. Likewise, pharmacological doses of biotin appear to decrease plasma lipid concentrations and modify lipid metabolism. The effects of biotin on carbohydrate metabolism and the lack of toxic effects of the vitamin at pharmacological doses suggest that biotin could be used in the development of new therapeutics in the treatment of hyperglycemia and hyperlipidemia, an area that we are actively investigating.

  14. Current approaches to enhance CNS delivery of drugs across the brain barriers

    Directory of Open Access Journals (Sweden)

    Lu CT

    2014-05-01

    Full Text Available Cui-Tao Lu,1 Ying-Zheng Zhao,2,3 Ho Lun Wong,4 Jun Cai,5 Lei Peng,2 Xin-Qiao Tian1 1The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou City, Zhejiang Province, People’s Republic of China; 2Hainan Medical College, Haikou City, Hainan Province, People’s Republic of China; 3College of Pharmaceutical Sciences, Wenzhou Medical University, Zhejiang Province, People’s Republic of China; 4School of Pharmacy, Temple University, Philadelphia, PA, USA; 5Departments of Pediatrics and Anatomical Sciences and Neurobiology, University of Louisville School of Medicine Louisville, KY, USA Abstract: Although many agents have therapeutic potentials for central nervous system (CNS diseases, few of these agents have been clinically used because of the brain barriers. As the protective barrier of the CNS, the blood–brain barrier and the blood–cerebrospinal fluid barrier maintain the brain microenvironment, neuronal activity, and proper functioning of the CNS. Different strategies for efficient CNS delivery have been studied. This article reviews the current approaches to open or facilitate penetration across these barriers for enhanced drug delivery to the CNS. These approaches are summarized into three broad categories: noninvasive, invasive, and miscellaneous techniques. The progresses made using these approaches are reviewed, and the associated mechanisms and problems are discussed. Keywords: drug delivery system, blood–brain barrier (BBB, central nervous system, brain-targeted therapy, cerebrospinal fluid (CSF

  15. Flow Regime Identification of Co-Current Downward Two-Phase Flow With Neural Network Approach

    International Nuclear Information System (INIS)

    Hiroshi Goda; Seungjin Kim; Ye Mi; Finch, Joshua P.; Mamoru Ishii; Jennifer Uhle

    2002-01-01

    Flow regime identification for an adiabatic vertical co-current downward air-water two-phase flow in the 25.4 mm ID and the 50.8 mm ID round tubes was performed by employing an impedance void meter coupled with the neural network classification approach. This approach minimizes the subjective judgment in determining the flow regimes. The signals obtained by an impedance void meter were applied to train the self-organizing neural network to categorize these impedance signals into a certain number of groups. The characteristic parameters set into the neural network classification included the mean, standard deviation and skewness of impedance signals in the present experiment. The classification categories adopted in the present investigation were four widely accepted flow regimes, viz. bubbly, slug, churn-turbulent, and annular flows. These four flow regimes were recognized based upon the conventional flow visualization approach by a high-speed motion analyzer. The resulting flow regime maps classified by the neural network were compared with the results obtained through the flow visualization method, and consequently the efficiency of the neural network classification for flow regime identification was demonstrated. (authors)

  16. Modelling geomagnetically induced currents in midlatitude Central Europe using a thin-sheet approach

    Science.gov (United States)

    Bailey, Rachel L.; Halbedl, Thomas S.; Schattauer, Ingrid; Römer, Alexander; Achleitner, Georg; Beggan, Ciaran D.; Wesztergom, Viktor; Egli, Ramon; Leonhardt, Roman

    2017-06-01

    Geomagnetically induced currents (GICs) in power systems, which can lead to transformer damage over the short and the long term, are a result of space weather events and geomagnetic variations. For a long time, only high-latitude areas were considered to be at risk from these currents, but recent studies show that considerable GICs also appear in midlatitude and equatorial countries. In this paper, we present initial results from a GIC model using a thin-sheet approach with detailed surface and subsurface conductivity models to compute the induced geoelectric field. The results are compared to measurements of direct currents in a transformer neutral and show very good agreement for short-period variations such as geomagnetic storms. Long-period signals such as quiet-day diurnal variations are not represented accurately, and we examine the cause of this misfit. The modelling of GICs from regionally varying geoelectric fields is discussed and shown to be an important factor contributing to overall model accuracy. We demonstrate that the Austrian power grid is susceptible to large GICs in the range of tens of amperes, particularly from strong geomagnetic variations in the east-west direction.

  17. Understanding the Effect of Statins and Patient Adherence in Atherosclerosis via a Quantitative Systems Pharmacology Model Using a Novel, Hybrid, and Multi-Scale Approach

    Directory of Open Access Journals (Sweden)

    Cesar Pichardo-Almarza

    2017-09-01

    by ~1% (after 2 years compared to the same “regular” patient under a 1-year treatment with statins.Conclusions: The results in this paper describe the effect of pharmacological intervention combined with biological/physiological or behavioral factors in atherosclerosis progression and treatment in specific patients. It also provides an exemplar of basic research that can be practically developed into an application software.

  18. 76 FR 38188 - Advisory Committee for Pharmaceutical Science and Clinical Pharmacology; Notice of Meeting

    Science.gov (United States)

    2011-06-29

    ...] Advisory Committee for Pharmaceutical Science and Clinical Pharmacology; Notice of Meeting AGENCY: Food and... of Committee: Advisory Committee for Pharmaceutical Science and Clinical Pharmacology. General..., 2011, the committee will discuss current strategies for FDA's Office of Pharmaceutical Science...

  19. Perinatal pharmacology: applications for neonatal neurology.

    Science.gov (United States)

    Smits, Anne; Allegaert, Karel

    2011-11-01

    The principles of clinical pharmacology also apply to neonates, but their characteristics warrant a tailored approach. We focus on aspects of both developmental pharmacokinetics (concentration/time relationship) and developmental pharmacodynamics (concentration/effect relationship) in neonates. We hereby aimed to link concepts used in clinical pharmacology with compound-specific observations (anti-epileptics, analgosedatives) in the field of neonatal neurology. Although in part anecdotal, we subsequently illustrate the relevance of developmental pharmacology in the field of neonatal neurology by a specific intervention (e.g. whole body cooling), specific clinical presentations (e.g. short and long term outcome following fetal exposure to antidepressive agents, the development of new biomarkers for fetal alcohol syndrome) and specific clinical needs (e.g. analgosedation in neonates, excitocytosis versus neuro-apoptosis/impaired synaptogenesis). Copyright © 2011 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  20. Eddy current crack detection capability assessment approach using crack specimens with differing electrical conductivity

    Science.gov (United States)

    Koshti, Ajay M.

    2018-03-01

    Like other NDE methods, eddy current surface crack detectability is determined using probability of detection (POD) demonstration. The POD demonstration involves eddy current testing of surface crack specimens with known crack sizes. Reliably detectable flaw size, denoted by, a90/95 is determined by statistical analysis of POD test data. The surface crack specimens shall be made from a similar material with electrical conductivity close to the part conductivity. A calibration standard with electro-discharged machined (EDM) notches is typically used in eddy current testing for surface crack detection. The calibration standard conductivity shall be within +/- 15% of the part conductivity. This condition is also applicable to the POD demonstration crack set. Here, a case is considered, where conductivity of the crack specimens available for POD testing differs by more than 15% from that of the part to be inspected. Therefore, a direct POD demonstration of reliably detectable flaw size is not applicable. Additional testing is necessary to use the demonstrated POD test data. An approach to estimate the reliably detectable flaw size in eddy current testing for part made from material A using POD crack specimens made from material B with different conductivity is provided. The approach uses additional test data obtained on EDM notch specimens made from materials A and B. EDM notch test data from the two materials is used to create a transfer function between the demonstrated a90/95 size on crack specimens made of material B and the estimated a90/95 size for part made of material A. Two methods are given. For method A, a90/95 crack size for material B is given and POD data is available. Objective of method A is to determine a90/95 crack size for material A using the same relative decision threshold that was used for material B. For method B, target crack size a90/95 for material A is known. Objective is to determine decision threshold for inspecting material A.

  1. Combining Upper Limb Robotic Rehabilitation with Other Therapeutic Approaches after Stroke: Current Status, Rationale, and Challenges

    Directory of Open Access Journals (Sweden)

    Stefano Mazzoleni

    2017-01-01

    Full Text Available A better understanding of the neural substrates that underlie motor recovery after stroke has led to the development of innovative rehabilitation strategies and tools that incorporate key elements of motor skill relearning, that is, intensive motor training involving goal-oriented repeated movements. Robotic devices for the upper limb are increasingly used in rehabilitation. Studies have demonstrated the effectiveness of these devices in reducing motor impairments, but less so for the improvement of upper limb function. Other studies have begun to investigate the benefits of combined approaches that target muscle function (functional electrical stimulation and botulinum toxin injections, modulate neural activity (noninvasive brain stimulation, and enhance motivation (virtual reality in an attempt to potentialize the benefits of robot-mediated training. The aim of this paper is to overview the current status of such combined treatments and to analyze the rationale behind them.

  2. Standard and biological treatment in large vessel vasculitis: guidelines and current approaches.

    Science.gov (United States)

    Muratore, Francesco; Pipitone, Nicolò; Salvarani, Carlo

    2017-04-01

    Giant cell arteritis and Takayasu arteritis are the two major forms of idiopathic large vessel vasculitis. High doses of glucocorticoids are effective in inducing remission in both conditions, but relapses and recurrences are common, requiring prolonged glucocorticoid treatment with the risk of the related adverse events. Areas covered: In this article, we will review the standard and biological treatment strategies in large vessel vasculitis, and we will focus on the current approaches to these diseases. Expert commentary: The results of treatment trials with conventional immunosuppressive agents such as methotrexate, azathioprine, mycophenolate mofetil, and cyclophosphamide have overall been disappointing. TNF-α blockers are ineffective in giant cell arteritis, while observational evidence and a phase 2 randomized trial support the use of tocilizumab in relapsing giant cell arteritis. Observational evidence strongly supports the use of anti-TNF-α agents and tocilizumab in Takayasu patients with relapsing disease. However biological agents are not curative, and relapses remain common.

  3. A Review of Player Monitoring Approaches in Basketball: Current Trends and Future Directions.

    Science.gov (United States)

    Fox, Jordan L; Scanlan, Aaron T; Stanton, Robert

    2017-07-01

    Fox, JL, Scanlan, AT, and Stanton, R. A review of player monitoring approaches in basketball: current trends and future directions. J Strength Cond Res 31(7): 2021-2029, 2017-Effective monitoring of players in team sports such as basketball requires an understanding of the external demands and internal responses, as they relate to training phases and competition. Monitoring of external demands and internal responses allows coaching staff to determine the dose-response associated with the imposed training load (TL), and subsequently, if players are adequately prepared for competition. This review discusses measures reported in the literature for monitoring the external demands and internal responses of basketball players during training and competition. The external demands of training and competition were primarily monitored using time-motion analysis, with limited use of microtechnology being reported. Internal responses during training were typically measured using hematological markers, heart rate, various TL models, and perceptual responses such as rating of perceived exertion (RPE). Heart rate was the most commonly reported indicator of internal responses during competition with limited reporting of hematological markers or RPE. These findings show a large discrepancy between the reporting of external and internal measures and training and competition demands. Microsensors, however, may be a practical and convenient method of player monitoring in basketball to overcome the limitations associated with current approaches while allowing for external demands and internal responses to be recorded simultaneously. The triaxial accelerometers of microsensors seem well suited for basketball and warrant validation to definitively determine their place in the monitoring of basketball players. Coaching staff should make use of this technology by tracking individual player responses across the annual plan and using real-time monitoring to minimize factors such as fatigue

  4. Towards the design of 3D multiscale instructive tissue engineering constructs: Current approaches and trends.

    Science.gov (United States)

    Oliveira, Sara M; Reis, Rui L; Mano, João F

    2015-11-01

    The design of 3D constructs with adequate properties to instruct and guide cells both in vitro and in vivo is one of the major focuses of tissue engineering. Successful tissue regeneration depends on the favorable crosstalk between the supporting structure, the cells and the host tissue so that a balanced matrix production and degradation are achieved. Herein, the major occurring events and players in normal and regenerative tissue are overviewed. These have been inspiring the selection or synthesis of instructive cues to include into the 3D constructs. We further highlight the importance of a multiscale perception of the range of features that can be included on the biomimetic structures. Lastly, we focus on the current and developing tissue-engineering approaches for the preparation of such 3D constructs: top-down, bottom-up and integrative. Bottom-up and integrative approaches present a higher potential for the design of tissue engineering devices with multiscale features and higher biochemical control than top-down strategies, and are the main focus of this review. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Mite Pests in Plant Crops – Current Issues, Inovative Approaches and Possibilities for Controlling Them (2

    Directory of Open Access Journals (Sweden)

    Radmila Petanović

    2010-01-01

    Full Text Available Part one discusses some principal mite pests in agroecosystems and urban horticulturein European countries, Serbia and its neighbouring countries focusing primarily on issueswith regard to plant production, novel methods and approaches in applied acaralogy. Parttwo displays some major properties of acaricides inhibiting respiration, growth and developmentand other synthetic substances with acaricide action on the market in the last decadeof the 20th century and the first decade of the 21st century. Also some products of naturalorigin (azadirachtin, oils, micoacaricides are said to be gaining in importance. Issues withregard to the fact that mites can readily develop resistance to acardicides are discussed anda survey on the results of biochemical, physiological and genetical causes of resistance areanalyzed. Some basic principles of biological control of phytophagous mites and modernadvances and approaches are discussed as well as current knowledge on host plant resistanceto mites. Eventually, the possibility of using a combination of selective acaricides andbiological control agents is discussed but also the inclusion of other modes of control (agriculturalpractices and physical measures expected to contribute to an integrated managementof pest populations.

  6. The territorial approach to EU cohesion policy: Current issues and evidence from Greece

    Directory of Open Access Journals (Sweden)

    Thoidou Elisavet

    2011-01-01

    Full Text Available The importance attributed to the territorial dimension of the European Union cohesion policy steadily influences its successive reforms and adaptations, while in recent years there has been an evolution in the way this particular dimension of cohesion policy is perceived. Important evidence for this is the way in which the Community Strategic Guidelines on cohesion 2007-13 take account of the territorial dimension of cohesion policy. This paper discusses the territorial approach to cohesion policy in relation to both policy and practice. Specifically, it examines the territorial dimension of regional development planning in Greece as it has emerged in the relevant official documents, namely the successive three Community Support Frameworks since 1989 and the National Strategic Reference Framework for the current 2007-13 period. The territorial dimension of the organization of the planning system is also considered in an effort to understand limitations and prospects, in light of the importance of the territorial approach to cohesion policy post-2013.

  7. Current Advance and Future Prospects of Tissue Engineering Approach to Dentin/Pulp Regenerative Therapy

    Directory of Open Access Journals (Sweden)

    Ting Gong

    2016-01-01

    Full Text Available Recent advances in biomaterial science and tissue engineering technology have greatly spurred the development of regenerative endodontics. This has led to a paradigm shift in endodontic treatment from simply filling the root canal systems with biologically inert materials to restoring the infected dental pulp with functional replacement tissues. Currently, cell transplantation has gained increasing attention as a scientifically valid method for dentin-pulp complex regeneration. This multidisciplinary approach which involves the interplay of three key elements of tissue engineering—stem cells, scaffolds, and signaling molecules—has produced an impressive number of favorable outcomes in preclinical animal studies. Nevertheless, many practical hurdles need to be overcome prior to its application in clinical settings. Apart from the potential health risks of immunological rejection and pathogenic transmission, the lack of a well-established banking system for the isolation and storage of dental-derived stem cells is the most pressing issue that awaits resolution and the properties of supportive scaffold materials vary across different studies and remain inconsistent. This review critically examines the classic triad of tissue engineering utilized in current regenerative endodontics and summarizes the possible techniques developed for dentin/pulp regeneration.

  8. Current Advance and Future Prospects of Tissue Engineering Approach to Dentin/Pulp Regenerative Therapy

    Science.gov (United States)

    Gong, Ting; Heng, Boon Chin; Lo, Edward Chin Man; Zhang, Chengfei

    2016-01-01

    Recent advances in biomaterial science and tissue engineering technology have greatly spurred the development of regenerative endodontics. This has led to a paradigm shift in endodontic treatment from simply filling the root canal systems with biologically inert materials to restoring the infected dental pulp with functional replacement tissues. Currently, cell transplantation has gained increasing attention as a scientifically valid method for dentin-pulp complex regeneration. This multidisciplinary approach which involves the interplay of three key elements of tissue engineering—stem cells, scaffolds, and signaling molecules—has produced an impressive number of favorable outcomes in preclinical animal studies. Nevertheless, many practical hurdles need to be overcome prior to its application in clinical settings. Apart from the potential health risks of immunological rejection and pathogenic transmission, the lack of a well-established banking system for the isolation and storage of dental-derived stem cells is the most pressing issue that awaits resolution and the properties of supportive scaffold materials vary across different studies and remain inconsistent. This review critically examines the classic triad of tissue engineering utilized in current regenerative endodontics and summarizes the possible techniques developed for dentin/pulp regeneration. PMID:27069484

  9. Exchange processes at geosphere-biosphere interface. Current SKB approach and example of coupled hydrological-ecological approach

    Energy Technology Data Exchange (ETDEWEB)

    Woerman, Anders [Swedish Univ. of Agricultural Sciences, Uppsala (Sweden). Dept. of Biometry and Technology

    2003-09-01

    The design of the repository for final disposal of spent nuclear fuel proposed by SKB is based on a multi-barrier system, in which the geosphere and biosphere are the utmost barrier surrounding the engineer barriers. This report briefly reviews the current approach taken by SKB to account for hydrological and ecological processes at the geosphere-biosphere interface (GBI) and their future plans in this area. A simple analysis was performed to shift the focus of performance assessment involving geosphere-biosphere interface modelling from the very simplistic assumption that the quaternary sediments are bypassed to one in which a more detailed model for sub-surface flows is included. This study indicated that, for many assumed ecosystem descriptions, the presence of the GBI leads to lower maximum doses to individual humans compared to a case when the GBI is neglected. This effect is due to the additional 'barrier' offered by the GBI. The main exposure pathways were assumed to occur through the food web. However, particularly the leakage on land through the stream-network and lakes can lead to higher doses due to ecosystem interaction with arable land. A scenario that gives particularly long duration of doses occurs due to land rise and with the transformation of the former bay and lake bed sediments into agricultural land. This effect is due to the significant retention or accumulation in aquatic sediment, which causes high activities to build up with time. Particularly, in combination with changing conditions in climate, humans life-style or geographic conditions (land rise, deforestation,etc.) doses to individual humans can be large.

  10. Exchange processes at geosphere-biosphere interface. Current SKB approach and example of coupled hydrological-ecological approach

    International Nuclear Information System (INIS)

    Woerman, Anders

    2003-09-01

    The design of the repository for final disposal of spent nuclear fuel proposed by SKB is based on a multi-barrier system, in which the geosphere and biosphere are the utmost barrier surrounding the engineer barriers. This report briefly reviews the current approach taken by SKB to account for hydrological and ecological processes at the geosphere-biosphere interface (GBI) and their future plans in this area. A simple analysis was performed to shift the focus of performance assessment involving geosphere-biosphere interface modelling from the very simplistic assumption that the quaternary sediments are bypassed to one in which a more detailed model for sub-surface flows is included. This study indicated that, for many assumed ecosystem descriptions, the presence of the GBI leads to lower maximum doses to individual humans compared to a case when the GBI is neglected. This effect is due to the additional 'barrier' offered by the GBI. The main exposure pathways were assumed to occur through the food web. However, particularly the leakage on land through the stream-network and lakes can lead to higher doses due to ecosystem interaction with arable land. A scenario that gives particularly long duration of doses occurs due to land rise and with the transformation of the former bay and lake bed sediments into agricultural land. This effect is due to the significant retention or accumulation in aquatic sediment, which causes high activities to build up with time. Particularly, in combination with changing conditions in climate, humans life-style or geographic conditions (land rise, deforestation,etc.) doses to individual humans can be large

  11. Pharmacological Profile of Quinoxalinone

    Directory of Open Access Journals (Sweden)

    Youssef Ramli

    2014-01-01

    Full Text Available Quinoxalinone and its derivatives are used in organic synthesis for building natural and designed synthetic compounds and they have been frequently utilized as suitable skeletons for the design of biologically active compound. This review covers updated information on the most active quinoxalinone derivatives that have been reported to show considerable pharmacological actions such as antimicrobial, anti-inflammatory, antidiabetic, antiviral, antitumor, and antitubercular activity. It can act as an important tool for chemists to develop newer quinoxalinone derivatives that may prove to be better agents in terms of efficacy and safety.

  12. Pharmacological inhibition of feline immunodeficiency virus (FIV).

    Science.gov (United States)

    Mohammadi, Hakimeh; Bienzle, Dorothee

    2012-05-01

    Feline immunodeficiency virus (FIV) is a member of the retroviridae family of viruses and causes an acquired immunodeficiency syndrome (AIDS) in domestic and non-domestic cats worldwide. Genome organization of FIV and clinical characteristics of the disease caused by the virus are similar to those of human immunodeficiency virus (HIV). Both viruses infect T lymphocytes, monocytes and macrophages, and their replication cycle in infected cells is analogous. Due to marked similarity in genomic organization, virus structure, virus replication and disease pathogenesis of FIV and HIV, infection of cats with FIV is a useful tool to study and develop novel drugs and vaccines for HIV. Anti-retroviral drugs studied extensively in HIV infection have targeted different steps of the virus replication cycle: (1) inhibition of virus entry into susceptible cells at the level of attachment to host cell surface receptors and co-receptors; (2) inhibition of fusion of the virus membrane with the cell membrane; (3) blockade of reverse transcription of viral genomic RNA; (4) interruption of nuclear translocation and viral DNA integration into host genomes; (5) prevention of viral transcript processing and nuclear export; and (6) inhibition of virion assembly and maturation. Despite much success of anti-retroviral therapy slowing disease progression in people, similar therapy has not been thoroughly investigated in cats. In this article we review current pharmacological approaches and novel targets for anti-lentiviral therapy, and critically assess potentially suitable applications against FIV infection in cats.

  13. Human-carnivore conflict in China: a review of current approaches with recommendations for improved management.

    Science.gov (United States)

    Pettigrew, Melissa; Xie, Yan; Kang, Aili; Rao, Madhu; Goodrich, John; Liu, Tong; Berger, Joshua

    2012-06-01

    Human-wildlife conflict (HWC) is a conservation concern that increasingly threatens the continued existence of some of the world's most endangered species. With an increase in human population, urban sprawl and subsequent encroachment on wild land, human and wildlife interaction has become inevitable. In the majority of cases, this interaction results in a negative outcome for humans, wildlife or both. In China, these key elements, along with a decrease in wild prey species, have resulted in the expansion of HWC encounters, and the need for alleviating this conflict has become a conservation priority. Loss of human life, livestock and/or crops is most often the catalysts that fuel HWC. Techniques to alleviate conflict around the world have included preventative measures and mitigation techniques, such as financial compensation and other incentive programs. Both types of measures have had variable success. We review the current status of human-carnivore conflict management in China, and, drawing lessons from around the globe, we make recommendations for improving conservation management in China. For example, an increase in law enforcement in nature reserves is vital to reducing human disturbance in prime carnivore habitat, thereby reducing conflict encounters. Also, modifications to current wildlife compensation programs, so that they are linked with preventative measures, will ensure that moral hazards are avoided. Furthermore, investigating the potential for a community self-financed insurance scheme to fund compensation and increasing efforts to restore wild prey populations will improve the outcome for wildlife conservation. Ultimately, HWC management in China will greatly benefit from an integrative approach. © 2012 ISZS, Blackwell Publishing and IOZ/CAS.

  14. Review: Current trends in coral transplantation – an approach to preserve biodiversity

    Directory of Open Access Journals (Sweden)

    ABDELNABY ORABI

    2013-04-01

    Full Text Available Ammar MSA,El-Gammal F, Nassar M, Belal A, Farag W, El-Mesiry G, El-Haddad K, Orabi A, Abdelreheem A, Shaaban A. 2013. Review: Current trends in coral transplantation – an approach to preserve biodiversity. Biodiversitas 14: 43-53. The increasing rates of coral mortality associated with the rise in stress factors and the lack of adequate recovery worldwide have urged recent calls for actions by the scientific, conservation, and reef management communities. This work reviews the current trends in coral transplantation. Transplantation of coral colonies or fragments, whether from aqua-, mariculture or harvesting from a healthy colony, has been the most frequently recommended action for increasing coral abundance on damaged or degraded reefs and for conserving listed or “at-risk” species. Phytoplanktons are important for providing transplanted corals with complex organic compounds through photosynthesis. Artificial surfaces like concrete blocks, wrecks or other purpose-designed structures can be introduced for larval settlement. New surfaces can also be created through electrolysis. Molecular biological tools can be used to select sites for rehabilitation by asexual recruits. Surface chemistry and possible inputs of toxic leachate from artificial substrates are considered as important factors affecting natural recruitment. Transplants should be carefully maintained , revisited and reattached at least weekly in the first month and at least fortnightly in the next three months. Studies on survivorship and the reproductive ability of transplanted coral fragments are important for coral reef restoration. A coral nursery may be considered as a pool for local species that supplies reef-managers with unlimited coral colonies for sustainable management. Transplanting corals for making artificial reefs can be useful for increasing biodiversity, providing tourist diving, fishing and surfing; creating new artisanal and commercial fishing opportunities

  15. Current and future perspectives on the development, evaluation and application of in silico approaches for predicting toxicity

    Science.gov (United States)

    Safety-related problems continue to be one of the major reasons of attrition in drug development. Non-testing approaches to predict toxicity could form part of the solution. This review provides a perspective of current status of non-testing approaches available for the predictio...

  16. Approach to integrate current safeguards measures with additional protocol requirements at national level

    International Nuclear Information System (INIS)

    Ramirez, R.

    2001-01-01

    Peru adhered to the Additional Protocol in March 2000 which was also approved by the Congress in May 2001. After approval by law the obligations derived from this Additional Protocol will be in force after 180 days. After the signing of the Protocol an approach was designed to help better fulfill these requirements in an integrated way with the previous measures. As first stage, a review of the current state of safeguards was undertaken. Under the current agreement (an INFCIRC/153 type agreement) the reporting is less complicated and inexpensive to be carried out because these reports include only the declared nuclear material and the features of declared facilities where the nuclear material is used. No other related facility or material or activity needs to be declared. In Peru there are only two MBAs where low enriched uranium (LEU) is used and the record system includes general ledgers, inventory records and operational books. The results of national inspections and copies of reports and communications sent to the IAEA are also kept in this system. Under the agreement and subsidiary arrangements material balance reports (MBR), physical inventory listings (PIL) and inventory change reports (ICR) are prepared and submitted to the IAEA at scheduled periods. The MBR and PIL reports are sent after yearly regular inspections carried out by the IAEA. The ICR is sent just every time when an import or export of nuclear material is made. The time devoted to carry out all of these activities is not so extensive for both the State System for Accountability and Control (SSAC) and the users because of the limited nuclear activities in the country. Because of the characteristics and limited quantities of nuclear material the efforts for inspection and reporting activities are few. Another subject under review was the procedure for controlling the imports of nuclear material. Under the current agreement this subject was not a problem, as all of the radioactive and nuclear

  17. Examination of the Current Approaches to State-Level Nuclear Security Evaluation

    International Nuclear Information System (INIS)

    Kim, Chan; Yim, Mansung; Kim, So Young

    2014-01-01

    An effective global nuclear materials security system will cover all materials, employ international standards and best practices, and reduce risks by reducing weapons-usable nuclear material stocks and the number of locations where they are found. Such a system must also encourage states to accept peer reviews by outside experts in order to demonstrate that effective security is in place. It is thus critically important to create an integrative framework of state-level evaluation of nuclear security as a basis for measuring the level and progress of international effort to secure and control all nuclear materials. There have been studies to represent state-level nuclear security with a quantitative metric. A prime example is the Nuclear Materials Security Index (NMSI) by the Nuclear Threat Initiative (NTI). Another comprehensive study is the State Level Risk Metric by Texas A and M University (TAMU). This paper examines the current methods with respect to their strengths and weaknesses and identifies the directions for future research to improve upon the existing approaches

  18. Asthma and obesity in children: current evidence and potential systems biology approaches.

    Science.gov (United States)

    Frey, U; Latzin, P; Usemann, J; Maccora, J; Zumsteg, U; Kriemler, S

    2015-01-01

    Both obesity and asthma are highly prevalent, complex diseases modified by multiple factors. Genetic, developmental, lung mechanical, immunological and behavioural factors have all been suggested as playing a causal role between the two entities; however, their complex mechanistic interactions are still poorly understood and evidence of causality in children remains scant. Equally lacking is evidence of effective treatment strategies, despite the fact that imbalances at vulnerable phases in childhood can impact long-term health. This review is targeted at both clinicians frequently faced with the dilemma of how to investigate and treat the obese asthmatic child and researchers interested in the topic. Highlighting the breadth of the spectrum of factors involved, this review collates evidence regarding the investigation and treatment of asthma in obese children, particularly in comparison with current approaches in 'difficult-to-treat' childhood asthma. Finally, the authors propose hypotheses for future research from a systems-based perspective. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Current Approaches to the Treatment of Systemic-Sclerosis-Associated Pulmonary Arterial Hypertension (SSc-PAH).

    Science.gov (United States)

    Sobanski, Vincent; Launay, David; Hachulla, Eric; Humbert, Marc

    2016-02-01

    Pulmonary arterial hypertension (PAH) is a severe condition causing significant morbidity and mortality in patients with systemic sclerosis (SSc). Despite the use of specific treatments, SSc-PAH survival remains poorer than in idiopathic PAH (IPAH). Recent therapeutic advances in PAH show a lower magnitude of response in SSc-PAH and a higher risk of adverse events, as compared to IPAH. The multifaceted underlying mechanisms and the multisystem nature of SSc probably explain part of the worse outcomes in SSc-PAH compared to IPAH. This review describes the current management of SSc-PAH with an emphasis on the impact of the different organ involvements in the prognosis and treatment response. An earlier detection of PAH and a better characterization of the clinical phenotypes of SSc-PAH are warranted in clinical practice and future trials. Determinants of prognosis, surrogate markers of clinical improvement or worsening, and relevance of the common endpoints used in clinical trials should be evaluated in this specific population. A multidisciplinary approach in expert referral centers is mandatory for SSc-PAH management.

  20. The effects of strontium on bone mineral: A review on current knowledge and microanalytical approaches.

    Science.gov (United States)

    Querido, William; Rossi, Andre L; Farina, Marcos

    2016-01-01

    The interest in effects of strontium (Sr) on bone has greatly increased in the last decade due to the development of the promising drug strontium ranelate. This drug is used for treating osteoporosis, a major bone disease affecting hundreds of millions of people worldwide, especially postmenopausal women. The novelty of strontium ranelate compared to other treatments for osteoporosis is its unique effect on bone: it simultaneously promotes bone formation by osteoblasts and inhibits bone resorption by osteoclasts. Besides affecting bone cells, treatment with strontium ranelate also has a direct effect on the mineralized bone matrix. Due to the chemical similarities between Sr and Ca, a topic that has long been of particular interest is the incorporation of Sr into bones replacing Ca from the mineral phase, which is composed by carbonated hydroxyapatite nanocrystals. Several groups have analyzed the mineral produced during treatment; however, most analysis were done with relatively large samples containing numerous nanocrystals, resulting thus on data that represents an average of many crystalline domains. The nanoscale analysis of the bone apatite crystals containing Sr has only been described in a few studies. In this study, we review the current knowledge on the effects of Sr on bone mineral and discuss the methodological approaches that have been used in the field. In particular, we focus on the great potential that advanced microscopy and microanalytical techniques may have on the detailed analysis of the nanostructure and composition of bone apatite nanocrystals produced during treatment with strontium ranelate. Copyright © 2015. Published by Elsevier Ltd.

  1. Quality management in European screening laboratories in blood establishments: A view of current approaches and trends.

    Science.gov (United States)

    Pereira, Paulo; Westgard, James O; Encarnação, Pedro; Seghatchian, Jerard; de Sousa, Gracinda

    2015-04-01

    The screening laboratory has a critical role in the post-transfusion safety. The success of its targets and efficiency depends on the management system used. Even though the European Union directive 2002/98/EC requires a quality management system in blood establishments, its requirements for screening laboratories are generic. Complementary approaches are needed to implement a quality management system focused on screening laboratories. This article briefly discusses the current good manufacturing practices and good laboratory practices, as well as the trends in quality management system standards. ISO 9001 is widely accepted in some European Union blood establishments as the quality management standard, however this is not synonymous of its successful application. The ISO "risk-based thinking" is interrelated with the quality risk-management process of the EuBIS "Standards and criteria for the inspection of blood establishments". ISO 15189 should be the next step on the quality assurance of a screening laboratory, since it is focused on medical laboratory. To standardize the quality management systems in blood establishments' screening laboratories, new national and European claims focused on technical requirements following ISO 15189 is needed. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Combining non-invasive transcranial brain stimulation with neuroimaging and electrophysiology: Current approaches and future perspectives.

    Science.gov (United States)

    Bergmann, Til Ole; Karabanov, Anke; Hartwigsen, Gesa; Thielscher, Axel; Siebner, Hartwig Roman

    2016-10-15

    Non-invasive transcranial brain stimulation (NTBS) techniques such as transcranial magnetic stimulation (TMS) and transcranial current stimulation (TCS) are important tools in human systems and cognitive neuroscience because they are able to reveal the relevance of certain brain structures or neuronal activity patterns for a given brain function. It is nowadays feasible to combine NTBS, either consecutively or concurrently, with a variety of neuroimaging and electrophysiological techniques. Here we discuss what kind of information can be gained from combined approaches, which often are technically demanding. We argue that the benefit from this combination is twofold. Firstly, neuroimaging and electrophysiology can inform subsequent NTBS, providing the required information to optimize where, when, and how to stimulate the brain. Information can be achieved both before and during the NTBS experiment, requiring consecutive and concurrent applications, respectively. Secondly, neuroimaging and electrophysiology can provide the readout for neural changes induced by NTBS. Again, using either concurrent or consecutive applications, both "online" NTBS effects immediately following the stimulation and "offline" NTBS effects outlasting plasticity-inducing NTBS protocols can be assessed. Finally, both strategies can be combined to close the loop between measuring and modulating brain activity by means of closed-loop brain state-dependent NTBS. In this paper, we will provide a conceptual framework, emphasizing principal strategies and highlighting promising future directions to exploit the benefits of combining NTBS with neuroimaging or electrophysiology. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  3. Econometric modelling of Serbian current account determinants: Jackknife Model Averaging approach

    Directory of Open Access Journals (Sweden)

    Petrović Predrag

    2014-01-01

    Full Text Available This research aims to model Serbian current account determinants for the period Q1 2002 - Q4 2012. Taking into account the majority of relevant determinants, using the Jackknife Model Averaging approach, 48 different models have been estimated, where 1254 equations needed to be estimated and averaged for each of the models. The results of selected representative models indicate moderate persistence of the CA and positive influence of: fiscal balance, oil trade balance, terms of trade, relative income and real effective exchange rates, where we should emphasise: (i a rather strong influence of relative income, (ii the fact that the worsening of oil trade balance results in worsening of other components (probably non-oil trade balance of CA and (iii that the positive influence of terms of trade reveals functionality of the Harberger-Laursen-Metzler effect in Serbia. On the other hand, negative influence is evident in case of: relative economic growth, gross fixed capital formation, net foreign assets and trade openness. What particularly stands out is the strong effect of relative economic growth that, most likely, reveals high citizens' future income growth expectations, which has negative impact on the CA.

  4. Current Approaches to Tactical Performance Analyses in Soccer Using Position Data.

    Science.gov (United States)

    Memmert, Daniel; Lemmink, Koen A P M; Sampaio, Jaime

    2017-01-01

    Tactical match performance depends on the quality of actions of individual players or teams in space and time during match-play in order to be successful. Technological innovations have led to new possibilities to capture accurate spatio-temporal information of all players and unravel the dynamics and complexity of soccer matches. The main aim of this article is to give an overview of the current state of development of the analysis of position data in soccer. Based on the same single set of position data of a high-level 11 versus 11 match (Bayern Munich against FC Barcelona) three different promising approaches from the perspective of dynamic systems and neural networks will be presented: Tactical performance analysis revealed inter-player coordination, inter-team and inter-line coordination before critical events, as well as team-team interaction and compactness coefficients. This could lead to a multi-disciplinary discussion on match analyses in sport science and new avenues for theoretical and practical implications in soccer.

  5. Citizenship Education in the Kingdom of Saudi Arabia: History and Current Instructional Approaches

    Directory of Open Access Journals (Sweden)

    Badr Abdullah Alharbi

    2017-10-01

    Full Text Available This review article attempts to review current studies related to Citizenship Education (CE in order to shed light on the provisions of citizenship education in the Kingdom of Saudi Arabia (KSA. The review examines the significance of   CE in the KSA. It also explores the history of CE in the KSA followed by its national identity, as this too, affects the nature of the CE offered in the country. Then the article identifies and explores the implementation of CE in the KSA. In addition, the article discusses the approaches of introducing Citizenship Education in the KSA, its content and implementation. It can be argued that Islam has played a crucial role in shaping Saudi citizens’ private and national identities and their national values. The study also found that CE in Saudi Arabia faces multiple challenges. It emphasizes citizens’ responsibilities, duties, identity formation, and obedience towards the system and how one can achieve them. It also appears that promoting freedom, equality, fairness, freedom of expression and participation in the decision making process is poorly addressed. Moreover, lack of teaching aids and lack of specialist teachers and training are some major challenges to implement CE in the KSA. The article ends by drawing some conclusions.

  6. Pharmacological therapy for amblyopia

    Directory of Open Access Journals (Sweden)

    Anupam Singh

    2017-01-01

    Full Text Available Amblyopia is the most common cause of preventable blindness in children and young adults. Most of the amblyopic visual loss is reversible if detected and treated at appropriate time. It affects 1.0 to 5.0% of the general population. Various treatment modalities have been tried like refractive correction, patching (both full time and part time, penalization and pharmacological therapy. Refractive correction alone improves visual acuity in one third of patients with anisometropic amblyopia. Various drugs have also been tried of which carbidopa & levodopa have been popular. Most of these agents are still in experimental stage, though levodopa-carbidopa combination therapy has been widely studied in human amblyopes with good outcomes. Levodopa therapy may be considered in cases with residual amblyopia, although occlusion therapy remains the initial treatment choice. Regression of effect after stoppage of therapy remains a concern. Further studies are therefore needed to evaluate the full efficacy and side effect profile of these agents.

  7. Pharmacological therapy for amblyopia

    Science.gov (United States)

    Singh, Anupam; Nagpal, Ritu; Mittal, Sanjeev Kumar; Bahuguna, Chirag; Kumar, Prashant

    2017-01-01

    Amblyopia is the most common cause of preventable blindness in children and young adults. Most of the amblyopic visual loss is reversible if detected and treated at appropriate time. It affects 1.0 to 5.0% of the general population. Various treatment modalities have been tried like refractive correction, patching (both full time and part time), penalization and pharmacological therapy. Refractive correction alone improves visual acuity in one third of patients with anisometropic amblyopia. Various drugs have also been tried of which carbidopa & levodopa have been popular. Most of these agents are still in experimental stage, though levodopa-carbidopa combination therapy has been widely studied in human amblyopes with good outcomes. Levodopa therapy may be considered in cases with residual amblyopia, although occlusion therapy remains the initial treatment choice. Regression of effect after stoppage of therapy remains a concern. Further studies are therefore needed to evaluate the full efficacy and side effect profile of these agents. PMID:29018759

  8. Phenotypic variability in LQT3 human induced pluripotent stem cell-derived cardiomyocytes and their response to antiarrhythmic pharmacologic therapy: An in silico approach.

    Science.gov (United States)

    Paci, Michelangelo; Passini, Elisa; Severi, Stefano; Hyttinen, Jari; Rodriguez, Blanca

    2017-11-01

    Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are in vitro models with the clear advantages of their human origin and suitability for human disease investigations. However, limitations include their incomplete characterization and variability reported in different cell lines and laboratories. The purpose of this study was to investigate in silico ionic mechanisms potentially explaining the phenotypic variability of hiPSC-CMs in long QT syndrome type 3 (LQT3) and their response to antiarrhythmic drugs. Populations of in silico hiPSC-CM models were constructed and calibrated for control (n = 1,463 models) and LQT3 caused by I NaL channelopathy (n = 1,401 models), using experimental recordings for late sodium current (I NaL ) and action potentials (APs). Antiarrhythmic drug therapy was evaluated by simulating mexiletine and ranolazine multichannel effects. As in experiments, LQT3 hiPSC-CMs yield prolonged action potential duration at 90% repolarization (APD 90 ) (+34.3% than controls) and large electrophysiological variability. LQT3 hiPSC-CMs with symptomatic APs showed overexpression of I CaL , I K1 , and I NaL , underexpression of I Kr , and increased sensitivity to both drugs compared to asymptomatic LQT3 models. Simulations showed that both mexiletine and ranolazine corrected APD prolongation in the LQT3 population but also highlighted differences in drug response. Mexiletine stops spontaneous APs in more LQT3 hiPSC-CMs models than ranolazine (784/1,401 vs 53/1,401) due to its stronger action on I Na . In silico simulations demonstrate our ability to recapitulate variability in LQT3 and control hiPSC-CM phenotypes, and the ability of mexiletine and ranolazine to reduce APD prolongation, in agreement with experiments. The in silico models also identify potential ionic mechanisms of phenotypic variability in LQT3 hiPSC-CMs, explaining APD prolongation in symptomatic vs asymptomatic LQT3 hiPSC-CMs. Copyright © 2017 The Authors. Published by

  9. Pharmacological interventions to treat phlebitis: systematic review.

    Science.gov (United States)

    dos Reis, Paula Elaine Diniz; Silveira, Renata Cristina de Campos Pereira; Vasques, Christiane Inocêncio; de Carvalho, Emilia Campos

    2009-01-01

    This study presents a systematic review for evaluating effective pharmacological actions for the treatment of phlebitis stemming from infusion therapy. The studies reviewed were categorized according to the type of therapeutic approach proposed by the author and by the level of evidence presented. The review found that topical nitroglycerin and notoginseny were more effective in the reduction of the inflammatory process when compared with other proposed alternatives. Nevertheless, the development of research related to possible alternatives for the treatment of phlebitis is important.

  10. Local Anesthetics: Review of Pharmacological Considerations

    Science.gov (United States)

    Becker, Daniel E; Reed, Kenneth L

    2012-01-01

    Local anesthetics have an impressive history of efficacy and safety in medical and dental practice. Their use is so routine, and adverse effects are so infrequent, that providers may understandably overlook many of their pharmacotherapeutic principles. The purpose of this continuing education article is to provide a review and update of essential pharmacology for the various local anesthetic formulations in current use. Technical considerations will be addressed in a subsequent article. PMID:22822998

  11. Using a clinical protocol for orthognathic surgery and assessing a 3-dimensional virtual approach: current therapy.

    Science.gov (United States)

    Quevedo, Luis A; Ruiz, Jessica V; Quevedo, Cristobal A

    2011-03-01

    Oral and maxillofacial surgeons who perform orthognathic surgery face major changes in their practices, and these challenges will increase in the near future, because the extraordinary advances in technology applied to our profession are not only amazing but are becoming the standard of care as they promote improved outcomes for our patients. Orthognathic surgery is one of the favorite areas of practicing within the scope of practice of an oral and maxillofacial surgeon. Our own practice in orthognathic surgery has completed over 1,000 surgeries of this type. Success is directly related to the consistency and capability of the surgical-orthodontic team to achieve predictable, stable results, and our hypothesis is that a successful result is directly related to the way we take our records and perform diagnosis and treatment planning following basic general principles. Now that we have the opportunity to plan and treat 3-dimensional (3D) problems with 3D technology, we should enter into this new era with appropriate standards to ensure better results, instead of simply enjoying these new tools, which will clearly show not only us but everyone what we do when we perform orthognathic surgery. Appropriate principles need to be taken into account when implementing this new technology. In other words, new technology is welcome, but we do not have to reinvent the wheel. The purpose of this article is to review the current protocol that we use for orthognathic surgery and compare it with published protocols that incorporate new 3D and virtual technology. This report also describes our approach to this new technology. Copyright © 2011 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  12. Prevalence and Current Approaches of Ebola Virus Disease in ASEAN Countries.

    Science.gov (United States)

    Rajiah, Kingston; San, Kok Pui; Jiun, Ting Wei; May, Tam Ai; Neng, Yap Chan; Seng, Hee Kah; Soon, Lim Jing; Pazooki, Nazanin

    2015-09-01

    As indicated by the World Health Organization as of year 2014, around 10,000 people have been influenced with Ebola infection. The episode of Ebola in African locale is courged with a high death rate. Notwithstanding, in the United States, people influenced by Ebola have been given brilliant wellbeing offices, as the U.S. is one of the highest nations that have taken sterner wellbeing measures and principles against Ebola. Aside from the U.S., individuals in Asia, where billions live in indigence and general wellbeing frameworks are frequently extremely powerless, are under more serious danger of the Ebola infection. Despite the fact that nations like Singapore, Malaysia, South Korea and Japan can take stretched out measures to battle against the infection, nations like Philippines and Indonesia have unfathomable quantities of poor who may be incredibly influenced by a conceivable episode. At this moment, the chances that Asia will take a critical hit from the Ebola infection appear to be genuinely little. Yet, while it is far-fetched that Asia will encounter a real flare-up, genuine concerns stay about the infection coming to urban communities like Hong Kong, Beijing, Shanghai and Singapore through their worldwide airplane terminals. Wellbeing priests from the Association of Southeast Asian Nations (ASEAN) reported key measures not long ago to keep the Ebola plague from coming to the locale and to backing influenced nations. This article accordingly will concentrate on the prevalence and current approaches of Ebola Virus Disease in ASEAN nations which is the need of the hour.

  13. A Serviced-based Approach to Connect Seismological Infrastructures: Current Efforts at the IRIS DMC

    Science.gov (United States)

    Ahern, Tim; Trabant, Chad

    2014-05-01

    As part of the COOPEUS initiative to build infrastructure that connects European and US research infrastructures, IRIS has advocated for the development of Federated services based upon internationally recognized standards using web services. By deploying International Federation of Digital Seismograph Networks (FDSN) endorsed web services at multiple data centers in the US and Europe, we have shown that integration within seismological domain can be realized. By deploying identical methods to invoke the web services at multiple centers this approach can significantly ease the methods through which a scientist can access seismic data (time series, metadata, and earthquake catalogs) from distributed federated centers. IRIS has developed an IRIS federator that helps a user identify where seismic data from global seismic networks can be accessed. The web services based federator can build the appropriate URLs and return them to client software running on the scientists own computer. These URLs are then used to directly pull data from the distributed center in a very peer-based fashion. IRIS is also involved in deploying web services across horizontal domains. As part of the US National Science Foundation's (NSF) EarthCube effort, an IRIS led EarthCube Building Block's project is underway. When completed this project will aid in the discovery, access, and usability of data across multiple geoscienece domains. This presentation will summarize current IRIS efforts in building vertical integration infrastructure within seismology working closely with 5 centers in Europe and 2 centers in the US, as well as how we are taking first steps toward horizontal integration of data from 14 different domains in the US, in Europe, and around the world.

  14. A current value Hamiltonian Approach for Discrete time Optimal Control Problems arising in Economic Growth

    OpenAIRE

    Naz, Rehana

    2018-01-01

    Pontrygin-type maximum principle is extended for the present value Hamiltonian systems and current value Hamiltonian systems of nonlinear difference equations for uniform time step $h$. A new method termed as a discrete time current value Hamiltonian method is established for the construction of first integrals for current value Hamiltonian systems of ordinary difference equations arising in Economic growth theory.

  15. Agulhas Current variability determined from space: a multi-sensor approach

    CSIR Research Space (South Africa)

    Rouault, M

    2011-11-01

    Full Text Available to the Doppler shift signal, the ASAR surface current velocities are able to consistently highlight regions of strong current and shear. The synaptic nature and relatively high resolution of ASAR acquisitions make the ASAR derived current velocities a good...

  16. VPAC receptors: structure, molecular pharmacology and interaction with accessory proteins.

    Science.gov (United States)

    Couvineau, Alain; Laburthe, Marc

    2012-05-01

    The vasoactive intestinal peptide (VIP) is a neuropeptide with wide distribution in both central and peripheral nervous systems, where it plays important regulatory role in many physiological processes. VIP displays a large biological functions including regulation of exocrine secretions, hormone release, fetal development, immune responses, etc. VIP appears to exert beneficial effect in neuro-degenerative and inflammatory diseases. The mechanism of action of VIP implicates two subtypes of receptors (VPAC1 and VPAC2), which are members of class B receptors belonging to the super-family of GPCR. This article reviews the current knowledge regarding the structure and molecular pharmacology of VPAC receptors. The structure-function relationship of VPAC1 receptor has been extensively studied, allowing to understand the molecular basis for receptor affinity, specificity, desensitization and coupling to adenylyl cyclase. Those studies have clearly demonstrated the crucial role of the N-terminal ectodomain (N-ted) of VPAC1 receptor in VIP recognition. By using different approaches including directed mutagenesis, photoaffinity labelling, NMR, molecular modelling and molecular dynamic simulation, it has been shown that the VIP molecule interacts with the N-ted of VPAC1 receptor, which is itself structured as a 'Sushi' domain. VPAC1 receptor also interacts with a few accessory proteins that play a role in cell signalling of receptors. Recent advances in the structural characterization of VPAC receptor and more generally of class B GPCRs will lead to the design of new molecules, which could have considerable interest for the treatment of inflammatory and neuro-degenerative diseases. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

  17. Pharmacology of midazolam.

    Science.gov (United States)

    Pieri, L; Schaffner, R; Scherschlicht, R; Polc, P; Sepinwall, J; Davidson, A; Möhler, H; Cumin, R; Da Prada, M; Burkard, W P; Keller, H H; Müller, R K; Gerold, M; Pieri, M; Cook, L; Haefely, W

    1981-01-01

    8-Chloro-6-(2-fluorophenyl)-1-methyl-4H-imidazo[1,5-a][1,4]benzodiazepine (midazolam, Ro 21-3981, Dormicum) is an imidazobenzodiazepine whose salts are soluble and stable in aqueous solution. It has a quick onset and, due to rapid metabolic inactivation, a rather short duration of action in all species studied. Midazolam has a similar pharmacologic potency and broad therapeutic range as diazepam. It produces all the characteristic effects of the benzodiazepine class, i.e., anticonvulsant, anxiolytic, sleep-inducing, muscle relaxant, and "sedative" effects. The magnitude of the anticonflict effect of midazolam is smaller than that of diazepam in rats and squirrel monkeys, probably because a more pronounced sedative component interferes with the increase of punished responses. In rodents, surgical anaesthesia is not attained with midazolam alone even in high i.v. doses, whereas this state is obtained in monkeys. The drug potentiates the effect of various central depressant agents. Midazolam is virtually free of effects on the cardiovascular system in conscious animals and produces only slight decreases in cardiac performance in dogs anaesthetized with barbiturates. No direct effects of the drugs on autonomic functions were found, however, stress-induced autonomic disturbances are prevented, probably by an effect on central regulatory systems. All animal data suggest the usefulness of midazolam as a sleep-inducer and i.v. anaesthetic of rapid onset and short duration.

  18. Pharmaceutical and pharmacological approaches for bioavailability ...

    Indian Academy of Sciences (India)

    Fleischhack G, Reif S, Hasan C, Jaehde U, Hettmer S and Bode. U 2001 Feasibility of intraventricular administration of etoposide in patients with metastatic brain tumours. Br. J. Cancer 84 1453-1459. 2001. Fractionated doses of oral etoposide in the treatment of patients with AIDS-related Kaposi sarcoma: a clinical and.

  19. Management of Depression in Patients with Dementia: Is Pharmacological Treatment Justified?

    Science.gov (United States)

    Ford, Andrew H; Almeida, Osvaldo P

    2017-02-01

    Depression in the context of dementia is common and contributes to poorer outcomes in individuals and those who care for them. Non-pharmacological treatments are the preferred initial approach to managing these symptoms but data in support of these are scarce. There are a number of pharmacological treatment options available to clinicians but efficacy is uncertain and concern about potential side effects in an aging and vulnerable population needs to be taken into consideration. This review aims to provide a concise overview of pharmacological treatments for depression in dementia. Antidepressants are the mainstay of pharmacological treatment for clinically significant depression in the general population but evidence to support their use in dementia is mixed. Trials of antidepressants should generally be reserved for individuals with depression where the symptoms are distressing and surpass the threshold for major depression. Acetylcholinesterase inhibitors and memantine are effective in the symptomatic treatment of Alzheimer's disease but current evidence does not support their use to treat depressive symptoms in dementia. Similarly, antipsychotics and mood stabilizers have no proven efficacy for depression and the risk of adverse effects seems to outweigh any potential benefit. Pain can be a frequent problem in dementia and may have significant effects on behavior and mood. Preliminary evidence supports a role of adequate analgesia in improving mood in people with dementia.

  20. Current status and perspectives of neurobehavioral approaches in guideline—oriented animal testing

    Institute of Scientific and Technical Information of China (English)

    TakaH

    2002-01-01

    This presentation aims to overview the current status and perspective of behavioral approaches used in guideline-oriented toxicological studies for agricultural chemicals.Guidelines revised recently (MAFF,OECD,EPA) require sytematic observation of non-learning behavior using defined scales.The observational endpoints are organized into a battery (e.g.functional observational battery,FOB) and inculde home-cage and open-field observation of behavior reactivity to various stimuli(e.g.auditory,tactile,visual),grip strength,and motor activity under a novel environment.The outline of FOB will be illustrated and discussed in the first half of the presentation.One social concern in neurotoxicology is the impact of chemical exposure on cnognitive functions such as learning and memory as well as non-learning behavior.Guidelines describe the necessity of learning and memory tests when other data suggest potential effects on brain function,even though little information regarding cognitive status other than brain pathology can be obtained with FOB.This discrepancy arises from the lack of a simple method compatible with regular studies.One candidate method is fear-induced freezing of rats conditioned to context and auditory cue(Kim & Fanselow,1992).In order to evaluate this paradigm as a screening method,the effects of trimethyltin chloride (TMT) have been studied.Prior to the study,it has been characterized that oral administration of TMT to rats produces excitatory clinical signs and massive neural cell death in the hippocampal CA1 and CA3 regions at lethal dose(8mg·kg-1),but not any abnormalities at sub-lethal doses (4mg·kg-1 or less).Oral administration of TMT at a sub-lethal dose produced a significant decrease in freezing time to the context (hippocampal-dependent measure),but not to the auditory cue.Administration of TMT at a sublethal dose significantly inhibited long-term potentiation in the CA1,but not in the dentate gyrus.These results suggest that the model can be

  1. Quantitative Systems Pharmacology: A Case for Disease Models.

    Science.gov (United States)

    Musante, C J; Ramanujan, S; Schmidt, B J; Ghobrial, O G; Lu, J; Heatherington, A C

    2017-01-01

    Quantitative systems pharmacology (QSP) has emerged as an innovative approach in model-informed drug discovery and development, supporting program decisions from exploratory research through late-stage clinical trials. In this commentary, we discuss the unique value of disease-scale "platform" QSP models that are amenable to reuse and repurposing to support diverse clinical decisions in ways distinct from other pharmacometrics strategies. © 2016 The Authors Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of The American Society for Clinical Pharmacology and Therapeutics.

  2. Impaired cognition and attention in adults: pharmacological management strategies.

    Science.gov (United States)

    Allain, Hervé; Akwa, Yvette; Lacomblez, Lucette; Lieury, Alain; Bentué-Ferrer, Danièle

    2007-02-01

    Cognitive psychology has provided clinicians with specific tools for analyzing the processes of cognition (memory, language) and executive functions (attention-concentration, abstract reasoning, planning). Neuropsychology, coupled with the neurosciences (including neuroimaging techniques), has authenticated the existence of early disorders affecting the "superior or intellectual" functions of the human brain. The prevalence of cognitive and attention disorders is high in adults because all the diseases implicating the central nervous system are associated with cognitive correlates of variable intensity depending on the disease process and the age of the patient. In some pathologies, cognitive impairment can be a leading symptom such as in schizophrenia, posttraumatic stress disorder or an emblematic stigmata as in dementia including Alzheimer's disease. Paradoxically, public health authorities have only recognized as medications for improving cognitive symptoms those with proven efficacy in the symptomatic treatment of patients with Alzheimer's disease; the other cognitive impairments are relegated to the orphanage of syndromes and symptoms dispossessed of medication. The purpose of this review is to promote a true "pharmacology of cognition" based on the recent knowledge in neurosciences. Data from adult human beings, mainly concerning memory, language, and attention processes, will be reported. "Drug therapeutic strategies" for improving cognition (except for memory function) are currently rather scarce, but promising perspectives for a new neurobiological approach to cognitive pharmacology will be highlighted.

  3. The pharmacology of regenerative medicine.

    Science.gov (United States)

    Christ, George J; Saul, Justin M; Furth, Mark E; Andersson, Karl-Erik

    2013-07-01

    Regenerative medicine is a rapidly evolving multidisciplinary, translational research enterprise whose explicit purpose is to advance technologies for the repair and replacement of damaged cells, tissues, and organs. Scientific progress in the field has been steady and expectations for its robust clinical application continue to rise. The major thesis of this review is that the pharmacological sciences will contribute critically to the accelerated translational progress and clinical utility of regenerative medicine technologies. In 2007, we coined the phrase "regenerative pharmacology" to describe the enormous possibilities that could occur at the interface between pharmacology, regenerative medicine, and tissue engineering. The operational definition of regenerative pharmacology is "the application of pharmacological sciences to accelerate, optimize, and characterize (either in vitro or in vivo) the development, maturation, and function of bioengineered and regenerating tissues." As such, regenerative pharmacology seeks to cure disease through restoration of tissue/organ function. This strategy is distinct from standard pharmacotherapy, which is often limited to the amelioration of symptoms. Our goal here is to get pharmacologists more involved in this field of research by exposing them to the tools, opportunities, challenges, and interdisciplinary expertise that will be required to ensure awareness and galvanize involvement. To this end, we illustrate ways in which the pharmacological sciences can drive future innovations in regenerative medicine and tissue engineering and thus help to revolutionize the discovery of curative therapeutics. Hopefully, the broad foundational knowledge provided herein will spark sustained conversations among experts in diverse fields of scientific research to the benefit of all.

  4. [History and pharmacology of trazodone].

    Science.gov (United States)

    Agnoli, A

    1986-10-01

    Trazodone, a non-tricyclic molecule, represents the first of a new generation of antidepressants. It is currently marketed in a number of European countries, in the United States and in Latin America. The pharmacological and biochemical data, the mechanism of action and the preferential indications of trazodone are presented and compared to those of imipramine and other tricyclics. Unlike imipramine, trazodone inhibits the adrenergic system. The two molecules have anti-nociceptive properties, similar effects on the serotoninergic system and, after repeated administrations, they both reduce the density of beta-receptors. The clinical implications of the alpha-blocking activity of trazodone are reported. Trazodone is preferable to tricyclic anti-depressants in the treatment of depression in elderly subjects in general, and especially when they present closed angle glaucoma, prostatic hypertrophy, tremor or cardiovascular problems due to hyperactivity of the adrenergic system, as well as in organic depressions and in depression secondary to schizophrenia, alcoholism and in patients with Parkinson's disease.

  5. Cardiovascular Safety Pharmacology of Sibutramine.

    Science.gov (United States)

    Yun, Jaesuk; Chung, Eunyong; Choi, Ki Hwan; Cho, Dae Hyun; Song, Yun Jeong; Han, Kyoung Moon; Cha, Hey Jin; Shin, Ji Soon; Seong, Won-Keun; Kim, Young-Hoon; Kim, Hyung Soo

    2015-07-01

    Sibutramine is an anorectic that has been banned since 2010 due to cardiovascular safety issues. However, counterfeit drugs or slimming products that include sibutramine are still available in the market. It has been reported that illegal sibutramine-contained pharmaceutical products induce cardiovascular crisis. However, the mechanism underlying sibutramine-induced cardiovascular adverse effect has not been fully evaluated yet. In this study, we performed cardiovascular safety pharmacology studies of sibutramine systemically using by hERG channel inhibition, action potential duration, and telemetry assays. Sibutramine inhibited hERG channel current of HEK293 cells with an IC50 of 3.92 μM in patch clamp assay and increased the heart rate and blood pressure (76 Δbpm in heart rate and 51 ΔmmHg in blood pressure) in beagle dogs at a dose of 30 mg/kg (per oral), while it shortened action potential duration (at 10 μM and 30 μM, resulted in 15% and 29% decreases in APD50, and 9% and 17% decreases in APD90, respectively) in the Purkinje fibers of rabbits and had no effects on the QTc interval in beagle dogs. These results suggest that sibutramine has a considerable adverse effect on the cardiovascular system and may contribute to accurate drug safety regulation.

  6. Feasibility of the current-duration approach to studying human fecundity

    DEFF Research Database (Denmark)

    Slama, Rémy; Ducot, Béatrice; Carstensen, Lisbeth

    2006-01-01

    of unprotected intercourse was defined for 69 women (5.7%). An additional 15 women (1.2%) were planning to start trying to become pregnant within the next 6 months. Parametric methods allowed, based on current duration of unprotected intercourse, estimation of fecundity as if the couples had been followed...... up (current-duration design). To illustrate the feasibility of the current-duration design, we contacted a random sample of 1204 French women age 18 to 44 years in 2004 and recruited those who were currently having unprotected sexual intercourse. The current duration since the beginning...... prospectively. The estimated proportion of couples not pregnant after 12 months of unprotected intercourse was 34% (95% confidence interval [CI] = 15-54%). The accelerated-failure time model allows study of the influence of environmental factors on fecundity. As an illustration, tobacco smoking by the woman...

  7. Post-stroke Movement Disorders: Clinical Manifestations and Pharmacological Management.

    Science.gov (United States)

    Siniscalchi, Antonio; Gallelli, Luca; Labate, Angelo; Malferrari, Giovanni; Palleria, Caterina; Sarro, Giovambattista De

    2012-09-01

    Involuntary abnormal movements have been reported after ischaemic and haemorrhagic stroke. Post stroke movement disorders can appear as acute or delayed sequel. At the moment, for many of these disorders the knowledge of pharmacological treatment is still inadequate. Dopaminergic and GABAergic systems may be mainly involved in post-stroke movement disorders. This article provides a review on drugs commonly used in post-stroke movement disorders, given that some post-stroke movement disorders have shown a partial benefit with pharmacological approach.

  8. Pharmacologic management of chronic neuropathic pain

    Science.gov (United States)

    Mu, Alex; Weinberg, Erica; Moulin, Dwight E.; Clarke, Hance

    2017-01-01

    Abstract Objective To provide family physicians with a practical clinical summary of the Canadian Pain Society (CPS) revised consensus statement on the pharmacologic management of neuropathic pain. Quality of evidence A multidisciplinary interest group within the CPS conducted a systematic review of the literature on the current treatments of neuropathic pain in drafting the revised consensus statement. Main message Gabapentinoids, tricyclic antidepressants, and serotonin-norepinephrine reuptake inhibitors are the first-line agents for treating neuropathic pain. Tramadol and other opioids are recommended as second-line agents, while cannabinoids are newly recommended as third-line agents. Other anticonvulsants, methadone, tapentadol, topical lidocaine, and botulinum toxin are recommended as fourth-line agents. Conclusion Many pharmacologic analgesics exist for the treatment of neuropathic pain. Through evidence-based recommendations, the CPS revised consensus statement helps guide family physicians in the management of patients with neuropathic pain. PMID:29138154

  9. Pyrrolizidine Alkaloids: Chemistry, Pharmacology, Toxicology and Food Safety.

    Science.gov (United States)

    Moreira, Rute; Pereira, David M; Valentão, Patrícia; Andrade, Paula B

    2018-06-05

    Pyrrolizidine alkaloids (PA) are widely distributed in plants throughout the world, frequently in species relevant for human consumption. Apart from the toxicity that these molecules can cause in humans and livestock, PA are also known for their wide range of pharmacological properties, which can be exploited in drug discovery programs. In this work we review the current body of knowledge regarding the chemistry, toxicology, pharmacology and food safety of PA.

  10. Psychosocial and pharmacological management of pain in pediatric sickle cell disease.

    Science.gov (United States)

    Hildenbrand, Aimee K; Nicholls, Elizabeth G; Daly, Brian P; Marsac, Meghan L; Tarazi, Reem; Deepti, Raybagkar

    2014-03-01

    For children with sickle cell disease (SCD), pain is associated with significant current and future morbidity and mortality. Unfortunately, few evidence-based guidelines exist for the management of pain episodes in children with SCD. To inform empirically based treatment strategies for pain management in pediatric SCD, this review integrates and evaluates the extant literature on psychosocial and pharmacological approaches to the management of pain. Findings reveal a paucity of rigorous investigations of psychosocial and pharmacological pain management interventions in children with SCD. Psychosocial interventions included were primarily cognitive-behavioral in nature, whereas pharmacological approaches targeted non-opioid analgesics (ie, nonsteroidal anti-inflammatory drugs and corticosteroids) and opioid medications (ie, morphine and oxycodone). However, to date there is not a "gold standard" for pain management among children with SCD. Because psychosocial and physiological processes each play a role in the etiology and experience of pain, effective pain management requires multidimensional, comprehensive treatment approaches. Considering the significant impact of pain on functional outcomes and quality of life among children with SCD, additional clinical trials are warranted to ensure that interventions are safe and efficacious.

  11. Particle currents in a space-time dependent and CP-violating Higgs background: a field theory approach

    International Nuclear Information System (INIS)

    Comelli, D.; Riotto, A.

    1995-06-01

    Motivated by cosmological applications like electroweak baryogenesis, we develop a field theoretic approach to the computation of particle currents on a space-time dependent and CP-violating Higgs background. We consider the Standard Model model with two Higgs doublets and CP violation in the scalar sector, and compute both fermionic and Higgs currents by means of an expansion in the background fields. We discuss the gauge dependence of the results and the renormalization of the current operators, showing that in the limit of local equilibrium, no extra renormalization conditions are needed in order to specify the system completely. (orig.)

  12. Pharmacology Portal: An Open Database for Clinical Pharmacologic Laboratory Services.

    Science.gov (United States)

    Karlsen Bjånes, Tormod; Mjåset Hjertø, Espen; Lønne, Lars; Aronsen, Lena; Andsnes Berg, Jon; Bergan, Stein; Otto Berg-Hansen, Grim; Bernard, Jean-Paul; Larsen Burns, Margrete; Toralf Fosen, Jan; Frost, Joachim; Hilberg, Thor; Krabseth, Hege-Merete; Kvan, Elena; Narum, Sigrid; Austgulen Westin, Andreas

    2016-01-01

    More than 50 Norwegian public and private laboratories provide one or more analyses for therapeutic drug monitoring or testing for drugs of abuse. Practices differ among laboratories, and analytical repertoires can change rapidly as new substances become available for analysis. The Pharmacology Portal was developed to provide an overview of these activities and to standardize the practices and terminology among laboratories. The Pharmacology Portal is a modern dynamic web database comprising all available analyses within therapeutic drug monitoring and testing for drugs of abuse in Norway. Content can be retrieved by using the search engine or by scrolling through substance lists. The core content is a substance registry updated by a national editorial board of experts within the field of clinical pharmacology. This ensures quality and consistency regarding substance terminologies and classification. All laboratories publish their own repertoires in a user-friendly workflow, adding laboratory-specific details to the core information in the substance registry. The user management system ensures that laboratories are restricted from editing content in the database core or in repertoires within other laboratory subpages. The portal is for nonprofit use, and has been fully funded by the Norwegian Medical Association, the Norwegian Society of Clinical Pharmacology, and the 8 largest pharmacologic institutions in Norway. The database server runs an open-source content management system that ensures flexibility with respect to further development projects, including the potential expansion of the Pharmacology Portal to other countries. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.

  13. The current approach to human error and blame in the NHS.

    Science.gov (United States)

    Ottewill, Melanie

    There is a large body of research to suggest that serious errors are widespread throughout medicine. The traditional response to these adverse events has been to adopt a 'person approach' - blaming the individual seen as 'responsible'. The culture of medicine is highly complicit in this response. Such an approach results in enormous personal costs to the individuals concerned and does little to address the root causes of errors and thus prevent their recurrence. Other industries, such as aviation, where safety is a paramount concern and which have similar structures to the medical profession, have, over the past decade or so, adopted a 'systems' approach to error, recognizing that human error is ubiquitous and inevitable and that systems need to be developed with this in mind. This approach has been highly successful, but has necessitated, first and foremost, a cultural shift. It is in the best interests of patients, and medical professionals alike, that such a shift is embraced in the NHS.

  14. Current Counter-Drone Technology Solutions to Shield Airports and Approach and Departure Corridors

    Science.gov (United States)

    2016-12-15

    The proliferation of drones has the potential to harm people and property. In particular, drones flying near airports and airport approaches can cause flight disruptions, as well as other serious challenges and incidents. There is a need to understan...

  15. Angular approach combined to mechanical model for tool breakage detection by eddy current sensors

    OpenAIRE

    Ritou , Mathieu; Garnier , Sébastien; Furet , Benoît; Hascoët , Jean-Yves

    2014-01-01

    International audience; The paper presents a new complete approach for Tool Condition Monitoring (TCM) in milling. The aim is the early detection of small damages so that catastrophic tool failures are prevented. A versatile in-process monitoring system is introduced for reliability concerns. The tool condition is determined by estimates of the radial eccentricity of the teeth. An adequate criterion is proposed combining mechanical model of milling and angular approach. Then, a new solution i...

  16. Positive feedback : exploring current approaches in iterative travel demand model implementation.

    Science.gov (United States)

    2012-01-01

    Currently, the models that TxDOTs Transportation Planning and Programming Division (TPP) developed are : traditional three-step models (i.e., trip generation, trip distribution, and traffic assignment) that are sequentially : applied. A limitation...

  17. Off-equatorial current-driven instabilities ahead of approaching dipolarization fronts

    Science.gov (United States)

    Zhang, Xu; Angelopoulos, V.; Pritchett, P. L.; Liu, Jiang

    2017-05-01

    Recent kinetic simulations have revealed that electromagnetic instabilities near the ion gyrofrequency and slightly away from the equatorial plane can be driven by a current parallel to the magnetic field prior to the arrival of dipolarization fronts. Such instabilities are important because of their potential contribution to global electromagnetic energy conversion near dipolarization fronts. Of the several instabilities that may be consistent with such waves, the most notable are the current-driven electromagnetic ion cyclotron instability and the current-driven kink-like instability. To confirm the existence and characteristics of these instabilities, we used observations by two Time History of Events and Macroscale Interactions during Substorms satellites, one near the neutral sheet observing dipolarization fronts and the other at the boundary layer observing precursor waves and currents. We found that such instabilities with monochromatic signatures are rare, but one of the few cases was selected for further study. Two different instabilities, one at about 0.3 Hz and the other at a much lower frequency, 0.02 Hz, were seen in the data from the off-equatorial spacecraft. A parallel current attributed to an electron beam coexisted with the waves. Our instability analysis attributes the higher-frequency instability to a current-driven ion cyclotron instability and the lower frequency instability to a kink-like instability. The current-driven kink-like instability we observed is consistent with the instabilities observed in the simulation. We suggest that the currents needed to excite these low-frequency instabilities are so intense that the associated electron beams are easily thermalized and hence difficult to observe.

  18. Determinants of Current Account Deficit in Turkey: The Conditional and Partial Granger Causality Approach

    OpenAIRE

    YURDAKUL, Funda; CEVHER, Erdogan

    2015-01-01

    This study aims to reveal the causality relations between the macro aggregates that affect current deficit using conditional and partial Granger causality test. Current deficit/GDP, growth rate, real effective exchange rate, direct foreign capital investment, openness, and energy import were selected as variables for this purpose. 2003.1-2014.2 quarterly data for Turkey’s economy were used for analysis. The results of the conditional and partial Granger causality test demonstrate that real ef...

  19. Electrophysiological and Behavioral Effects of Combined Transcranial Direct Current Stimulation and Alcohol Approach Bias Retraining in Hazardous Drinkers

    NARCIS (Netherlands)

    den Uyl, T.E.; Gladwin, T.E.; Wiers, R.W.

    2016-01-01

    BACKGROUND: Cognitive bias modification (CBM) can be used to retrain automatic approach tendencies for alcohol. We investigated whether changing cortical excitability with transcranial direct current stimulation (tDCS) could enhance CBM effects in hazardous drinkers. We also studied the underlying

  20. Land administration in Ecuador; Current situation and opportunities with adoption of fit-for-purpose land administration approach

    NARCIS (Netherlands)

    Todorovski, D.; Salazar, Rodolfo; Jacome, Ginella; Bermeo, Antonio; Orellana, Esteban; Zambrano, Fatima; Teran, Andrea; Mejia, Raul

    2018-01-01

    The aim of this paper is to explore current land administration situation in Ecuador and identify opportunities for fit-for-purpose (FFP) land administration approach that could improve the land administration functions for the country and its citizens. In this paper, initially literature about land

  1. Approaches to chronic disease management evaluation in use in Europe : A review of current methods and performance measures

    NARCIS (Netherlands)

    Conklin, A.; Nolte, E.; Vrijhoef, H.J.M.

    2013-01-01

    Objectives: An overview was produced of approaches currently used to evaluate chronic disease management in selected European countries. The study aims to describe the methods and metrics used in Europe as a first to help advance the methodological basis for their assessment. Methods: A common

  2. Drug repurposing: translational pharmacology, chemistry, computers and the clinic.

    Science.gov (United States)

    Issa, Naiem T; Byers, Stephen W; Dakshanamurthy, Sivanesan

    2013-01-01

    The process of discovering a pharmacological compound that elicits a desired clinical effect with minimal side effects is a challenge. Prior to the advent of high-performance computing and large-scale screening technologies, drug discovery was largely a serendipitous endeavor, as in the case of thalidomide for erythema nodosum leprosum or cancer drugs in general derived from flora located in far-reaching geographic locations. More recently, de novo drug discovery has become a more rationalized process where drug-target-effect hypotheses are formulated on the basis of already known compounds/protein targets and their structures. Although this approach is hypothesis-driven, the actual success has been very low, contributing to the soaring costs of research and development as well as the diminished pharmaceutical pipeline in the United States. In this review, we discuss the evolution in computational pharmacology as the next generation of successful drug discovery and implementation in the clinic where high-performance computing (HPC) is used to generate and validate drug-target-effect hypotheses completely in silico. The use of HPC would decrease development time and errors while increasing productivity prior to in vitro, animal and human testing. We highlight approaches in chemoinformatics, bioinformatics as well as network biopharmacology to illustrate potential avenues from which to design clinically efficacious drugs. We further discuss the implications of combining these approaches into an integrative methodology for high-accuracy computational predictions within the context of drug repositioning for the efficient streamlining of currently approved drugs back into clinical trials for possible new indications.

  3. Fuzzy pharmacology: theory and applications.

    Science.gov (United States)

    Sproule, Beth A; Naranjo, Claudio A; Türksen, I Burhan

    2002-09-01

    Fuzzy pharmacology is a term coined to represent the application of fuzzy logic and fuzzy set theory to pharmacological problems. Fuzzy logic is the science of reasoning, thinking and inference that recognizes and uses the real world phenomenon that everything is a matter of degree. It is an extension of binary logic that is able to deal with complex systems because it does not require crisp definitions and distinctions for the system components. In pharmacology, fuzzy modeling has been used for the mechanical control of drug delivery in surgical settings, and work has begun evaluating its use in other pharmacokinetic and pharmacodynamic applications. Fuzzy pharmacology is an emerging field that, based on these initial explorations, warrants further investigation.

  4. Rotor cage fault diagnosis in three-phase induction motors based on a current and virtual flux approach

    International Nuclear Information System (INIS)

    Pires, Dulce F.; Pires, V. Fernao; Martins, J.F.; Pires, A.J.

    2009-01-01

    This paper focuses on the detection of a rotor cage fault in a three-phase PWM feed induction motor. In inverter-fed machines there are some difficulties for the detection of a rotor cage fault. These difficulties are due to the fault signature that will be contained in the currents or voltages applied to the machine. In this way, a new approach based on the current and a virtual flux is proposed. The use of the virtual flux allows the improving of the signal to noise ratio. This approach also allows the identification of a rotor cage fault independently of the type of control used in the ac drive. The theoretical principle of this method is discussed. Simulation and experimental results are presented in order to show the effectiveness of the proposed approach

  5. A new approach to control a deflection of an electroplated microstructure: dual current electroplating methods

    International Nuclear Information System (INIS)

    Yang, Hyun-Ho; Seo, Min-Ho; Han, Chang-Hoon; Yoon, Jun-Bo

    2013-01-01

    We propose and demonstrate a simple and novel method to control the deflection in a suspended microstructure by using a dual current electroplating (DuCE) method. The key concept of this method is to divide the structure into two layers—a bottom layer and a top layer—and then apply respective current densities in electroplating to those two layers while all other conditions are kept the same. In addition to a flat structure, the direction of structure bending is freely controlled by virtue of the DuCE method. Cantilever Ni beams with a length of 400 µm, which were electroplated by the conventional single current electroplating method, bent downward with a deflection of 3.4 µm. On the contrary, by the DuCE method, cantilever beams with a length of 400 µm showed an almost flat structure as desired. (The current densities of the bottom layer, the top layer, and the ratio of the two current densities, are 0.15, 1.24 A dm −2 , and 8.3, respectively.) Consequently, a nickel electroplated spiral structure with a length of 8600 µm was suspended flat with an end deflection of less than 0.7 µm (the ratio between the deflection and length is 0.007%). This work therefore represents the unprecedented ultra-long suspended microstructure with submicrometer deflection. (paper)

  6. Cognitive-behavior therapy for problem gambling: a critique of current treatments and proposed new unified approach.

    Science.gov (United States)

    Tolchard, Barry

    2017-06-01

    There is evidence supporting the use of cognitive-behavioral therapy (CBT) in the treatment of problem gambling. Despite this, little is known about how CBT works and which particular approach is most effective. This paper aims to synthesize the evidence for current CBT and propose a more unified approach to treatment. A literature review and narrative synthesis of the current research evidence of CBT for the treatment of problem gambling was conducted, focusing on the underlying mechanisms within the treatment approach. Several CBT approaches were critiqued. These can be divided into forms of exposure therapy (including aversion techniques, systematic desensitization and other behavioral experiments) those focusing on cognitive restructuring techniques (such as reinforcement of nongambling activity, use of diaries, motivational enhancement and audio-playback techniques and third wave techniques including mindfulness. Findings, in relation to the treatment actions, from this synthesis are reported. The debate surrounding the treatment of problem gambling has been conducted as an either/or rather than a both/and discourse. This paper proposes a new, unified approach to the treatment of problem gambling that incorporates the best elements of both exposure and cognitive restructuring techniques, alongside the use of techniques borrowed from mindfulness and other CBT approaches.

  7. A Novel Magnetic Resonance Imaging (MRI) Approach for Measuring Weak Electric Currents Inside the Human Brain

    DEFF Research Database (Denmark)

    Göksu, Cihan

    of individual ohmic conductivity values may open up the possibility of creating more realistic and accurate head models, which may ameliorate the simulations and practical use of NIBS techniques. Magnetic resonance current density imaging (MRCDI) and magnetic resonance electrical impedance tomography (MREIT......Knowing the electrical conductivity and current density distribution inside the human brain will be useful in various biomedical applications, i.e. for improving the efficiency of non-invasive brain stimulation (NIBS) techniques, the accuracy of electroencephalography (EEG......) and magnetoencephalography (MEG) source localization, or localization of pathological tissues. For example, the accuracy of electric field simulations for NIBS techniques is currently reduced by assigning inaccurate ohmic conductivity values taken from literature to different brain tissues. Therefore, the knowledge...

  8. The "Magic Cure" A Review of the Current Controversial Approaches for Treating Learning Disabilities.

    Science.gov (United States)

    Silver, Larry B.

    1987-01-01

    In view of popular press coverage of controversial approaches to treating learning disabilities, the article briefly reviews evidence concerning the following: neurophysiological retraining (patterning, optometric visual training, cerebellar-vestibular remediation, and applied kinesiology); and orthomolecular medicine (concerning megavitamins,…

  9. Approaches to Learning with Media and Media Literacy Education--Trends and Current Situation in Germany

    Science.gov (United States)

    Tulodziecki, Gerhard; Grafe, Silke

    2012-01-01

    German approaches to media literacy education are concerned with the questions, how the variety of media can be used in a meaningful way for learning and teaching and what educational tasks result from the extensive use of media. Considering these questions there are various conceptual ideas, research and development projects as well as…

  10. Overview of current multiparametric magnetic resonance imaging approach in the diagnosis and staging of prostate cancer

    Directory of Open Access Journals (Sweden)

    Hasan Aydın

    2015-04-01

    Full Text Available This article is primarily based on the utility and validity of multiparametric magnetic resonance imaging in the diagnosis and staging of prostate gland tumors. Multiparametric magnetic resonance imaging is an emerging, useful approach for evaluating and detecting prostate cancers. It also aids in the management of a tumor and improve the care and follow-up of patients.

  11. 3-D time-domain induced polarization tomography: a new approach based on a source current density formulation

    Science.gov (United States)

    Soueid Ahmed, A.; Revil, A.

    2018-04-01

    Induced polarization (IP) of porous rocks can be associated with a secondary source current density, which is proportional to both the intrinsic chargeability and the primary (applied) current density. This gives the possibility of reformulating the time domain induced polarization (TDIP) problem as a time-dependent self-potential-type problem. This new approach implies a change of strategy regarding data acquisition and inversion, allowing major time savings for both. For inverting TDIP data, we first retrieve the electrical resistivity distribution. Then, we use this electrical resistivity distribution to reconstruct the primary current density during the injection/retrieval of the (primary) current between the current electrodes A and B. The time-lapse secondary source current density distribution is determined given the primary source current density and a distribution of chargeability (forward modelling step). The inverse problem is linear between the secondary voltages (measured at all the electrodes) and the computed secondary source current density. A kernel matrix relating the secondary observed voltages data to the source current density model is computed once (using the electrical conductivity distribution), and then used throughout the inversion process. This recovered source current density model is in turn used to estimate the time-dependent chargeability (normalized voltages) in each cell of the domain of interest. Assuming a Cole-Cole model for simplicity, we can reconstruct the 3-D distributions of the relaxation time τ and the Cole-Cole exponent c by fitting the intrinsic chargeability decay curve to a Cole-Cole relaxation model for each cell. Two simple cases are studied in details to explain this new approach. In the first case, we estimate the Cole-Cole parameters as well as the source current density field from a synthetic TDIP data set. Our approach is successfully able to reveal the presence of the anomaly and to invert its Cole

  12. Factitious prey and artificial diets for predatory lady beetles: current situation, obstacles, and approaches for improvement

    Science.gov (United States)

    Predatory lady beetles (Coleoptera: Coccinellidae) are important natural enemies of many pests in crop ecosystems throughout the world. Although several species are currently mass-reared and sold by biocontrol companies, there is an urgent need to reduce rearing costs. Cost effective mass rearing of...

  13. Current Approaches to the Assessment of Graphic Design in a Higher Education Context

    Science.gov (United States)

    Giloi, Susan; du Toit, Pieter

    2013-01-01

    This article provides an overview of the current trends in assessment practice within the field of graphic design. The demands placed on educators to apply sound assessment practice for Higher Education subjects is as intense in the field of graphic design as in any other. Forcing the assessment of creative visual work into existing assessment…

  14. Trade reform, policy uncertainty, and the current account: a non expected-utility approach

    NARCIS (Netherlands)

    van Wijnbergen, S.J.G.

    1992-01-01

    Rapid and comprehensive reduction in barriers to international trade has often been followed by a sharp deterioration in the current account. The macroeconomic counterpart of the deterioration has typically been a decline in private savings; no clear response pattern has been observed for private

  15. [Current approaches to evaluating the anatomic and functional status of the cornea].

    Science.gov (United States)

    Avetisov, S E; Borodina, N V; Kobzova, M V; Musaeva, G M

    2010-01-01

    The review provides data on current methods for evaluating the anatomic and functional status of the cornea (light refraction, light transmission, and biomechanical properties, in particular). It analyzes the main advantages and disadvantages of basic (biomicroscopy, endothelial microscopy, ophthalmometry, topography, and pachymetry) and special (confocal microscopy, optical coherence tomography, ultrasound biomicroscopy, aberrometry, bidirectional corneal applanation, and keratoesthesiometry) studies.

  16. Soft regulations in pharmaceutical policy making : an overview of current approaches and their consequences

    NARCIS (Netherlands)

    Wettermark, B.; Godman, B.; Jacobsson, B.; Haaijer-Ruskamp, F.M.

    2009-01-01

    It is a challenge to improve public health within limited resources. Pharmaceutical policy making is a greater challenge due to conflicting interests between key stakeholder groups. This paper reviews current and future strategies to help improve the quality and efficiency of care, with special

  17. A Holistic Theoretical Approach to Intellectual Disability: Going beyond the Four Current Perspectives

    Science.gov (United States)

    Schalock, Robert L.; Luckasson, Ruth; Tassé, Marc J.; Verdugo, Miguel Angel

    2018-01-01

    This article describes a holistic theoretical framework that can be used to explain intellectual disability (ID) and organize relevant information into a usable roadmap to guide understanding and application. Developing the framework involved analyzing the four current perspectives on ID and synthesizing this information into a holistic…

  18. Pharmacological Effects of Biotin in Animals.

    Science.gov (United States)

    Riveron-Negrete, Leticia; Fernandez-Mejia, Cristina

    2017-01-01

    In recent decades, it was found that vitamins affect biological functions in ways other than their long-known functions; niacin is the best example of a water-soluble vitamin known to possess multiple actions. Biotin, also known as vitamin B7 or vitamin H, is a water-soluble B-complex vitamin that serves as a covalently-bound coenzyme of carboxylases. It is now well documented that biotin has actions other than participating in classical enzyme catalysis reactions. Several lines of evidence have demonstrated that pharmacological concentrations of biotin affect glucose and lipid metabolism, hypertension, reproduction, development, and immunity. The effect of biotin on these functions is related to its actions at the transcriptional, translational, and post-translational levels. The bestsupported mechanism involved in the genetic effects of biotin is the soluble guanylate cyclase/protein kinase G (PKG) signaling cascade. Although there are commercially-available products containing pharmacological concentrations of biotin, the toxic effects of biotin have been poorly studied. This review summarizes the known actions and molecular mechanisms of pharmacological doses of biotin in animals and current information regarding biotin toxicity. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  19. An Approach to Model Earth Conductivity Structures with Lateral Changes for Calculating Induced Currents and Geoelectric Fields during Geomagnetic Disturbances

    Directory of Open Access Journals (Sweden)

    Bo Dong

    2015-01-01

    Full Text Available During geomagnetic disturbances, the telluric currents which are driven by the induced electric fields will flow in conductive Earth. An approach to model the Earth conductivity structures with lateral conductivity changes for calculating geoelectric fields is presented in this paper. Numerical results, which are obtained by the Finite Element Method (FEM with a planar grid in two-dimensional modelling and a solid grid in three-dimensional modelling, are compared, and the flow of induced telluric currents in different conductivity regions is demonstrated. Then a three-dimensional conductivity structure is modelled and the induced currents in different depths and the geoelectric field at the Earth’s surface are shown. The geovoltages by integrating the geoelectric field along specific paths can be obtained, which are very important regarding calculations of geomagnetically induced currents (GIC in ground-based technical networks, such as power systems.

  20. A Quantitative Analysis of Undisclosed Conflicts of Interest in Pharmacology Textbooks.

    Science.gov (United States)

    Piper, Brian J; Telku, Hassenet M; Lambert, Drew A

    2015-01-01

    Disclosure of potential conflicts of interest (CoI) is a standard practice for many biomedical journals but not for educational materials. The goal of this investigation was to determine whether the authors of pharmacology textbooks have undisclosed financial CoIs and to identify author characteristics associated with CoIs. The presence of potential CoIs was evaluated by submitting author names (N = 403; 36.3% female) to a patent database (Google Scholar) as well as a database that reports on the compensation ($USD) received from 15 pharmaceutical companies (ProPublica's Dollars for Docs). All publications (N = 410) of the ten highest compensated authors from 2009 to 2013 and indexed in Pubmed were also examined for disclosure of additional companies that the authors received research support, consulted, or served on speaker's bureaus. A total of 134 patents had been awarded (Maximum = 18/author) to textbook authors. Relative to DiPiro's Pharmacotherapy: A Pathophysiologic Approach, contributors to Goodman and Gilman's Pharmacological Basis of Therapeutics and Katzung's Basic and Clinical Pharmacology were more frequently patent holders (OR = 6.45, P 1 patent (OR = 0.15, P < .0005). A total of $2,411,080 USD (28.3% for speaking, 27.0% for consulting, and 23.9% for research), was received by 53 authors (Range = $299 to $310,000/author). Highly compensated authors were from multiple fields including oncology, psychiatry, neurology, and urology. The maximum number of additional companies, not currently indexed in the Dollars for Docs database, for which an author had potential CoIs was 73. Financial CoIs are common among the authors of pharmacology and pharmacotherapy textbooks. Full transparency of potential CoIs, particularly patents, should become standard procedure for future editions of educational materials in pharmacology.

  1. Pharmacological Aspects of Neuro-Immune Interactions.

    Science.gov (United States)

    Tarasov, Vadim V; Kudryashov, Nikita V; Chubarev, Vladimir N; Kalinina, Tatiana S; Barreto, George E; Ashraf, Ghulam Md; Aliev, Gjumrakch

    2018-01-01

    The use of systematic approach for the analysis of mechanism of action of drugs at different levels of biological organization of organisms is an important task in experimental and clinical pharmacology for drug designing and increasing the efficacy and safety of drugs. The analysis of published data on pharmacological effects of psychotropic drugs possessing immunomodulatory and/or antiviral properties have shown a correlation between central effects of examined drugs associated with the impact on the processes of neurogenesis of adult brain and survival of neurons, and their ability to alter levels of key proinflammatory cytokines. The changes that occur as a result of the influence of pharmacological agents at one of the systems should inevitably lead to the functional reorganization at another. Integrative mechanisms underlying the neuro-immune interactions may explain the "pleiotropic" pharmacological effects of some antiviral and immunomodulatory drugs. Amantadine, which was originally considered as an antiviral agent, was approved as anti-parkinsonic drug after its wide medical use. The prolonged administration of interferon alpha caused depression in 30-45% of patients, thus limiting its clinical use. The antiviral drug "Oseltamivir" may provoke the development of central side effects, including abnormal behavior, delirium, impaired perception and suicides. Anti-herpethetical drug "Panavir" shows pronounced neuroprotective properties. The purpose of this review is to analyze the experimental and clinical data related to central effects of drugs with antiviral or/and immunotropic activity, and to discover the relationship of these effects with changes in reactivity of immune system and proinflammatory response. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  2. Breastfeeding information in pharmacology textbooks: a content analysis.

    Science.gov (United States)

    Amir, Lisa H; Raval, Manjri; Hussainy, Safeera Y

    2013-07-01

    Women often need to take medicines while breastfeeding and pharmacists need to provide accurate information in order to avoid undue caution about the compatibility of medicines and breastfeeding. The objective of this study was to review information provided about breastfeeding in commonly used pharmacology textbooks. We asked 15 Australian universities teaching pharmacy courses to provide a list of recommended pharmacology textbooks in 2011. Ten universities responded, generating a list of 11 textbooks that we analysed for content relating to breastfeeding. Pharmacology textbooks outline the mechanisms of actions of medicines and their use: however, only a small emphasis is placed on the safety/compatibility of medicines for women during breastfeeding. Current pharmacology textbooks recommended by Australian universities have significant gaps in their coverage of medicine use in breastfeeding. Authors of textbooks should address this gap, so academic staff can recommend texts with the best lactation content.

  3. Systemic Right Ventricle in Adults With Congenital Heart Disease: Anatomic and Phenotypic Spectrum and Current Approach to Management.

    Science.gov (United States)

    Brida, Margarita; Diller, Gerhard-Paul; Gatzoulis, Michael A

    2018-01-30

    The systemic right ventricle (SRV) is commonly encountered in congenital heart disease representing a distinctly different model in terms of its anatomic spectrum, adaptation, clinical phenotype, and variable, but overall guarded prognosis. The most common clinical scenarios where an SRV is encountered are complete transposition of the great arteries with previous atrial switch repair, congenitally corrected transposition of the great arteries, double inlet right ventricle mostly with previous Fontan palliation, and hypoplastic left heart syndrome palliated with the Norwood-Fontan protocol. The reasons for the guarded prognosis of the SRV in comparison with the systemic left ventricle are multifactorial, including distinct fibromuscular architecture, shape and function, coronary artery supply mismatch, intrinsic abnormalities of the tricuspid valve, intrinsic or acquired conduction abnormalities, and varied SRV adaptation to pressure or volume overload. Management of the SRV remains an ongoing challenge because SRV dysfunction has implications on short- and long-term outcomes for all patients irrespective of underlying cardiac morphology. SRV dysfunction can be subclinical, underscoring the need for tertiary follow-up and timely management of target hemodynamic lesions. Catheter interventions and surgery have an established role in selected patients. Cardiac resynchronization therapy is increasingly used, whereas pharmacological therapy is largely empirical. Mechanical assist device and heart transplantation remain options in end-stage heart failure when other management strategies have been exhausted. The present report focuses on the SRV with its pathological subtypes, pathophysiology, clinical features, current management strategies, and long-term sequelae. Although our article touches on issues applicable to neonates and children, its main focus is on adults with SRV. © 2018 American Heart Association, Inc.

  4. Neuropathic pain in people with cancer (part 2): pharmacological and non-pharmacological management.

    Science.gov (United States)

    Taverner, Tarnia

    2015-08-01

    The aim of this paper is to provide an overview of the management of neuropathic pain associated with cancer and to provide helpful clinical advice for nurses working with patients who may have neuropathic pain. While cancer pain is a mixed-mechanism pain, this article will focus only on neuropathic pain management. The impact of neuropathic pain on patients' quality of life is great and while many patients recover from their cancer, a significant number continue to suffer from a neuropathic pain syndrome. Management of neuropathic pain is significantly different from management of nociceptive pain with respect to pharmacological and non-pharmacological strategies. Neuropathic pain is complex, and as such requires complex management using pharmacological as well as non-pharmacological approaches. Specific drugs for neuropathic pain may be effective for some patients, but not all; therefore, ongoing and comprehensive assessment and management are required. Furthermore, these patients may require trials of several drugs before they find one that works for them. It is important for nurses to understand neuropathic pain, its manifestation, impact on quality of life and management when nursing patients with neuropathic pain associated with cancer.

  5. Risk assessment of mixtures of pesticides. Current approaches and future strategies

    DEFF Research Database (Denmark)

    Reffstrup, Trine Klein; Larsen, John Christian; Meyer, Otto A.

    2010-01-01

    The risk assessment of pesticide residues in food is based on toxicological evaluation of the single compounds and no internationally accepted procedure exists for evaluation of cumulative exposure to multiple residues of pesticides in crops, except for a few groups of pesticides sharing a group...... several approaches are available for the risk assessment of mixtures of pesticides. However, no single simple approach is available to judge upon potential interactions at the low doses that humans are exposed to from pesticide residues in food. In these cases, PBTK models could be useful as tools...... to assess combined tissue doses and to help predict potential interactions including thresholds for such effects. This would improve the quality of the risk assessment....

  6. Evaluation of Current Approaches to Stream Classification and a Heuristic Guide to Developing Classifications of Integrated Aquatic Networks

    Science.gov (United States)

    Melles, S. J.; Jones, N. E.; Schmidt, B. J.

    2014-03-01

    Conservation and management of fresh flowing waters involves evaluating and managing effects of cumulative impacts on the aquatic environment from disturbances such as: land use change, point and nonpoint source pollution, the creation of dams and reservoirs, mining, and fishing. To assess effects of these changes on associated biotic communities it is necessary to monitor and report on the status of lotic ecosystems. A variety of stream classification methods are available to assist with these tasks, and such methods attempt to provide a systematic approach to modeling and understanding complex aquatic systems at various spatial and temporal scales. Of the vast number of approaches that exist, it is useful to group them into three main types. The first involves modeling longitudinal species turnover patterns within large drainage basins and relating these patterns to environmental predictors collected at reach and upstream catchment scales; the second uses regionalized hierarchical classification to create multi-scale, spatially homogenous aquatic ecoregions by grouping adjacent catchments together based on environmental similarities; and the third approach groups sites together on the basis of similarities in their environmental conditions both within and between catchments, independent of their geographic location. We review the literature with a focus on more recent classifications to examine the strengths and weaknesses of the different approaches. We identify gaps or problems with the current approaches, and we propose an eight-step heuristic process that may assist with development of more flexible and integrated aquatic classifications based on the current understanding, network thinking, and theoretical underpinnings.

  7. Current diagnostic approach of bone tumors in childhood; Abordagem diagnostica atual dos tumores osseos na infancia

    Energy Technology Data Exchange (ETDEWEB)

    Torre, Marcia Barbosa; Scatigno Neto, Andre [Sao Paulo Univ., SP (Brazil). Faculdade de Medicina. Hospital das Clinicas

    1995-09-01

    The authors analyze the magnetic resonance imaging (MRI) as the imaging modality of choice for evaluation of patients with bone tumors or soft tissue tumors. The advent of such a sensitive imaging modality is fortuitous and coincides with a recent change in the therapeutic approach to primary bone tumors. MRI is extremely valuable in monitoring the tumor response to the initial chemotherapy and is accurate defining the margins of tumor, facilitating planning of limb salvage surgical procedures. (author). 5 refs., 8 figs.

  8. [From tic disorders to Tourette syndrome: current data, comorbidities, and therapeutic approach in children].

    Science.gov (United States)

    Fourneret, P; Desombre, H; Broussolle, E

    2014-06-01

    Motor tics are frequently observed in children during development. Usually transient and benign, they can become chronic over time, join various morbid disorders (vocal tics, attention deficit and hyperactivity disorder, and obsessive-compulsive disorders) and move toward genuine Tourette syndrome. In this case, it will be necessary to prevent impacts - mainly in terms of quality of life and emotional and relational problems - using a global therapeutic strategy combining psychoeducational approaches with appropriate medication. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  9. Current psychological therapeutic approaches for gambling disorder with psychiatric comorbidities: A narrative review

    OpenAIRE

    Echeburúa, Enrique; Amor, Pedro J.; Gómez, Montserrat

    2017-01-01

    Abstract: Background: Although the presence of a gambling disorder (GD) together with another mental disorder poses special treatment challenges, such as relapses, severe outcomes for patients and families, and increased number of hospitalizations, there are only a few critical reviews in the literature. Objective: To review empirical evidence of psychological approaches to cope specifically with these dual disorders. Method: A narrative review of the relevant bibliography on this topic wa...

  10. Molecular Phytopathology: Current Approaches and Main Directions in Diagnostics of Woody Plant Diseases

    Directory of Open Access Journals (Sweden)

    O. Yu. Baranov

    2014-08-01

    Full Text Available In the article the authors describe the prospects for diagnosis of woody plants diseases based on the use of modern methods of molecular plant pathology. The metagenomic approach based on the analysis of complex pathogens, including non-pathogenic microflora is described. The use the multicopy universal loci characterized by a number of advantages in determining taxonomic affiliation of infectious agents during phytopathological molecular analysis is proposed.

  11. Leadless Cardiac Pacemakers: Current status of a modern approach in pacing

    Directory of Open Access Journals (Sweden)

    Skevos Sideris

    2017-11-01

    Full Text Available Since the first transvenous pacemaker implantation, which took place 50 years ago, important progress has been achieved in pacing technology. Consequently, at present, more than 700,000 pacemakers are implanted annually worldwide. However, conventional pacemakers' implantation has a non-negligible risk of periprocedural and long-term complications associated with the transvenous leads and pacemaker pocket. Recently, leadless pacing systems have emerged as a therapeutic alternative to conventional pacing systems that provide therapy for patients with bradyarrhythmias, while eliminating potential transvenous lead- and pacemaker pocket-related complications. Initial studies have demonstrated favorable efficacy and safety of currently developed leadless pacing systems, compared to transvenous pacemakers. In the present paper, we review the current evidence and highlight the advantages and disadvantages of this novel technology. New technological advances may allow the next generation of leadless pacemakers to further expand, thereby offering a wireless cardiac pacing in future. Keywords: cardiac pacing, pacemaker, leadless pacemaker, bradycardia

  12. AC losses in superconductors: a multi-scale approach for the design of high current cables

    International Nuclear Information System (INIS)

    Escamez, Guillaume

    2016-01-01

    The work reported in this PhD deals with AC losses in superconducting material for large scale applications such as cables or magnets. Numerical models involving FEM or integral methods have been developed to solve the time transient electromagnetic distributions of field and current densities with the peculiarity of the superconducting constitutive E-J equation. Two main conductors have been investigated. First, REBCO superconductors for applications operating at 77 K are studied and a new architecture of conductor (round wires) for 3 kA cables. Secondly, for very high current cables, 3-D simulations on MgB_2 wires are built and solved using FEM modeling. The following chapter introduced new development used for the calculation of AC losses in DC cables with ripples. The thesis ends with the use of the developed numerical model on a practical example in the european BEST-PATHS project: a 10 kA MgB_2 demonstrator [fr

  13. A new approach to the inverse problem for current mapping in thin-film superconductors

    Science.gov (United States)

    Zuber, J. W.; Wells, F. S.; Fedoseev, S. A.; Johansen, T. H.; Rosenfeld, A. B.; Pan, A. V.

    2018-03-01

    A novel mathematical approach has been developed to complete the inversion of the Biot-Savart law in one- and two-dimensional cases from measurements of the perpendicular component of the magnetic field using the well-developed Magneto-Optical Imaging technique. Our approach, especially in the 2D case, is provided in great detail to allow a straightforward implementation as opposed to those found in the literature. Our new approach also refines our previous results for the 1D case [Johansen et al., Phys. Rev. B 54, 16264 (1996)], and streamlines the method developed by Jooss et al. [Physica C 299, 215 (1998)] deemed as the most accurate if compared to that of Roth et al. [J. Appl. Phys. 65, 361 (1989)]. We also verify and streamline the iterative technique, which was developed following Laviano et al. [Supercond. Sci. Technol. 16, 71 (2002)] to account for in-plane magnetic fields caused by the bending of the applied magnetic field due to the demagnetising effect. After testing on magneto-optical images of a high quality YBa2Cu3O7 superconducting thin film, we show that the procedure employed is effective.

  14. A Finite Element Versus Analytical Approach to the Solution of the Current Diffusion Equation in Tokamaks

    Czech Academy of Sciences Publication Activity Database

    Šesnic, S.; Dorić, V.; Poljak, D.; Šušnjara, A.; Artaud, J.F.

    2018-01-01

    Roč. 46, č. 4 (2018), s. 1027-1034 ISSN 0093-3813 R&D Projects: GA MŠk(CZ) 8D15001 Institutional support: RVO:61389021 Keywords : Finite element analysis * Tokamaks * current diffusion equation (CDE) * finite-element method (FEM) Subject RIV: BL - Plasma and Gas Discharge Physics OBOR OECD: Fluids and plasma physics (including surface physics) Impact factor: 1.052, year: 2016

  15. State of Corporate Social Responsibility in India – Current scenario, Approach and Drivers

    OpenAIRE

    Nagpal, Kshitij

    2016-01-01

    Purpose – The aim of the study is to examine the state of Corporate Social Responsibility (CSR)in India. The report attempts to investigate the current scenario of CSR ctivities and examine how corporations in India interpret CSR. The study also seeks to identify the reported driving forces behind implementation of CSR practices by firms in India. Methodology – CSR personnel from 3O companies that are obligated to spend on CSR activities under the Companies Act, 2013 were surveyed. To cr...

  16. Our Approach to Toxic Epidermal Necrolysis and Review of Current Treatment Alternatives

    Directory of Open Access Journals (Sweden)

    Fatih Uygur

    2008-09-01

    Full Text Available Toxic epidermal necrolysis (TEN is a clinical entity which has a 30 to 40 % mortality rate, with necrolysis affecting the entire epidermis. Antibiotics, nonsteroidal anti-inflammatory drugs and anticonvulsants are offender drugs in TEN etiology. A standard treatment protocol with proven efficacy is still lacking. In this study, current treatment practice and our treatment strategy for TEN is discussed and eight patients treated in our clinic between the years 2001 and 2008 are reviewed.

  17. Quality management of pharmacology and safety pharmacology studies

    DEFF Research Database (Denmark)

    Spindler, Per; Seiler, Jürg P

    2002-01-01

    to safety pharmacology studies, and, when indicated, to secondary pharmacodynamic studies, does not influence the scientific standards of studies. However, applying formal GLP standards will ensure the quality, reliability and integrity of studies, which reflect sound study management. It is important...... to encourage a positive attitude among researchers and academics towards these lines, whenever possible. GLP principles applied to the management of non-clinical safety studies are appropriate quality standards when studies are used in the context of protecting public health, and these quality standards...... of pharmacology studies (ICH S7A): primary pharmacodynamic, secondary pharmacodynamic and safety pharmacology studies, and guidance on the quality standards (expectations for GLP conformity) for these study types have been provided. Primary pharmacodynamic studies are the only study types that are fully exempt...

  18. The reflection of evolving bearing faults in the stator current's extended park vector approach for induction machines

    Science.gov (United States)

    Corne, Bram; Vervisch, Bram; Derammelaere, Stijn; Knockaert, Jos; Desmet, Jan

    2018-07-01

    Stator current analysis has the potential of becoming the most cost-effective condition monitoring technology regarding electric rotating machinery. Since both electrical and mechanical faults are detected by inexpensive and robust current-sensors, measuring current is advantageous on other techniques such as vibration, acoustic or temperature analysis. However, this technology is struggling to breach into the market of condition monitoring as the electrical interpretation of mechanical machine-problems is highly complicated. Recently, the authors built a test-rig which facilitates the emulation of several representative mechanical faults on an 11 kW induction machine with high accuracy and reproducibility. Operating this test-rig, the stator current of the induction machine under test can be analyzed while mechanical faults are emulated. Furthermore, while emulating, the fault-severity can be manipulated adaptively under controllable environmental conditions. This creates the opportunity of examining the relation between the magnitude of the well-known current fault components and the corresponding fault-severity. This paper presents the emulation of evolving bearing faults and their reflection in the Extended Park Vector Approach for the 11 kW induction machine under test. The results confirm the strong relation between the bearing faults and the stator current fault components in both identification and fault-severity. Conclusively, stator current analysis increases reliability in the application as a complete, robust, on-line condition monitoring technology.

  19. New approaches in the design of magnetic tweezers–current magnetic tweezers

    Energy Technology Data Exchange (ETDEWEB)

    Bessalova, Valentina [Lomonosov Moscow State University, Leninskie Gory 1-2, 119991 Moscow (Russian Federation); Perov, Nikolai [Lomonosov Moscow State University, Leninskie Gory 1-2, 119991 Moscow (Russian Federation); Immanuel Kant Baltic Federal University, Nevskogo 14, 236004 Kaliningrad (Russian Federation); Rodionova, Valeria [Immanuel Kant Baltic Federal University, Nevskogo 14, 236004 Kaliningrad (Russian Federation); National University of Science and Technology ' MISiS' , Leninsky Prospect 4, 119049 Moscow (Russian Federation)

    2016-10-01

    The main advantages of the magnetic tweezers are the low price and simplicity of use. However the range of their application is reduced due to shortcomings like, for example, the remanent induction of the core and interaction between ferromagnetic cores. We present the new design of magnetic tweezers–Current Magnetic Tweezers (CMT) that allow particle manipulation by means of the magnetic field generated by the electric currents flowing through the non-magnetic wires. Arranging wires in different geometric shapes allows the particle movement either in two or three dimensions. Forces acting on the magnetic particles with the magnetic moment of 2·10{sup −11} A m{sup 2} at distances up to 1 mm had been experimentally measured. It is established that a current of about 1 A at a 1 mm distance generates force of (approximately) 3 pN which is consistent with theoretical estimates. - Highlights: • We suggest the idea and the results of the test the prototype based on 3 wire's system that allows manipulation of nanoparticles on XY plane.

  20. New approaches in the design of magnetic tweezers–current magnetic tweezers

    International Nuclear Information System (INIS)

    Bessalova, Valentina; Perov, Nikolai; Rodionova, Valeria

    2016-01-01

    The main advantages of the magnetic tweezers are the low price and simplicity of use. However the range of their application is reduced due to shortcomings like, for example, the remanent induction of the core and interaction between ferromagnetic cores. We present the new design of magnetic tweezers–Current Magnetic Tweezers (CMT) that allow particle manipulation by means of the magnetic field generated by the electric currents flowing through the non-magnetic wires. Arranging wires in different geometric shapes allows the particle movement either in two or three dimensions. Forces acting on the magnetic particles with the magnetic moment of 2·10 −11 A m 2 at distances up to 1 mm had been experimentally measured. It is established that a current of about 1 A at a 1 mm distance generates force of (approximately) 3 pN which is consistent with theoretical estimates. - Highlights: • We suggest the idea and the results of the test the prototype based on 3 wire's system that allows manipulation of nanoparticles on XY plane.

  1. Artificial Intelligence approaches in hematopoietic cell transplant: A review of the current status and future directions.

    Science.gov (United States)

    Muhsen, Ibrahim N; ElHassan, Tusneem; Hashmi, Shahrukh K

    2018-06-08

    Currently, the evidence-based literature on healthcare is expanding exponentially. The opportunities provided by the advancement in artificial intelligence (AI) tools i.e. machine learning are appealing in tackling many of the current healthcare challenges. Thus, AI integration is expanding in most fields of healthcare, including the field of hematology. This study aims to review the current applications of AI in the field hematopoietic cell transplant (HCT). Literature search was done involving the following databases: Ovid-Medline including in-Process and Other Non-Indexed Citations and google scholar. The abstracts of the following professional societies: American Society of Haematology (ASH), American Society for Blood and Marrow Transplantation (ASBMT) and European Society for Blood and Marrow Transplantation (EBMT) were also screened. Literature review showed that the integration of AI in the field of HCT has grown remarkably in the last decade and confers promising avenues in diagnosis and prognosis within HCT populations targeting both pre and post-transplant challenges. Studies on AI integration in HCT have many limitations that include poorly tested algorithms, lack of generalizability and limited use of different AI tools. Machine learning techniques in HCT is an intense area of research that needs a lot of development and needs extensive support from hematology and HCT societies / organizations globally since we believe that this would be the future practice paradigm. Key words: Artificial intelligence, machine learning, hematopoietic cell transplant.

  2. Stem cell therapy for cardiovascular disease: the demise of alchemy and rise of pharmacology.

    Science.gov (United States)

    Jadczyk, T; Faulkner, A; Madeddu, P

    2013-05-01

    Regenerative medicine holds great promise as a way of addressing the limitations of current treatments of ischaemic disease. In preclinical models, transplantation of different types of stem cells or progenitor cells results in improved recovery from ischaemia. Furthermore, experimental studies indicate that cell therapy influences a spectrum of processes, including neovascularization and cardiomyogenesis as well as inflammation, apoptosis and interstitial fibrosis. Thus, distinct strategies might be required for specific regenerative needs. Nonetheless, clinical studies have so far investigated a relatively small number of options, focusing mainly on the use of bone marrow-derived cells. Rapid clinical translation resulted in a number of small clinical trials that do not have sufficient power to address the therapeutic potential of the new approach. Moreover, full exploitation has been hindered so far by the absence of a solid theoretical framework and inadequate development plans. This article reviews the current knowledge on cell therapy and proposes a model theory for interpretation of experimental and clinical outcomes from a pharmacological perspective. Eventually, with an increased association between cell therapy and traditional pharmacotherapy, we will soon need to adopt a unified theory for understanding how the two practices additively interact for a patient's benefit. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

  3. Current National Approach to Healthcare ICT Standardization: Focus on Progress in New Zealand.

    Science.gov (United States)

    Park, Young-Taek; Atalag, Koray

    2015-07-01

    Many countries try to efficiently deliver high quality healthcare services at lower and manageable costs where healthcare information and communication technologies (ICT) standardisation may play an important role. New Zealand provides a good model of healthcare ICT standardisation. The purpose of this study was to review the current healthcare ICT standardisation and progress in New Zealand. This study reviewed the reports regarding the healthcare ICT standardisation in New Zealand. We also investigated relevant websites related with the healthcare ICT standards, most of which were run by the government. Then, we summarised the governance structure, standardisation processes, and their output regarding the current healthcare ICT standards status of New Zealand. New Zealand government bodies have established a set of healthcare ICT standards and clear guidelines and procedures for healthcare ICT standardisation. Government has actively participated in various enactments of healthcare ICT standards from the inception of ideas to their eventual retirement. Great achievements in eHealth have already been realized, and various standards are currently utilised at all levels of healthcare regionally and nationally. Standard clinical terminologies, such as International Classification of Diseases (ICD) and Systematized Nomenclature of Medicine - Clinical Terms (SNOMED-CT) have been adopted and Health Level Seven (HL7) standards are actively used in health information exchanges. The government to New Zealand has well organised ICT institutions, guidelines, and regulations, as well as various programs, such as e-Medications and integrated care services. Local district health boards directly running hospitals have effectively adopted various new ICT standards. They might already be benefiting from improved efficiency resulting from healthcare ICT standardisation.

  4. Patient centric approach for clinical trials: Current trend and new opportunities.

    Science.gov (United States)

    Sharma, Neha Shankar

    2015-01-01

    The clinical research industry today is undergoing a major facelift. Companies are continuously looking to adopt and implement effective and innovative ways to accelerate drug launches in the market. Companies today are more open and do not view patients as mere "subjects" who generate data, - but as informed collaborators whose participation is "core" to the overall success of trials leading to the emergence of the concept of "patient-centric trials." This paper is intended to highlight the current trends and new opportunities that can be seen in industry -indicative of crucial role patients today play in their own health care using technology, social media and self education.

  5. Patient centric approach for clinical trials: Current trend and new opportunities

    Directory of Open Access Journals (Sweden)

    Neha Shankar Sharma

    2015-01-01

    Full Text Available The clinical research industry today is undergoing a major facelift. Companies are continuously looking to adopt and implement effective and innovative ways to accelerate drug launches in the market. Companies today are more open and do not view patients as mere "subjects" who generate data, - but as informed collaborators whose participation is "core" to the overall success of trials leading to the emergence of the concept of "patient-centric trials." This paper is intended to highlight the current trends and new opportunities that can be seen in industry -indicative of crucial role patients today play in their own health care using technology, social media and self education.

  6. The current status of theoretically based approaches to the prediction of the critical heat flux in flow boiling

    International Nuclear Information System (INIS)

    Weisman, J.

    1991-01-01

    This paper reports on the phenomena governing the critical heat flux in flow boiling. Inducts which vary with the flow pattern. Separate models are needed for dryout in annular flow, wall overheating in plug or slug flow and formation of a vapor blanket in dispersed flow. The major theories and their current status are described for the annular and dispersed regions. The need for development of the theoretical approach in the plug and slug flow region is indicated

  7. Review: Current Approaches to Business and Institutional Translation. Proceedings of the International Conference on Economic, Business, Financial and Institutional Translation

    Directory of Open Access Journals (Sweden)

    Miguel Tolosa Igualada

    2016-08-01

    Full Text Available Daniel Gallego-Hernández (ed.. Current Approaches to Business and Institutional Translation. Proceedings of the International Conference on Economic, Business, Financial and Institutional Translation / Enfoques actuales en traducción económica e institucional. Actas del Congreso Internacional de Traducción Económica, Comercial, Financiera e Institucional. Suíça: Peter Lang, 2015, 254 páginas. ISBN 978-3-0343-1656-9.

  8. Reappraisal of GIP Pharmacology for Metabolic Diseases

    DEFF Research Database (Denmark)

    Finan, Brian; Müller, Timo D; Clemmensen, Christoffer

    2016-01-01

    Glucagon-like peptide-1 (GLP-1) analogs are considered the best current medicines for type 2 diabetes (T2D) and obesity due to their actions in lowering blood glucose and body weight. Despite similarities to GLP-1, glucose-dependent insulinotropic polypeptide (GIP) has not been extensively pursue...... be beneficial for metabolic diseases. However, a growing body of new evidence - including data based on refined genetically modified models and improved pharmacological agents - suggests a paradigm shift on how the GIP system should be manipulated for metabolic benefits....

  9. Current approach to male infertility treatment: sperm selection procedure based on hyaluronic acid binding ability

    Directory of Open Access Journals (Sweden)

    A. V. Zobova

    2015-01-01

    Full Text Available Intracytoplasmic sperm injection into an oocyte is widely used throughout the world in assisted reproductive technologies programs in the presence of male infertility factor. However, this approach can allow selection of a single sperm, which is carrying different types of pathologies. Minimizing of any potential risks, entailing the occurrence of abnormalities in the embryos development (apoptosis, fragmentation of embryos, alterations in gene expression, aneuploidies is a very important condition for reducing the potential negative consequences resulting the manipulation with gametes. Processes that could be influenced by the embryologist must be fulfilled in safe and physiological way as much as it is possible. Data of numerous publications reporting about the positive effects of using the technology of sperm selection by hyaluronic acid binding, let make a conclusion about the high prospects of this approach in the treatment of male infertility by methods of in vitro fertilization. The selection of sperm with improved characteristics, which determine the maturity and genetic integrity, provides an opportunity to improve the parameters of pre-implantation embryogenesis, having thus a positive effect on clinical outcomes of assisted reproductive technologies programs.

  10. Current Approaches for Phenotyping as a Target for Precision Medicine in COPD Management.

    Science.gov (United States)

    Lopez-Campos, Jose Luis; Centanni, Stefano

    2018-03-20

    The study of airway diseases continues to present several challenges for modern medicine. The different disease presentations with variables and overlapping features may result in a real challenge for the clinician. In this context, the concept of precision medicine has started to emerge in order to give answers to some of these challenges from a diagnostic and therapeutic point of view. The main reasons to target for precision medicine in chronic obstructive pulmonary disease (COPD) include that there is variability in the clinical presentation, there is no correlation between the different clinical variables at the patient level, there are a number of relevant clinical variables associated with outcomes, we do have specific therapies for specific patient types, and that there is variability in the clinical response to different therapies. To bring precision medicine into clinical practice several approaches have been used, including the use of independent variables to identify subjects, the use of multidimensional indexes, the so-called clinical phenotypes, and the approximation by the so-called treatable traits. All these approaches have their strengths and weaknesses which are reviewed in the present document. Although there is no universally accepted proposal, the available initiatives provide us with a framework on which to start working and move toward precision medicine in COPD, with the ultimate goal of bringing the best possible medicine to each patient in particular.

  11. Applying quantitative structure–activity relationship approaches to nanotoxicology: Current status and future potential

    International Nuclear Information System (INIS)

    Winkler, David A.; Mombelli, Enrico; Pietroiusti, Antonio; Tran, Lang; Worth, Andrew; Fadeel, Bengt; McCall, Maxine J.

    2013-01-01

    The potential (eco)toxicological hazard posed by engineered nanoparticles is a major scientific and societal concern since several industrial sectors (e.g. electronics, biomedicine, and cosmetics) are exploiting the innovative properties of nanostructures resulting in their large-scale production. Many consumer products contain nanomaterials and, given their complex life-cycle, it is essential to anticipate their (eco)toxicological properties in a fast and inexpensive way in order to mitigate adverse effects on human health and the environment. In this context, the application of the structure–toxicity paradigm to nanomaterials represents a promising approach. Indeed, according to this paradigm, it is possible to predict toxicological effects induced by chemicals on the basis of their structural similarity with chemicals for which toxicological endpoints have been previously measured. These structure–toxicity relationships can be quantitative or qualitative in nature and they can predict toxicological effects directly from the physicochemical properties of the entities (e.g. nanoparticles) of interest. Therefore, this approach can aid in prioritizing resources in toxicological investigations while reducing the ethical and monetary costs that are related to animal testing. The purpose of this review is to provide a summary of recent key advances in the field of QSAR modelling of nanomaterial toxicity, to identify the major gaps in research required to accelerate the use of quantitative structure–activity relationship (QSAR) methods, and to provide a roadmap for future research needed to achieve QSAR models useful for regulatory purposes

  12. Comprehensive assessment of energy systems: approach and current results of the Swiss activities

    International Nuclear Information System (INIS)

    Hirschberg, S.; Dones, R.; Kypreos, S.

    1994-01-01

    This paper provides an overview of the approaches used and results obtained to this date within the Swiss Project GaBE on ''Comprehensive Assessment of Energy Systems''. Based on the ''cradle to grave'' approach detailed environmental inventories for major fuel cycles have been generated. In comparison to earlier studies a very broad spectrum of resources and air and water pollutants has been covered. Also non-energetic resources such as land depreciation have been considered. Numerous examples of evaluations are provided in the paper, including comparisons of greenhouse gas emissions, land use, radiation and wastes, and illustrating the impact of consideration of full energy chains. In the part concerning severe accidents some evaluations based on the database established as the Paul Scherrer Institute are presented as well as the estimated contribution of hypothetical severe accidents to the external costs associated with a specific Swiss nuclear power plant. Results of applications of the large scale energy-economy model MARKAL to the Swiss energy system and greenhouse gas scenarios are described. This includes cost-optimal contributions of different technologies to reduce CO 2 emissions, and trade-offs on the national and international level. Finally, the content of other GaBE activities either being in progress or planned is provided. (orig.)

  13. Current Technical Approaches for the Early Detection of Foodborne Pathogens: Challenges and Opportunities

    Directory of Open Access Journals (Sweden)

    Il-Hoon Cho

    2017-09-01

    Full Text Available The development of novel and high-tech solutions for rapid, accurate, and non-laborious microbial detection methods is imperative to improve the global food supply. Such solutions have begun to address the need for microbial detection that is faster and more sensitive than existing methodologies (e.g., classic culture enrichment methods. Multiple reviews report the technical functions and structures of conventional microbial detection tools. These tools, used to detect pathogens in food and food homogenates, were designed via qualitative analysis methods. The inherent disadvantage of these analytical methods is the necessity for specimen preparation, which is a time-consuming process. While some literature describes the challenges and opportunities to overcome the technical issues related to food industry legal guidelines, there is a lack of reviews of the current trials to overcome technological limitations related to sample preparation and microbial detection via nano and micro technologies. In this review, we primarily explore current analytical technologies, including metallic and magnetic nanomaterials, optics, electrochemistry, and spectroscopy. These techniques rely on the early detection of pathogens via enhanced analytical sensitivity and specificity. In order to introduce the potential combination and comparative analysis of various advanced methods, we also reference a novel sample preparation protocol that uses microbial concentration and recovery technologies. This technology has the potential to expedite the pre-enrichment step that precedes the detection process.

  14. Current applications and different approaches for microbial L-asparaginase production

    Directory of Open Access Journals (Sweden)

    Jorge Javier Muso Cachumba

    Full Text Available ABSTRACT L-asparaginase (EC 3.5.1.1 is an enzyme that catalysis mainly the asparagine hydrolysis in L-aspartic acid and ammonium. This enzyme is presented in different organisms, such as microorganisms, vegetal, and some animals, including certain rodent's serum, but not unveiled in humans. It can be used as important chemotherapeutic agent for the treatment of a variety of lymphoproliferative disorders and lymphomas (particularly acute lymphoblastic leukemia (ALL and Hodgkin's lymphoma, and has been a pivotal agent in chemotherapy protocols from around 30 years. Also, other important application is in food industry, by using the properties of this enzyme to reduce acrylamide levels in commercial fried foods, maintaining their characteristics (color, flavor, texture, security, etc. Actually, L-asparaginase catalyzes the hydrolysis of L-asparagine, not allowing the reaction of reducing sugars with this aminoacid for the generation of acrylamide. Currently, production of L-asparaginase is mainly based in biotechnological production by using some bacteria. However, industrial production also needs research work aiming to obtain better production yields, as well as novel process by applying different microorganisms to increase the range of applications of the produced enzyme. Within this context, this mini-review presents L-asparaginase applications, production by different microorganisms and some limitations, current investigations, as well as some challenges to be achieved for profitable industrial production.

  15. Current Technical Approaches for the Early Detection of Foodborne Pathogens: Challenges and Opportunities.

    Science.gov (United States)

    Cho, Il-Hoon; Ku, Seockmo

    2017-09-30

    The development of novel and high-tech solutions for rapid, accurate, and non-laborious microbial detection methods is imperative to improve the global food supply. Such solutions have begun to address the need for microbial detection that is faster and more sensitive than existing methodologies (e.g., classic culture enrichment methods). Multiple reviews report the technical functions and structures of conventional microbial detection tools. These tools, used to detect pathogens in food and food homogenates, were designed via qualitative analysis methods. The inherent disadvantage of these analytical methods is the necessity for specimen preparation, which is a time-consuming process. While some literature describes the challenges and opportunities to overcome the technical issues related to food industry legal guidelines, there is a lack of reviews of the current trials to overcome technological limitations related to sample preparation and microbial detection via nano and micro technologies. In this review, we primarily explore current analytical technologies, including metallic and magnetic nanomaterials, optics, electrochemistry, and spectroscopy. These techniques rely on the early detection of pathogens via enhanced analytical sensitivity and specificity. In order to introduce the potential combination and comparative analysis of various advanced methods, we also reference a novel sample preparation protocol that uses microbial concentration and recovery technologies. This technology has the potential to expedite the pre-enrichment step that precedes the detection process.

  16. A Gradually Varied Approach to Model Turbidity Currents in Submarine Channels

    Science.gov (United States)

    Bolla Pittaluga, M.; Frascati, A.; Falivene, O.

    2018-01-01

    We develop a one-dimensional model to describe the dynamics of turbidity current flowing in submarine channels. We consider the flow as a steady state polydisperse suspension accounting for water detrainment from the clear water-turbid interface, for spatial variations of the channel width and for water and sediment lateral overspill from the channel levees. Moreover, we account for sediment exchange with the bed extending the model to deal with situations where the current meets a nonerodible bed. Results show that when water detrainment is accounted for, the flow thickness becomes approximately constant proceeding downstream. Similarly, in the presence of channel levees, the flow tends to adjust to channel relief through the lateral loss of water and sediment. As more mud is spilled above the levees relative to sand, the flow becomes more sand rich proceeding downstream when lateral overspill is present. Velocity and flow thickness predicted by the model are then validated by showing good agreement with laboratory observations. Finally, the model is applied to the Monterey Canyon bathymetric data matching satisfactorily the December 2002 event field measurements and predicting a runout length consistent with observations.

  17. Contemporary pharmacological obesity treatments

    Directory of Open Access Journals (Sweden)

    Kaszubska Katarzyna

    2016-06-01

    Full Text Available In the last few years, obesity has become a global epidemic. Consequently, worldwide costs associated with managing obesity and obesity-related comorbidities are huge. Numerous studies have focused on discerning the appropriate proper treatment of weight related problems such as overweight and obesity. Moreover, many clinical trials have been conducted for many years in order to introduce effective anti-obesity drugs. The aim of the present review is to provide an overview of current and future pharmacotherapy for obesity, and to provide the reader with a determination of the concentration and composition of long and short term anti-obesity drugs, doing so by placing emphasis on pharmacotherapy and up-to-day solutions. It should be noted that, currently, the worldwide pharmacotherapy is represented by phendimetrazine, benzphetamine and diethylpropion, as well as by orlistat, lorcaserin, phentermine/topiramate, naltrexone/bupropion and liraglutide. In our paper, individual cases of patients’ needs are thoroughly illustrated by way of examples. Medical prescriptions and contraindications are also described.

  18. Post-operative complications after removal of sporadic vestibular schwannoma via retrosigmoid-suboccipital approach: current diagnosis and management.

    Science.gov (United States)

    Charalampakis, Stylianos; Koutsimpelas, Dimitrios; Gouveris, Haralampos; Mann, Wolf

    2011-05-01

    The retrosigmoid (suboccipital) approach is one of four surgical approaches for the treatment of vestibular schwannomas (acoustic neuromas). It is increasingly used by otologic surgeons, and in experienced hands is associated with improved results and more limited complications. Mortality rates are minimal and often zero, while postoperative sequelae, on the other hand, are not rare. In order to not only save the patient's life, but also to assure good quality of life after the surgery, one must consider many different aspects of management of the respective complications. In this review the issues of current management of CSF leak and meningitis, facial paresis, headache, hearing loss, unsteadiness, disequilibrium, vertigo, tinnitus, cerebellar and brain stem injuries or abscess, vascular complications and venous air embolism after retrosigmoid approach for removal of vestibular schwannomas are presented. © Springer-Verlag 2011

  19. Investigation of eddy currents in the components of the dynamic ergodic divertor of TEXTOR using analytical and numerical approaches

    International Nuclear Information System (INIS)

    Giesen, B.; Neubauer, O.; Bondarchuk, E.; Doinikov, N.; Kitaev, B.; Obidenko, T.; Panin, A.

    2003-01-01

    Analytical and numerical approaches for the calculation of eddy currents in mechanical structures of the TEXTOR tokamak in view of operating the dynamic ergodic divertor (DED) coil system fed with the alternating current up to 15 kA at frequencies up to 10 kHz are described. The design of the in-vessel components located close to the DED coils requires detailed investigation of eddy current effects to avoid unacceptable heating and forces. Different approaches depending on skin-layer depths compared with the body dimensions are analyzed. The applied algorithms are based on analytical and simplified numerical methods. Precision and application range of these algorithms have been checked by a numerical code. The simplified technique is rather effective for first step engineering estimation and gives a good understanding for the problem. In a certain parameter range, it results in even precise values and can be used for design optimization of the structures without huge efforts in numerical modeling. After modification of the component's shape prototypes have been manufactured and successfully tested in a full-scale model under the real DED field. The design recommendations resulting from the eddy current studies contributed significantly to the optimized lay out of the DED in-vessel components

  20. Human gene therapy: novel approaches to improve the current gene delivery systems.

    Science.gov (United States)

    Cucchiarini, Magali

    2016-06-01

    Even though gene therapy made its way through the clinics to treat a number of human pathologies since the early years of experimental research and despite the recent approval of the first gene-based product (Glybera) in Europe, the safe and effective use of gene transfer vectors remains a challenge in human gene therapy due to the existence of barriers in the host organism. While work is under active investigation to improve the gene transfer systems themselves, the use of controlled release approaches may offer alternative, convenient tools of vector delivery to achieve a performant gene transfer in vivo while overcoming the various physiological barriers that preclude its wide use in patients. This article provides an overview of the most significant contributions showing how the principles of controlled release strategies may be adapted for human gene therapy.

  1. Current Trend Towards Using Soft Computing Approaches to Phase Synchronization in Communication Systems

    Science.gov (United States)

    Drake, Jeffrey T.; Prasad, Nadipuram R.

    1999-01-01

    This paper surveys recent advances in communications that utilize soft computing approaches to phase synchronization. Soft computing, as opposed to hard computing, is a collection of complementary methodologies that act in producing the most desirable control, decision, or estimation strategies. Recently, the communications area has explored the use of the principal constituents of soft computing, namely, fuzzy logic, neural networks, and genetic algorithms, for modeling, control, and most recently for the estimation of phase in phase-coherent communications. If the receiver in a digital communications system is phase-coherent, as is often the case, phase synchronization is required. Synchronization thus requires estimation and/or control at the receiver of an unknown or random phase offset.

  2. The unique entity of nodular lymphocyte-predominant Hodgkin lymphoma: current approaches to diagnosis and management.

    Science.gov (United States)

    Hawkes, Eliza A; Wotherspoon, Andrew; Cunningham, David

    2012-03-01

    Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare disease constituting only 3-8% of all Hodgkin lymphoma. It has a distinct histological and clinical presentation as well as significantly different natural history compared to the classical form of Hodgkin lymphoma. Presenting most often as early-stage disease, NLPHL is characterized by frequent relapses, but paradoxically an overall good prognosis. The approach to management should therefore reflect this pattern and focus on attaining prolonged remissions, with long-term follow-up paramount. Due to the rarity of the disease, few prospective data exist. Options for treatment include radiotherapy, chemotherapy or combined chemotherapy plus radiotherapy and targeted anti-CD20 antibody therapy, as well as observation in selected patients.

  3. Combining non-invasive transcranial brain stimulation with neuroimaging and electrophysiology: Current approaches and future perspectives

    DEFF Research Database (Denmark)

    Bergmann, Til Ole; Karabanov, Anke; Hartwigsen, Gesa

    2016-01-01

    Non-invasive transcranial brain stimulation (NTBS) techniques such as transcranial magnetic stimulation (TMS) and transcranial current stimulation (TCS) are important tools in human systems and cognitive neuroscience because they are able to reveal the relevance of certain brain structures...... are technically demanding. We argue that the benefit from this combination is twofold. Firstly, neuroimaging and electrophysiology can inform subsequent NTBS, providing the required information to optimize where, when, and how to stimulate the brain. Information can be achieved both before and during the NTBS...... experiment, requiring consecutive and concurrent applications, respectively. Secondly, neuroimaging and electrophysiology can provide the readout for neural changes induced by NTBS. Again, using either concurrent or consecutive applications, both "online" NTBS effects immediately following the stimulation...

  4. Characterisation of plastic packaging waste for recycling: problems related to current approaches

    DEFF Research Database (Denmark)

    Götze, Ramona; Astrup, Thomas Fruergaard

    2013-01-01

    criteria of recycling processes. A lack of information in current waste characterisation practise on polymer resin composition, black coloured material content and the influence of surface adherent material on physico-chemical characteristics of plastic packaging waste were identified. These shortcomings...... were addressed by a resin type-based sorting analysis and a washing test for plastic packaging material from Danish household waste. Preliminary results show that, for a quarter of the hand sorted material, no resin type could be identified and that Polypropylene and Polyethylene terephthalate were...... the dominating resin types in plastic packaging. The suggested washing procedure caused a decrease of 70% of the ash content of the plastic material. The analysed metals and nutrients were reduced by up to 24%...

  5. The current role of on-line extraction approaches in clinical and forensic toxicology.

    Science.gov (United States)

    Mueller, Daniel M

    2014-08-01

    In today's clinical and forensic toxicological laboratories, automation is of interest because of its ability to optimize processes, to reduce manual workload and handling errors and to minimize exposition to potentially infectious samples. Extraction is usually the most time-consuming step; therefore, automation of this step is reasonable. Currently, from the field of clinical and forensic toxicology, methods using the following on-line extraction techniques have been published: on-line solid-phase extraction, turbulent flow chromatography, solid-phase microextraction, microextraction by packed sorbent, single-drop microextraction and on-line desorption of dried blood spots. Most of these published methods are either single-analyte or multicomponent procedures; methods intended for systematic toxicological analysis are relatively scarce. However, the use of on-line extraction will certainly increase in the near future.

  6. Advantages of the non-stationary approach: test on eddy current signals

    International Nuclear Information System (INIS)

    Brunel, P.

    1993-12-01

    Conventional signal processing is often unsuitable for the interpretation of intrinsically non-stationary signals, such as surveillance or non destructive testing signals. In these cases, ''advanced'' methods are required. This report presents two applications of non-stationary signal processing methods to the complex signals obtained in eddy current non destructive testing of steam generator tubes. The first application consists in segmenting the absolute channel, which can be likened to a piecewise constant signal. The Page-Hinkley cumulative sum algorithm is used, enabling detection of unknown mean amplitude jumps in a piecewise constant signal disturbed by a white noise. Results are comparable to those obtained with the empirical method currently in use. As easy to implement as the latter, the Page-Hinkley algorithm has the added advantage of being well formalized and of identifying whether the jumps in mean are positive or negative. The second application concerns assistance in detecting characteristic fault transients in the differential channels, using the continuous wavelet transform. The useful signal and noise spectra are fairly close, but not strictly identical. With the continuous wavelet transform, these frequency differences can be turned to account. The method was tested on synthetic signals obtained by summing noise and real defect signals. Using the continuous wavelet transform reduces the minimum signal-to-noise ratio by 5 dB for detection of a transient as compared with direct detection on the original signal. Finally, a summary of non-stationary methods using our data is presented. The two investigations described confirm that non-stationary methods may be considered as interesting signal and image analysis tools, as an efficient complement to conventional methods. (author). 24 figs., 13 refs

  7. Current approaches to geochemical reconnaissance for uranium in the Canadian Shield

    International Nuclear Information System (INIS)

    Cameron, E.M.; Hornbrook, E.H.W.

    1976-01-01

    Wide-interval geochemical reconnaissance is currently being carried out over large areas of the Canadian Shield by the Geological Survey of Canada. This work is in support of the federal-provincial Uranium Reconnaissance Program. The paper reviews the methodology employed for this reconnaissance to outline areas of enhanced potential for uranium and other mineral commodities. The generally low relief of the Shield virtually restricts wide-interval reconnaissance to the mobile elements that can travel some distance in solution. The high mobility of uranium, particularly in waters of neutral pH, makes it one of the most suitable types of mineralization for detection. For much of the Shield the most appropriate sampling media are lake sediments and lake waters. Centre-lake sediments are homogeneous, and are readily and economically collected utilizing helicopter support. They provide a good response for uranium and a variety of other indicator elements. Waters collected at the same sample sites are a useful supplement in the search for uranium mineralization, particularly in carbonate terrain. However, because of the very low content of uranium in many Shield waters, they present as yet unresolved problems of analysis and storage. The influence of organic material, iron and manganese on the uranium content of lake sediments are examined. Their scavenging influence has been found to be significant only at their lower concentration levels, particularly for organic matter and iron. For the majority of centre-lake samples the effect is negligible. The choice of sample interval is related to total survey costs, to speed of coverage, and to ability to detect uranium and other types of mineralization. For current G.S.C. programs a sample density of one per five square mile appears optimal. The results are presented as l:250,000 symbol maps that are prepared largely by computer, and as 1:1,000,000 contoured compilation maps. (author)

  8. Neuroscience of behavioral and pharmacological treatments for addictions

    Science.gov (United States)

    Potenza, Marc N.; Sofuoglu, Mehmet; Carroll, Kathleen M.; Rounsaville, Bruce J.

    2011-01-01

    Summary Although substantial advances have been made in behavioral and pharmacological treatments for addictions, moving treatment development to the next stage may require novel ways of approaching addictions, particularly those derived from new findings regarding of the neurobiological underpinnings of addictions, while assimilating and incorporating relevant information from earlier approaches. In this review, we first briefly review theoretical and biological models of addiction and then describe existing behavioral and pharmacologic therapies for the addictions within this framework. We then propose new directions for treatment development and targets that are informed by recent evidence regarding the heterogeneity of addictions and the neurobiological contributions to these disorders. PMID:21338880

  9. Current approaches to cyanotoxin risk assessment and risk management around the globe

    Science.gov (United States)

    Ibelings, Bas W.; Backer, Lorraine C.; Kardinaal, W. Edwin A.; Chorus, Ingrid

    2015-01-01

    Toxic cyanobacteria became more widely recognized as a potential health hazard in the 1990s, and in 1998 the World Health Organization (WHO) first published a provisional Guideline Value of 1 μg L−1 for microcystin-LR in drinking-water. In this publication we compare risk assessment and risk management of toxic cyanobacteria in 17 countries across all five continents. We focus on the three main (oral) exposure vehicles to cyanotoxins: drinking-water, water related recreational and freshwater seafood. Most countries have implemented the provisional WHO Guideline Value, some as legally binding standard, to ensure the distribution of safe drinking-water with respect to microcystins. Regulation, however, also needs to address the possible presence of a wide range of other cyanotoxins and bioactive compounds, for which no guideline values can be derived due to insufficient toxicological data. The presence of microcystins (commonly expressed as microcystin-LR equivalents) may be used as proxy for overall guidance on risk management, but this simplification may miss certain risks, for instance from dissolved fractions of cylindrospermopsin and cyanobacterial neurotoxins. An alternative approach, often taken for risk assessment and management in recreational waters, is to regulate cyanobacterial presence – as cell numbers or biomass – rather than individual toxins. Here, many countries have implemented a two or three tier alert level system with incremental severity. These systems define the levels where responses are switched from Surveillance to Alert and finally to Action Mode and they specify the short-term actions that follow. Surface bloom formation is commonly judged to be a significant risk because of the elevated concentration of microcystins in a scum. Countries have based their derivations of legally binding standards, guideline values, maximally allowed concentrations (or limits named otherwise) on very similar scientific methodology, but underlying

  10. Current approaches to cyanotoxin risk assessment and risk management around the globe.

    Science.gov (United States)

    Ibelings, Bas W; Backer, Lorraine C; Kardinaal, W Edwin A; Chorus, Ingrid

    2015-12-01

    Toxic cyanobacteria became more widely recognized as a potential health hazard in the 1990s, and in 1998 the World Health Organization (WHO) first published a provisional Guideline Value of 1 μg L -1 for microcystin-LR in drinking-water. In this publication we compare risk assessment and risk management of toxic cyanobacteria in 17 countries across all five continents. We focus on the three main (oral) exposure vehicles to cyanotoxins: drinking-water, water related recreational and freshwater seafood. Most countries have implemented the provisional WHO Guideline Value, some as legally binding standard, to ensure the distribution of safe drinking-water with respect to microcystins. Regulation, however, also needs to address the possible presence of a wide range of other cyanotoxins and bioactive compounds, for which no guideline values can be derived due to insufficient toxicological data. The presence of microcystins (commonly expressed as microcystin-LR equivalents) may be used as proxy for overall guidance on risk management, but this simplification may miss certain risks, for instance from dissolved fractions of cylindrospermopsin and cyanobacterial neurotoxins. An alternative approach, often taken for risk assessment and management in recreational waters, is to regulate cyanobacterial presence - as cell numbers or biomass - rather than individual toxins. Here, many countries have implemented a two or three tier alert level system with incremental severity. These systems define the levels where responses are switched from Surveillance to Alert and finally to Action Mode and they specify the short-term actions that follow. Surface bloom formation is commonly judged to be a significant risk because of the elevated concentration of microcystins in a scum. Countries have based their derivations of legally binding standards, guideline values, maximally allowed concentrations (or limits named otherwise) on very similar scientific methodology, but underlying

  11. Current approaches to journal club by general surgery programs within the Southwestern surgical congress.

    Science.gov (United States)

    Shifflette, Vanessa; Mitchell, Chris; Mangram, Alicia; Dunn, Ernest

    2012-01-01

    Journal club (JC) is a well-recognized education tool for many postgraduate medical education programs. Journal club helps residents learn critical analytic skills and keep up to date with current medical practices. To our knowledge, there is minimal evidence in the current literature detailing modern JC practices of general surgery training programs. Our study attempts to define how general surgery residency programs are implementing JC in their training process. We distributed by mail a 14-question survey to general surgery program directors within the Southwestern Surgical Congress. These surveys were redistributed 1 month after the initial attempt. The responses were collected and analyzed. Survey questions aimed to define JC practice characteristics, such as where JC is held, when JC is held, who directs JC, what journals are used, the perceived importance of JC, and average attendance. The surveys were sent to 32 program directors (PDs), which included 26 university and 6 community-based programs. We received responses from 26 (81%) PDs. Ninety-two percent of the programs have a consistent journal club (JC). Most JCs meet monthly (64%) or weekly (16%). The meeting places ranged from conference rooms (60%), faculty homes (20%), restaurants (8%), or in the hospital (12%). The meeting times were divided between morning (29%), midday (29%), and evening (42%). Most JCs lasted between 1 and 2 hours (88%), reviewed 1-4 articles (88%), and are attended by more than 60% of residents routinely (75%). Half of the programs (50%) had 3-4 faculty members present during discussion; 29% of the programs had only 1-2 faculty present. The articles were selected from more than 10 different journals. Seventy-five percent of the programs used the American Journal of Surgery and Annals of Surgery to find articles; only 13% of the programs used evidence-based reviews in surgery. PDs believe JC is very beneficial (42%), moderately beneficial (42%), or only fairly beneficial (16

  12. IMRT dose fractionation for head and neck cancer: Variation in current approaches will make standardisation difficult

    Energy Technology Data Exchange (ETDEWEB)

    Ho, Kean F. (Academic Dept. of Radiation Oncology, Univ. of Manchester, Manchester (United Kingdom)); Fowler, Jack F. (Dept. of Human Oncology and Medical Physics, Univ. of Wisconsin, Wisconsin (United States)); Sykes, Andrew J.; Yap, Beng K.; Lee, Lip W.; Slevin, Nick J. (Dept. of Clinical Oncology, Christie Hospital NHS Foundation Trust, Manchester (United Kingdom))

    2009-04-15

    Introduction. Altered fractionation has demonstrated clinical benefits compared to the conventional 2 Gy/day standard of 70 Gy. When using synchronous chemotherapy, there is uncertainty about optimum fractionation. IMRT with its potential for Simultaneous Integrated Boost (SIB) adds further to this uncertainty. This survey will examine international practice of IMRT fractionation and suggest possible reasons for diversity in approach. Material and methods. Fourteen international cancer centres were surveyed for IMRT dose/fractionation practised in each centre. Results. Twelve different types of dose fractionation were reported. Conventional 70-72 Gy (daily 2 Gy/fraction) was used in 3/14 centres with concurrent chemotherapy while 11/14 centres used altered fractionation. Two centres used >1 schedule. Reported schedules and number of centres included 6 fractions/week DAHANCA regime (3), modest hypofractionation (=2.2 Gy/fraction) (3), dose-escalated hypofractionation (=2.3 Gy/fraction) (4), hyperfractionation (1), continuous acceleration (1) and concomitant boost (1). Reasons for dose fractionation variability include (i) dose escalation; (ii) total irradiated volume; (iii) number of target volumes; (iv) synchronous systemic treatment; (v) shorter overall treatment time; (vi) resources availability; (vii) longer time on treatment couch; (viii) variable GTV margins; (ix) confidence in treatment setup; (x) late tissue toxicity and (xi) use of lower neck anterior fields. Conclusions. This variability in IMRT fractionation makes any meaningful comparison of treatment results difficult. Some standardization is needed particularly for design of multi-centre randomized clinical trials.

  13. Current legal regime for environmental impact assessment in areas beyond national jurisdiction and its future approaches

    International Nuclear Information System (INIS)

    Ma, Deqiang; Fang, Qinhua; Guan, Song

    2016-01-01

    In 2004, the United Nations launched an Ad Hoc Open-ended Informal Working Group to study issues relating to the conservation and sustainable use of marine biological diversity in areas beyond national jurisdiction. Since then, the topic of governing marine areas beyond national jurisdiction (ABNJ) has been widely discussed by politicians, policy makers and scholars. As one of management tools to protect marine biodiversity in ABNJ, environmental impact assessment (EIA) has been widely recognized and accepted by the international community, however, the biggest challenge is how to effectively implement the EIA regime in ABNJ. This paper explores the impacts of anthropogenic activities in ABNJ on marine ecosystems, reviews the existing legal regime for EIA in ABNJ and discusses possible measures to strengthen the implementation of EIA in ABNJ. - Highlights: • We identify human activities in ABNJ and their impacts on marine ecosystems. • We analyze the characters and gaps of the existing legal regime for EIA in ABNJ. • We analyze the pros and cons of alternative approaches of EIA in ABNJ.

  14. The "Biogenetic Law" in zoology: from Ernst Haeckel's formulation to current approaches.

    Science.gov (United States)

    Olsson, Lennart; Levit, Georgy S; Hoßfeld, Uwe

    2017-06-01

    150 years ago, in 1866, Ernst Haeckel published a book in two volumes called "Generelle Morphologie der Organismen" (General Morphology of Organisms) in which he formulated his biogenetic law, famously stating that ontogeny recapitulates phylogeny. Here we describe Haeckel's original idea and follow its development in the thinking of two scientists inspired by Haeckel, Alexei Sewertzoff and Adolf Naef. Sewertzoff and Naef initially approached the problem of reformulating Haeckel's law in similar ways, and formulated comparable hypotheses at a purely descriptive level. But their theoretical viewpoints were crucially different. While Sewertzoff laid the foundations for a Darwinian evolutionary morphology and is regarded as a forerunner of the Modern Synthesis, Naef was one of the most important figures in 'idealistic morphology', usually seen as a type of anti-Darwinism. Both Naef and Sewertzoff aimed to revise Haeckel's biogenetic law and came to comparable conclusions at the empirical level. We end our review with a brief look at the present situation in which molecular data are used to test the "hour-glass model", which can be seen as a modern version of the biogenetic law.

  15. Current legal regime for environmental impact assessment in areas beyond national jurisdiction and its future approaches

    Energy Technology Data Exchange (ETDEWEB)

    Ma, Deqiang [Fujian Provincial Key Laboratory for Coastal Ecology and Environmental Studies, Xiamen University, 361102 (China); Coastal and Ocean Management Institute, Xiamen University, 361102 (China); Fang, Qinhua, E-mail: qhfang@xmu.edu.cn [Fujian Provincial Key Laboratory for Coastal Ecology and Environmental Studies, Xiamen University, 361102 (China); Coastal and Ocean Management Institute, Xiamen University, 361102 (China); Guan, Song [Coastal and Ocean Management Institute, Xiamen University, 361102 (China)

    2016-01-15

    In 2004, the United Nations launched an Ad Hoc Open-ended Informal Working Group to study issues relating to the conservation and sustainable use of marine biological diversity in areas beyond national jurisdiction. Since then, the topic of governing marine areas beyond national jurisdiction (ABNJ) has been widely discussed by politicians, policy makers and scholars. As one of management tools to protect marine biodiversity in ABNJ, environmental impact assessment (EIA) has been widely recognized and accepted by the international community, however, the biggest challenge is how to effectively implement the EIA regime in ABNJ. This paper explores the impacts of anthropogenic activities in ABNJ on marine ecosystems, reviews the existing legal regime for EIA in ABNJ and discusses possible measures to strengthen the implementation of EIA in ABNJ. - Highlights: • We identify human activities in ABNJ and their impacts on marine ecosystems. • We analyze the characters and gaps of the existing legal regime for EIA in ABNJ. • We analyze the pros and cons of alternative approaches of EIA in ABNJ.

  16. Approaches to LLW disposal site selection and current progress of host states

    International Nuclear Information System (INIS)

    Walsh, J.J.; Kerr, T.A.

    1990-11-01

    In accordance with the Low-Level Radioactive Waste Policy Amendments Act of 1985 and under the guidance of 10 CFR 61, States have begun entering into compacts to establish and operate regional disposal facilities for low-level radioactive waste. The progress a state makes in implementing a process to identify a specific location for a disposal site is one indication of the level of a state's commitment to meeting its responsibilities under Federal law and interstate compact agreements. During the past few years, several States have been engaged in site selection processes. The purpose of this report is to summarize the site selection approaches of some of the Host States (California, Michigan, Nebraska, New York, North Carolina, Texas, and Illinois), and their progress to date. An additional purpose of the report is to discern whether the Host States's site selection processes were heavily influenced by any common factors. One factor each state held in common was that political and public processes exerted a powerful influence on the site selection process at virtually every stage. 1 ref

  17. How to measure the international development of palliative care? A critique and discussion of current approaches.

    Science.gov (United States)

    Loucka, Martin; Payne, Sheila; Brearley, Sarah

    2014-01-01

    A number of research projects have been conducted that aim to gather data on the international development of palliative care. These data are important for policy makers and palliative care advocates. The aim of this article was to provide a critical comparative analysis of methodological approaches used to assess the development and status of palliative care services and infrastructure at an international level. A selective literature review that focused on the methodological features of eight identified reports was undertaken. Reviewed reports were found to differ in adopted methodologies and provided uneven amounts of methodological information. Five major methodological limitations were identified (lack of theory, use of experts as source of information, grey literature, difficulties in ranking, and the problematic nature of data on service provision). A set of recommendations on how to deal with these issues in future research is provided. Measuring the international development of palliative care is a difficult and challenging task. The results of this study could be used to improve the validity of future research in this field. Copyright © 2014 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

  18. Approaches of Taxation under the Current Circumstances between Desiderata and Results – I

    Directory of Open Access Journals (Sweden)

    Georgeta Dragomir

    2011-02-01

    Full Text Available As a basic component of modern society, the taxation should combine the main objectivefor the public authority, to ensure most of the resources necessary to carry out state functions, withtargets at least as important on the country's economic development, supporting social issues,respecting the law and the financial discipline, in terms of efficiency, stability and sustainability. Forthese reasons, the level of taxation is very important for the present and future developments of acountry and the relevance of the analysis in this direction exceeds the economic, social or politicallevel. They practice different ways to understand and determine the impact of taxation in an economyand their uniform and realistic approach is important in order to succeed effective internationalcomparability and responsible actions at all levels, now and in the future. The public policy must findsolutions that can be adapted and implemented following the response that it gives the result ofanalysis that has as its starting point the economy, stimulating the private interest, which may leadimplicitly to obtaining parameters of superior quality at general level.

  19. Pharmacotherapy of Traumatic Brain Injury: State of the Science and the Road Forward: Report of the Department of Defense Neurotrauma Pharmacology Workgroup

    Science.gov (United States)

    Kochanek, Patrick M.; Bergold, Peter; Kenney, Kimbra; Marx, Christine E.; Grimes, Col. Jamie B.; Loh, LTC Yince; Adam, LTC Gina E.; Oskvig, Devon; Curley, Kenneth C.; Salzer, Col. Wanda

    2014-01-01

    Abstract Despite substantial investments by government, philanthropic, and commercial sources over the past several decades, traumatic brain injury (TBI) remains an unmet medical need and a major source of disability and mortality in both developed and developing societies. The U.S. Department of Defense neurotrauma research portfolio contains more than 500 research projects funded at more than $700 million and is aimed at developing interventions that mitigate the effects of trauma to the nervous system and lead to improved quality of life outcomes. A key area of this portfolio focuses on the need for effective pharmacological approaches for treating patients with TBI and its associated symptoms. The Neurotrauma Pharmacology Workgroup was established by the U.S. Army Medical Research and Materiel Command (USAMRMC) with the overarching goal of providing a strategic research plan for developing pharmacological treatments that improve clinical outcomes after TBI. To inform this plan, the Workgroup (a) assessed the current state of the science and ongoing research and (b) identified research gaps to inform future development of research priorities for the neurotrauma research portfolio. The Workgroup identified the six most critical research priority areas in the field of pharmacological treatment for persons with TBI. The priority areas represent parallel efforts needed to advance clinical care; each requires independent effort and sufficient investment. These priority areas will help the USAMRMC and other funding agencies strategically guide their research portfolios to ensure the development of effective pharmacological approaches for treating patients with TBI. PMID:23968241

  20. Mite Pests in Plant Crops – Current Issues, Inovative Approaches and Possibilities for Controlling Them (1

    Directory of Open Access Journals (Sweden)

    Radmila Petanović

    2010-01-01

    Full Text Available In the middle of the last century, mites moved into the focus of attention as pests relevantto agriculture, forestry and landscape horticulture, presumably in direct reactionto the “green revolution” that involved plant cultivation in large-plot monocropping systems,improved methods of cultivation, selection of high-yielding cultivars and intensifieduse of pesticides and mineral fertilizers. Agroecosystems in which phytophagous miteshave become harmful organisms are primarily orchards, vineyards, greenhouses, urbangreeneries, plant nurseries and stored plant products, as well as annual field crops to asomewhat lesser degree. Phytophagous mite species belong to a variety of spider mites(Tetranychidae, false spider mites (Tenuipalpidae, gall and rust mites (Eriophyoidae, tarsonemidmites (Tarsonemidae and acarid mites (Acaridae. Most of these harmful speciesare widespread, some of them having more economic impact than others and being moredetrimental as depending on various specificities of each outdoor agroecosystem in anyparticular climatic region.The first segment of this overview focuses on the most significant mite pests ofagroecosystemsand urban horticultural areas in European countries, our own region andin Serbia today, primarily on species that have caused problems in recent years regardingplant production, and it also discusses various molecular methods available for investigatingdifferent aspects of the biology of phytophagous mites. Also, acaricides are discussedas a method of controlling mite pests in the light of the current situation and trends on pesticidemarkets in Serbia and the European Union member-countries

  1. A Review of Current Neuromorphic Approaches for Vision, Auditory, and Olfactory Sensors.

    Science.gov (United States)

    Vanarse, Anup; Osseiran, Adam; Rassau, Alexander

    2016-01-01

    Conventional vision, auditory, and olfactory sensors generate large volumes of redundant data and as a result tend to consume excessive power. To address these shortcomings, neuromorphic sensors have been developed. These sensors mimic the neuro-biological architecture of sensory organs using aVLSI (analog Very Large Scale Integration) and generate asynchronous spiking output that represents sensing information in ways that are similar to neural signals. This allows for much lower power consumption due to an ability to extract useful sensory information from sparse captured data. The foundation for research in neuromorphic sensors was laid more than two decades ago, but recent developments in understanding of biological sensing and advanced electronics, have stimulated research on sophisticated neuromorphic sensors that provide numerous advantages over conventional sensors. In this paper, we review the current state-of-the-art in neuromorphic implementation of vision, auditory, and olfactory sensors and identify key contributions across these fields. Bringing together these key contributions we suggest a future research direction for further development of the neuromorphic sensing field.

  2. Bacterial Diseases of Bananas and Enset: Current State of Knowledge and Integrated Approaches Toward Sustainable Management

    Directory of Open Access Journals (Sweden)

    Guy Blomme

    2017-07-01

    Full Text Available Bacterial diseases of bananas and enset have not received, until recently, an equal amount of attention compared to other major threats to banana production such as the fungal diseases black leaf streak (Mycosphaerella fijiensis and Fusarium wilt (Fusarium oxysporum f. sp. cubense. However, bacteria cause significant impacts on bananas globally and management practices are not always well known or adopted by farmers. Bacterial diseases in bananas and enset can be divided into three groups: (1 Ralstonia-associated diseases (Moko/Bugtok disease caused by Ralstonia solanacearum and banana blood disease caused by R. syzygii subsp. celebesensis; (2 Xanthomonas wilt of banana and enset, caused by Xanthomonas campestris pv. musacearum and (3 Erwinia-associated diseases (bacterial head rot or tip-over disease Erwinia carotovora ssp. carotovora and E. chrysanthemi, bacterial rhizome and pseudostem wet rot (Dickeya paradisiaca formerly E. chrysanthemi pv. paradisiaca. Other bacterial diseases of less widespread importance include: bacterial wilt of abaca, Javanese vascular wilt and bacterial fingertip rot (probably caused by Ralstonia spp., unconfirmed. This review describes global distribution, symptoms, pathogenic diversity, epidemiology and the state of the art for sustainable disease management of the major bacterial wilts currently affecting banana and enset.

  3. Current and previous eating practices among women recovered from anorexia nervosa: a qualitative approach

    Directory of Open Access Journals (Sweden)

    Mariana Dimitrov Ulian

    2013-12-01

    Full Text Available OBJECTIVE: The aim of this study was to analyze qualitatively how women, who have recovered from anorexia nervosa, perceive and describe their current eating practices, as well as the ones developed during the eating disorder period. METHODS: Seven women were interviewed individually with the objective of investigating their eating practices, transition phases and all relevant aspects that somewhat contributed to the habit-forming; experiences, feelings and perceptions related to mealtime and the influence that food has had over the present subjects' life. The interviews were analyzed by the discourse of the collective subject method. RESULTS: The results brought up the following topics: a control; b concerns and feelings; c deprivation d beauty dictatorship; e eating competence; f importance of food; g food cacophony. CONCLUSIONS: What stands out is a multiplicity of eating practices, which during the eating disorder were similar to and characterized by restriction; however, after recovery, part of the subjects seem to have developed a higher eating competence, whereas others show a practice similar to the one acquired during the anorexia nervosa, such as the difficulty in realizing when they are satisfied and a feeling of discomfort when facing social interactions.

  4. Current approaches to prevent NSAID-induced gastropathy – COX selectivity and beyond

    Science.gov (United States)

    Becker, Jan C; Domschke, Wolfram; Pohle, Thorsten

    2004-01-01

    Gastrointestinal (GI) toxicity associated with nonsteroidal anti-inflammatory drugs (NSAIDs) is still an important medical and socio-economic problem – despite recent pharmaceutical advances. To prevent NSAID-induced gastropathy, three strategies are followed in clinical routine: (i) coprescription of a gastroprotective drug, (ii) use of selective COX-2 inhibitors, and (iii) eradication of Helicobacter pylori. Proton pump inhibitors are the comedication of choice as they effectively reduce gastrointestinal adverse events of NSAIDs and are safe even in long-term use. Co-medication with vitamin C has only been little studied in the prevention of NSAID-induced gastropathy. Apart from scavenging free radicals it is able to induce haeme-oxgenase 1 in gastric cells, a protective enzyme with antioxidant and vasodilative properties. Final results of the celecoxib outcome study (CLASS study) attenuated the initial enthusiasm about the GI safety of selective COX-2 inhibitors, especially in patients concomitantly taking aspirin for cardiovascular prophylaxis. Helicobacter pylori increases the risk for ulcers particularly in NSAID-naive patients and therefore eradication is recommended prior to long-term NSAID therapy at least in patients at high risk. New classes of COX-inhibitors are currently evaluated in clinical studies with very promising results: NSAIDs combined with a nitric oxide releasing moiety (NO-NSAID) and dual inhibitors of COX and 5-LOX. These drugs offer extended anti-inflammatory potency while sparing gastric mucosa. PMID:15563357

  5. Low prevalence of hypertension with pharmacological treatments and associated factors

    Directory of Open Access Journals (Sweden)

    Helena Gama

    2013-06-01

    Full Text Available OBJECTIVE: To assess the determinants of the lack of pharmacological treatment for hypertension. METHODS: In 2005, 3,323 Mozambicans aged 25-64 years old were evaluated. Blood pressure, weight, height and smoking status were assessed following the Stepwise Approach to Chronic Disease Risk Factor Surveillance. Hypertensives (systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg and/or antihypertensive drug therapy were evaluated for awareness of their condition, pharmacological and non-pharmacological management, as well as use of herbal or traditional remedies. Prevalence ratios (PR were calculated, adjusted for sociodemographic characteristics, cardiovascular risk factors and non-pharmacological treatment. RESULTS: Most of the hypertensive subjects (92.3%, and nearly half of those aware of their condition were not treated pharmacologically. Among the aware, the prevalence of untreated hypertension was higher in men {PR = 1.61; 95% confidence interval (95%CI 1.10;2.36} and was lower in subjects under non-pharmacological treatment (PR = 0.58; 95%CI 0.42;0.79; there was no significant association with traditional treatments (PR = 0.75; 95%CI 0.44;1.26. CONCLUSIONS: The lack of pharmacological treatment for hypertension was more frequent in men, and was not influenced by the presence of other cardiovascular risk factors; it could not be explained by the use of alternative treatments as herbal/traditional medicines or non-pharmacological management. It is important to understand the reasons behind the lack of management of diagnosed hypertension and to implement appropriate corrective actions to reduce the gap in the access to healthcare between developed and developing countries.

  6. Sleep Interventions Designed to Improve Athletic Performance and Recovery: A Systematic Review of Current Approaches.

    Science.gov (United States)

    Bonnar, Daniel; Bartel, Kate; Kakoschke, Naomi; Lang, Christin

    2018-03-01

    Athletes experience various situations and conditions that can interfere with their sleep, which is crucial for optimal psychological and physiological recovery as well as subsequent performance. Conventional sleep screening and intervention approaches may not be efficacious for athletes given their lifestyle, the demands of training and travel associated with interstate/international competition. The present systematic review aimed to summarize and evaluate sleep intervention studies targeting subsequent performance and recovery in competitive athletes. Based on the findings, a secondary aim was to outline a possible sleep intervention for athletes, including recommendations for content, mode of delivery and evaluation. A systematic review was conducted based on the PRISMA guidelines in May 2016 with an update completed in September 2017. Ten studies met our inclusion criteria comprising a total of 218 participants in the age range of 18-24 years with athletes from various sports (e.g., swimming, soccer, basketball, tennis). A modified version of the quality assessment scale developed by Abernethy and Bleakley was used to evaluate the quality of the studies. The included studies implemented several sleep interventions, including sleep extension and napping, sleep hygiene, and post-exercise recovery strategies. Evidence suggests that sleep extension had the most beneficial effects on subsequent performance. Consistent with previous research, these results suggest that sleep plays an important role in some, but not all, aspects of athletes' performance and recovery. Future researchers should aim to conduct sleep interventions among different athlete populations, compare results, and further establish guidelines and intervention tools for athletes to address their specific sleep demands and disturbances.

  7. Prevention of venous thromboembolism in cancer patients: current approaches and opportunities for improvement

    Directory of Open Access Journals (Sweden)

    Alpesh N. Amin

    2011-09-01

    Full Text Available Venous thromboembolism (VTE, a common complication in patients with cancer, is associated with increased risk of morbidity, mortality, and recurrent VTE. Risk factors for VTE in cancer patients include the type and stage of cancer, comorbidities, age, major surgery, and active chemotherapy. Evidence-based guidelines for thromboprophylaxis in cancer patients have been published: the National Comprehensive Cancer Network and American Society for Clinical Oncology guidelines recommend thromboprophylaxis for hospitalized cancer patients, while the American College of Chest Physician guidelines recommend thromboprophylaxis for surgical patients with cancer and bedridden cancer patients with an acute medical illness. Guidelines do not generally recommend routine thromboprophylaxis in ambulatory patients during chemotherapy, but there is evidence that some of these patients are at risk of VTE; some may be at higher risk while on active chemotherapy. Approaches are needed to identify those patients most likely to benefit from thromboprophylaxis, and, to this end, a risk assessment model has been developed and validated. Despite the benefits, many at-risk patients do not receive any thromboprophylaxis, or receive prophylaxis that is not compliant with guideline recommendations. Quality improvement initiatives have been developed by the Centers for Medicare and Medicaid Services, National Quality Forum, and Joint Commission to encourage closure of the gap between guideline recommendations and clinical practice for prevention, diagnosis, and treatment of VTE in hospitalized patients. Health-care institutions and providers need to take seriously the burden of VTE, improve prophylaxis rates in patients with cancer, and address the need for prophylaxis across the patient continuum.

  8. Where should Momma go? Current nursing home performance measurement strategies and a less ambitious approach

    Directory of Open Access Journals (Sweden)

    Lieberman Trudy

    2007-06-01

    Full Text Available Abstract Background Nursing home performance measurement systems are practically ubiquitous. The vast majority of these systems aspire to rank order all nursing homes based on quantitative measures of quality. However, the ability of such systems to identify homes differing in quality is hampered by the multidimensional nature of nursing homes and their residents. As a result, the authors doubt the ability of many nursing home performance systems to truly help consumers differentiate among homes providing different levels of quality. We also argue that, for consumers, performance measurement models are better at identifying problem facilities than potentially good homes. Discussion In response to these concerns we present a proposal for a less ambitious approach to nursing home performance measurement than previously used. We believe consumers can make better informed choice using a simpler system designed to pinpoint poor-quality nursing homes, rather than one designed to rank hundreds of facilities based on differences in quality-of-care indicators that are of questionable importance. The suggested performance model is based on five principles used in the development of the Consumers Union 2006 Nursing Home Quality Monitor. Summary We can best serve policy-makers and consumers by eschewing nursing home reporting systems that present information about all the facilities in a city, a state, or the nation on a website or in a report. We argue for greater modesty in our efforts and a focus on identifying only the potentially poorest or best homes. In the end, however, it is important to remember that information from any performance measurement website or report is no substitute for multiple visits to a home at different times of the day to personally assess quality.

  9. STUDY OF CURRENT APPROACHES FOR WEB PUBLISHING OF OPEN SCIENTIFIC DATA

    Directory of Open Access Journals (Sweden)

    D. I. Mouromtsev

    2015-11-01

    Full Text Available Subject of Study. The subject of study of this work is closely related to the development of tools and technologies for Internet publishing of open data in machine-readable formats with regard to data of universities, educational and research organizations and scientific laboratories. We analyze the trends in the publishing formats most commonly used including not only popular formats such as pdf, csv, excel, but also the Semantic Web formats such as RDF. The paper describes the way of scientific data publication in semantic formats on the example of import and convertation of the information from University database. Methods. We describe the methods of publication for scientific open data in the network consisting of a set of transformations of the original data sets to the final semantic representation. These transformation steps include data upload from a relational database, data mapping on the ontological model (schema and the generation of a set of RDF-triples corresponding to the initial database fragment. A description is given to the popular open data publishing systems, such as CKAN, VIVO, and others. OpenLink Virtuoso system is selected as the primary storage and data publication. The description of RDF data model is used as a way of presenting open data of ITMO University. Main Results. The authors have described the methods of scientific open data publication and identified their shortcomings. To demonstrate the efficiency of the proposed method of university open data publication, a software prototype has been developed available online at: http://lod.ifmo.ru/. The example of the system usage is also given. Practical Relevance. Implementation of the proposed approach will improve significantly the effect of the publication of university open data and make it available for third-party applications, such as applications for information retrieval about educational activities and research results, analysis of scientific activities in

  10. The crucial role of habits in energy consumption: an evolutionary approach on changing current patterns

    Energy Technology Data Exchange (ETDEWEB)

    Marechal, Kevin (Centre for Economic and Social Studies on the Environment (CESSE), Univ. Libre de Bruxelles, Univ. d' Europe (Belgium)). e-mail: kevin.marechal@ulb.ac.be

    2009-07-01

    A substantial body of literature has shown that our behaviour is often guided by habits. The existence of habits - not fully conscious forms of behaviour - is important as it contradicts rational choice theory. Their presence thus calls for the setting of new instruments as they make it unlikely that consumers be capable of exercising control over their energy consumption in reaction to given incentives. This is further increased in the evolutionary perspective where the current carbon-based Socio-Technical System constraints and shapes consumers' choices through structural forces. Habits being potentially 'counterintentional', they may explain the 'efficiency paradox' in energy as well as the continued increase of energy consumption despite the rising environmental awareness among the population. Policies aiming at reducing energy consumption should thus specifically address the performance context of habits. For instance, targeting new residents has proven to be more effective given that their preceding habits have been disturbed. The results of our empirical analysis confirm this idea by showing how a change of context makes people more receptive to a proposed measure. Our analysis of the role played by habits also suggests that individuals do not consider the need to change existing habits as an obstacle even though this is contradicted implicitly in the answers they provided to open questions. This 'unconsciousness' is one of the most delicate features of habits and it should thus be accounted for when designing measures. Given the other characteristics of habits, the joint use of feedbacks and commitment strategies appears promising.

  11. Review of Current Experience on Intermediate Heat Exchanger (IHX) and A Recommended Code Approach

    Energy Technology Data Exchange (ETDEWEB)

    Duane Spencer; Kevin McCoy

    2010-02-02

    The purpose of the ASME/DOE Gen IV Task 7 Part I is to review the current experience on various high temperature reactor intermediate heat exchanger (IHX) concepts. There are several different IHX concepts that could be envisioned for HTR/VHTR applications in a range of temperature from 850C to 950C. The concepts that will be primarily discussed herein are: (1) Tubular Helical Coil Heat Exchanger (THCHE); (2) Plate-Stamped Heat Exchanger (PSHE); (3) Plate-Fin Heat Exchanger (PFHE); and (4) Plate-Machined Heat Exchanger (PMHE). The primary coolant of the NGNP is potentially subject to radioactive contamination by the core as well as contamination from the secondary loop fluid. To isolate the radioactivity to minimize radiation doses to personnel, and protect the primary circuit from contamination, intermediate heat exchangers (IHXs) have been proposed as a means for separating the primary circuit of the NGNP (Next Generation Nuclear Plant) or other process heat application from the remainder of the plant. This task will first review the different concepts of IHX that could be envisioned for HTR/VHTR applications in a range of temperature from 850 to 950 C. This will cover shell-and-tube and compact designs (including the platefin concept). The review will then discuss the maturity of the concepts in terms of design, fabricability and component testing (or feedback from experience when applicable). Particular attention will be paid to the feasibility of developing the IHX concepts for the NGNP with operation expected in 2018-2021. This report will also discuss material candidates for IHX applications and will discuss specific issues that will have to be addressed in the context of the HTR design (thermal aging, corrosion, creep, creep-fatigue, etc). Particular attention will be paid to specific issues associated with operation at the upper end of the creep regime.

  12. Review of Current Experience on Intermediate Heat Exchanger (IHX) and A Recommended Code Approach

    International Nuclear Information System (INIS)

    Spencer, Duane; McCoy, Kevin

    2010-01-01

    The purpose of the ASME/DOE Gen IV Task 7 Part I is to review the current experience on various high temperature reactor intermediate heat exchanger (IHX) concepts. There are several different IHX concepts that could be envisioned for HTR/VHTR applications in a range of temperature from 850C to 950C. The concepts that will be primarily discussed herein are: (1) Tubular Helical Coil Heat Exchanger (THCHE); (2) Plate-Stamped Heat Exchanger (PSHE); (3) Plate-Fin Heat Exchanger (PFHE); and (4) Plate-Machined Heat Exchanger (PMHE). The primary coolant of the NGNP is potentially subject to radioactive contamination by the core as well as contamination from the secondary loop fluid. To isolate the radioactivity to minimize radiation doses to personnel, and protect the primary circuit from contamination, intermediate heat exchangers (IHXs) have been proposed as a means for separating the primary circuit of the NGNP (Next Generation Nuclear Plant) or other process heat application from the remainder of the plant. This task will first review the different concepts of IHX that could be envisioned for HTR/VHTR applications in a range of temperature from 850 to 950 C. This will cover shell-and-tube and compact designs (including the platefin concept). The review will then discuss the maturity of the concepts in terms of design, fabricability and component testing (or feedback from experience when applicable). Particular attention will be paid to the feasibility of developing the IHX concepts for the NGNP with operation expected in 2018-2021. This report will also discuss material candidates for IHX applications and will discuss specific issues that will have to be addressed in the context of the HTR design (thermal aging, corrosion, creep, creep-fatigue, etc). Particular attention will be paid to specific issues associated with operation at the upper end of the creep regime.

  13. Long-term catheterization: current approaches in the diagnosis and treatment of port-related infections

    Directory of Open Access Journals (Sweden)

    Bustos C

    2014-02-01

    Full Text Available Cesar Bustos,1 Aitziber Aguinaga,1 Francisco Carmona-Torre,2 Jose Luis Del Pozo1,3 1Department of Clinical Microbiology, 2Department of Internal Medicine, 3Division of Infectious Diseases, Clinica Universidad de Navarra, Pamplona, Spain Abstract: Since the first description in 1982, totally implanted venous access ports have progressively improved patients' quality of life and medical assistance when a medical condition requires the use of long-term venous access. Currently, they are part of the standard medical care for oncohematologic patients. However, apart from mechanical and thrombotic complications, there are also complications associated with biofilm development inside the catheters. These biofilms increase the cost of medical assistance and extend hospitalization. The most frequently involved micro-organisms in these infections are gram-positive cocci. Many efforts have been made to understand biofilm formation within the lumen catheters, and to resolve catheter-related infection once it has been established. Apart from systemic antibiotic treatment, the use of local catheter treatment (ie, antibiotic lock technique is widely employed. Many different antimicrobial options have been tested, with different outcomes, in clinical and in in vitro assays. The stability of antibiotic concentration in the lock solution once instilled inside the catheter lumen remains unresolved. To prevent infection, it is mandatory to perform hand hygiene before catheter insertion and manipulation, and to disinfect catheter hubs, connectors, and injection ports before accessing the catheter. At present, there are still unresolved questions regarding the best antimicrobial agent for catheter-related bloodstream infection treatment and the duration of concentration stability of the antibiotic solution within the lumen of the port. Keywords: catheter-related infection, bacteremia, biofilm

  14. Pharmacology Experiments on the Computer.

    Science.gov (United States)

    Keller, Daniel

    1990-01-01

    A computer program that replaces a set of pharmacology and physiology laboratory experiments on live animals or isolated organs is described and illustrated. Five experiments are simulated: dose-effect relationships on smooth muscle, blood pressure and catecholamines, neuromuscular signal transmission, acetylcholine and the circulation, and…

  15. Pharmacology of Marihuana (Cannabis sativa)

    Science.gov (United States)

    Maickel, Roger P.

    1973-01-01

    A detailed discussion of marihuana (Cannabis sativa) providing the modes of use, history, chemistry, and physiologic properties of the drug. Cites research results relating to the pharmacologic effects of marihuana. These effects are categorized into five areas: behavioral, cardiovascular-respiratory, central nervous system, toxicity-toxicology,…

  16. Chemotaxonomy and pharmacology of Gentianaceae

    DEFF Research Database (Denmark)

    Jensen, Søren Rosendal; Schripsema, Jan

    2002-01-01

    the remaining six are members of the Gentianeae. Based on the above results, a tentative list of chemical characteristics for the tribes of the Gentianaceae is presented. Finally, some pharmacologically interesting properties of plant extracts or compounds from taxa within Gentianaceae are listed....

  17. Cancer-related anorexia/cachexia syndrome and oxidative stress: an innovative approach beyond current treatment.

    Science.gov (United States)

    Mantovani, Giovanni; Madeddu, Clelia; Macciò, Antonio; Gramignano, Giulia; Lusso, Maria Rita; Massa, Elena; Astara, Giorgio; Serpe, Roberto

    2004-10-01

    Cancer-related anorexia/cachexia syndrome and oxidative stress play a key role in the progression and outcome of neoplastic disease. On the basis of our previously published studies and clinical experience, we have developed an innovative approach consisting of diet with high polyphenol content (400 mg), p.o. pharmaconutritional support enriched with n - 3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid) 2 cans (237 mL each) per day, medroxiprogesterone acetate 500 mg/d, antioxidant treatment with alpha-lipoic acid 300 mg/d plus carbocysteine lysine salt 2.7 g/d plus vitamin E 400 mg/d plus vitamin A 30,000 IU/d plus vitamin C 500 mg/d, and selective cyclooxygenase-2 inhibitor Celecoxib 200 mg/d. The treatment is administered for 16 weeks. The following variables are evaluated: (a) clinical variables (stage and Eastern Cooperative Oncology Group performance status); (b) nutritional variables (lean body mass, appetite, and resting energy expenditure); (c) laboratory variables (serum levels of proinflammatory cytokines, C-reactive protein, and leptin and blood levels of reactive oxygen species and antioxidant enzymes); and (d) quality of life variables (European Organization for Research and Treatment of Cancer QLQ-C30, EQ-5Dindex, and EQ-5DVAS). A phase II nonrandomized study has been designed to enroll 40 patients with advanced cancer at different sites with symptoms of cancer-related anorexia/cachexia syndrome and oxidative stress. As of January 2004, 28 patients have been enrolled: 25 patients were evaluable and 14 of them have completed the treatment (20 patients have completed 2 months of treatment). As for clinical response, five patients improved, three patients remained unchanged, and six patients worsened. The Eastern Cooperative Oncology Group performance status (grade) 1 remained unchanged. As for nutritional/functional variables, the lean body mass increased significantly at 2 and 4 months. As for laboratory variables, reactive oxygen species

  18. Using text mining for study identification in systematic reviews: a systematic review of current approaches.

    Science.gov (United States)

    O'Mara-Eves, Alison; Thomas, James; McNaught, John; Miwa, Makoto; Ananiadou, Sophia

    2015-01-14

    The large and growing number of published studies, and their increasing rate of publication, makes the task of identifying relevant studies in an unbiased way for inclusion in systematic reviews both complex and time consuming. Text mining has been offered as a potential solution: through automating some of the screening process, reviewer time can be saved. The evidence base around the use of text mining for screening has not yet been pulled together systematically; this systematic review fills that research gap. Focusing mainly on non-technical issues, the review aims to increase awareness of the potential of these technologies and promote further collaborative research between the computer science and systematic review communities. Five research questions led our review: what is the state of the evidence base; how has workload reduction been evaluated; what are the purposes of semi-automation and how effective are they; how have key contextual problems of applying text mining to the systematic review field been addressed; and what challenges to implementation have emerged? We answered these questions using standard systematic review methods: systematic and exhaustive searching, quality-assured data extraction and a narrative synthesis to synthesise findings. The evidence base is active and diverse; there is almost no replication between studies or collaboration between research teams and, whilst it is difficult to establish any overall conclusions about best approaches, it is clear that efficiencies and reductions in workload are potentially achievable. On the whole, most suggested that a saving in workload of between 30% and 70% might be possible, though sometimes the saving in workload is accompanied by the loss of 5% of relevant studies (i.e. a 95% recall). Using text mining to prioritise the order in which items are screened should be considered safe and ready for use in 'live' reviews. The use of text mining as a 'second screener' may also be used cautiously

  19. Underlying role of mitochondrial mutagenesis in the pathogenesis of a disease and current approaches for translational research.

    Science.gov (United States)

    Paraskevaidi, Maria; Martin-Hirsch, Pierre L; Kyrgiou, Maria; Martin, Francis L

    2017-05-01

    Mitochondrial diseases have been extensively investigated over the last three decades, but many questions regarding their underlying aetiologies remain unanswered. Mitochondrial dysfunction is not only responsible for a range of neurological and myopathy diseases but also considered pivotal in a broader spectrum of common diseases such as epilepsy, autism and bipolar disorder. These disorders are a challenge to diagnose and treat, as their aetiology might be multifactorial. In this review, the focus is placed on potential mechanisms capable of introducing defects in mitochondria resulting in disease. Special attention is given to the influence of xenobiotics on mitochondria; environmental factors inducing mutations or epigenetic changes in the mitochondrial genome can alter its expression and impair the whole cell's functionality. Specifically, we suggest that environmental agents can cause damage in mitochondrial DNA and consequently lead to mutagenesis. Moreover, we describe current approaches for handling mitochondrial diseases, as well as available prenatal diagnostic tests, towards eliminating these maternally inherited diseases. Undoubtedly, more research is required, as current therapeutic approaches mostly employ palliative therapies rather than targeting primary mechanisms or prophylactic approaches. Much effort is needed into further unravelling the relationship between xenobiotics and mitochondria, as the extent of influence in mitochondrial pathogenesis is increasingly recognised. © The Author 2016. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  20. CURRENT APPROACHES TO THE LABORATORY DIAGNOSIS OF RHEUMATIC DISEASES: ROLE OF MOLECULAR AND CELLULAR BIOMARKERS

    Directory of Open Access Journals (Sweden)

    E. N. Aleksandrova

    2016-01-01

    .The alternative therapies of RD include the use of low-molecular-weight chemically synthesized agents that suppress the activity of tyrosine kinases. The important area of this therapy is to restore immunological tolerance and to correct autoimmune disorders by means of autologous hematopoietic stem cells, mesenchymal stromal cells, autologous tolerogenic dendritic cells, regulatory T and B cells, gene therapy, and peptide antigens. The prospects for the laboratory diagnosis of RD are associated with the necessity of harmonizing and standardizing the current methods to determine autoantibodies and with the search for and clinical validation of novel proteomic, transcriptomic, and genomic biomarkers.

  1. [Overwork and its health effects--current status and future approach regarding Karoshi].

    Science.gov (United States)

    Hoshuyama, Tsutomu

    2003-09-01

    The word karoshi, i.e. death due to overwork, is not defined for medical diagnosis, but in Japan it means cases of compensation awarded by reason of fatal occupational diseases, particularly ischemic heart diseases and cerebrovascular diseases which are recognized as caused by a heavy workload. Current studies have shown that 1) almost definitely there is evidence of an association between overwork and cardiovascular diseases and the risk factors were found, 2) no reports have been published on evidence of a causal relationship between overwork and fatal effects even though the possibility remains, and 3) the adverse health effects can vary according to workers' characteristics such as gender, age, stress coping and perception. Recently there has been an increase in the proportion of compensated cases versus claims from 3.1% in the 1988 fiscal year to 20.7% in the 2001 fiscal year. This may be related to the deregulation of criteria for compensation, or nintei-kijun. The period of determination of overwork for victims has been extended to a maximum of six months in the newest criteria set in 2001, up from only one week in the criteria set in 1987. According to sociological analysis, long working hours in Japan are related not only to the structure of the working-time system but also the sociocultural background of labor. In 2002, the Japanese government provided the first countermeasures for the prevention of karoshi for all employees stating that they should not work more than 45 h overtime per month and that government intervention in the form of administrative guidance to employees and their employers should be conducted if overtime exceeds 100 h per month. It is a population strategy targeting all workers equally, not just a high-risk strategy targeting only those with some risk factors, and is expected to provide more fruitful results with flexibility, i.e. differentially reinforced management for older workers and those working under highly stressful

  2. Pharmacological modulation of mitochondrial calcium homeostasis.

    Science.gov (United States)

    Arduino, Daniela M; Perocchi, Fabiana

    2018-01-10

    Mitochondria are pivotal organelles in calcium (Ca 2+ ) handling and signalling, constituting intracellular checkpoints for numerous processes that are vital for cell life. Alterations in mitochondrial Ca 2+ homeostasis have been linked to a variety of pathological conditions and are critical in the aetiology of several human diseases. Efforts have been taken to harness mitochondrial Ca 2+ transport mechanisms for therapeutic intervention, but pharmacological compounds that direct and selectively modulate mitochondrial Ca 2+ homeostasis are currently lacking. New avenues have, however, emerged with the breakthrough discoveries on the genetic identification of the main players involved in mitochondrial Ca 2+ influx and efflux pathways and with recent hints towards a deep understanding of the function of these molecular systems. Here, we review the current advances in the understanding of the mechanisms and regulation of mitochondrial Ca 2+ homeostasis and its contribution to physiology and human disease. We also introduce and comment on the recent progress towards a systems-level pharmacological targeting of mitochondrial Ca 2+ homeostasis. © 2018 The Authors. The Journal of Physiology © 2018 The Physiological Society.

  3. Precision pharmacology for Alzheimer's disease.

    Science.gov (United States)

    Hampel, Harald; Vergallo, Andrea; Aguilar, Lisi Flores; Benda, Norbert; Broich, Karl; Cuello, A Claudio; Cummings, Jeffrey; Dubois, Bruno; Federoff, Howard J; Fiandaca, Massimo; Genthon, Remy; Haberkamp, Marion; Karran, Eric; Mapstone, Mark; Perry, George; Schneider, Lon S; Welikovitch, Lindsay A; Woodcock, Janet; Baldacci, Filippo; Lista, Simone

    2018-04-01

    The complex multifactorial nature of polygenic Alzheimer's disease (AD) presents significant challenges for drug development. AD pathophysiology is progressing in a non-linear dynamic fashion across multiple systems levels - from molecules to organ systems - and through adaptation, to compensation, and decompensation to systems failure. Adaptation and compensation maintain homeostasis: a dynamic equilibrium resulting from the dynamic non-linear interaction between genome, epigenome, and environment. An individual vulnerability to stressors exists on the basis of individual triggers, drivers, and thresholds accounting for the initiation and failure of adaptive and compensatory responses. Consequently, the distinct pattern of AD pathophysiology in space and time must be investigated on the basis of the individual biological makeup. This requires the implementation of systems biology and neurophysiology to facilitate Precision Medicine (PM) and Precision Pharmacology (PP). The regulation of several processes at multiple levels of complexity from gene expression to cellular cycle to tissue repair and system-wide network activation has different time delays (temporal scale) according to the affected systems (spatial scale). The initial failure might originate and occur at every level potentially affecting the whole dynamic interrelated systems within an organism. Unraveling the spatial and temporal dynamics of non-linear pathophysiological mechanisms across the continuum of hierarchical self-organized systems levels and from systems homeostasis to systems failure is key to understand AD. Measuring and, possibly, controlling space- and time-scaled adaptive and compensatory responses occurring during AD will represent a crucial step to achieve the capacity to substantially modify the disease course and progression at the best suitable timepoints, thus counteracting disrupting critical pathophysiological inputs. This approach will provide the conceptual basis for effective

  4. Geriatric pharmacology and pharmacotherapy education for health professionals and students: a systematic review

    Science.gov (United States)

    Keijsers, Carolina J P W; van Hensbergen, Larissa; Jacobs, Lotte; Brouwers, Jacobus R B J; de Wildt, Dick J; ten Cate, Olle Th J; Jansen, Paul A F

    2012-01-01

    AIMS Given the reported high rates of medication errors, especially in elderly patients, we hypothesized that current curricula do not devote enough time to the teaching of geriatric pharmacology. This review explores the quantity and nature of geriatric pharmacology education in undergraduate and postgraduate curricula for health professionals. METHODS Pubmed, Embase and PsycINFO databases were searched (from 1 January 2000 to 11 January 2011), using the terms ‘pharmacology’ and ‘education’ in combination. Articles describing content or evaluation of pharmacology education for health professionals were included. Education in general and geriatric pharmacology was compared. RESULTS Articles on general pharmacology education (252) and geriatric pharmacology education (39) were included. The number of publications on education in general pharmacology, but not geriatric pharmacology, has increased over the last 10 years. Articles on undergraduate and postgraduate education for 12 different health disciplines were identified. A median of 24 h (from 15 min to 4956 h) devoted to pharmacology education and 2 h (1–935 h) devoted to geriatric pharmacology were reported. Of the articles on education in geriatric pharmacology, 61.5% evaluated the teaching provided, mostly student satisfaction with the course. The strength of findings was low. Similar educational interventions were not identified, and evaluation studies were not replicated. CONCLUSIONS Recently, interest in pharmacology education has increased, possibly because of the high rate of medication errors and the recognized importance of evidence-based medical education. Nevertheless, courses on geriatric pharmacology have not been evaluated thoroughly and none can be recommended for use in training programmes. Suggestions for improvements in education in general and geriatric pharmacology are given. PMID:22416832

  5. Anodal transcranial direct current stimulation over right dorsolateral prefrontal cortex alters decision making during approach-avoidance conflict.

    Science.gov (United States)

    Chrysikou, Evangelia G; Gorey, Claire; Aupperle, Robin L

    2017-03-01

    Approach-avoidance conflict (AAC) refers to situations associated with both rewarding and threatening outcomes. The AAC task was developed to measure AAC decision-making. Approach behavior during this task has been linked to self-reported anxiety sensitivity and has elicited anterior cingulate, insula, caudate and right dorsolateral prefrontal cortex (dlPFC) activity, with right lateral PFC tracking the extent of approach behavior. Guided by these results, we used excitatory transcranial direct current stimulation (tDCS) to demonstrate the causal involvement of right dlPFC in AAC decision-making. Participants received anodal tDCS at 1.5mA over either left or right dlPFC or sham stimulation, while performing the AAC task and a control short-term memory task. Analyses of variance (ANOVA) revealed that for individuals with high anxiety sensitivity excitatory right (but not left or sham) dlPFC stimulation elicited measurable decreases in approach behavior during conflict. Excitatory left (but not right or sham) dlPFC simulation improved performance on the control task. These results support a possible asymmetry between the contributions of right and left dlPFC to AAC resolution during emotional decision-making. Increased activity in right dlPFC may contribute to anxiety-related symptoms and, as such, serve as a neurobehavioral target of anxiolytic treatments aiming to decrease avoidance behavior. © The Author (2016). Published by Oxford University Press.

  6. World Antimalarial Resistance Network (WARN IV: Clinical pharmacology

    Directory of Open Access Journals (Sweden)

    Gbotosho Grace O

    2007-09-01

    Full Text Available Abstract A World Antimalarial Resistance Network (WARN database has the potential to improve the treatment of malaria, through informing current drug selection and use and providing a prompt warning of when treatment policies need changing. This manuscript outlines the contribution and structure of the clinical pharmacology component of this database. The determinants of treatment response are multi-factorial, but clearly providing adequate blood concentrations is pivotal to curing malaria. The ability of available antimalarial pharmacokinetic data to inform optimal dosing is constrained by the small number of patients studied, with even fewer (if any studies conducted in the most vulnerable populations. There are even less data relating blood concentration data to the therapeutic response (pharmacodynamics. By pooling all available pharmacokinetic data, while paying careful attention to the analytical methodologies used, the limitations of small (and thus underpowered individual studies may be overcome and factors that contribute to inter-individual variability in pharmacokinetic parameters defined. Key variables for pharmacokinetic studies are defined in terms of patient (or study subject characteristics, the formulation and route of administration of the antimalarial studied, the sampling and assay methodology, and the approach taken to data analysis. Better defining these information needs and criteria of acceptability of pharmacokinetic-pharmacodynamic (PK-PD studies should contribute to improving the quantity, relevance and quality of these studies. A better understanding of the pharmacokinetic properties of antimalarials and a more clear definition of what constitutes "therapeutic drug levels" would allow more precise use of the term "antimalarial resistance", as it would indicate when treatment failure is not caused by intrinsic parasite resistance but is instead the result of inadequate drug levels. The clinical pharmacology component

  7. Light-cone AdS/CFT-adapted approach to AdS fields/currents, shadows, and conformal fields

    Energy Technology Data Exchange (ETDEWEB)

    Metsaev, R.R. [Department of Theoretical Physics, P.N. Lebedev Physical Institute, Leninsky prospect 53, Moscow 119991 (Russian Federation)

    2015-10-16

    Light-cone gauge formulation of fields in AdS space and conformal field theory in flat space adapted for the study of AdS/CFT correspondence is developed. Arbitrary spin mixed-symmetry fields in AdS space and arbitrary spin mixed-symmetry currents, shadows, and conformal fields in flat space are considered on an equal footing. For the massless and massive fields in AdS and the conformal fields in flat space, simple light-cone gauge actions leading to decoupled equations of motion are found. For the currents and shadows, simple expressions for all 2-point functions are also found. We demonstrate that representation of conformal algebra generators on space of currents, shadows, and conformal fields can be built in terms of spin operators entering the light-cone gauge formulation of AdS fields. This considerably simplifies the study of AdS/CFT correspondence. Light-cone gauge actions for totally symmetric arbitrary spin long conformal fields in flat space are presented. We apply our approach to the study of totally antisymmetric (one-column) and mixed-symmetry (two-column) fields in AdS space and currents, shadows, and conformal fields in flat space.

  8. Non-pharmacological management of abdominal pain-related functional gastrointestinal disorders in children.

    Science.gov (United States)

    Paul, Siba Prosad; Basude, Dharamveer

    2016-11-01

    Abdominal pain-related functional gastrointestinal disorder (AP-FGID) comprises of 4 main conditions: functional dyspepsia, irritable bowel syndrome, abdominal migraine and functional abdominal pain. AP-FGIDs are diagnosed clinically based on the Rome IV criteria for FGIDs of childhood. There is limited evidence for pharmacological therapies. This review article discusses nonpharmacological management of AP-FGID based on the current literature including systematic reviews, randomized controlled trials, cohort and case control studies. We aim to provide a comprehensive overview on the available evidence for the pediatricians and pediatric gastroenterologists involved in managing children with AP-FGID. Managing AP-FGIDs can be challenging. This should follow a stepwise approach with focused history, identification of "red flag" signs and symptoms, physical examination and investigations done following initial consultation. Family needs explaining that there is nothing seriously wrong with the child's abdomen. This explanation and reassurance can achieve symptom control in large number of cases. Non-pharmacological interventions are delivered through lifestyle and dietary changes and bio-psychosocial therapies. Dietary interventions vary depending on the type of AP-FGID. Bio-psychosocial therapies such as hypnotherapy, cognitive behavioral therapy and yoga aim at stress reduction. There is increasing evidence for use of non-pharmacological interventions in children with APFGID.

  9. Pharmacological potential and conservation prospect of the genus Eucomis (Hyacinthaceae) endemic to southern Africa.

    Science.gov (United States)

    Masondo, Nqobile A; Finnie, Jeffrey F; Van Staden, Johannes

    2014-01-01

    The genus Eucomis (Hyacinthaceae) consists of 10 species that are extensively used in African traditional medicine. This review is an appraisal of current information on the distribution and morphology, traditional uses, pharmacology, toxicology and approaches devised to enhance the conservation of the genus. A systematic and comprehensive literature search using electronic searches such as Scopus, Google Scholar, Web of Science and ethnobotanical books was conducted. Evidence from traditional medicine usage shows wide utilization of this genus for ailments such as respiratory, venereal diseases, rheumatism as well as kidney and bladder infections. Pharmacological screening reported antimicrobial, antiplasmodial, antitumor, cytotoxic, phytotoxic and anti-inflammatory properties. The potential of the genus Eucomis especially in terms of pharmacology cannot be overemphasized. Apart from the anti-inflammatory properties, the antifungal activity of Eucomis remains a valuable reservoir with potential application in the agriculture sector as a source of an affordable biocontrol agent. Based on the speculated toxic constituents in the genus Eucomis, it will be valuable to conduct detailed toxicological studies. Extensive utilization of members of the genus Eucomis is causing severe strain on wild populations. Although conventional propagation has been relatively effective in the alleviation of the declining status, micropropagation of members may be vital to guarantee the conservation of wild populations. © 2013 Elsevier Ireland Ltd. All rights reserved.

  10. Pharmacologically directed strategies in academic anticancer drug discovery based on the European NCI compounds initiative.

    Science.gov (United States)

    Hendriks, Hans R; Govaerts, Anne-Sophie; Fichtner, Iduna; Burtles, Sally; Westwell, Andrew D; Peters, Godefridus J

    2017-07-11

    The European NCI compounds programme, a joint initiative of the EORTC Research Branch, Cancer Research Campaign and the US National Cancer Institute, was initiated in 1993. The objective was to help the NCI in reducing the backlog of in vivo testing of potential anticancer compounds, synthesised in Europe that emerged from the NCI in vitro 60-cell screen. Over a period of more than twenty years the EORTC-Cancer Research Campaign panel reviewed ∼2000 compounds of which 95 were selected for further evaluation. Selected compounds were stepwise developed with clear go/no go decision points using a pharmacologically directed programme. This approach eliminated quickly compounds with unsuitable pharmacological properties. A few compounds went into Phase I clinical evaluation. The lessons learned and many of the principles outlined in the paper can easily be applied to current and future drug discovery and development programmes. Changes in the review panel, restrictions regarding numbers and types of compounds tested in the NCI in vitro screen and the appearance of targeted agents led to the discontinuation of the European NCI programme in 2017 and its transformation into an academic platform of excellence for anticancer drug discovery and development within the EORTC-PAMM group. This group remains open for advice and collaboration with interested parties in the field of cancer pharmacology.

  11. A human rights approach to advocacy for people with dementia: A review of current provision in England and Wales.

    Science.gov (United States)

    Dixon, Jeremy; Laing, Judy; Valentine, Christine

    2018-01-01

    In this article, we review current advocacy services for people with dementia in England and Wales (provided, respectively, under the Mental Capacity Act 2005 , the Mental Health Act 1983 /2007 and the Care Act 2014) through the lens of the United Nations Convention on the Rights of Persons with Disabilities (CRPD). We examine what a human rights' approach to advocacy support would entail, and whether current frameworks in England and Wales are adequate for this approach and provide a sufficient safeguard. First, we consider how the human rights of persons with dementia have become increasingly important and the extent to which the CRPD provides an opportunity to bolster safeguards and protection. Second, we discuss cause and case advocacy, and how these advocacy models could be shaped by the CRPD to promote the rights of persons with dementia at each stage of the disease. Third, we highlight current dilemmas and challenges in the provision of advocacy support in England and Wales by focusing on case law, commissioning of services and current practice. In particular, we analyse how the different legislative schemes have given rise to some confusion about the various advocacy provisions, as well as potential for overlap and discrepancies between different regimes. We also highlight the need for further research to address important gaps in knowledge, including the scale of need, patterns of referral and attitudes to advocacy services. The article concludes by highlighting how advocacy support could be recalibrated as a universal right to promote the aims and aspirations of the CRPD, and how education is needed to address the stigma of dementia and promote the benefits of advocacy in protecting the rights of those with dementia.

  12. BPS Pharmacology 2014 - Drug Discovery Pathways symposium Report

    OpenAIRE

    Marsh, Andrew

    2015-01-01

    Report on BPS Pharmacology 2014, BPS Industry Committe and Learned Societies Drug Discovery Pathways Group symposium: "Realizing the potential of new approaches to target identification and validation" by Dr Andrew Marsh Associate Professor Department of Chemistry University of Warwick go.warwick.ac.uk/marshgroup Twitter @marshgroup

  13. Teaching Medical Students Basic Neurotransmitter Pharmacology Using Primary Research Resources

    Science.gov (United States)

    Halliday, Amy C.; Devonshire, Ian M.; Greenfield, Susan A.; Dommett, Eleanor J.

    2010-01-01

    Teaching pharmacology to medical students has long been seen as a challenge, and one to which a number of innovative approaches have been taken. In this article, we describe and evaluate the use of primary research articles in teaching second-year medical students both in terms of the information learned and the use of the papers themselves. We…

  14. The neurobiology and pharmacology of depression: A comparative ...

    African Journals Online (AJOL)

    Background. Over the past decade, targeted drug design has led to significant advances in the pharmacological management of depression. A serendipitous approach to drug discovery has therefore been replaced by the development of drugs acting on predetermined neurobiological targets recognised to be involved in ...

  15. A diagrammatic description of the equations of motion, current and noise within the second-order von Neumann approach

    International Nuclear Information System (INIS)

    Karlström, O; Pedersen, J N; Bergenfeldt, C; Samuelsson, P; Wacker, A; Emary, C; Zedler, P; Brandes, T

    2013-01-01

    We investigate the second-order von Neumann approach from a diagrammatic point of view and demonstrate its equivalence with the resonant tunneling approximation. The investigation of higher order diagrams shows that the method correctly reproduces the equation of motion for the single-particle reduced density matrix of an arbitrary non-interacting many-body system. This explains why the method reproduces the current exactly for such systems. We go on to show, however, that diagrams not included in the method are needed to calculate exactly higher cumulants of the charge transport. This thorough comparison sheds light on the validity of all these self-consistent second-order approaches. We analyze the discrepancy between the noise calculated by our method and the exact Levitov formula for a simple non-interacting quantum dot model. Furthermore, we study the noise of the canyon of current suppression in a two-level dot, a phenomenon that requires the inclusion of electron–electron interaction as well as higher order tunneling processes. (paper)

  16. PHARMACOLOGICAL AND MEDICINAL CHEMISTRY ASPECTS OF CANNABIS COMPOUNDS

    Directory of Open Access Journals (Sweden)

    T. Cotelea

    2011-12-01

    Full Text Available The current communication includes a general overview of the scientific interest and medicianl chemistry aspects of Cannabis compounds. It relates to metabolism, pharmacological action and phisico-chemical analysis of these compounds, as well as of some isomers differing in spatial arrangement of functional groups.

  17. Pharmacological Treatment for Atrial Fibrillation

    Directory of Open Access Journals (Sweden)

    Kaoru Sugi, MD PhD

    2005-01-01

    Full Text Available Pharmacological treatment for atrial fibrillation has a variety of purposes, such as pharmacological defibrillation, maintenance of sinus rhythm, heart rate control to prevent congestive heart failure and prevention of both cerebral infarction and atrial remodeling. Sodium channel blockers are superior to potassium channel blockers for atrial defibrillation, while both sodium and potassium channel blockers are effective in the maintenance of sinus rhythm. In general, digitalis or Ca antagonists are used to control heart rate during atrial fibrillation to prevent congestive heart failure, while amiodarone or bepridil also reduce heart rates during atrial fibrillation. Anticoagulant therapy with warfarin is recommended to prevent cerebral infarction and angiotensin converting enzyme antagonists or angiotensin II receptor blockers are also used to prevent atrial remodeling. One should select appropriate drugs for treatment of atrial fibrillation according to the patient's condition.

  18. Label-free integrative pharmacology on-target of drugs at the β2-adrenergic receptor

    Science.gov (United States)

    Ferrie, Ann M.; Sun, Haiyan; Fang, Ye

    2011-07-01

    We describe a label-free integrative pharmacology on-target (iPOT) method to assess the pharmacology of drugs at the β2-adrenergic receptor. This method combines dynamic mass redistribution (DMR) assays using an array of probe molecule-hijacked cells with similarity analysis. The whole cell DMR assays track cell system-based, ligand-directed, and kinetics-dependent biased activities of the drugs, and translates their on-target pharmacology into numerical descriptors which are subject to similarity analysis. We demonstrate that the approach establishes an effective link between the label-free pharmacology and in vivo therapeutic indications of drugs.

  19. Pharmacological challenges in chronic pancreatitis

    OpenAIRE

    Olesen, Anne Estrup; Brokjaer, Anne; Fisher, Iben Wendelboe; Larsen, Isabelle Myriam

    2013-01-01

    Drug absorption in patients with chronic pancreatitis might be affected by the pathophysiology of the disease. The exocrine pancreatic insufficiency is associated with changes in gastrointestinal intraluminal pH, motility disorder, bacterial overgrowth and changed pancreatic gland secretion. Together these factors can result in malabsorption and may also affect the efficacy of pharmacological intervention. The lifestyle of chronic pancreatitis patients may also contribute to gastrointestinal ...

  20. CURRENT APPROACH TO SINUSITIS

    African Journals Online (AJOL)

    Enrique

    ment of bacterial resistance to the antibiotic.1. Very often antibiotics ... Acute sinusitis is a bacterial infection of one or more of the paranasal sinuses. It .... mathematical model of ABS is as fol- lows:1,8 ... The predicted spontaneous resolution.

  1. Patterns of persistence with pharmacological treatment among patients with current depressive episode and their impact on long-term outcome: a naturalistic study with 5-year follow-up

    Directory of Open Access Journals (Sweden)

    Li K

    2018-05-01

    Full Text Available Kanglai Li,1,* Jiong Tao,2,* Yuemei Li,3 Minhua Chen,2 Xiuhua Wu,2 Yingtao Liao,2 Xiaolan Lin,4 Zhaoyu Gan2 1Department of Very Important Patient, the 3rd Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China; 2Department of Psychiatry, the 3rd Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China; 3Department of Obstetrics, Wuzhou Gongren Hospital, Wuzhou, People’s Republic of China; 4Department of Infectious Diseases, the 3rd Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People’s Republic of China *These authors contributed equally to this work Background: The aim of the study was to describe and compare the patterns of medication persistence among patients with unipolar depression (UD or bipolar depression in a 5-year follow-up, and explore their impact on long-term outcome. Patients and methods: A total of 333 eligible patients with current major depressive episode were observed and followed up from the first index prescription for 5 years. Lack of persistence or treatment interruption was defined as a gap of at least 2 consecutive months without taking any medication. Time to lack of persistence in the first (TLP1 and the second (TLP2 episode of treatment, number of visits before the first treatment interruption (NV and number of treatment interruptions (NTI were measured. Results: During the 5-year follow-up, nearly 50% of patients experienced at least two times of treatment interruption. Pattern of medication persistence did not significantly differ between UD and bipolar disorder (BD patients. TLP1 was positively associated with TLP2. Shorter TLP1 predicted a higher possibility of subsequent visits because of recurrence or relapse and more NTI meant a lower likelihood of achieving full remission in the fifth year for both UD and BD patients. For UD patients, shorter TLP1 or less NV predicted a lower chance of achieving remission, while for BD patients

  2. Applications of stable isotopes in clinical pharmacology

    NARCIS (Netherlands)

    Schellekens, Reinout C A; Stellaard, Frans; Woerdenbag, Herman J; Frijlink, Henderik W; Kosterink, Jos G W

    2011-01-01

    This review aims to present an overview of the application of stable isotope technology in clinical pharmacology. Three main categories of stable isotope technology can be distinguished in clinical pharmacology. Firstly, it is applied in the assessment of drug pharmacology to determine the

  3. Pharmacological treatment of diabetic neuropathic pain.

    Science.gov (United States)

    Smith, Howard S; Argoff, Charles E

    2011-03-26

    Neuropathic pain continues to be a difficult and challenging clinical issue to deal with effectively. Painful diabetic polyneuropathy is a complex pain condition that occurs with reasonable frequency in the population and it may be extremely difficult for clinicians to provide patients with effective analgesia. Chronic neuropathic pain may occur in approximately one of every four diabetic patients. The pain may be described as burning or a deep-seated ache with sporadic paroxysms of lancinating painful exacerbations. The pain is often constant, moderate to severe in intensity, usually primarily involves the feet and generally tends to worsen at night. Treatment may be multimodal but largely involves pharmacological approaches. Pharmacological therapeutic options include antidepressants (tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors), α2δ ligands and topical (5%) lidocaine patch. Other agents may be different antiepileptic drugs (carbamazepine, lamotrigine, topiramate), topical capsaicin, tramadol and other opioids. Progress continues with respect to understanding various mechanisms that may contribute to painful diabetic neuropathy. Agents that may hold some promise include neurotrophic factors, growth factors, immunomodulators, gene therapy and poly (adenosine diphosphate-ribose) polymerase inhibitors. It is hoped that in the future clinicians will be able to assess patient pathophysiology, which may help them to match optimal therapeutic agents to target individual patient aberrant mechanisms.

  4. Approaches to chronic disease management evaluation in use in Europe: a review of current methods and performance measures.

    Science.gov (United States)

    Conklin, Annalijn; Nolte, Ellen; Vrijhoef, Hubertus

    2013-01-01

    An overview was produced of approaches currently used to evaluate chronic disease management in selected European countries. The study aims to describe the methods and metrics used in Europe as a first to help advance the methodological basis for their assessment. A common template for collection of evaluation methods and performance measures was sent to key informants in twelve European countries; responses were summarized in tables based on template evaluation categories. Extracted data were descriptively analyzed. Approaches to the evaluation of chronic disease management vary widely in objectives, designs, metrics, observation period, and data collection methods. Half of the reported studies used noncontrolled designs. The majority measure clinical process measures, patient behavior and satisfaction, cost and utilization; several also used a range of structural indicators. Effects are usually observed over 1 or 3 years on patient populations with a single, commonly prevalent, chronic disease. There is wide variation within and between European countries on approaches to evaluating chronic disease management in their objectives, designs, indicators, target audiences, and actors involved. This study is the first extensive, international overview of the area reported in the literature.

  5. The current CEA/DRN safety approach for the design and the assessment of future nuclear installations

    International Nuclear Information System (INIS)

    Fiorini, G.L.; Pinto, P.L.; Costa, M.

    1999-01-01

    The purpose of the document is to present the basis of the safety approach currently implemented by the CEA/DRN, both for the design and the assessment of innovative systems and future nuclear installations. This approach is the result of the experience maturated, within the context of the CEA/DRN Innovative Programme through practical applications over several future concepts, both for fission and fusion reactors, as well as for waste disposal. The background of this experience is structured coherently with the European Safety Authorities recommendations and the European Utilities Requirements (EUR). The Defence In Depth principle and its application, by means, among others, of the barrier concept, remains the basis of the safety design process of future nuclear installations. Its adequacy is checked through the safety assessment. The methodology for Lines Of Defence (LOD) implementation as well as the one for the LOD architecture assessment is shown and motivated. The document shows that the clear and unambiguous definition of the safety approach provides an essential base for the organisation of the design tasks, being sure that the safety aspects are correctly taken into account and implemented, and for an adequate safety assessment of the final design, both from qualitative point of view as well as for the quantitative safety analysis. (author)

  6. From Medicinal Chemistry to Human Health: Current Approaches to Drug Discovery for Cancer and Neglected Tropical Diseases

    Directory of Open Access Journals (Sweden)

    LEONARDO G. FERREIRA

    2018-02-01

    Full Text Available ABSTRACT Scientific and technological breakthroughs have compelled the current players in drug discovery to increasingly incorporate knowledge-based approaches. This evolving paradigm, which has its roots attached to the recent advances in medicinal chemistry, molecular and structural biology, has unprecedentedly demanded the development of up-to-date computational approaches, such as bio- and chemo-informatics. These tools have been pivotal to catalyzing the ever-increasing amount of data generated by the molecular sciences, and to converting the data into insightful guidelines for use in the research pipeline. As a result, ligand- and structure-based drug design have emerged as key pathways to address the pharmaceutical industry’s striking demands for innovation. These approaches depend on a keen integration of experimental and molecular modeling methods to surmount the main challenges faced by drug candidates - in vivo efficacy, pharmacodynamics, metabolism, pharmacokinetics and safety. To that end, the Laboratório de Química Medicinal e Computacional (LQMC of the Universidade de São Paulo has developed forefront research on highly prevalent and life-threatening neglected tropical diseases and cancer. By taking part in global initiatives for pharmaceutical innovation, the laboratory has contributed to the advance of these critical therapeutic areas through the use of cutting-edge strategies in medicinal chemistry.

  7. Rotor Current Control of DFIG for Improving Fault Ride - Through Using a Novel Sliding Mode Control Approach

    Science.gov (United States)

    Cai, Guowei; Liu, Cheng; Yang, Deyou

    2013-11-01

    The doubly fed induction generators (DFIG) have been recognized as the dominant technology used in wind power generation systems with the rapid development of wind power. However, continuous operation of DFIG may cause a serious wind turbine generators tripping accident, due to destructive over-current in the rotor winding which is caused by the power system fault or inefficient fault ride-through (FRT) strategy. A new rotor current control scheme in the rotor-side converter (RSC) ispresented to enhance FRT capacities of grid-connected DFIG. Due to the strongly nonlinear nature of DFIG and insensitive to DFIG parameter's variations, a novel sliding mode controller was designed. The controller combines extended state observer (ESO) with sliding model variable structure control theory. The simulation is carried out to verify the effectiveness of the proposed control approach under various types of grid disturbances. It is shown that the proposed controller provides enhanced transient features than the classic proportional-integral control. The proposed control method can effectively reduce over-current in the RSC, and the transient pulse value of electromagnetic torque is too large under power grid fault.

  8. Electronic cigarettes and nicotine clinical pharmacology.

    Science.gov (United States)

    Schroeder, Megan J; Hoffman, Allison C

    2014-05-01

    To review the available literature evaluating electronic cigarette (e-cigarette) nicotine clinical pharmacology in order to understand the potential impact of e-cigarettes on individual users, nicotine dependence and public health. Literature searches were conducted between 1 October 2012 and 30 September 2013 using key terms in five electronic databases. Studies were included in the review if they were in English and publicly available; non-clinical studies, conference abstracts and studies exclusively measuring nicotine content in e-cigarette cartridges were excluded from the review. Nicotine yields from automated smoking machines suggest that e-cigarettes deliver less nicotine per puff than traditional cigarettes, and clinical studies indicate that e-cigarettes deliver only modest nicotine concentrations to the inexperienced e-cigarette user. However, current e-cigarette smokers are able to achieve systemic nicotine and/or cotinine concentrations similar to those produced from traditional cigarettes. Therefore, user experience is critically important for nicotine exposure, and may contribute to the products' ability to support and maintain nicotine dependence. Knowledge about e-cigarette nicotine pharmacology remains limited. Because a user's e-cigarette experience may significantly impact nicotine delivery, future nicotine pharmacokinetic and pharmacodynamic studies should be conducted in experienced users to accurately assess the products' impact on public health.

  9. Electronic cigarettes and nicotine clinical pharmacology

    Science.gov (United States)

    Schroeder, Megan J; Hoffman, Allison C

    2014-01-01

    Objective To review the available literature evaluating electronic cigarette (e-cigarette) nicotine clinical pharmacology in order to understand the potential impact of e-cigarettes on individual users, nicotine dependence and public health. Methods Literature searches were conducted between 1 October 2012 and 30 September 2013 using key terms in five electronic databases. Studies were included in the review if they were in English and publicly available; non-clinical studies, conference abstracts and studies exclusively measuring nicotine content in e-cigarette cartridges were excluded from the review. Results Nicotine yields from automated smoking machines suggest that e-cigarettes deliver less nicotine per puff than traditional cigarettes, and clinical studies indicate that e-cigarettes deliver only modest nicotine concentrations to the inexperienced e-cigarette user. However, current e-cigarette smokers are able to achieve systemic nicotine and/or cotinine concentrations similar to those produced from traditional cigarettes. Therefore, user experience is critically important for nicotine exposure, and may contribute to the products’ ability to support and maintain nicotine dependence. Conclusions Knowledge about e-cigarette nicotine pharmacology remains limited. Because a user's e-cigarette experience may significantly impact nicotine delivery, future nicotine pharmacokinetic and pharmacodynamic studies should be conducted in experienced users to accurately assess the products’ impact on public health. PMID:24732160

  10. Harnessing Big Data for Systems Pharmacology.

    Science.gov (United States)

    Xie, Lei; Draizen, Eli J; Bourne, Philip E

    2017-01-06

    Systems pharmacology aims to holistically understand mechanisms of drug actions to support drug discovery and clinical practice. Systems pharmacology modeling (SPM) is data driven. It integrates an exponentially growing amount of data at multiple scales (genetic, molecular, cellular, organismal, and environmental). The goal of SPM is to develop mechanistic or predictive multiscale models that are interpretable and actionable. The current explosions in genomics and other omics data, as well as the tremendous advances in big data technologies, have already enabled biologists to generate novel hypotheses and gain new knowledge through computational models of genome-wide, heterogeneous, and dynamic data sets. More work is needed to interpret and predict a drug response phenotype, which is dependent on many known and unknown factors. To gain a comprehensive understanding of drug actions, SPM requires close collaborations between domain experts from diverse fields and integration of heterogeneous models from biophysics, mathematics, statistics, machine learning, and semantic webs. This creates challenges in model management, model integration, model translation, and knowledge integration. In this review, we discuss several emergent issues in SPM and potential solutions using big data technology and analytics. The concurrent development of high-throughput techniques, cloud computing, data science, and the semantic web will likely allow SPM to be findable, accessible, interoperable, reusable, reliable, interpretable, and actionable.

  11. Polymeric drugs: Advances in the development of pharmacologically active polymers

    Science.gov (United States)

    Li, Jing; Yu, Fei; Chen, Yi; Oupický, David

    2015-01-01

    Synthetic polymers play a critical role in pharmaceutical discovery and development. Current research and applications of pharmaceutical polymers are mainly focused on their functions as excipients and inert carriers of other pharmacologically active agents. This review article surveys recent advances in alternative pharmaceutical use of polymers as pharmacologically active agents known as polymeric drugs. Emphasis is placed on the benefits of polymeric drugs that are associated with their macromolecular character and their ability to explore biologically relevant multivalency processes. We discuss the main therapeutic uses of polymeric drugs as sequestrants, antimicrobials, antivirals, and anticancer and anti-inflammatory agents. PMID:26410809

  12. Noradrenergic augmentation strategies in the pharmacological treatment of depression and schizophrenia : An experimental study

    OpenAIRE

    Linnér, Love

    2002-01-01

    The pharmacological treatment of depression and schizophrenia, two major psychiatric disorders, is largely based on modulation of central monoaminergic neurotransmission. However, currently available pharmacological treatment alternatives possess a relatively modest clinical efficacy, making them less than optimal. The present series of studies, using in vivo electrophysiological, biochemical and behavioral techniques in rats, aim at the disclosure of mechanisms whereby an ...

  13. What is a food and what is a medicinal product in the European Union? Use of the benchmark dose (BMD) methodology to define a threshold for "pharmacological action".

    Science.gov (United States)

    Lachenmeier, Dirk W; Steffen, Christian; el-Atma, Oliver; Maixner, Sibylle; Löbell-Behrends, Sigrid; Kohl-Himmelseher, Matthias

    2012-11-01

    The decision criterion for the demarcation between foods and medicinal products in the EU is the significant "pharmacological action". Based on six examples of substances with ambivalent status, the benchmark dose (BMD) method is evaluated to provide a threshold for pharmacological action. Using significant dose-response models from literature clinical trial data or epidemiology, the BMD values were 63mg/day for caffeine, 5g/day for alcohol, 6mg/day for lovastatin, 769mg/day for glucosamine sulfate, 151mg/day for Ginkgo biloba extract, and 0.4mg/day for melatonin. The examples for caffeine and alcohol validate the approach because intake above BMD clearly exhibits pharmacological action. Nevertheless, due to uncertainties in dose-response modelling as well as the need for additional uncertainty factors to consider differences in sensitivity within the human population, a "borderline range" on the dose-response curve remains. "Pharmacological action" has proven to be not very well suited as binary decision criterion between foods and medicinal product. The European legislator should rethink the definition of medicinal products, as the current situation based on complicated case-by-case decisions on pharmacological action leads to an unregulated market flooded with potentially illegal food supplements. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. The current status of exposure-driven approaches for chemical safety assessment: A cross-sector perspective.

    Science.gov (United States)

    Sewell, Fiona; Aggarwal, Manoj; Bachler, Gerald; Broadmeadow, Alan; Gellatly, Nichola; Moore, Emma; Robinson, Sally; Rooseboom, Martijn; Stevens, Alexander; Terry, Claire; Burden, Natalie

    2017-08-15

    For the purposes of chemical safety assessment, the value of using non-animal (in silico and in vitro) approaches and generating mechanistic information on toxic effects is being increasingly recognised. For sectors where in vivo toxicity tests continue to be a regulatory requirement, there has been a parallel focus on how to refine studies (i.e. reduce suffering and improve animal welfare) and increase the value that in vivo data adds to the safety assessment process, as well as where to reduce animal numbers where possible. A key element necessary to ensure the transition towards successfully utilising both non-animal and refined safety testing is the better understanding of chemical exposure. This includes approaches such as measuring chemical concentrations within cell-based assays and during in vivo studies, understanding how predicted human exposures relate to levels tested, and using existing information on human exposures to aid in toxicity study design. Such approaches promise to increase the human relevance of safety assessment, and shift the focus from hazard-driven to risk-driven strategies similar to those used in the pharmaceutical sectors. Human exposure-based safety assessment offers scientific and 3Rs benefits across all sectors marketing chemical or medicinal products. The UK's National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) convened an expert working group of scientists across the agrochemical, industrial chemical and pharmaceutical industries plus a contract research organisation (CRO) to discuss the current status of the utilisation of exposure-driven approaches, and the challenges and potential next steps for wider uptake and acceptance. This paper summarises these discussions, highlights the challenges - particularly those identified by industry - and proposes initial steps for moving the field forward. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

  15. Factors Affecting the Pharmacology of Antibody–Drug Conjugates

    Directory of Open Access Journals (Sweden)

    Andrew T. Lucas

    2018-02-01

    Full Text Available Major advances in therapeutic proteins, including antibody–drug conjugates (ADCs, have created revolutionary drug delivery systems in cancer over the past decade. While these immunoconjugate agents provide several advantages compared to their small-molecule counterparts, their clinical use is still in its infancy. The considerations in their development and clinical use are complex, and consist of multiple components and variables that can affect the pharmacologic characteristics. It is critical to understand the mechanisms employed by ADCs in navigating biological barriers and how these factors affect their biodistribution, delivery to tumors, efficacy, and toxicity. Thus, future studies are warranted to better understand the complex pharmacology and interaction between ADC carriers and biological systems, such as the mononuclear phagocyte system (MPS and tumor microenvironment. This review provides an overview of factors that affect the pharmacologic profiles of ADC therapies that are currently in clinical use and development.

  16. Rehmannia glutinosa: review of botany, chemistry and pharmacology.

    Science.gov (United States)

    Zhang, Ru-Xue; Li, Mao-Xing; Jia, Zheng-Ping

    2008-05-08

    Rehmannia glutinosa, a widely used traditional Chinese herb, belongs to the family of Scrophulariaceae, and is taken to nourish Yin and invigorate the kidney in traditional Chinese medicine (TCM) and has a very high medicinal value. In recent decades, a great number of chemical and pharmacological studies have been done on Rehmannia glutinosa. More than 70 compounds including iridoids, saccharides, amino acid, inorganic ions, as well as other trace elements have been found in the herb. Studies show that Rehmannia glutinosa and its active principles possess wide pharmacological actions on the blood system, immune system, endocrine system, cardiovascular system and the nervous system. Currently, the effective monomeric compounds or active parts have been screened for the pharmacological activity of Rehmannia glutinosa and the highest quality scientific data is delivered to support the further application and exploitation for new drug development.

  17. Current approaches to treatments for schizophrenia spectrum disorders, part II: psychosocial interventions and patient-focused perspectives in psychiatric care

    Directory of Open Access Journals (Sweden)

    Chien WT

    2013-09-01

    functioning, and/or relapse rate. However, the comparative effects between these five approaches have not been well studied; thus, we are not able to clearly understand the superiority of any of these interventions. With the exception of patient relapse, the longer-term (eg, >2 years effects of these approaches on most psychosocial outcomes are not well-established among these patients. Despite the fact that patients' perspectives on treatment and care have been increasingly concerned, not many studies have evaluated the effect of interventions on this perspective, and where they did, the findings were inconclusive. To conclude, current approaches to psychosocial interventions for schizophrenia have their strengths and weaknesses, particularly indicating limited evidence on long-term effects. To improve the longer-term outcomes of people with schizophrenia, future treatment strategies should focus on risk identification, early intervention, person-focused therapy, partnership with family caregivers, and the integration of evidence-based psychosocial interventions into existing services. Keywords: schizophrenia, psychosocial intervention, patient-focused perspectives

  18. Pharmacological chaperoning: a primer on mechanism and pharmacology.

    Science.gov (United States)

    Leidenheimer, Nancy J; Ryder, Katelyn G

    2014-05-01

    Approximately forty percent of diseases are attributable to protein misfolding, including those for which genetic mutation produces misfolding mutants. Intriguingly, many of these mutants are not terminally misfolded since native-like folding, and subsequent trafficking to functional locations, can be induced by target-specific, small molecules variably termed pharmacological chaperones, pharmacoperones, or pharmacochaperones (PCs). PC targets include enzymes, receptors, transporters, and ion channels, revealing the breadth of proteins that can be engaged by ligand-assisted folding. The purpose of this review is to provide an integrated primer of the diverse mechanisms and pharmacology of PCs. In this regard, we examine the structural mechanisms that underlie PC rescue of misfolding mutants, including the ability of PCs to act as surrogates for defective intramolecular interactions and, at the intermolecular level, overcome oligomerization deficiencies and dominant negative effects, as well as influence the subunit stoichiometry of heteropentameric receptors. Not surprisingly, PC-mediated structural correction of misfolding mutants normalizes interactions with molecular chaperones that participate in protein quality control and forward-trafficking. A variety of small molecules have proven to be efficacious PCs and the advantages and disadvantages of employing orthostatic antagonists, active-site inhibitors, orthostatic agonists, and allosteric modulator PCs are considered. Also examined is the possibility that several therapeutic agents may have unrecognized activity as PCs, and this chaperoning activity may mediate/contribute to therapeutic action and/or account for adverse effects. Lastly, we explore evidence that pharmacological chaperoning exploits intrinsic ligand-assisted folding mechanisms. Given the widespread applicability of PC rescue of mutants associated with protein folding disorders, both in vitro and in vivo, the therapeutic potential of PCs is vast

  19. Economic evaluations of pharmacogenetic approaches in infectious diseases: a review of current approaches and evaluation of critical aspects affecting their quality

    Directory of Open Access Journals (Sweden)

    Paolo Meoni

    2013-11-01

    Full Text Available Pharmacogenetics holds great potential for improving the effectiveness of treatment modalities in infectious diseases by taking into account the genetic determinants of both the host and infectious agents’ individuality. Better utilization of resources and improved therapeutic efficiency are the expected outcomes of personalized medicine using pharmacogenetic and pharmacogenomics information made available by technological advances. However, there has been growing concern in the clinical community regarding the evaluation of the true benefits of these approaches. This perception is partly due to the limited number and perceived poor quality of economic evaluations in this field, and initiatives aimed at harmonizing and communicating strategies improving the quality of these studies and their acceptance by the clinical community are greatly needed. This paper reviews current literature of economic evaluations of pharmacogenetics interventions guiding pharmacotherapy in infectious diseases. PubMed and the NHS Centre for Reviews and Dissemination databases were searched using a combination of five broad research terms related to pharmacogenetic approaches, and papers relative to economic evaluations of pharmacogenetic interventions in infectious diseases retained for further analysis. Using these criteria, a total of 14 papers were included in this review. The area of economic evaluation of pharmacogenetic interventions in infectious diseases remains understudied and would benefit from greater harmonization. The main weaknesses of evaluations reviewed in this paper seem to be represented by poor evidence of pharmacogenetic marker validation, inconsistencies in the selection of costs and utility included in the economic models and the choice of sensitivity analysis. All these factors limit the overall transparency of the studies, greater acceptance of their results and applicability to diverse and possibly resourcelimited environments where these

  20. Current approaches to improve the anticancer chemotherapy with alkylating agents: state of the problem in world and Ukraine.

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    Iatsyshyna A. P.

    2012-01-01

    Full Text Available Alkylating agents are frequently used in many established anticancer chemotherapies. They alkylate the genomic DNA at various sites. Alkylation of the guanine at the O6-position is cytotoxic, it has the strongest mutagenic potential, as well as can cause the tumor development. Alkyl groups at the O6-position of guanine are removed by the DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT. The effectiveness of alkylating chemotherapy is limited by MGMT in cancer cells and adverse toxic side effects in normal cells. Different approaches consisting in the modulation of the MGMT expression and activity are under development now to improve the cancer chemotherapy. They include two main directions, in particular, the increase in chemosensitivity of cancer cells to alkylating drugs and the protection of normal cells from the toxic side effects of chemotherapy. This review is focused on current attempts to improve the alkylating chemotherapy of malignant tumours worldwide and state of the issue in Ukraine